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Sample records for dysfunction redirects cellular

  1. Asteroid Redirect

    OpenAIRE

    De Aquino, Fran

    2017-01-01

    Asteroids are a great threat to mankind. Here we will show that it is possible to redirect them from their trajectories by means of a strong gravitational repulsion, produced by the gravitational interaction between the asteroid and a Gravitational Spacecraft positioned close to the asteroid.

  2. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy

    Science.gov (United States)

    Hotchkiss, Richard S.; Monneret, Guillaume; Payen, Didier

    2014-01-01

    Sepsis — severe life-threatening infection with organ dysfunction — initiates a complex interplay of host pro- and anti-inflammatory processes. In a real sense, sepsis can be considered a race to the death between the pathogens and the host immune system. It is the proper balance between the often competing pro- and anti-inflammatory pathways that determines the fate of the individual. Although the field of sepsis research has witnessed the failure of many highly-touted clinical trials, a better understanding of the pathophysiological basis of the disorder and the mechanisms responsible for the associated pro- and anti-inflammatory responses is leading to a novel approach to treat this highly lethal condition. Biomarker-guided immunotherapy administered to patients at the proper immune phase of sepsis represents a potential major advance in the treatment of sepsis and more broadly in the field of infectious disease. PMID:24232462

  3. Cellular dysfunction in diabetes as maladaptive response to mitochondrial oxidative stress.

    Science.gov (United States)

    Naudi, Alba; Jove, Mariona; Ayala, Victoria; Cassanye, Anna; Serrano, Jose; Gonzalo, Hugo; Boada, Jordi; Prat, Joan; Portero-Otin, Manuel; Pamplona, Reinald

    2012-01-01

    Oxidative stress has been implicated in diabetes long-term complications. In this paper, we summarize the growing evidence suggesting that hyperglycemia-induced overproduction of superoxide by mitochondrial electron transport chain triggers a maladaptive response by affecting several metabolic and signaling pathways involved in the pathophysiology of cellular dysfunction and diabetic complications. In particular, it is our goal to describe physiological mechanisms underlying the mitochondrial free radical production and regulation to explain the oxidative stress derived from a high intracellular glucose concentration and the resulting maladaptive response that leads to a cellular dysfunction and pathological state. Finally, we outline potential therapies for diabetes focused to the prevention of mitochondrial oxidative damage.

  4. Redirecting International Trade

    DEFF Research Database (Denmark)

    Kokko, Ari; Söderlund, Bengt; Tingvall, Patrik Gustavsson

    The global financial crisis has accelerated the redirection of trade towards new markets, outside the OECD area, where both demand patterns and the institutional environment differ from those in the OECD. This study provides an empirical examination of the consequences of this shift. Results...... difficult to redirect towards markets with weak institutions....... suggest that weak institutions hamper trade and reduces the length of trade relations, especially for small firms. Furthermore, trade in industries that are characterized by a high degree of trade conflicts and that requires extensive relationship specific investments for trade to occur are comparatively...

  5. Redirecting International Trade

    DEFF Research Database (Denmark)

    Kokko, Ari; Söderlund, Bengt; Tingvall, Patrik Gustavsson

    2014-01-01

    The global financial crisis has contributed to the redirection of trade towards new markets outside the OECD area, where both demand patterns and the institutional environment differ from those in the OECD. This study provides an empirical examination of the consequences of this shift, based......-specific investments are particularly difficult to redirect towards markets with weak institutions....... on Swedish firm-level trade data. Results suggest that weak institutions hamper trade and reduce the length of trade relations, especially for small firms. Trade in industries that are characterized by a high frequency of trade conflicts and where transactions require extensive relationship...

  6. Redirecting by Injector

    Science.gov (United States)

    Filman, Robert E.; Lee, Diana D.; Norvig, Peter (Technical Monitor)

    2000-01-01

    We describe the Object Infrastructure Framework, a system that seeks to simplify the creation of distributed applications by injecting behavior on the communication paths between components. We touch on some of the ilities and services that can be achieved with injector technology, and then focus on the uses of redirecting injectors, injectors that take requests directed at a particular server and generate requests directed at others. We close by noting that OIF is an Aspect-Oriented Programming system, and comparing OIF to related work.

  7. Mitochondrial dysfunction induced by frataxin deficiency is associated with cellular senescence and abnormal calcium metabolism

    Directory of Open Access Journals (Sweden)

    Arantxa eBolinches-Amorós

    2014-05-01

    Full Text Available Friedreich ataxia is considered a neurodegenerative disorder involving both the peripheral and central nervous systems. Dorsal root ganglia (DRG are the major target tissue structures. This neuropathy is caused by mutations in the FXN gene that encodes frataxin. Here, we investigated the mitochondrial and cell consequences of frataxin depletion in a cellular model based on frataxin silencing in SH-SY5Y human neuroblastoma cells, a cell line that has been used widely as in vitro models for studies on neurological diseases. We showed that the reduction of frataxin induced mitochondrial dysfunction due to a bioenergetic deficit and abnormal Ca2+ homeostasis in the mitochondria that were associated with oxidative and endoplasmic reticulum stresses. The depletion of frataxin did not cause cell death but increased autophagy, which may have a cytoprotective effect against cellular insults such as oxidative stress. Frataxin silencing provoked slow cell growth associated with cellular senescence, as demonstrated by increased SA-βgal activity and cell cycle arrest at the G1 phase. We postulate that cellular senescence might be related to a hypoplastic defect in the DRG during neurodevelopment, as suggested by necropsy studies.

  8. Molecular and cellular mechanisms of tight junction dysfunction in the irritable bowel syndrome.

    Science.gov (United States)

    Cheng, Peng; Yao, Jianning; Wang, Chunfeng; Zhang, Lianfeng; Kong, Wuming

    2015-09-01

    The pathophysiological mechanisms of the irritable bowel syndrome (IBS), one of the most prevalent gastrointestinal disorders, are complex and have not been fully elucidated. The present study aimed to investigate the molecular and cellular mechanisms of tight junction (TJ) dysfunction in IBS. Intestinal tissues of IBS and non‑IBS patients were examined to observe cellular changes by cell chemical tracer electron microscopy and transmission electron microscopy, and intestinal claudin‑1 protein was detected by immunohistochemistry, western blot analysis and fluorescence quantitative polymerase chain reaction. Compared with the control group, TJ broadening and the tracer extravasation phenomenon were observed in the diarrhea‑predominant IBS group, and a greater number of neuroendocrine cells and mast cells filled with high‑density particles in the endocrine package pulp as well as a certain extent of vacuolization were present. The expression of claudin‑1 in diarrhea‑predominant IBS patients was decreased, while it was increased in constipation‑predominant IBS patients. In conclusion, the results of the present study indicated that changes in cellular structure and claudin‑1 levels were associated with Tjs in IBS.

  9. Mitochondria localization induced self-assembly of peptide amphiphiles for cellular dysfunction.

    Science.gov (United States)

    Jeena, M T; Palanikumar, L; Go, Eun Min; Kim, Inhye; Kang, Myoung Gyun; Lee, Seonik; Park, Sooham; Choi, Huyeon; Kim, Chaekyu; Jin, Seon-Mi; Bae, Sung Chul; Rhee, Hyun Woo; Lee, Eunji; Kwak, Sang Kyu; Ryu, Ja-Hyoung

    2017-06-21

    Achieving spatiotemporal control of molecular self-assembly associated with actuation of biological functions inside living cells remains a challenge owing to the complexity of the cellular environments and the lack of characterization tools. We present, for the first time, the organelle-localized self-assembly of a peptide amphiphile as a powerful strategy for controlling cellular fate. A phenylalanine dipeptide (FF) with a mitochondria-targeting moiety, triphenyl phosphonium (Mito-FF), preferentially accumulates inside mitochondria and reaches the critical aggregation concentration to form a fibrous nanostructure, which is monitored by confocal laser scanning microscopy and transmission electron microscopy. The Mito-FF fibrils induce mitochondrial dysfunction via membrane disruption to cause apoptosis. The organelle-specific supramolecular system provides a new opportunity for therapeutics and in-depth investigations of cellular functions.Spatiotemporal control of intracellular molecular self-assembly holds promise for therapeutic applications. Here the authors develop a peptide consisting of a phenylalanine dipeptide with a mitochondrial targeting moiety to form self-assembling fibrous nanostructures within mitochondria, leading to apoptosis.

  10. NASA's Asteroid Redirect Mission (ARM)

    Science.gov (United States)

    Abell, P. A.; Mazanek, D. D.; Reeves, D. M.; Chodas, P. W.; Gates, M. M.; Johnson, L. N.; Ticker, R. L.

    2017-01-01

    Mission Description and Objectives: NASA's Asteroid Redirect Mission (ARM) consists of two mission segments: 1) the Asteroid Redirect Robotic Mission (ARRM), a robotic mission to visit a large (greater than approximately 100 meters diameter) near-Earth asteroid (NEA), collect a multi-ton boulder from its surface along with regolith samples, and return the asteroidal material to a stable orbit around the Moon; and 2) the Asteroid Redirect Crewed Mission (ARCM), in which astronauts will explore and investigate the boulder and return to Earth with samples. The ARRM is currently planned to launch at the end of 2021 and the ARCM is scheduled for late 2026.

  11. Aldolase B knockdown prevents high glucose-induced methylglyoxal overproduction and cellular dysfunction in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Jianghai Liu

    Full Text Available We used cultured endothelial cells as a model to examine whether up-regulation of aldolase B and enhanced methylglyoxal (MG formation play an important role in high glucose-induced overproduction of advanced glycosylation endproducts (AGEs, oxidative stress and cellular dysfunction. High glucose (25 mM incubation up-regulated mRNA levels of aldose reductase (an enzyme converting glucose to fructose and aldolase B (a key enzyme that catalyzes MG formation from fructose and enhanced MG formation in human umbilical vein endothelial cells (HUVECs and HUVEC-derived EA. hy926 cells. High glucose-increased MG production in EA. hy926 cells was completely prevented by siRNA knockdown of aldolase B, but unaffected by siRNA knockdown of aldolase A, an enzyme responsible for MG formation during glycolysis. In addition, inhibition of cytochrome P450 2E1 or semicarbazide-sensitive amine oxidase which produces MG during the metabolism of lipid and proteins, respectively, did not alter MG production. Both high glucose (25 mM and MG (30, 100 µM increased the formation of N(ε-carboxyethyl-lysine (CEL, a MG-induced AGE, oxidative stress (determined by the generation of oxidized DCF, H(2O(2, protein carbonyls and 8-oxo-dG, O-GlcNAc modification (product of the hexosamine pathway, membrane protein kinase C activity and nuclear translocation of NF-κB in EA. hy926 cells. However, the above metabolic and signaling alterations induced by high glucose were completely prevented by knockdown of aldolase B and partially by application of aminoguanidine (a MG scavenger or alagebrium (an AGEs breaker. In conclusion, efficient inhibition of aldolase B can prevent high glucose-induced overproduction of MG and related cellular dysfunction in endothelial cells.

  12. Redirecting treatment during neonatal transport.

    Science.gov (United States)

    Dulkerian, Susan J; Douglas, Webra Price; Taylor, Renee McCraine

    2011-01-01

    Neonatal transport teams comprise multidisciplinary health care providers who are skilled in patient care, communication and customer service, and equipment mechanics. They are extensively trained in resuscitation and stabilization, preparing for accelerating care, and their focus is preservation of life. In any situation focused on caring for critically ill patients, ethical issues and questions may arise. For instance, is it compassionate and/or cost-effective to separate mothers and infants when continuing/accelerating care is futile, and when and how should care be redirected from acute and lifesaving care to comfort care and bereavement support for the family? The knowledge and skills required to address such situations and communicate and participate in a redirection of care may not be adequately emphasized in the preparation of the professionals responsible for stabilizing and transporting critically ill newborns. This article raises issues relating to transport and redirecting care such as eligibility for transport, parental request and consent, separation of mothers and infants, palliative and bereavement care, ethical considerations, competitive transport environment, and customer service. A shared mental model is essential. The focus of this article is not to provide answers to all of these issues, but to highlight the complexity of the topic of redirecting treatment during neonatal transport. Redirecting treatment needs to be discussed, and health care professionals should be prepared during their transport team training. Each family and situation must be approached individually, with the acceptance that there will always be more questions than answers.

  13. Stress testing at the cellular and molecular level to unravel cellular dysfunction and growth factor signal transduction defects: what Molecular Cell Biology can learn from Cardiology.

    Science.gov (United States)

    Waltenberger, Johannes

    2007-11-01

    Clinical medicine has been revolutionized by the impact of cellular and molecular biology in the past 30 years. This article focuses on a novel approach, whereby the clinically proven and important concept of patient or organ stress testing is being applied to cellular models, thereby developing and validating novel quantitative molecular and cellular stress tests. One example is monocyte chemotaxis analysis, whereby circulating monocytes freshly isolated from peripheral blood are being tested for their migratory responsiveness towards relevant biological stimuli such as growth factors or chemokines. These stimuli are relevant for recruiting monocytes to sites of local inflammation such as during wound healing or arteriogenesis, i.e. growth of collateral arteries. Initial clinical studies to validate "ligand-induced monocyte chemotaxis" indicate that this parameter is impaired in the presence of various cardiovascular risk factors including diabetes mellitus, hypercholesterolemia or smoking. In addition, there is proof of concept that impaired monocyte chemotaxis is reversible as shown for anti-oxidants in smokers. Moreover, the parameter "ligand-induced monocyte chemotaxis" is of great relevance for basic science (including Molecular Cell Biology) as unravelling the underlying molecular mechanisms of cellular dysfunction will certainly stimulate our understanding of the molecular basis of cellular function. This article highlights the concept of stress testing in modern medicine. Cellular stress testing is introduced as a novel and intriguing approach, which was developed as bedside-to-bench. Future prospective clinical trials will have to validate the predictive value of cellular stress testing.

  14. Dysfunction of nucleus accumbens-1 activates cellular senescence and inhibits tumor cell proliferation and oncogenesis.

    Science.gov (United States)

    Zhang, Yi; Cheng, Yan; Ren, Xingcong; Hori, Tsukasa; Huber-Keener, Kathryn J; Zhang, Li; Yap, Kai Lee; Liu, David; Shantz, Lisa; Qin, Zheng-Hong; Zhang, Suping; Wang, Jianrong; Wang, Hong-Gang; Shih, Ie-Ming; Yang, Jin-Ming

    2012-08-15

    Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the BTB/POZ gene family, has emerging roles in cancer. We report here that NAC1 acts as a negative regulator of cellular senescence in transformed and nontransformed cells, and dysfunction of NAC1 induces senescence and inhibits its oncogenic potential. We show that NAC1 deficiency markedly activates senescence and inhibits proliferation in tumor cells treated with sublethal doses of γ-irradiation. In mouse embryonic fibroblasts from NAC1 knockout mice, following infection with a Ras virus, NAC1-/- cells undergo significantly more senescence and are either nontransformed or less transformed in vitro and less tumorigenic in vivo when compared with NAC1+/+ cells. Furthermore, we show that the NAC1-caused senescence blunting is mediated by ΔNp63, which exerts its effect on senescence through p21, and that NAC1 activates transcription of ΔNp63 under stressful conditions. Our results not only reveal a previously unrecognized function of NAC1, the molecular pathway involved and its impact on pathogenesis of tumor initiation and development, but also identify a novel senescence regulator that may be exploited as a potential target for cancer prevention and treatment.

  15. Does Institutional Theory Need Redirecting?

    DEFF Research Database (Denmark)

    Meyer, Renate; Höllerer, Markus A.

    2014-01-01

    Greenwood, Hinings and Whetten (2014) present two major criticisms of current institutional scholarship, and see need for a broad redirection: institutional organization theory, they argue, has lost sight of the claim to study organizations and, with its overwhelming focus on isomorphism and simi......Greenwood, Hinings and Whetten (2014) present two major criticisms of current institutional scholarship, and see need for a broad redirection: institutional organization theory, they argue, has lost sight of the claim to study organizations and, with its overwhelming focus on isomorphism...

  16. RTP redirection using a handheld device with Minisip

    OpenAIRE

    2007-01-01

    This report presents several different techniques for diverting RTP streams when using a handheld mobile device. This device is running a version of Minisip as the SIP user agent. An introduction to the SIP protocol is given to provide some background to the reader prior to focusing upon the main goal: redirecting RTP streams. A set of requirements are defined and an RTP media transfer mode is chosen based upon these requirements. The requirements are derived from a study of a Linux cellular ...

  17. The Parenteral Vitamin C Improves Sepsis and Sepsis-Induced Multiple Organ Dysfunction Syndrome via Preventing Cellular Immunosuppression

    Science.gov (United States)

    Chai, Yan-Fen

    2017-01-01

    Cellular immunosuppression appears to be involved in sepsis and sepsis-induced multiple organ dysfunction syndrome (MODS). Recent evidence showed that parenteral vitamin C (Vit C) had the ability to attenuate sepsis and sepsis-induced MODS. Herein, we investigated the impact of parenteral Vit C on cellular immunosuppression and the therapeutic value in sepsis. Using cecal ligation and puncture (CLP), sepsis was induced in WT and Gulo−/− mice followed with 200 mg/Kg parenteral Vit C administration. The immunologic functions of CD4+CD25+ regulatory T cells (Tregs) and CD4+CD25− T cells, as well as the organ functions, were determined. Administration of parenteral Vit C per se markedly improved the outcome of sepsis and sepsis-induced MODS of WT and Gulo−/− mice. The negative immunoregulation of Tregs was inhibited, mainly including inhibiting the expression of forkhead helix transcription factor- (Foxp-) 3, cytotoxic T lymphocyte associated antigen- (CTLA-) 4, membrane associated transforming growth factor-β (TGF-βm+), and the secretion of inhibitory cytokines [including TGF-β and interleukin- (IL-) 10], as well as CD4+ T cells-mediated cellular immunosuppression which was improved by parenteral Vit C in WT and Gulo−/− septic mice. These results suggested that parenteral Vit C has the ability to improve the outcome of sepsis and sepsis-induced MODS and is associated with improvement in cellular immunosuppression. PMID:28210072

  18. [Glycotoxins and cellular dysfunction. A new mechanism for understanding the preventive effects of lifestyle modifications].

    Science.gov (United States)

    Michalsen, A; Bierhaus, A; Nawroth, P P; Dobos, G J

    2006-08-01

    Recently the AGE-RAGE interaction was identified as a potential mechanism underlying chronic and inflammatory diseases like atherosclerosis, diabetes mellitus and kidney disease. Advanced glycation end products (AGEs) are the derivatives of glucose-protein or glucose-lipid reactions and are mainly generated from the diet (depending on intensity of heating, cooking time and oxygenation). Binding of AGEs or other ligands to the AGE receptor (RAGE) results in cellular activation, i.e. increased expression of inflammatory mediators and oxidative stress. Diet-derived AGEs thus induce deleterious effects on tissues and the cardiovascular system. Recent research also found that other lifestyle factors are associated with pronounced inflammatory activation, e.g. psychosocial stress and smoking. In addition, each intake of meals is associated with proinflammatory cellular changes. The AGE-RAGE model and investigations of the underlying cellular mechanisms thus may lead to a better understanding of the health benefits of diets (Mediterranean diet, uncooked vegetarian diets), caloric restriction and intermittent fasting. The clinical impact of low-AGE diets and fasting and the interaction between stress and food intake should be further investigated in controlled trials.

  19. Cellular adaptive response to glutathione depletion modulates endothelial dysfunction triggered by TNF-α.

    Science.gov (United States)

    Speciale, Antonio; Anwar, Sirajudheen; Ricciardi, Elisabetta; Chirafisi, Joselita; Saija, Antonella; Cimino, Francesco

    2011-12-15

    Several interrelated cellular signaling molecules are involved in modulating adaptive compensatory changes elicited by low exposures to toxins and other stressors. The most prominent example of signaling pathway typically involved in this adaptive stress response, is represented by the activation of a redox-sensitive gene regulatory network mediated by the NF-E2-related factor-2 (Nrf2) which is intimately involved in mediating the Antioxidant Responsive Element (ARE)-driven response to oxidative stress and xenobiotics. We investigated if Nrf2 pathway activation following intracellular glutathione depletion through buthionine sulfoximine (BSO) exposure, might be able to alter the response to TNF-α, a proinflammatory cytokine, in cultured human umbilical vein endothelial cells. Herein, we revealed that such a change in the cellular redox status is able to reduce TNF-α induced endothelial activation (as shown by a decreased gene expression of adhesion molecules) by activating an adaptive response mediated by an increased Nrf2 nuclear translocation and overexpression of the ARE genes HO-1 and NQO-1. Furthermore, we have demonstrated the involvement of ERK1/2 kinases in Nrf2 nuclear translocation activated by BSO-induced glutathione depletion. The coordinate induction of endogenous cytoprotective proteins through adaptive activation of Nrf2 pathway is a field of great interest for potential application in prevention and therapy of inflammatory diseases such as atherosclerosis. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. The Asteroid Redirect Mission (ARM)

    Science.gov (United States)

    Abell, Paul; Gates, Michele; Johnson, Lindley; Chodas, Paul; Mazanek, Dan; Reeves, David; Ticker, Ronald

    2016-07-01

    To achieve its long-term goal of sending humans to Mars, the National Aeronautics and Space Administration (NASA) plans to proceed in a series of incrementally more complex human spaceflight missions. Today, human flight experience extends only to Low-Earth Orbit (LEO), and should problems arise during a mission, the crew can return to Earth in a matter of minutes to hours. The next logical step for human spaceflight is to gain flight experience in the vicinity of the Moon. These cis-lunar missions provide a "proving ground" for the testing of systems and operations while still accommodating an emergency return path to the Earth that would last only several days. Cis-lunar mission experience will be essential for more ambitious human missions beyond the Earth-Moon system, which will require weeks, months, or even years of transit time. In addition, NASA has been given a Grand Challenge to find all asteroid threats to human populations and know what to do about them. Obtaining knowledge of asteroid physical properties combined with performing technology demonstrations for planetary defense provide much needed information to address the issue of future asteroid impacts on Earth. Hence the combined objectives of human exploration and planetary defense give a rationale for the Asteroid Re-direct Mission (ARM). Mission Description: NASA's ARM consists of two mission segments: 1) the Asteroid Redirect Robotic Mission (ARRM), the first robotic mission to visit a large (greater than ~100 m diameter) near-Earth asteroid (NEA), collect a multi-ton boulder from its surface along with regolith samples, demonstrate a planetary defense technique, and return the asteroidal material to a stable orbit around the Moon; and 2) the Asteroid Redirect Crewed Mission (ARCM), in which astronauts will take the Orion capsule to rendezvous and dock with the robotic vehicle, conduct multiple extravehicular activities to explore the boulder, and return to Earth with samples. NASA's proposed

  1. Stem cell therapy and cellular engineering for treatment of neuronal dysfunction in Huntington's disease.

    Science.gov (United States)

    Choi, Kyung-Ah; Hwang, Insik; Park, Hang-soo; Oh, Seung-Ick; Kang, Seongman; Hong, Sunghoi

    2014-07-01

    Huntington's disease (HD) is a fatal inherited neurodegenerative disorder characterized by progressive loss of neurons in the striatum, a sub-cortical region of the forebrain. The sub-cortical region of the forebrain is associated with the control of movement and behavior, thus HD initially presents with coordination difficulty and cognitive decline. Recent reprogramming technologies, including induced pluripotent stem cells (iPSCs) and induced neural stem cells (iNSCs), have created opportunities to understand the pathological cascades that underlie HD and to develop new treatments for this currently incurable neurological disease. The ultimate objectives of stem cell-based therapies for HD are to replace lost neurons and to prevent neuronal dysfunction and death. In this review, we examine the current understanding of the molecular and pathological mechanisms involved in HD. We discuss disease modeling with HD-iPSCs derived from the somatic cells of patients, which could provide an invaluable platform for understanding HD pathogenesis. We speculate about the benefits and drawbacks of using iNSCs as an alternative stem cell source for HD treatment. Finally, we discuss cell culture and engineering systems that promote the directed differentiation of pluripotent stem cell-derived NSCs into a striatal DARPP32(+) GABAergic MSN phenotype for HD. In conclusion, this review summarizes the potentials of cell reprogramming and engineering technologies relevant to the development of cell-based therapies for HD.

  2. Double Asteroid Redirection Test (DART)

    Science.gov (United States)

    Cheng, A. F.

    2016-12-01

    The Asteroid Impact Deflection Assessment (AIDA) mission will be the first space experiment to demonstrate asteroid impact hazard mitigation by using a kinetic impactor. AIDA is a joint ESA-NASA cooperative project, consisting of the NASA Double Asteroid Redirection Test (DART) kinetic impactor mission and the ESA Asteroid Impact Mission (AIM) which is the rendezvous spacecraft. The AIDA target is the near-Earth binary asteroid 65803 Didymos. During the Didymos close approach to Earth in October, 2022, the DART spacecraft will impact the Didymos secondary at 6 km/s and deflect its trajectory, changing the orbital period of the binary. This change can be measured by Earth-based optical and radar observations. The primary goals of AIDA are to (1) perform a full-scale demonstration of asteroid deflection by kinetic impact; (2) measure the resulting deflection; and (3) validate and improve models for momentum transfer in high-speed impacts on an asteroid. The combined DART and AIM missions will provide the first measurements of momentum transfer efficiency from a kinetic impact at full scale on an asteroid, where the impact conditions of the projectile are known, and physical properties and internal structures of the target asteroid are also characterized. In addition to a measurable change in the binary orbit period, the DART kinetic impact is predicted to induce forced librations of the Didymos secondary of up to several degrees amplitude. It will furthermore make a crater that will be studied in detail by the AIM spacecraft, and it will release a volume of particulate ejecta that may be directly observable from Earth or even resolvable as a coma or an ejecta tail by ground-based telescopes. Updates will be given on DART status and study results.

  3. Leptin Dysfunction and Alzheimer's Disease: Evidence from Cellular, Animal, and Human Studies.

    Science.gov (United States)

    McGuire, Matthew J; Ishii, Makoto

    2016-03-01

    There is accumulating evidence from epidemiological studies that changes in body weight are associated with Alzheimer's disease (AD) from mid-life obesity increasing the risk of developing AD to weight loss occurring at the earliest stages of AD. Therefore, factors that regulate body weight are likely to influence the development and progression of AD. The adipocyte-derived hormone leptin has emerged as a major regulator of body weight mainly by activating hypothalamic neural circuits. Leptin also has several pleotropic effects including regulating cognitive function and having neuroprotective effects, suggesting a potential link between leptin and AD. Here, we will examine the relationship between leptin and AD by reviewing the recent evidence from cellular and animal models to human studies. We present a model where leptin has a bidirectional role in AD. Not only can alterations in leptin levels and function worsen cognitive decline and progression of AD pathology, but AD pathology, in of itself, can disrupt leptin signaling, which together would lead to a downward spiral of progressive neurodegeneration and worsening body weight and systemic metabolic deficits. Collectively, these studies serve as a framework to highlight the importance of understanding the molecular mechanisms underlying the body weight and systemic metabolic deficits in AD, which has the potential to open new avenues that may ultimately lead to novel therapeutic targets and diagnostic tools.

  4. Leptin dysfunction and Alzheimer’s disease: evidence from cellular, animal, and human studies

    Science.gov (United States)

    McGuire, Matthew J.; Ishii, Makoto

    2016-01-01

    There is accumulating evidence from epidemiological studies that changes in body weight are associated with Alzheimer’s disease (AD) from mid-life obesity increasing the risk of developing AD to weight loss occurring at the earliest stages of AD. Therefore, factors that regulate body weight are likely to influence the development and progression of AD. The adipocyte-derived hormone leptin has emerged as a major regulator of body weight mainly by activating hypothalamic neural circuits. Leptin also has several pleotropic effects including regulating cognitive function and having neuroprotective effects, suggesting a potential link between leptin and AD. Here, we will examine the relationship between leptin and AD by reviewing the recent evidence from cellular and animal models to human studies. We present a model where leptin has a bidirectional role in AD. Not only can alterations in leptin levels and function worsen cognitive decline and progression of AD pathology, but AD pathology, in of itself, can disrupt leptin signaling, which together would lead to a downward spiral of progressive neurodegeneration and worsening body weight and systemic metabolic deficits. Collectively, these studies serve as a framework to highlight the importance of understanding the molecular mechanisms underlying the body weight and systemic metabolic deficits in AD, which has the potential to open new avenues that may ultimately lead to novel therapeutic targets and diagnostic tools. PMID:26993509

  5. Standardized Kaempferia parviflora Extract Inhibits Intrinsic Aging Process in Human Dermal Fibroblasts and Hairless Mice by Inhibiting Cellular Senescence and Mitochondrial Dysfunction

    Directory of Open Access Journals (Sweden)

    Ji-Eun Park

    2017-01-01

    Full Text Available Intrinsic skin aging is a complex biological phenomenon mainly caused by cellular senescence and mitochondrial dysfunction. This study evaluated the inhibitory effect of Kaempferia parviflora Wall ex. Baker ethanol extract (KPE on H2O2-stimulated cellular senescence and mitochondrial dysfunction both in vitro and in vivo. KPE significantly increased cell growth and suppressed senescence-associated β-galactosidase activation. KPE inhibited the expression of cell-cycle inhibitors (p53, p21, p16, and pRb and stimulated the expression of cell-cycle activators (E2F1 and E2F2. H2O2-induced hyperactivation of the phosphatidylinositol 3-kinase/protein kinase B (AKT signaling pathway was suppressed by KPE through regulated expression of forkhead box O3a (FoxO3a and mammalian target of rapamycin (mTOR. KPE attenuated inflammatory mediators (interleukin-6 (IL-6, IL-8, nuclear factor kappa B (NF-κB, and cyclooxygenase-2 (COX-2 and increased the mRNA expression of PGC-1α, ERRα, NRF1, and Tfam, which modulate mitochondrial biogenesis and function. Consequently, reduced ATP levels and increased ROS level were also reversed by KPE treatment. In hairless mice, KPE inhibited wrinkle formation, skin atrophy, and loss of elasticity by increasing the collagen and elastic fibers. The results indicate that KPE prevents intrinsic aging process in hairless mice by inhibiting cellular senescence and mitochondrial dysfunction, suggesting its potential as a natural antiaging agent.

  6. Standardized Kaempferia parviflora Extract Inhibits Intrinsic Aging Process in Human Dermal Fibroblasts and Hairless Mice by Inhibiting Cellular Senescence and Mitochondrial Dysfunction.

    Science.gov (United States)

    Park, Ji-Eun; Woo, Seon Wook; Kim, Mi-Bo; Kim, Changhee; Hwang, Jae-Kwan

    2017-01-01

    Intrinsic skin aging is a complex biological phenomenon mainly caused by cellular senescence and mitochondrial dysfunction. This study evaluated the inhibitory effect of Kaempferia parviflora Wall ex. Baker ethanol extract (KPE) on H2O2-stimulated cellular senescence and mitochondrial dysfunction both in vitro and in vivo. KPE significantly increased cell growth and suppressed senescence-associated β-galactosidase activation. KPE inhibited the expression of cell-cycle inhibitors (p53, p21, p16, and pRb) and stimulated the expression of cell-cycle activators (E2F1 and E2F2). H2O2-induced hyperactivation of the phosphatidylinositol 3-kinase/protein kinase B (AKT) signaling pathway was suppressed by KPE through regulated expression of forkhead box O3a (FoxO3a) and mammalian target of rapamycin (mTOR). KPE attenuated inflammatory mediators (interleukin-6 (IL-6), IL-8, nuclear factor kappa B (NF-κB), and cyclooxygenase-2 (COX-2)) and increased the mRNA expression of PGC-1α, ERRα, NRF1, and Tfam, which modulate mitochondrial biogenesis and function. Consequently, reduced ATP levels and increased ROS level were also reversed by KPE treatment. In hairless mice, KPE inhibited wrinkle formation, skin atrophy, and loss of elasticity by increasing the collagen and elastic fibers. The results indicate that KPE prevents intrinsic aging process in hairless mice by inhibiting cellular senescence and mitochondrial dysfunction, suggesting its potential as a natural antiaging agent.

  7. Correction of involutional entropion with retractor redirection.

    Science.gov (United States)

    Chu, Yen-Chang; Yang, Ju-Wen; Tsai, Yueh-Ju; Wu, Shu-Ya; Liao, Yi-Lin; Chu, Hsueh-Yen

    2016-08-01

    The study aims to report the surgical outcome of a retractor redirection procedure for involutional entropion repair for Asians. The study included all cases diagnosed with involutional entropion and significant ocular irritation who presented from 2008 to 2012. Sixty-seven eyelids in 54 patients were included in this study. All cases were operated on by one surgeon and had a minimum of 12-months follow-up. Success was defined as cases showing no recurrence of entropion with forceful eyelid squeezing postoperatively. A retrospective chart review was performed to assess the success rate, recurrences and complications of the procedure. During a mean follow-up period of 26.2 months (range, 12-53 months), 5 patients died during the study period. Two eyelids (3%) of one patient had a recurrence at 34 months postoperatively. One eyelid (1.5%) with a significant horizontal laxity developed postoperative ectropion and required a secondary horizontal shortening procedure. No other postoperative complications or dissatisfaction were reported. The retractor redirection procedure aims to repair the retractors and prevent orbicularis muscle overriding via inserting the retractors to the anterior lamellae. It yields a long-term success rate of 95.5% and is an effective technique for correcting involutional entropion.

  8. Cyclosporine A treatment for Ullrich congenital muscular dystrophy: a cellular study of mitochondrial dysfunction and its rescue.

    Science.gov (United States)

    Hicks, D; Lampe, A K; Laval, S H; Allamand, V; Jimenez-Mallebrera, C; Walter, M C; Muntoni, F; Quijano-Roy, S; Richard, P; Straub, V; Lochmüller, H; Bushby, K M D

    2009-01-01

    Mutations in COL6A1, COL6A2 and COL6A3, the genes which encode the extra-cellular matrix component collagen VI, lead to Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD). Although the Col6a1(-/-) null mouse has an extremely mild neuromuscular phenotype, a mitochondrial defect has been demonstrated, linked to dysregulation of the mitochondrial permeability transition pore (PTP) opening. This finding has been replicated in UCMD muscle cells in culture, providing justification for a clinical trial using cyclosporine A, an inhibitor of PTP opening. We investigated whether PTP dysregulation could be detected in UCMD fibroblasts (the predominant source of muscle collagen VI), in myoblast cells from patients with other diseases and its response to rescue agents other than collagen VI. Although we confirm the presence of PTP dysregulation in muscle-derived cultures from two UCMD patients, fibroblasts from the same patients and the majority of fibroblasts from other well-characterized UCMD patients behave normally. PTP dysregulation is found in limb girdle muscular dystrophy (LGMD) type 2B myoblasts but not in myoblasts from patients with Bethlem myopathy, merosin-deficient congenital muscular dystrophy, LGMD2A, Duchenne muscular dystrophy and Leigh syndrome. In addition to rescue by cyclosporine A and collagen VI, this cellular phenotype was also rescued by other extra-cellular matrix constituents (laminin and collagen I). As the muscle derived cultures demonstrating PTP dysregulation shared poor growth in culture and lack of desmin labelling, we believe that PTP dysregulation may be a particular characteristic of the state of these cells in culture and is not specific to the collagen VI defect, and can in any case be rescued by a range of extra-cellular matrix components. Further work is needed on the relationship of PTP dysregulation with UCMD pathology.

  9. NASA's Asteroid Redirect Mission: Overview and Status

    Science.gov (United States)

    Abell, Paul; Gates, Michele; Johnson, Lindley; Chodas, Paul; Brophy, John; Mazanek, Dan; Muirhead, Brian

    A major element of the National Aeronautics and Space Administration’s (NASA) new Asteroid Initiative is the Asteroid Redirect Mission (ARM). This concept was first proposed in 2011 during a feasibility study at the Keck Institute for Space Studies (KISS)[1] and is under consideration for implementation by NASA. The ARM involves sending a high-efficiency (ISP 3000 s), high-power (40 kW) solar electric propulsion (SEP) robotic vehicle that leverages technology developed by NASA’s Space Technology Mission Directorate (STMD) to rendezvous with a near-Earth asteroid (NEA) and return asteroidal material to a stable lunar distant retrograde orbit (LDRO)[2]. There are two mission concepts currently under study, one that captures an entire 7 - 10 meter mean diameter NEA[3], and another that retrieves a 1 - 10 meter mean diameter boulder from a 100+ meter class NEA[4]. Once the retrieved asteroidal material is placed into the LDRO, a two person crew would launch aboard an Orion capsule to rendezvous and dock with the robotic SEP vehicle. After docking, the crew would conduct two extra-vehicular activities (EVA) to collect asteroid samples and deploy instruments prior to Earth return. The crewed portion of the mission is expected to last approximately 25 days and would represent the first human exploration mission beyond low-Earth orbit (LEO) since the Apollo program. The ARM concept leverages NASA’s activities in Human Exploration, Space Technology, and Planetary Defense to accomplish three primary objectives and several secondary objectives. The primary objective relevant to Human Exploration is to gain operational experience with vehicles, systems, and components that will be utilized for future deep space exploration. In regard to Space Technology, the ARM utilizes advanced SEP technology that has high power and long duration capabilities that enable future missions to deep space destinations, such as the Martian system. With respect to Planetary Defense, the ARM

  10. Understanding the cellular basis and pathophysiology of Peyronie’s disease to optimize treatment for erectile dysfunction

    Science.gov (United States)

    Alzubaidi, Raidh

    2017-01-01

    Erectile dysfunction (ED) is a common condition that significantly impacts a man’s physical and psychological well-being. ED is often associated with Peyronie’s disease (PD), which is an abnormal curvature of the penis. Delayed treatment of or surgical invention for PD often results in ED and therefore unsatisfied patients. The pathophysiology of PD is incompletely understood, but has been studied extensively and based on our current understanding of PD physiology, many medical treatment options have been proposed. In this paper, we will review what is known about the pathophysiology of PD and the medical treatment options that have been trialed as a result. More investigations in regards to the basic science of PD need to be carried out in order to elucidate the exact mechanisms of the fibrosis, and propose new, more successful treatment options which should be implemented prior to the onset of ED. PMID:28217450

  11. Working memory dysfunction associated with brain functional deficits and cellular metabolic changes in patients with generalized anxiety disorder.

    Science.gov (United States)

    Moon, Chung-Man; Sundaram, Thirunavukkarasu; Choi, Nam-Gil; Jeong, Gwang-Woo

    2016-08-30

    Generalized anxiety disorder (GAD) is associated with brain functional and morphological changes in connected with emotional dysregulation and cognitive deficit. This study dealt with the neural functional deficits and metabolic abnormalities in working memory (WM) task with emotion-inducing distractors in patients with GAD. Fourteen patients with GAD and 14 healthy controls underwent functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy ((1)H-MRS) at 3T. In response to the emotional distractors in WM tasks, the patients concurrently showed higher activity in the hippocampus and lower activities in the superior occipital gyrus, superior parietal gyrus, dorsolateral prefrontal cortex (DLPFC) and precentral gyrus compared to the controls. MRS revealed significantly lower choline/creatine (Cho/Cr) and choline/N-acetylaspartate (Cho/NAA) ratios in the DLPFC. In particular, the Cho ratios were positively correlated with the brain activities based on blood oxygenation level-dependent signal change in the DLPFC. This study provides the first evidence for the association between the metabolic alterations and functional deficit in WM processing with emotion-inducing distractors in GAD. These findings will be helpful to understand the neural dysfunction in connection with WM impairment in GAD.

  12. Dysfunctional lipoproteins from young smokers exacerbate cellular senescence and atherogenesis with smaller particle size and severe oxidation and glycation.

    Science.gov (United States)

    Park, Ki-Hoon; Shin, Dong-Gu; Cho, Kyung-Hyun

    2014-07-01

    Until now, there has been limited information on the effects of smoking on atherogenesis and senescence in the context of lipoprotein parameters, particularly in young smokers who have smoked fewer than 10 cigarettes per day for 3 years. In this study, lipoprotein profiles and functions were compared between smoker (n = 21) and control groups (n = 20). In the smoking group, ferric ion reduction abilities of serum and high-density lipoprotein (HDL) fractions were significantly reduced, and low-density lipoprotein (LDL) was severely oxidized. All lipoprotein particles from the smoker group showed higher advanced glycated end products with more triglyceride (TG) content compared with the control group. Lipoproteins from smokers showed faster agarose gel electromobility as well as greater smear band intensity in SDS-PAGE due to oxidation and glycation. LDL from smokers was more sensitive to oxidation and promoted foam cell forma-tion in macrophages. Gel filtration column chromatography revealed that the protein and cholesterol peaks of VLDL and LDL were elevated in the smoker group, whereas those of HDL were reduced. Human dermal fibroblast cells from the smoker group showed severe senescence following treatment with HDL2 and HDL3. Although HDL from young smokers showed impaired antioxidant ability, smaller particle size, and increased TG content, cholesteryl ester transfer protein activities were greatly enhanced in the serum and HDL fractions of the smoker group. In conclusion, smoking can cause production of dysfunctional lipoproteins having a smaller particle size that exacerbate senescence and atherogenic progress due to oxidation and glycation.

  13. Deranged Bioenergetics and Defective Redox Capacity in T Lymphocytes and Neutrophils Are Related to Cellular Dysfunction and Increased Oxidative Stress in Patients with Active Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Ko-Jen Li

    2012-01-01

    Full Text Available Urinary excretion of N-benzoyl-glycyl-Nε-(hexanonyllysine, a biomarker of oxidative stress, was higher in 26 patients with active systemic lupus erythematosus (SLE than in 11 non-SLE patients with connective tissue diseases and in 14 healthy volunteers. We hypothesized that increased oxidative stress in active SLE might be attributable to deranged bioenergetics, defective reduction-oxidation (redox capacity, or other factors. We demonstrated that, compared to normal cells, T lymphocytes (T and polymorphonuclear neutrophils (PMN of active SLE showed defective expression of facilitative glucose transporters GLUT-3 and GLUT-6, which led to increased intracellular basal lactate and decreased ATP production. In addition, the redox capacity, including intracellular GSH levels and the enzyme activity of glutathione peroxidase (GSH-Px and γ-glutamyl-transpeptidase (GGT, was decreased in SLE-T. Compared to normal cells, SLE-PMN showed decreased intracellular GSH levels, and GGT enzyme activity was found in SLE-PMN and enhanced expression of CD53, a coprecipitating molecule for GGT. We conclude that deranged cellular bioenergetics and defective redox capacity in T and PMN are responsible for cellular immune dysfunction and are related to increased oxidative stress in active SLE patients.

  14. Cell type-dependent induction of DNA damage by 1800 MHz radiofrequency electromagnetic fields does not result in significant cellular dysfunctions.

    Directory of Open Access Journals (Sweden)

    Shanshan Xu

    Full Text Available BACKGROUND: Although IARC clarifies radiofrequency electromagnetic fields (RF-EMF as possible human carcinogen, the debate on its health impact continues due to the inconsistent results. Genotoxic effect has been considered as a golden standard to determine if an environmental factor is a carcinogen, but the currently available data for RF-EMF remain controversial. As an environmental stimulus, the effect of RF-EMF on cellular DNA may be subtle. Therefore, more sensitive method and systematic research strategy are warranted to evaluate its genotoxicity. OBJECTIVES: To determine whether RF-EMF does induce DNA damage and if the effect is cell-type dependent by adopting a more sensitive method γH2AX foci formation; and to investigate the biological consequences if RF-EMF does increase γH2AX foci formation. METHODS: Six different types of cells were intermittently exposed to GSM 1800 MHz RF-EMF at a specific absorption rate of 3.0 W/kg for 1 h or 24 h, then subjected to immunostaining with anti-γH2AX antibody. The biological consequences in γH2AX-elevated cell type were further explored with comet and TUNEL assays, flow cytometry, and cell growth assay. RESULTS: Exposure to RF-EMF for 24 h significantly induced γH2AX foci formation in Chinese hamster lung cells and Human skin fibroblasts (HSFs, but not the other cells. However, RF-EMF-elevated γH2AX foci formation in HSF cells did not result in detectable DNA fragmentation, sustainable cell cycle arrest, cell proliferation or viability change. RF-EMF exposure slightly but not significantly increased the cellular ROS level. CONCLUSIONS: RF-EMF induces DNA damage in a cell type-dependent manner, but the elevated γH2AX foci formation in HSF cells does not result in significant cellular dysfunctions.

  15. Cell type-dependent induction of DNA damage by 1800 MHz radiofrequency electromagnetic fields does not result in significant cellular dysfunctions.

    Science.gov (United States)

    Xu, Shanshan; Chen, Guangdi; Chen, Chunjing; Sun, Chuan; Zhang, Danying; Murbach, Manuel; Kuster, Niels; Zeng, Qunli; Xu, Zhengping

    2013-01-01

    Although IARC clarifies radiofrequency electromagnetic fields (RF-EMF) as possible human carcinogen, the debate on its health impact continues due to the inconsistent results. Genotoxic effect has been considered as a golden standard to determine if an environmental factor is a carcinogen, but the currently available data for RF-EMF remain controversial. As an environmental stimulus, the effect of RF-EMF on cellular DNA may be subtle. Therefore, more sensitive method and systematic research strategy are warranted to evaluate its genotoxicity. To determine whether RF-EMF does induce DNA damage and if the effect is cell-type dependent by adopting a more sensitive method γH2AX foci formation; and to investigate the biological consequences if RF-EMF does increase γH2AX foci formation. Six different types of cells were intermittently exposed to GSM 1800 MHz RF-EMF at a specific absorption rate of 3.0 W/kg for 1 h or 24 h, then subjected to immunostaining with anti-γH2AX antibody. The biological consequences in γH2AX-elevated cell type were further explored with comet and TUNEL assays, flow cytometry, and cell growth assay. Exposure to RF-EMF for 24 h significantly induced γH2AX foci formation in Chinese hamster lung cells and Human skin fibroblasts (HSFs), but not the other cells. However, RF-EMF-elevated γH2AX foci formation in HSF cells did not result in detectable DNA fragmentation, sustainable cell cycle arrest, cell proliferation or viability change. RF-EMF exposure slightly but not significantly increased the cellular ROS level. RF-EMF induces DNA damage in a cell type-dependent manner, but the elevated γH2AX foci formation in HSF cells does not result in significant cellular dysfunctions.

  16. Extracorporeal shock wave therapy reverses ischemia-related left ventricular dysfunction and remodeling: molecular-cellular and functional assessment.

    Directory of Open Access Journals (Sweden)

    Morgan Fu

    Full Text Available An optimal treatment for patients with diffuse obstructive arterial disease unsuitable for catheter-based or surgical intervention is still pending. This study tested the hypothesis that extracorporeal shock wave (ECSW therapy may be a therapeutic alternative under such clinical situation. Myocardial ischemia was induced in male mini-pigs through applying an ameroid constrictor over mid-left anterior descending artery (LAD. Twelve mini-pigs were equally randomized into group 1 (Constrictor over LAD only and group 2 (Constrictor over LAD plus ECSW [800 impulses at 0.09 mJ/mm(2] once 3 months after the procedure. Results showed that the parameters measured by echocardiography did not differ between two groups on days 0 and 90. However, echocardiography and left ventricular (LV angiography showed higher LV ejection fraction and lower LV end-systolic dimension and volume in group 2 on day 180 (p<0.035. Besides, mRNA and protein expressions of CXCR4 and SDF-1α were increased in group 2 (p<0.04. Immunofluorescence staining also showed higher number of vWF-, CD31-, SDF-1α-, and CXCR4-positive cells in group 2 (all p<0.04. Moreover, immunohistochemical staining showed notably higher vessel density but lower mean fibrosis area, number of CD40-positive cells and apoptotic nuclei in group 2 (all p<0.045. Mitochondrial protein expression of oxidative stress was lower, whereas cytochrome-C was higher in group 2 (all p<0.03. Furthermore, mRNA expressions of MMP-9, Bax and caspase-3 were lower, whereas Bcl-2, eNOS, VEGF and PGC-1α were higher in group 2 (all p<0.01. In conclusion, ECSW therapy effectively reversed ischemia-elicited LV dysfunction and remodeling through enhancing angiogenesis and attenuating inflammation and oxidative stress.

  17. Up-regulation of leucocytes genes implicated in telomere dysfunction and cellular senescence correlates with depression and anxiety severity scores.

    Directory of Open Access Journals (Sweden)

    Jean-Raymond Teyssier

    Full Text Available BACKGROUND: Major depressive disorder (MDD is frequently associated with chronic medical illness responsible of increased disability and mortality. Inflammation and oxidative stress are considered to be the major mediators of the allostatic load, and has been shown to correlate with telomere erosion in the leucocytes of MDD patients, leading to the model of accelerated aging. However, the significance of telomere length as an exclusive biomarker of aging has been questioned on both methodological and biological grounds. Furthermore, telomeres significantly shorten only in patients with long lasting MDD. Sensitive and dynamic functional biomarkers of aging would be clinically useful to evaluate the somatic impact of MDD. METHODOLOGY: To address this issue we have measured in the blood leucocytes of MDD patients (N=17 and controls (N=16 the expression of two genes identified as robust biomarkers of human aging and telomere dysfunction: p16(INK4a and STMN1. We have also quantified the transcripts of genes involved in the repair of oxidative DNA damage at telomeres (OGG1, telomere regulation and elongation (TERT, and in the response to biopsychological stress (FOS and DUSP1. RESULTS: The OGG1, p16(INK4a, and STMN1 gene were significantly up-regulated (25 to 100% in the leucocytes of MDD patients. Expression of p16(INK4a and STMN1 was directly correlated with anxiety scores in the depression group, and that of p16(INK4a, STMN and TERT with the depression and anxiety scores in the combined sample (MDD plus controls. Furthermore, we identified a unique correlative pattern of gene expression in the leucocytes of MDD subjects. CONCLUSIONS: Expression of p16(INK4 and STMN1 is a promising biomarker for future epidemiological assessment of the somatic impact of depressive and anxious symptoms, at both clinical and subclinical level in both depressive patients and general population.

  18. Illumination of dense urban areas by light redirecting panels.

    Science.gov (United States)

    El-Henawy, Sally I; Mohamed, Mohamed W N; Mashaly, Islam A; Mohamed, Osama N; Galal, Ola; Taha, Iman; Nassar, Khaled; Safwat, Amr M E

    2014-05-05

    With the high population growth rate, especially in developing countries, and the scarcity of land resources, buildings are becoming so close to each other, depriving the lower floors and the alleys from sunlight and consequently causing health problems. Therefore, there is an urgent need for cost-effective efficient light redirecting panels that guide sun rays into those dim places. In this paper, we address this problem. A novel sine wave based panel is presented to redirect/diverge light downward and enhance the illumination level in those dark places. Simulation results show that the proposed panel improves the illuminance values by more than 200% and 400% in autumn and winter respectively, operates over wide solar altitude ranges, and redirects light efficiently. Experimental and simulation results are in good agreement.

  19. Redirection of pigment biosynthesis to isocoumarins in Fusarium

    DEFF Research Database (Denmark)

    Sørensen, Jens Laurids; Nielsen, Kristian Fog; Sondergaard, Teis Esben

    2012-01-01

    -type cyclase domain (CLC) in their N terminal. Disruption of the CLC domains has been shown to result in formation of the lactones citreoisocoumarin and SMA93 instead of YWA1 and pre-bikaverin.In the present study we have discovered a medium with low nitrogen content which partially redirects the aurofusarin...... and bikaverin pathways to produce citreoisocoumarin and SMA93, respectively. This is first time that SMA93 is identified in a fungus and we suggest that it is renamed bikisocoumarin, as it is derived from the bikaverin pathway. The redirection of the aurofusarin and bikaverin biosynthetic pathways was reverted...

  20. Mars orbiter redirected in bid to find Beagle

    CERN Multimedia

    2003-01-01

    "Mission controllers in Darmstadt, Germany, have successfully redirected Europe's Mars Express orbiter into a polar orbit, putting it on course for a last-ditch attempt to contact Beagle 2, the lander that has been missing since Christmas day when it should have touched down on the red planet" (1/2 page).

  1. Vídeo educativo sobre ICMP-Redirect

    OpenAIRE

    Ayala Millán, Francisco

    2011-01-01

    En este vídeo didáctico se muestra el funcionamiento de los mensajes de error ICMP Redirect. ¿Cuándo se generan? ¿En qué consisten? ¿Cuál es su formato?. Para ello se emplea la topología de red del laboratorio L24 de la Universidad de Alicante.

  2. Real Walking through Virtual Environments by Redirection Techniques

    Directory of Open Access Journals (Sweden)

    Jason Jerald

    2009-04-01

    Full Text Available We present redirection techniques that support exploration of large-scale virtual environments (VEs by means of real walking. We quantify to what degree users can unknowingly be redirected in order to guide them through VEs in which virtual paths differ from the physical paths. We further introduce the concept of dynamic passive haptics by which any number of virtual objects can be mapped to real physical proxy props having similar haptic properties (i. e., size, shape, and surface structure, such that the user can sense these virtual objects by touching their real world counterparts. Dynamic passive haptics provides the user with the illusion of interacting with a desired virtual object by redirecting her to the corresponding proxy prop. We describe the concepts of generic redirected walking and dynamic passive haptics and present experiments in which we have evaluated these concepts. Furthermore, we discuss implications that have been derived from a user study, and we present approaches that derive physical paths which may vary from the virtual counterparts.

  3. Barth syndrome: cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation.

    Science.gov (United States)

    Gonzalvez, François; D'Aurelio, Marilena; Boutant, Marie; Moustapha, Aoula; Puech, Jean-Philippe; Landes, Thomas; Arnauné-Pelloquin, Laeticia; Vial, Guillaume; Taleux, Nellie; Slomianny, Christian; Wanders, Ronald J; Houtkooper, Riekelt H; Bellenguer, Pascale; Møller, Ian Max; Gottlieb, Eyal; Vaz, Frederic M; Manfredi, Giovanni; Petit, Patrice X

    2013-08-01

    Cardiolipin is a mitochondrion-specific phospholipid that stabilizes the assembly of respiratory chain complexes, favoring full-yield operation. It also mediates key steps in apoptosis. In Barth syndrome, an X chromosome-linked cardiomyopathy caused by tafazzin mutations, cardiolipins display acyl chain modifications and are present at abnormally low concentrations, whereas monolysocardiolipin accumulates. Using immortalized lymphoblasts from Barth syndrome patients, we showed that the production of abnormal cardiolipin led to mitochondrial alterations. Indeed, the lack of normal cardiolipin led to changes in electron transport chain stability, resulting in cellular defects. We found a destabilization of the supercomplex (respirasome) I+III2+IVn but also decreased amounts of individual complexes I and IV and supercomplexes I+III and III+IV. No changes were observed in the amounts of individual complex III and complex II. We also found decreased levels of complex V. This complex is not part of the supercomplex suggesting that cardiolipin is required not only for the association/stabilization of the complexes into supercomplexes but also for the modulation of the amount of individual respiratory chain complexes. However, these alterations were compensated by an increase in mitochondrial mass, as demonstrated by electron microscopy and measurements of citrate synthase activity. We suggest that this compensatory increase in mitochondrial content prevents a decrease in mitochondrial respiration and ATP synthesis in the cells. We also show, by extensive flow cytometry analysis, that the type II apoptosis pathway was blocked at the mitochondrial level and that the mitochondria of patients with Barth syndrome cannot bind active caspase-8. Signal transduction is thus blocked before any mitochondrial event can occur. Remarkably, basal levels of superoxide anion production were slightly higher in patients' cells than in control cells as previously evidenced via an increased

  4. Performance of a daylight-redirecting glass-shading system

    DEFF Research Database (Denmark)

    Appelfeld, David; Svendsen, Svend

    2013-01-01

    with the prototype façade. This layout allowed the use of the same orientation and surroundings for both façades. The working plane illuminance was measured over several months and the measurements were accompanied with annual daylight simulations. The prototype system improved the daylighting conditions compared......This paper evaluates the daylighting performance of a prototype external dynamic shading and daylight-redirecting system, and the main focus is on the performance simulation. The demonstration project was carried out on a building with an open-plan office. Part of the original façade was replaced...... to the original system. The visual comfort was evaluated by glare analysis and the redirected daylight did not cause an additional discomfort glare. The higher utilization of daylight can save 20% of the lighting energy. The thermal insulation of the fenestration was maintained, with slightly increased solar...

  5. A Novel Approach for Redirecting Module in Honeypot Systems

    Institute of Scientific and Technical Information of China (English)

    YANG Geng; RONG Chun-ming; PENG Lei

    2005-01-01

    Honeypot is a recent developed computer security concept which uses active offense to against attacks from hackers. It lures hackers to attack a seemly vulnerable fake network where they could be well observed in order to learn about the tactics and tools used by the attackers, so that we may improve the system security accordingly later. In this paper, we propose a novel approach for redirecting technique in honeypot system. First, we introduce briefly concepts of the honeypot system. Then we describe a redirection technique and an implementation algorithm. Finally, using the IDS Snort and the firewall IPTable, we set up a testing environment and give some simulations results. We also discuss some future research topics.

  6. Wake redirection: comparison of analytical, numerical and experimental models

    Science.gov (United States)

    Wang, Jiangang; Bottasso, Carlo L.; Campagnolo, Filippo

    2016-09-01

    This paper focuses on wake redirection techniques for wind farm control. Two control strategies are investigated: yaw misalignment and cyclic pitch control. First, analytical formulas are derived for both techniques, with the goal of providing a simple physical interpretation of the behavior of the two methods. Next, more realistic results are obtained by numerical simulations performed with CFD and by experiments conducted with scaled wind turbine models operating in a boundary layer wind tunnel. Comparing the analytical, numerical and experimental models allows for a cross-validation of the results and a better understanding of the two wake redirection techniques. Results indicate that yaw misalignment is more effective than cyclic pitch control in displacing the wake laterally, although the latter may have positive effects on wake recovery.

  7. Disguising Rotational Gain for Redirected Walking in Virtual Reality

    DEFF Research Database (Denmark)

    Paludan, Anders Glud; Elbaek, Jacob; Mortensen, Mathias Helmuth

    2016-01-01

    In virtual reality environments that allow users to walk freely, the area of the virtual environment (VE) is constrained to the size of the tracking area. By using redirection techniques, this problem can be partially circumvented; one of the techniques involves rotating the user more or less...... in the virtual world than in the physical world; this technique is referred to as rotational gain. This paper seeks to further investigate this area, examining the effect of visual density in the VE....

  8. Asteroid Redirect Crewed Mission Nominal Design and Performance

    Science.gov (United States)

    Condon, Gerald; williams, Jacob

    2014-01-01

    In 2010, the President announced that, in 2025, the U.S. intended to launch a human mission to an asteroid [1]. This announcement was followed by the idea of a Capability Driven Framework (CDF) [2], which is based on the idea of evolving capabilities from less demanding to more demanding missions to multiple possible destinations and with increased flexibility, cost effectiveness and sustainability. Focused missions, such as a NASA inter-Center study that examined the viability and implications of sending a crew to a Near Earth Asteroid (NEA) [3], provided a way to better understand and evaluate the utility of these CDF capabilities when applied to an actual mission. The long duration of the NEA missions were contrasted with a concept described in a study prepared for the Keck Institute of Space Studies (KISS) [4] where a robotic spacecraft would redirect an asteroid to the Earth-Moon vicinity, where a relatively short duration crewed mission could be conducted to the captured asteroid. This mission concept was included in the National Aeronautics and Space Administration (NASA) fiscal year 2014 budget request, as submitted by the NASA Administrator [5]. NASA studies continued to examine the idea of a crewed mission to a captured asteroid in the Earth-Moon vicinity. During this time was an announcement of NASA's Asteroid Grand Challenge [6]. Key goals for the Asteroid Grand Challenge are to locate, redirect, and explore an asteroid, as well as find and plan for asteroid threats. An Asteroid Redirect Mission (ARM) study was being conducted, which supports this Grand Challenge by providing understanding in how to execute an asteroid rendezvous, capture it, and redirect it to Earth-Moon space, and, in particular, to a distant retrograde orbit (DRO). Subsequent to the returning of the asteroid to a DRO, would be the launch of a crewed mission to rendezvous with the redirected asteroid. This report examines that crewed mission by assessing the Asteroid Redirect Crewed

  9. Estimation of detection thresholds for redirected walking techniques.

    Science.gov (United States)

    Steinicke, Frank; Bruder, Gerd; Jerald, Jason; Frenz, Harald; Lappe, Markus

    2010-01-01

    In immersive virtual environments (IVEs), users can control their virtual viewpoint by moving their tracked head and walking through the real world. Usually, movements in the real world are mapped one-to-one to virtual camera motions. With redirection techniques, the virtual camera is manipulated by applying gains to user motion so that the virtual world moves differently than the real world. Thus, users can walk through large-scale IVEs while physically remaining in a reasonably small workspace. In psychophysical experiments with a two-alternative forced-choice task, we have quantified how much humans can unknowingly be redirected on physical paths that are different from the visually perceived paths. We tested 12 subjects in three different experiments: (E1) discrimination between virtual and physical rotations, (E2) discrimination between virtual and physical straightforward movements, and (E3) discrimination of path curvature. In experiment E1, subjects performed rotations with different gains, and then had to choose whether the visually perceived rotation was smaller or greater than the physical rotation. In experiment E2, subjects chose whether the physical walk was shorter or longer than the visually perceived scaled travel distance. In experiment E3, subjects estimate the path curvature when walking a curved path in the real world while the visual display shows a straight path in the virtual world. Our results show that users can be turned physically about 49 percent more or 20 percent less than the perceived virtual rotation, distances can be downscaled by 14 percent and upscaled by 26 percent, and users can be redirected on a circular arc with a radius greater than 22 m while they believe that they are walking straight.

  10. Activin receptor subunits in normal and dysfunctional adult human testis

    DEFF Research Database (Denmark)

    Dias, V; Meachem, S; Rajpert-De Meyts, E

    2008-01-01

    The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown.......The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown....

  11. Controlled angular redirection of light via nanoimprinted disordered gratings

    DEFF Research Database (Denmark)

    Buss, Thomas; Teisseire, Jérémie; Mazoyer, Simon

    2013-01-01

    Enhanced control of diffraction through transparent substrates is achieved via disordered gratings in a silica sol–gel film. Tailoring the degree of disorder allows tuning of the diffractive behavior from discrete orders into broad distributions over large angular range. Gratings of optical quality...... are formed by silica sol–gel nanoimprint lithography and an optical setup for the measurement of continuous diffraction patterns is presented. Sound agreement is found between measurements and simulation, validating both the approach for redirection of light and the fabrication process. The disordered...

  12. NASA Double Asteroid Redirection Test (Dart) Trajectory Validation and Robustness

    Science.gov (United States)

    Sarli, Bruno V.; Ozimek, Martin T.; Atchison, Justin A.; Englander, Jacob A.; Barbee, Brent W.

    2017-01-01

    The Double Asteroid Redirection Test (DART) mission will be the first to test the concept of a kinetic impactor. Several studies have been made on asteroid redirection and impact mitigation, however, to this date no mission tested the proposed concepts. An impact study on a representative body allows the measurement of the effects on the target's orbit and physical structure. With this goal, DART's objective is to verify the effectiveness of the kinetic impact concept for planetary defense. The spacecraft uses solar electric propulsion to escape Earth, flyby (138971) 2001 CB21 for impart rehearsal, and impact the secondary body of the (65803) Didymos system. This work focuses on the interplanetary trajectory design part of the mission with the validation of the baseline trajectory, performance comparison to other mission objectives, and assessment of the baseline robustness to missed thrust events. Results show a good performance of the selected trajectory for different mission objectives: latest possible escape date, maximum kinetic energy on impact, shortest possible time of flight, and use of an Earth swing-by. The baseline trajectory was shown to be robust to a missed thrust with 1% of fuel margin being enough to recover the mission for failures of more than 14 days.

  13. NASA Double Asteroid Redirection Test (DART) Trajectory Validation and Robutness

    Science.gov (United States)

    Sarli, Bruno V.; Ozimek, Martin T.; Atchison, Justin A.; Englander, Jacob A.; Barbee, Brent W.

    2017-01-01

    The Double Asteroid Redirection Test (DART) mission will be the first to test the concept of a kinetic impactor. Several studies have been made on asteroid redirection and impact mitigation, however, to this date no mission tested the proposed concepts. An impact study on a representative body allows the measurement of the effects on the target's orbit and physical structure. With this goal, DART's objective is to verify the effectiveness of the kinetic impact concept for planetary defense. The spacecraft uses solar electric propulsion to escape Earth, fly by (138971) 2001 CB21 for impact rehearsal, and impact Didymos-B, the secondary body of the binary (65803) Didymos system. This work focuses on the heliocentric transfer design part of the mission with the validation of the baseline trajectory, performance comparison to other mission objectives, and assessment of the baseline robustness to missed thrust events. Results show a good performance of the selected trajectory for different mission objectives: latest possible escape date, maximum kinetic energy on impact, shortest possible time of flight, and use of an Earth swing-by. The baseline trajectory was shown to be robust to a missed thrust with 1% of fuel margin being enough to recover the mission for failures of more than 14 days.

  14. Redirection of sound in straight fluid channel with elastic boundaries

    Science.gov (United States)

    Bozhko, Andrey; García-Chocano, Victor M.; Sánchez-Dehesa, José; Krokhin, Arkadii

    2015-03-01

    A fluid channel clad between two solid plates is an acoustic waveguide where excitation of elastic waves at the channel boundaries has been usually neglected. This work develops a rigorous theory of scattering of sound by a finite-length fluid channel which takes into account excitation of elastic eigenmodes of two plates acoustically coupled through a fluid channel. The theory predicts an evidently contradictory result that the transmission and reflection coefficients of a nondissipative channel do not sum up to one. Moreover, they both exhibit deep minima at the same series of frequencies. It is shown that conservation of acoustic energy occurs due to redirection of sound, since part of the acoustic flux escapes into the solid plates. This scattering becomes possible because the uniform flatness of the boundaries of a straight channel is broken by vibrations. Theoretical predictions are supported by the experiments with ultrasound transmission through a narrow slit obtained between two brass or aluminum plates submerged in water. Measured transmission spectra exhibit deep minima exactly at the frequencies where the theory predicts strong redirection of sound.

  15. Performance of redirected walking algorithms in a constrained virtual world.

    Science.gov (United States)

    Hodgson, Eric; Bachmann, Eric; Thrash, Tyler

    2014-04-01

    Redirected walking algorithms imperceptibly rotate a virtual scene about users of immersive virtual environment systems in order to guide them away from tracking area boundaries. Ideally, these distortions permit users to explore large unbounded virtual worlds while walking naturally within a physically limited space. Many potential virtual worlds are composed of corridors, passageways, or aisles. Assuming users are not expected to walk through walls or other objects within the virtual world, these constrained worlds limit the directions of travel and as well as the number of opportunities to change direction. The resulting differences in user movement characteristics within the physical world have an impact on redirected walking algorithm performance. This work presents a comparison of generalized RDW algorithm performance within a constrained virtual world. In contrast to previous studies involving unconstrained virtual worlds, experimental results indicate that the steer-to-orbit keeps users in a smaller area than the steer-to-center algorithm. Moreover, in comparison to steer-to-center, steer-to-orbit is shown to reduce potential wall contacts by over 29%.

  16. CDDO-Me Redirects Activation of Breast Tumor Associated Macrophages.

    Directory of Open Access Journals (Sweden)

    Michael S Ball

    Full Text Available Tumor-associated macrophages can account for up to 50% of the tumor mass in breast cancer patients and high TAM density is associated with poor clinical prognosis. Because TAMs enhance tumor growth, development, and metastatic potential, redirection of TAM activation may have significant therapeutic benefit. Our studies in primary human macrophages and murine breast TAMs suggest that the synthetic oleanane triterpenoid CDDO-methyl ester (CDDO-Me reprograms the activation profile of TAMs from tumor-promoting to tumor-inhibiting. We show that CDDO-Me treatment inhibits expression of IL-10 and VEGF in stimulated human M2 macrophages and TAMs but increases expression of TNF-α and IL-6. Surface expression of CD206 and CD163, which are characteristic of M2 activation, is significantly attenuated by CDDO-Me. In contrast, CDDO-Me up-regulates surface expression of HLA-DR and CD80, which are markers of M1 activation, and importantly potentiates macrophage activation of autologous T cells but inhibits endothelial cell vascularization. These results show for the first time that CDDO-Me redirects activation of M2 macrophages and TAMs from immune-suppressive to immune-stimulatory, and implicate a role for CDDO-Me as an immunotherapeutic in the treatment of breast and potentially other types of cancer.

  17. NASA's asteroid redirect mission: Robotic boulder capture option

    Science.gov (United States)

    Abell, P.; Nuth, J.; Mazanek, D.; Merrill, R.; Reeves, D.; Naasz, B.

    2014-07-01

    NASA is examining two options for the Asteroid Redirect Mission (ARM), which will return asteroid material to a Lunar Distant Retrograde Orbit (LDRO) using a robotic solar-electric-propulsion spacecraft, called the Asteroid Redirect Vehicle (ARV). Once the ARV places the asteroid material into the LDRO, a piloted mission will rendezvous and dock with the ARV. After docking, astronauts will conduct two extravehicular activities (EVAs) to inspect and sample the asteroid material before returning to Earth. One option involves capturing an entire small (˜4--10 m diameter) near-Earth asteroid (NEA) inside a large inflatable bag. However, NASA is also examining another option that entails retrieving a boulder (˜1--5 m) via robotic manipulators from the surface of a larger (˜100+ m) pre-characterized NEA. The Robotic Boulder Capture (RBC) option can leverage robotic mission data to help ensure success by targeting previously (or soon to be) well-characterized NEAs. For example, the data from the Japan Aerospace Exploration Agency's (JAXA) Hayabusa mission has been utilized to develop detailed mission designs that assess options and risks associated with proximity and surface operations. Hayabusa's target NEA, Itokawa, has been identified as a valid target and is known to possess hundreds of appropriately sized boulders on its surface. Further robotic characterization of additional NEAs (e.g., Bennu and 1999 JU_3) by NASA's OSIRIS REx and JAXA's Hayabusa 2 missions is planned to begin in 2018. This ARM option reduces mission risk and provides increased benefits for science, human exploration, resource utilization, and planetary defense.

  18. Flavonoids Redirect PIN-mediated Polar Auxin Fluxes during Root Gravitropic Responses*S⃞

    Science.gov (United States)

    Santelia, Diana; Henrichs, Sina; Vincenzetti, Vincent; Sauer, Michael; Bigler, Laurent; Klein, Markus; Bailly, Aurélien; Lee, Youngsook; Friml, Jir̆í; Geisler, Markus; Martinoia, Enrico

    2008-01-01

    The rate, polarity, and symmetry of the flow of the plant hormone auxin are determined by the polar cellular localization of PIN-FORMED (PIN) auxin efflux carriers. Flavonoids, a class of secondary plant metabolites, have been suspected to modulate auxin transport and tropic responses. Nevertheless, the identity of specific flavonoid compounds involved and their molecular function and targets in vivo are essentially unknown. Here we show that the root elongation zone of agravitropic pin2/eir1/wav6/agr1 has an altered pattern and amount of flavonol glycosides. Application of nanomolar concentrations of flavonols to pin2 roots is sufficient to partially restore root gravitropism. By employing a quantitative cell biological approach, we demonstrate that flavonoids partially restore the formation of lateral auxin gradients in the absence of PIN2. Chemical complementation by flavonoids correlates with an asymmetric distribution of the PIN1 protein. pin2 complementation probably does not result from inhibition of auxin efflux, as supply of the auxin transport inhibitor N-1-naphthylphthalamic acid failed to restore pin2 gravitropism. We propose that flavonoids promote asymmetric PIN shifts during gravity stimulation, thus redirecting basipetal auxin streams necessary for root bending. PMID:18718912

  19. NASA’s Asteroid Redirect Mission: The Boulder Capture Option

    Science.gov (United States)

    Abell, Paul; Nuth, Joseph A.; Mazanek, Dan D.; Merrill, Raymond G.; Reeves, David M.; Naasz, Bo J.

    2014-11-01

    NASA is examining two options for the Asteroid Redirect Mission (ARM), which will return asteroid material to a Lunar Distant Retrograde Orbit (LDRO) using a robotic solar-electric-propulsion spacecraft, called the Asteroid Redirect Vehicle (ARV). Once the ARV places the asteroid material into the LDRO, a piloted mission will rendezvous and dock with the ARV. After docking, astronauts will conduct two extravehicular activities (EVAs) to inspect and sample the asteroid material before returning to Earth. One option involves capturing an entire small (˜4-10 m diameter) near-Earth asteroid (NEA) inside a large inflatable bag. However, NASA is examining another option that entails retrieving a boulder (˜1-5 m) via robotic manipulators from the surface of a larger (˜100+ m) pre-characterized NEA. This option can leverage robotic mission data to help ensure success by targeting previously (or soon to be) well-characterized NEAs. For example, the data from the Hayabusa mission has been utilized to develop detailed mission designs that assess options and risks associated with proximity and surface operations. Hayabusa’s target NEA, Itokawa, has been identified as a valid target and is known to possess hundreds of appropriately sized boulders on its surface. Further robotic characterization of additional NEAs (e.g., Bennu and 1999 JU3) by NASA’s OSIRIS REx and JAXA’s Hayabusa 2 missions is planned to begin in 2018. The boulder option is an extremely large sample-return mission with the prospect of bringing back many tons of well-characterized asteroid material to the Earth-Moon system. The candidate boulder from the target NEA can be selected based on inputs from the world-wide science community, ensuring that the most scientifically interesting boulder be returned for subsequent sampling. This boulder option for NASA’s ARM can leverage knowledge of previously characterized NEAs from prior robotic missions, which provides more certainty of the target NEA

  20. Role and Redirection of IgE against Cancer

    Directory of Open Access Journals (Sweden)

    Elisa A. Nigro

    2013-05-01

    Full Text Available IgE is a highly elusive antibody class, yet a tremendously powerful elicitor of immune reactions. Despite huge efforts spent on the characterization and understanding of the IgE system many questions remain either unanswered or only marginally addressed. One above all relates to the role of IgE. A common doubt is based on whether IgE mode of action should only be relegated to anti-parasite immunity and allergic manifestations. In search for a hidden role of IgE, reports from several laboratories are described herein in which a natural IgE link to cancer or the experimental redirection of IgE against cancer have been investigated. Epidemiological and investigational studies are trying to elucidate a possible direct intervention of endogenous IgE against cancer, raising thus far no definitive evidence. Conversely, experimental approaches implementing several strategies and engineered IgE formats built up a series of convincing results indicating that cancer might be tackled by the effector functions of this immunoglobulin class. Because of its peculiar immune features, IgE may present a superior anti-tumor performance as compared to IgG. However, extreme care should be taken on how IgE-based anti-tumor approaches should be devised. Overall, IgE appears as a promising resource, likely destined to enrich the anti-cancer arsenal.

  1. Hypothalamic dysfunction

    Science.gov (United States)

    ... common causes of hypothalamic dysfunction are surgery, traumatic brain injury, tumors, and radiation. Other causes include: Anorexia nervosa or bulimia Bleeding Genetic disorders that cause iron ...

  2. Overview and Updated Status of the Asteroid Redirect Mission (ARM)

    Science.gov (United States)

    Abell, Paul; Mazanek, Daniel D.; Reeves, David M.; Chodas, Paul; Gates, Michele; Johnson, Lindley N.; Ticker, Ronald

    2016-10-01

    The National Aeronautics and Space Administration (NASA) is developing a mission to visit a large near-Earth asteroid (NEA), collect a multi-ton boulder and regolith samples from its surface, demonstrate a planetary defense technique known as the enhanced gravity tractor, and return the asteroidal material to a stable orbit around the Moon. Once returned to cislunar space in the mid-2020s, astronauts will explore the boulder and return to Earth with samples. This Asteroid Redirect Mission (ARM) is part of NASA's plan to advance the technologies, capabilities, and spaceflight experience needed for a human mission to the Martian system in the 2030s and other destinations, as well as provide other broader benefits. Subsequent human and robotic missions to the asteroidal material would also be facilitated by its return to cislunar space. Although ARM is primarily a capability demonstration mission (i.e., technologies and associated operations), there exist significant opportunities to advance our knowledge of small bodies in the synergistic areas of science, planetary defense, asteroidal resources and in-situ resource utilization (ISRU), and capability and technology demonstrations. Current plans are for the robotic mission to be launched in late 2021 with the crewed mission segment conducted using an Orion capsule via a Space Launch System rocket in 2026. In order to maximize the knowledge return from the mission, NASA is providing accommodations for payloads to be carried on the robotic segment of the mission and also organizing an ARM Investigation Team. The Investigation Team will be comprised of scientists, technologists, and other qualified and interested individuals from US industry, government, academia, and international institutions to help plan the implementation and execution of ARM. The presentation will provide a mission overview and the most recent update concerning the robotic and crewed segments of ARM, including the mission requirements, and potential

  3. Redirecting valvular myofibroblasts into dormant fibroblasts through light-mediated reduction in substrate modulus.

    Science.gov (United States)

    Wang, Huan; Haeger, Sarah M; Kloxin, April M; Leinwand, Leslie A; Anseth, Kristi S

    2012-01-01

    Fibroblasts residing in connective tissues throughout the body are responsible for extracellular matrix (ECM) homeostasis and repair. In response to tissue damage, they activate to become myofibroblasts, which have organized contractile cytoskeletons and produce a myriad of proteins for ECM remodeling. However, persistence of myofibroblasts can lead to fibrosis with excessive collagen deposition and tissue stiffening. Thus, understanding which signals regulate de-activation of myofibroblasts during normal tissue repair is critical. Substrate modulus has recently been shown to regulate fibrogenic properties, proliferation and apoptosis of fibroblasts isolated from different organs. However, few studies track the cellular responses of fibroblasts to dynamic changes in the microenvironmental modulus. Here, we utilized a light-responsive hydrogel system to probe the fate of valvular myofibroblasts when the Young's modulus of the substrate was reduced from ~32 kPa, mimicking pre-calcified diseased tissue, to ~7 kPa, mimicking healthy cardiac valve fibrosa. After softening the substrata, valvular myofibroblasts de-activated with decreases in α-smooth muscle actin (α-SMA) stress fibers and proliferation, indicating a dormant fibroblast state. Gene signatures of myofibroblasts (including α-SMA and connective tissue growth factor (CTGF)) were significantly down-regulated to fibroblast levels within 6 hours of in situ substrate elasticity reduction while a general fibroblast gene vimentin was not changed. Additionally, the de-activated fibroblasts were in a reversible state and could be re-activated to enter cell cycle by growth stimulation and to express fibrogenic genes, such as CTGF, collagen 1A1 and fibronectin 1, in response to TGF-β1. Our data suggest that lowering substrate modulus can serve as a cue to down-regulate the valvular myofibroblast phenotype resulting in a predominantly quiescent fibroblast population. These results provide insight in designing

  4. Redirecting valvular myofibroblasts into dormant fibroblasts through light-mediated reduction in substrate modulus.

    Directory of Open Access Journals (Sweden)

    Huan Wang

    Full Text Available Fibroblasts residing in connective tissues throughout the body are responsible for extracellular matrix (ECM homeostasis and repair. In response to tissue damage, they activate to become myofibroblasts, which have organized contractile cytoskeletons and produce a myriad of proteins for ECM remodeling. However, persistence of myofibroblasts can lead to fibrosis with excessive collagen deposition and tissue stiffening. Thus, understanding which signals regulate de-activation of myofibroblasts during normal tissue repair is critical. Substrate modulus has recently been shown to regulate fibrogenic properties, proliferation and apoptosis of fibroblasts isolated from different organs. However, few studies track the cellular responses of fibroblasts to dynamic changes in the microenvironmental modulus. Here, we utilized a light-responsive hydrogel system to probe the fate of valvular myofibroblasts when the Young's modulus of the substrate was reduced from ~32 kPa, mimicking pre-calcified diseased tissue, to ~7 kPa, mimicking healthy cardiac valve fibrosa. After softening the substrata, valvular myofibroblasts de-activated with decreases in α-smooth muscle actin (α-SMA stress fibers and proliferation, indicating a dormant fibroblast state. Gene signatures of myofibroblasts (including α-SMA and connective tissue growth factor (CTGF were significantly down-regulated to fibroblast levels within 6 hours of in situ substrate elasticity reduction while a general fibroblast gene vimentin was not changed. Additionally, the de-activated fibroblasts were in a reversible state and could be re-activated to enter cell cycle by growth stimulation and to express fibrogenic genes, such as CTGF, collagen 1A1 and fibronectin 1, in response to TGF-β1. Our data suggest that lowering substrate modulus can serve as a cue to down-regulate the valvular myofibroblast phenotype resulting in a predominantly quiescent fibroblast population. These results provide insight in

  5. Molecular and cellular basis for diastolic dysfunction

    NARCIS (Netherlands)

    Heerebeek, L. van; Franssen, C.P.; Hamdani, N.; Verheugt, F.W.A.; Somsen, G.A.; Paulus, W.J.

    2012-01-01

    Heart failure with preserved ejection fraction (HFpEF) is highly prevalent and is frequently associated with metabolic risk factors. Patients with HFpEF have only a slightly lower mortality than patients with HF and reduced EF. The pathophysiology of HFpEF is currently incompletely understood, which

  6. The Double Asteroid Redirection Test (DART) for the AIDA Mission

    Science.gov (United States)

    Stickle, Angela; Cheng, Andy F.; Michel, Patrick; Barnouin, Olivier S.; Campo Bagatin, Adriano; Miller, Paul L.; Pravec, Petr; Richardson, Derek C.; Schwartz, Stephen R.; Tsiganis, Kleomenis; Ulamec, Stephan; AIDA Impact Modeling and Simulation Working Group

    2016-10-01

    The Asteroid Impact Deflection Assessment (AIDA) mission will be the first space experiment to demonstrate asteroid impact hazard mitigation using a kinetic impactor. AIDA is a joint ESA-NASA cooperative project, consisting of the NASA Double Asteroid Redirection Test (DART) mission, which provides the kinetic impactor, and the ESA Asteroid Impact Mission (AIM) rendezvous spacecraft. DART is a Phase A study supported by NASA, and AIM is a Phase B1 study supported by ESA. The AIDA target is the near-Earth binary asteroid 65803 Didymos, which will make a close approach to Earth in October, 2022. The DART spacecraft is designed to impact the Didymos secondary at ~6 km/s and deflect its trajectory, changing the orbital period of the binary. This change can be measured by Earth-based optical and radar observations. The primary goals of AIDA are to (1) perform a full-scale demonstration of asteroid deflection by kinetic impact; (2) measure the resulting deflection; and (3) validate and improve models for momentum transfer in high-speed impacts on an asteroid. The combined DART and AIM missions will provide the first measurements of momentum transfer efficiency from a kinetic impact at full scale on an asteroid, where the impact conditions of the projectile are known, and physical properties and internal structures of the target asteroid are also characterized. In addition to a predicted 4.4 minute change in the binary orbit period, assuming unit momentum transfer efficiency, the DART kinetic impact is predicted to induce forced librations of the Didymos secondary of possibly several degrees amplitude. Models predict the impact will create a 6-17 meter diameter crater, depending on target physical properties, and it will release a volume of particulate ejecta that may be directly observable from Earth or even resolvable as a coma or an ejecta tail by ground-based telescopes. Current simulations of the DART impact provide predictions for momentum transfer, crater size, and

  7. Near Earth Asteroid redirect missions based on gravity assist maneuver

    Science.gov (United States)

    Ledkov, Anton; Shustov, Boris M.; Eismont, Natan; Boyarsky, Michael; Nazirov, Ravil; Fedyaev, Konstantin

    During last years several events attracted world community attention to the hazards of hitting the Earth by sky objects. One of these objects is Apophis asteroid what was expected with nonzero probability to hit the Earth in 2036. Luckily after more precise measurements this event is considered as practically improbable. But the other object has really reached the Earth, entered the atmosphere in the Chelyabinsk area and caused vast damages. After this the hazardous near Earth objects problem received practical confirmation of the necessity to find the methods of its resolution. The methods to prevent collision of the dangerous sky object with the Earth proposed up to now look not practical enough if one mentions such as gravitational tractor or changing the reflectivity of the asteroid surface. Even the method supposing the targeting of the spacecraft to the hazardous object in order to deflect it from initial trajectory by impact does not work because its low mass as compared with the mass of asteroid to be deflected. For example the mass of the Apophis is estimated to be about 40 million tons but the spacecraft which can be launched to intercept the asteroid using contemporary launchers has the mass not more than 5 tons. So the question arises where to find the heavier projectile which is possible to direct to the dangerous object? The answer proposed in our paper is very simple: to search it among small near Earth asteroids. As small ones we suppose those which have the cross section size not more than 12-15 meters and mass not exceeding 1500 -1700 tons. According to contemporary estimates the number of such asteroids is not less than 100000. The other question is how to redirect such asteroid to the dangerous one. In the paper the possibilities are studied to use for that purpose gravity assist maneuvers near Earth. It is shown that even among asteroids included in contemporary catalogue there are the ones which could be directed to the trajectory of the

  8. Autophagy and mitophagy in cellular damage control

    Directory of Open Access Journals (Sweden)

    Jianhua Zhang

    2013-01-01

    Full Text Available Autophagy and mitophagy are important cellular processes that are responsible for breaking down cellular contents, preserving energy and safeguarding against accumulation of damaged and aggregated biomolecules. This graphic review gives a broad summary of autophagy and discusses examples where autophagy is important in controlling protein degradation. In addition we highlight how autophagy and mitophagy are involved in the cellular responses to reactive species and mitochondrial dysfunction. The key signaling pathways for mitophagy are described in the context of bioenergetic dysfunction.

  9. Redirecting walking and driving for natural navigation in immersive virtual environments.

    Science.gov (United States)

    Bruder, Gerd; Interrante, Victoria; Phillips, Lane; Steinicke, Frank

    2012-04-01

    Walking is the most natural form of locomotion for humans, and real walking interfaces have demonstrated their benefits for several navigation tasks. With recently proposed redirection techniques it becomes possible to overcome space limitations as imposed by tracking sensors or laboratory setups, and, theoretically, it is now possible to walk through arbitrarily large virtual environments. However, walking as sole locomotion technique has drawbacks, in particular, for long distances, such that even in the real world we tend to support walking with passive or active transportation for longer-distance travel. In this article we show that concepts from the field of redirected walking can be applied to movements with transportation devices. We conducted psychophysical experiments to determine perceptual detection thresholds for redirected driving, and set these in relation to results from redirected walking. We show that redirected walking-and-driving approaches can easily be realized in immersive virtual reality laboratories, e. g., with electric wheelchairs, and show that such systems can combine advantages of real walking in confined spaces with benefits of using vehicle-based self-motion for longer-distance travel.

  10. The effects of preservice teacher's cognitive questioning level and redirecting on student science achievement

    Science.gov (United States)

    Riley, Joseph P., II

    The objectives of this experimental study were to investigate the effects of 100% high cognitive questions, 50% high cognitive questions and 0% high cognitive questions on primary and intermediate students' achievement at the knowledge, comprehension, and analysis levels. A second purpose was to examine the effects of redirecting questions on student achievement. Groups of 5 subjects were randomly selected from 16 intermediate and 16 primary classrooms and then randomly assigned to one of three treatment levels. Data were collected on 154 subjects. Within the three cognitive questioning treatment levels the subjects were also randomly assigned to one of two questioning strategies: (1) redirected and (2) directed. Redirection occurs when the teacher asks the same question to a number of students (in this case 2). Thirty preservice teachers conducted the treatments. The teachers were trained to follow a prescribed behavior pattern and were video taped during the treatment to insure fidelity to the scripted questions. At the end of the lesson a criterion test was administered with 3 subtests measuring at the knowledge, comprehension, and analysis levels of Bloom's Taxonomy. There was no significant difference among scores on the total criterion measure or the sub tests due to cognitive questioning level. There was a significant difference due to redirecting questions (p = 0.05). Students assigned to teachers using redirection scored significantly higher than those assigned to teachers not using this strategy. This difference was found on the knowledge subtest. Significant interactions occurred between questioning level and questioning strategy on the comprehension and total test.

  11. The Double Asteroid Redirection Test in the AIDA Mission

    Science.gov (United States)

    Cheng, Andrew; Reed, Cheryl; Rivkin, Andrew

    2016-07-01

    The Asteroid Impact & Deflection Assessment (AIDA) mission will be the first space experiment to demonstrate asteroid impact hazard mitigation by using a kinetic impactor. AIDA is a joint ESA-NASA cooperative project, consisting of the ESA Asteroid Impact Mission (AIM) rendezvous mission and the NASA Double Asteroid Redirection Test (DART) mission. The AIDA target is the near-Earth binary asteroid 65803 Didymos, which will make an unusually close approach to Earth in October, 2022. The DART spacecraft is designed to impact the Didymos secondary at 7 km/s and demonstrate the ability to modify its trajectory through momentum transfer. DART and AIM are currently Phase A studies supported by NASA and ESA respectively. The primary goals of AIDA are (1) perform a full-scale demonstration of the spacecraft kinetic impact technique for deflection of an asteroid; (2) measure the resulting asteroid deflection, by targeting the secondary member of a binary NEO and measuring the resulting changes of the binary orbit; and (3) study hyper-velocity collision effects on an asteroid, validating models for momentum transfer in asteroid impacts based on measured physical properties of the asteroid surface and sub-surface, and including long-term dynamics of impact ejecta. The primary DART objectives are to demonstrate a hyper-velocity impact on the Didymos moon and to determine the resulting deflection from ground-based observations. The DART impact on the Didymos secondary will change the orbital period of the binary which can be measured by supporting Earth-based optical and radar observations. The baseline DART mission launches in December, 2020 to impact the Didymos secondary in September,2022. There are multiple launch opportunities for DART leading to impact around the 2022 Didymos close approach to Earth. The AIM spacecraft will be launched in Dec. 2020 and arrive at Didymos in spring, 2022, several months before the DART impact. AIM will characterize the Didymos binary system

  12. The Double Asteroid Redirection Test in the AIDA Project

    Science.gov (United States)

    Cheng, Andrew; Rivkin, Andrew; Michel, Patrick

    2016-04-01

    The Asteroid Impact & Deflection Assessment (AIDA) mission will be the first space experiment to demonstrate asteroid impact hazard mitigation by using a kinetic impactor. AIDA is a joint ESA-NASA cooperative project, that includes the ESA Asteroid Impact Mission (AIM) rendezvous mission and the NASA Double Asteroid Redirection Test (DART) mission. The AIDA target is the near-Earth binary asteroid 65803 Didymos, which will make an unusually close approach to Earth in October, 2022. The ~300-kg DART spacecraft is designed to impact the Didymos secondary at 7 km/s and demonstrate the ability to modify its trajectory through momentum transfer. DART and AIM are currently Phase A studies supported by NASA and ESA respectively. The primary goals of AIDA are (1) perform a full-scale demonstration of the spacecraft kinetic impact technique for deflection of an asteroid, by targeting an object larger than ~100 m and large enough to qualify as a Potentially Hazardous Asteroid; (2) measure the resulting asteroid deflection, by targeting the secondary member of a binary NEO and measuring the period change of the binary orbit; (3) understand the hyper-velocity collision effects on an asteroid, including the long-term dynamics of impact ejecta; and validate models for momentum transfer in asteroid impacts, based on measured physical properties of the asteroid surface and sub-surface. The primary DART objectives are to demonstrate a hyper-velocity impact on the Didymos moon and to determine the resulting deflection from ground-based observatories. The DART impact on the Didymos secondary will cause a measurable change in the orbital period of the binary. Supporting Earth-based optical and radar observations and numerical simulation studies are an integral part of the DART mission. The baseline DART mission launches in December, 2020 to impact the Didymos secondary in September, 2022. There are multiple launch opportunities for DART leading to impact around the 2022 Didymos close

  13. Suicide Gene Therapy to Increase the Safety of Chimeric Antigen Receptor-Redirected T Lymphocytes

    Directory of Open Access Journals (Sweden)

    Monica Casucci, Attilio Bondanza

    2011-01-01

    Full Text Available Chimeric antigen receptors (CARs are generated by fusing the antigen-binding motif of a monoclonal antibody (mAb with the signal transduction machinery of the T-cell receptor (TCR. The genetic modification of T lymphocytes with chimeric receptors specific for tumor-associated antigens (TAAs allows for the redirection towards tumor cells. Clinical experience with CAR-redirected T cells suggests that antitumor efficacy associates with some degree of toxicity, especially when TAA expression is shared with healthy tissues. This situation closely resembles the case of allogeneic hematopoietic stem cell transplantation (HSCT, wherein allorecognition causes both the graft-versus-leukemia (GVL effect and graft-versus-host disease (GVHD. Suicide gene therapy, i.e. the genetic induction of a conditional suicide phenotype into donor T cells, enables dissociating the GVL effect from GVHD. Applying suicide gene modification to CAR-redirected T cells may therefore greatly increase their safety profile and facilitate their clinical development.

  14. Pathophysiology of shunt dysfunction in shunt treated hydrocephalus

    DEFF Research Database (Denmark)

    Blegvad, C.; Skjolding, A D; Broholm, H

    2013-01-01

    We hypothesized that shunt dysfunction in the ventricular catheter and the shunt valve is caused by different cellular responses. We also hypothesized that the cellular responses depend on different pathophysiological mechanisms....

  15. An Analysis and Design of the Redirection Schema in ForCES

    Directory of Open Access Journals (Sweden)

    Ming Gao

    2013-01-01

    Full Text Available The idea of Forwarding and Control Element Separation has widely accepted by next generation network researchers, the regain attention of IETF (The Internet Engineering Task Force ForCES (Forwarding and Control Element Separation is the best proof. An IP tunnel-based redirection schema was proposed to solve the problem of routing protocol messages interaction between ForCES router and the external merchant routers. The technology of network virtualization is introduced to map network interface from ForCES FE (Forwarding Element to CE (Control Element which collaborating with the redirect schema.

  16. Pointright: a system to redirect mouse and keyboard control among multiple machines

    Science.gov (United States)

    Johanson, Bradley E.; Winograd, Terry A.; Hutchins, Gregory M.

    2008-09-30

    The present invention provides a software system, PointRight, that allows for smooth and effortless control of pointing and input devices among multiple displays. With PointRight, a single free-floating mouse and keyboard can be used to control multiple screens. When the cursor reaches the edge of a screen it seamlessly moves to the adjacent screen and keyboard control is simultaneously redirected to the appropriate machine. Laptops may also redirect their keyboard and pointing device, and multiple pointers are supported simultaneously. The system automatically reconfigures itself as displays go on, go off, or change the machine they display.

  17. Erectile dysfunction.

    Science.gov (United States)

    Wylie, Kevan

    2008-01-01

    Erectile dysfunction is a common problem affecting sexual function in men. Approximately one in 10 men over the age of 40 is affected by this condition and the incidence is age related. Erectile dysfunction is a sentinel marker for several reversible conditions including peripheral and coronary vascular disease, hypertension and diabetes mellitus. Endothelial dysfunction is a common factor between the disease states. Concurrent conditions such as depression, late-onset hypogonadism, Peyronie's disease and lower urinary tract symptoms may significantly worsen erectile function, other sexual and relationship issues and penis dysmorphophobia. A focused physical examination and baseline laboratory investigations are mandatory. Management consists of initiating modifiable lifestyle changes, psychological and psychosexual/couples interventions and pharmacological and other interventions. In combination and with treatment of concurrent comorbid states, these interventions will often bring about successful resolution of symptoms and avoid the need for surgical interventions.

  18. Mitochondrial Dysfunction in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    P. C. Keane

    2011-01-01

    Full Text Available Parkinson's disease (PD is a progressive, neurodegenerative condition that has increasingly been linked with mitochondrial dysfunction and inhibition of the electron transport chain. This inhibition leads to the generation of reactive oxygen species and depletion of cellular energy levels, which can consequently cause cellular damage and death mediated by oxidative stress and excitotoxicity. A number of genes that have been shown to have links with inherited forms of PD encode mitochondrial proteins or proteins implicated in mitochondrial dysfunction, supporting the central involvement of mitochondria in PD. This involvement is corroborated by reports that environmental toxins that inhibit the mitochondrial respiratory chain have been shown to be associated with PD. This paper aims to illustrate the considerable body of evidence linking mitochondrial dysfunction with neuronal cell death in the substantia nigra pars compacta (SNpc of PD patients and to highlight the important need for further research in this area.

  19. Erectile dysfunction

    African Journals Online (AJOL)

    that increase blood flow to the penis. The blood ... The pressure of the blood in the chambers makes the ... What are the risk factors for erectile dysfunction? The most .... losing excessive weight and increasing physical activity, may improve the ...

  20. Effect of joint mechanism on vehicle redirectional capability of water-filled road safety barrier systems.

    Science.gov (United States)

    Thiyahuddin, M I; Thambiratnam, D P; Gu, Y T

    2014-10-01

    Portable water-filled barriers (PWFBs) are roadside appurtenances that prevent vehicles from penetrating into temporary construction zones on roadways. PWFBs are required to satisfy the strict regulations for vehicle re-direction in tests. However, many of the current PWFBs fail to re-direct the vehicle at high speeds due to the inability of the joints to provide appropriate stiffness. The joint mechanism hence plays a crucial role in the performance of a PWFB system at high speed impacts. This paper investigates the desired features of the joint mechanism in a PWFB system that can re-direct vehicles at high speeds, while limiting the lateral displacement to acceptable limits. A rectangular "wall" representative of a 30m long barrier system was modeled and a novel method of joining adjacent road barriers was introduced through appropriate pin-joint connections. The impact response of the barrier "wall" and the vehicle was obtained and the results show that a rotational stiffness of 3000kNm/rad at the joints seems to provide the desired features of the PWFB system to re-direct impacting vehicles and restrict the lateral deflection. These research findings will be useful to safety engineers and road barrier designers in developing a new generation of PWFBs for increased road safety.

  1. Evaluation of the Immediate and Subsequent Effects of Response Interruption and Redirection on Vocal Stereotypy

    Science.gov (United States)

    Schumacher, Brittany I.; Rapp, John T.

    2011-01-01

    We evaluated 2 3-component multiple-schedule sequences--a response interruption and redirection (RIRD) treatment sequence and a no-interaction control sequence--using a multielement design. With this design, we were able to evaluate the immediate and subsequent effects of RIRD on 2 participants' vocal stereotypy. For both participants, RIRD…

  2. Sub-wavelength surface gratings for light redirection in transparent substrates

    DEFF Research Database (Denmark)

    Buss, Thomas; Smith, Cameron; Christiansen, Mads Brøkner

    2012-01-01

    based on diffraction and ray-optics, and complemented by numerical simulations. We show that our approach is suitable for redirecting and guiding light over a broad range of incident angles and wavelengths in transparent substrates. The technique has potential applications for solar harvesting in window...

  3. Asteroid Redirect Mission Proximity Operations for Reference Target Asteroid 2008 EV5

    Science.gov (United States)

    Reeves, David M.; Mazanek, Daniel D.; Cichy, Benjamin D.; Broschart, Steve B.; Deweese, Keith D.

    2016-01-01

    NASA's Asteroid Redirect Mission (ARM) is composed of two segments, the Asteroid Redirect Robotic Mission (ARRM), and the Asteroid Redirect Crewed Mission (ARCM). In March of 2015, NASA selected the Robotic Boulder Capture Option1 as the baseline for the ARRM. This option will capture a multi-ton boulder, (typically 2-4 meters in size) from the surface of a large (greater than approx.100 m diameter) Near-Earth Asteroid (NEA) and return it to cis-lunar space for subsequent human exploration during the ARCM. Further human and robotic missions to the asteroidal material would also be facilitated by its return to cis-lunar space. In addition, prior to departing the asteroid, the Asteroid Redirect Vehicle (ARV) will perform a demonstration of the Enhanced Gravity Tractor (EGT) planetary defense technique2. This paper will discuss the proximity operations which have been broken into three phases: Approach and Characterization, Boulder Capture, and Planetary Defense Demonstration. Each of these phases has been analyzed for the ARRM reference target, 2008 EV5, and a detailed baseline operations concept has been developed.

  4. 2º vídeo educativo sobre ICMP-Redirect

    OpenAIRE

    Díaz Quintanilla, David

    2011-01-01

    En este vídeo didáctico se muestra el funcionamiento de los mensajes de error ICMP Redirect. ¿Cuándo se generan? ¿En qué consisten? ¿Cuál es su formato?. Para ello se emplea la topología de red del laboratorio L24 de la Universidad de Alicante.

  5. The Effects of Response Interruption and Redirection and Sertraline on Vocal Stereotypy

    Science.gov (United States)

    Miguel, Caio F.; Clark, Kathy; Tereshko, Lisa; Ahearn, William H.

    2009-01-01

    Although response interruption and redirection (RIRD) has been shown to be successful in reducing vocal stereotypy, recent reports have suggested that selective serotonin reuptake inhibitors (SSRIs) may also reduce these behaviors. The purpose of the current investigation was to examine the effects of RIRD with and without sertraline on…

  6. CFD analysis on gas distribution for different scrubber redirection configurations in sump cut.

    Science.gov (United States)

    Zheng, Y; Organiscak, J A; Zhou, L; Beck, T W; Rider, J P

    2015-01-01

    The National Institute for Occupational Safety and Health's Office of Mine Safety and Health Research recently developed a series of models using computational fluid dynamics (CFD) to study the gas distribution around a continuous mining machine with various fan-powered flooded bed scrubber discharge configurations. CFD models using Species Transport Model without reactions in FLUENT were constructed to evaluate the redirection of scrubber discharge toward the mining face rather than behind the return curtain. The following scenarios are considered in this study: 100 percent of the discharge redirected back toward the face on the off-curtain side of the continuous miner; 100 percent of the discharge redirected back toward the face, but divided equally to both sides of the machine; and 15 percent of the discharge redirected toward the face on the off-curtain side of the machine, with 85 percent directed into the return. These models were compared against a model with a conventional scrubber discharge, where air is directed away from the face into the return. The CFD models were calibrated and validated based on experimental data and accurately predicted sulfur hexafluoride (SF6) gas levels at four gas monitoring locations. One additional prediction model was simulated to consider a different scrubber discharge angle for the 100 percent redirected, equally divided case. These models identified relatively high gassy areas around the continuous miner, which may not warrant their use in coal mines with medium to high methane liberation rates. This paper describes the methodology used to develop the CFD models, and the validation of the models based on experimental data.

  7. Epigenetics and Cellular Metabolism

    Science.gov (United States)

    Xu, Wenyi; Wang, Fengzhong; Yu, Zhongsheng; Xin, Fengjiao

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well. PMID:27695375

  8. Staphylococcus aureus redirects central metabolism to increase iron availability.

    Directory of Open Access Journals (Sweden)

    David B Friedman

    2006-08-01

    Full Text Available Staphylococcus aureus pathogenesis is significantly influenced by the iron status of the host. However, the regulatory impact of host iron sources on S. aureus gene expression remains unknown. In this study, we combine multivariable difference gel electrophoresis and mass spectrometry with multivariate statistical analyses to systematically cluster cellular protein response across distinct iron-exposure conditions. Quadruplicate samples were simultaneously analyzed for alterations in protein abundance and/or post-translational modification state in response to environmental (iron chelation, hemin treatment or genetic (Deltafur alterations in bacterial iron exposure. We identified 120 proteins representing several coordinated biochemical pathways that are affected by changes in iron-exposure status. Highlighted in these experiments is the identification of the heme-regulated transport system (HrtAB, a novel transport system which plays a critical role in staphylococcal heme metabolism. Further, we show that regulated overproduction of acidic end-products brought on by iron starvation decreases local pH resulting in the release of iron from the host iron-sequestering protein transferrin. These findings reveal novel strategies used by S. aureus to acquire scarce nutrients in the hostile host environment and begin to define the iron and heme-dependent regulons of S. aureus.

  9. Staphylococcus aureus redirects central metabolism to increase iron availability.

    Directory of Open Access Journals (Sweden)

    David B Friedman

    2006-08-01

    Full Text Available Staphylococcus aureus pathogenesis is significantly influenced by the iron status of the host. However, the regulatory impact of host iron sources on S. aureus gene expression remains unknown. In this study, we combine multivariable difference gel electrophoresis and mass spectrometry with multivariate statistical analyses to systematically cluster cellular protein response across distinct iron-exposure conditions. Quadruplicate samples were simultaneously analyzed for alterations in protein abundance and/or post-translational modification state in response to environmental (iron chelation, hemin treatment or genetic (Deltafur alterations in bacterial iron exposure. We identified 120 proteins representing several coordinated biochemical pathways that are affected by changes in iron-exposure status. Highlighted in these experiments is the identification of the heme-regulated transport system (HrtAB, a novel transport system which plays a critical role in staphylococcal heme metabolism. Further, we show that regulated overproduction of acidic end-products brought on by iron starvation decreases local pH resulting in the release of iron from the host iron-sequestering protein transferrin. These findings reveal novel strategies used by S. aureus to acquire scarce nutrients in the hostile host environment and begin to define the iron and heme-dependent regulons of S. aureus.

  10. Oral Dysfunction

    OpenAIRE

    鈴木, 規子; スズキ, ノリコ; Noriko, SUZUKI

    2004-01-01

    The major oral functions can be categorized as mastication, swallowing, speech and respiratory functions. Dysfunction of these results in dysphagia, speech disorders and abnormal respiration (such as Sleep Apnea). These functions relate to dentistry in the occurrence of : (1) oral preparatory and oral phases, (2) articulation disorders and velopharyngeal incompetence (VPI), and (3) mouth breathing, respiratory and blowing disorders. These disorders are related to oral and maxillofacial diseas...

  11. Redirecting Therapeutic T Cells against Myelin-Specific T Lymphocytes Using a Humanized Myelin Basic Protein-HLA-DR2-{zeta} Chimeric Receptor

    DEFF Research Database (Denmark)

    Moisini, Ioana; Nguyen, Phuong; Fugger, Lars

    2008-01-01

    Therapies that Ag-specifically target pathologic T lymphocytes responsible for multiple sclerosis (MS) and other autoimmune diseases would be expected to have improved therapeutic indices compared with Ag-nonspecific therapies. We have developed a cellular immunotherapy that uses chimeric receptors...... to selectively redirect therapeutic T cells against myelin basic protein (MBP)-specific T lymphocytes implicated in MS. We generated two heterodimeric receptors that genetically link the human MBP(84-102) epitope to HLA-DR2 and either incorporate or lack a TCRzeta signaling domain. The Ag-MHC domain serves...... as a bait, binding the TCR of MBP-specific target cells. The zeta signaling region stimulates the therapeutic cell after cognate T cell engagement. Both receptors were well expressed on primary T cells or T hybridomas using a tricistronic (alpha, beta, green fluorescent protein) retroviral expression system...

  12. Sensitivity of the Asteroid Redirect Robotic Mission (ARRM) to Launch Date and Asteroid Stay Time

    Science.gov (United States)

    Mcguire, Melissa L.; Burke, Laura M.; McCarty, Steven L.; Strange, Nathan J.; Qu, Min; Shen, Haijun; Vavrina, Matthew A.

    2017-01-01

    National Aeronautics and Space Administrations (NASAs) proposed Asteroid Redirect Mission (ARM) is being designed to robotically capture and then redirect an asteroidal boulder mass into a stable orbit in the vicinity of the moon, where astronauts would be able to visit and study it. The current reference trajectory for the robotic portion, ARRM, assumes a launch on a Delta IV H in the end of the calendar year 2021, with a return for astronaut operations in cislunar space in 2026. The current baseline design allocates 245 days of stay time at the asteroid for operations and boulder collection. This paper outlines analysis completed by the ARRM mission design team to understand the sensitivity of the reference trajectory to launch date and asteroid stay time.

  13. Cellular automata

    CERN Document Server

    Codd, E F

    1968-01-01

    Cellular Automata presents the fundamental principles of homogeneous cellular systems. This book discusses the possibility of biochemical computers with self-reproducing capability.Organized into eight chapters, this book begins with an overview of some theorems dealing with conditions under which universal computation and construction can be exhibited in cellular spaces. This text then presents a design for a machine embedded in a cellular space or a machine that can compute all computable functions and construct a replica of itself in any accessible and sufficiently large region of t

  14. Disguising Rotational Gain for Redirected Walking in Virtual Reality:Effect of Visual Density

    DEFF Research Database (Denmark)

    Paludan, Anders Glud; Elbaek, Jacob; Mortensen, Mathias;

    2016-01-01

    In virtual reality environments that allow users to walk freely, the area of the virtual environment (VE) is constrained to the size of the tracking area. By using redirection techniques, this problem can be partially circumvented; one of the techniques involves rotating the user more or less...... in the virtual world than in the physical world; this technique is referred to as rotational gain. This paper seeks to further investigate this area, examining the effect of visual density in the VE....

  15. Redirecting traditional professional values to support safety: changing organisational culture in health care

    OpenAIRE

    Carroll, J.; Quijada, M.

    2004-01-01

    Professionals in healthcare organisations who seek to enhance safety and quality in an increasingly demanding industry environment often identify culture as a barrier to change. The cultural focus on individual autonomy, for example, seems to conflict with desired norms of teamwork, problem reporting, and learning. We offer a definition and explication of why culture is important to change efforts. A cultural analysis of health care suggests professional values that can be redirected to suppo...

  16. Using multi-disciplinary strategic master facilities planning for organizations experiencing programmatic re-direction

    Energy Technology Data Exchange (ETDEWEB)

    Heubach, J.G.; Weimer, W.C.; Bruce, W.A.

    1993-12-01

    Facility master planning is critical to the future productivity of a laboratory and the quality of worklife for the laboratory staff. For organizations undergoing programmatic re-direction, a master facility planning approach linked to the organization`s strategic planning process is even more important. Major changes in an organization such as programmatic re-direction can significantly impact a broad range of variables which exceed the expertise of traditional planning teams, e.g., capacity variability, work team organization, organizational culture, and work process simplification. By expanding the diversity of the participants of the planning team, there is a greater likelihood that a research organization`s scientific, organizational, economic, and employees` needs can be meshed in the strategic plan and facility plan. Recent recommendations from facility planners suggest drawing from diverse fields in building multi-disciplinary planning teams: Architecture, engineering, natural science, social psychology, and strategic planning (Gibson,1993). For organizations undergoing significant operational or culture change, the master facility planning team should also include members with expertise in organizational effectiveness, industrial engineering, human resources, and environmental psychology. A recent planning and design project provides an example which illustrates the use of an expanded multi-disciplinary team engaged in planning laboratory renovations for a research organization undergoing programmatic re-direction. The purpose of the proposed poster session is to present a multi-disciplinary master facility planning process linked to an organization`s strategic planning process or organizational strategies.

  17. Modeling Cognitive Dysfunction in Neurofibromatosis-1

    OpenAIRE

    Diggs-Andrews, Kelly A.; David H Gutmann

    2013-01-01

    Cognitive dysfunction, including significant impairments in learning, behavior, and attention, is found in over 10% of children in the general population. However, in the common inherited cancer predisposition syndrome, Neurofibromatosis type 1 (NF1), the prevalence of these cognitive deficits approaches 70%. As a monogenic disorder, NF1 provides a unique genetic tool to identify and mechanistically dissect the molecular and cellular bases underlying cognitive dysfunction. In this review, we ...

  18. Mitochondrial dysfunction and organophosphorus compounds

    Energy Technology Data Exchange (ETDEWEB)

    Karami-Mohajeri, Somayyeh [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Kerman University of Medical Sciences, Kerman (Iran, Islamic Republic of); Abdollahi, Mohammad, E-mail: Mohammad.Abdollahi@UToronto.Ca [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2013-07-01

    Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of complexes I, II, III, IV and V activities and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy. The OPs disrupt cellular and mitochondrial antioxidant defense, reactive oxygen species generation, and calcium uptake and promote oxidative and genotoxic damage triggering cell death via cytochrome C released from mitochondria and consequent activation of caspases. The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C, alpha-tocopherol, electron donors, and through increasing the cytosolic ATP level. However, to elucidate many aspect of mitochondrial toxicity of Ops, further studies should be performed. - Highlights: • As a non-cholinergic mechanism of toxicity, mitochondria is a target for OPs. • OPs affect action of complexes I, II, III, IV and V in the mitochondria. • OPs reduce mitochondrial ATP. • OPs promote oxidative and genotoxic damage via release of cytochrome C from mitochondria. • OP-induced mitochondrial dysfunction can be restored by increasing the cytosolic ATP.

  19. Blast shock wave mitigation using the hydraulic energy redirection and release technology.

    Science.gov (United States)

    Chen, Yun; Huang, Wei; Constantini, Shlomi

    2012-01-01

    A hydraulic energy redirection and release technology has been developed for mitigating the effects of blast shock waves on protected objects. The technology employs a liquid-filled plastic tubing as a blast overpressure transformer to transfer kinetic energy of blast shock waves into hydraulic energy in the plastic tubings. The hydraulic energy is redirected through the plastic tubings to the openings at the lower ends, and then is quickly released with the liquid flowing out through the openings. The samples of the specifically designed body armor in which the liquid-filled plastic tubings were installed vertically as the outer layer of the body armor were tested. The blast test results demonstrated that blast overpressure behind the body armor samples was remarkably reduced by 97% in 0.2 msec after the liquid flowed out of its appropriate volume through the openings. The results also suggested that a volumetric liquid surge might be created when kinetic energy of blast shock wave was transferred into hydraulic energy to cause a rapid physical movement or displacement of the liquid. The volumetric liquid surge has a strong destructive power, and can cause a noncontact, remote injury in humans (such as blast-induced traumatic brain injury and post-traumatic stress disorder) if it is created in cardiovascular system. The hydraulic energy redirection and release technology can successfully mitigate blast shock waves from the outer surface of the body armor. It should be further explored as an innovative approach to effectively protect against blast threats to civilian and military personnel.

  20. Use of the Amplatzer Type 2 Plug for Flow Redirection in Failing Autogenous Hemodialysis Fistulae

    Energy Technology Data Exchange (ETDEWEB)

    Bozkurt, Alper, E-mail: bozkurtalper@yahoo.com; Kırbaş, İsmail, E-mail: drismailk@yahoo.com [Turgut Ozal University Hospital, Radiology Department (Turkey); Kasapoglu, Benan, E-mail: benankasapoglu@hotmail.com [Turgut Ozal University Hospital, Internal Medicine Department (Turkey); Teber, Mehmet Akif, E-mail: drteberma@hotmail.com [Ataturk Education and Training Hospital, Radiology Department (Turkey)

    2015-08-15

    PurposeTo present our experience with redirecting the outflow of mature arteriovenous fistulae (AVFs) in patients with cannulation and/or suboptimal flow problems by percutaneous intervention using the Amplatzer Vascular Plug II (AVP II).MethodsWe retrospectively reviewed patients who presented with difficulty in cannulation and/or suboptimal flow in the puncture zone of the AVF and who underwent intervention using the AVP II to redirect the outflow through a better cannulation zone from March 2009 to November 2012. The mean survival rate of all AVFs was estimated, and the effects of patient age, sex, and AVF age on the AVF survival time were determined.ResultsIn total, 31 patients (17 male and 14 female) with a mean age of 57.8 years (range, 20–79 years) were included. In 2 patients, the AVF failed within the first 15 days because of rapid thrombosis. In 9 patients, the new AVF route was working effectively until unsalvageable thrombosis developed. One of the 31 patients died 9 months before the last radiologic evaluation. The new AVF route was still being used for dialysis in the remaining 19 patients. The mean AVF survival rate was 1,061.4 ± 139.4 days (range, 788–1,334 days). Patient age, sex, and AVF age did not affect the survival time.ConclusionWe suggest that the AVP II is useful for redirecting the outflow of AVFs with cannulation problems and suboptimal flow. Patency of existing AVFs may be extended, thereby extending surgery-free or catheter intervention-free survival period.

  1. The Asteroid Redirect Mission (ARM): Exploration of a Former Binary NEA?

    Science.gov (United States)

    Abell, P. A.; Mazanek, D. D.; Reeves, D. M.; Chodas, P. W.; Gates, M. M.; Johnson, L. N.; Ticker, R. L.

    2016-01-01

    The National Aeronautics and Space Administration (NASA) is developing the Asteroid Redirect Mission (ARM) as a capability demonstration for future human exploration, including use of high-power solar electric propulsion, which allows for the efficient movement of large masses through deep space. The ARM will also demonstrate the capability to conduct proximity operations with natural space objects and crewed operations beyond the security of quick Earth return. The Asteroid Redirect Robotic Mission (ARRM), currently in formulation, will visit a large near-Earth asteroid (NEA), collect a multi-ton boulder from its surface, conduct a demonstration of a slow push planetary defense technique, and redirect the multi-ton boulder into a stable orbit around the Moon. Once returned to cislunar space in the mid-2020s, astronauts aboard an Orion spacecraft will dock with the robotic vehicle to explore the boulder and return samples to Earth. The ARM is part of NASA's plan to advance technologies, capabilities, and spaceflight experience needed for a human mission to the Martian system in the 2030s. The ARM and subsequent availability of the asteroidal material in cis-lunar space, provide significant opportunities to advance our knowledge of small bodies in the synergistic areas of science, planetary defense, and in-situ resource utilization (ISRU). The current reference target for the ARM is NEA (341843) 2008 EV5, which may have been the primary body of a former binary system (Busch et al., 2011; Tardivel et al., 2016). The ARRM will perform several close proximity operations to investigate the NEA and map its surface. A detailed investigation of this object may allow a better understanding of binary NEA physical characteristics and the possible outcomes for their evolution. An overview of the ARM robotic and crewed segments, including mission operations, and a discussion of potential opportunities for participation with the ARM will be provided in this presentation.

  2. Wind Turbine Wake-Redirection Control at the Fishermen's Atlantic City Windfarm: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Churchfield, M.; Fleming, P.; Bulder, B.; White, S.

    2015-05-06

    In this paper, we will present our work towards designing a control strategy to mitigate wind turbine wake effects by redirecting the wakes, specifically applied to the Fishermen’s Atlantic City Windfarm (FACW), proposed for deployment off the shore of Atlantic City, New Jersey. As wind turbines extract energy from the air, they create low-speed wakes that extend behind them. Full wake recovery Full wake recovery to the undisturbed wind speed takes a significant distance. In a wind energy plant the wakes of upstream turbines may travel downstream to the next row of turbines, effectively subjecting them to lower wind speeds, meaning these waked turbines will produce less power.

  3. Redirecting traditional professional values to support safety: changing organisational culture in health care.

    Science.gov (United States)

    Carroll, J S; Quijada, M A

    2004-12-01

    Professionals in healthcare organisations who seek to enhance safety and quality in an increasingly demanding industry environment often identify culture as a barrier to change. The cultural focus on individual autonomy, for example, seems to conflict with desired norms of teamwork, problem reporting, and learning. We offer a definition and explication of why culture is important to change efforts. A cultural analysis of health care suggests professional values that can be redirected to support change. We offer examples of organisations that drew upon cultural strengths to create new ways of working and gradually shifted the culture.

  4. Targeted energy transfers and passive acoustic wave redirection in a two-dimensional granular network under periodic excitation

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yijing, E-mail: yzhng123@illinois.edu; Moore, Keegan J.; Vakakis, Alexander F. [Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States); McFarland, D. Michael [Department of Aerospace Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States)

    2015-12-21

    We study passive pulse redirection and nonlinear targeted energy transfer in a granular network composed of two semi-infinite, ordered homogeneous granular chains mounted on linear elastic foundations and coupled by weak linear stiffnesses. Periodic excitation in the form of repetitive half-sine pulses is applied to one of the chains, designated as the “excited chain,” whereas the other chain is initially at rest and is regarded as the “absorbing chain.” We show that passive pulse redirection and targeted energy transfer from the excited to the absorbing chain can be achieved by macro-scale realization of the spatial analog of the Landau-Zener quantum tunneling effect. This is realized by finite stratification of the elastic foundation of the excited chain and depends on the system parameters (e.g., the percentage of stratification) and on the parameters of the periodic excitation. Utilizing empirical mode decomposition and numerical Hilbert transforms, we detect the existence of two distinct nonlinear phenomena in the periodically forced network; namely, (i) energy localization in the absorbing chain due to sustained 1:1 resonance capture leading to irreversible pulse redirection from the excited chain, and (ii) continuous energy exchanges in the form of nonlinear beats between the two chains in the absence of resonance capture. Our results extend previous findings of transient passive energy redirection in impulsively excited granular networks and demonstrate that steady state passive pulse redirection in these networks can be robustly achieved under periodic excitation.

  5. Antigen-specific in vitro expansion of functional redirected NY-ESO-1-specific human CD8+ T-cells in a cell-free system.

    Science.gov (United States)

    Jakka, Gopinadh; Schuberth, Petra C; Thiel, Markus; Held, Gerhard; Stenner, Frank; Van Den Broek, Maries; Renner, Christoph; Mischo, Axel; Petrausch, Ulf

    2013-10-01

    Tumors can be targeted by the adoptive transfer of chimeric antigen receptor (CAR) redirected T-cells. Antigen-specific expansion protocols are needed to generate large quantities of redirected T-cells. We aimed to establish a protocol to expand functional active NY-ESO-1-specific redirected human CD8(+) T-cells. The anti-idiotypic Fab antibody A4 with specificity for HLA-A 0201/NY-ESO-1157-165 was tested by competition assays using a HLA-A 0201/NY-ESO-1157-165 tetramer. HLA-A 0201/NY-ESO-1157-165 redirected T-cells were generated, expanded and tested for CAR expression, cytokine release, in vitro cytolysis and protection against xenografted HLA-A 0201/NY-ESO-1157-165-positive multiple myeloma cells. A4 demonstrated antigen-specific binding to HLA-A 0201/NY-ESO-1157-165 redirected T-cells. Expansion with A4 resulted in 98% of HLA-A 0201/NY-ESO-1157-165 redirected T-cells. A4 induced strong proliferation, resulting in a 300-fold increase of redirected T-cells. After expansion protocols, redirected T-cells secreted Interleukin-2, (IL-2), interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) and lysed target cells in vitro and were protective in vivo. A4 expanded HLA-A 0201/NY-ESO-1157-165 redirected T-cells with preservation of antigen-specific function.

  6. Changes in Effective Connectivity of the Superior Parietal Lobe during Inhibition and Redirection of Eye Movements

    Science.gov (United States)

    Asscheman, Susanne J.; Thakkar, Katharine N.; Neggers, Sebastiaan F.W.

    2015-01-01

    Executive control is the ability to flexibly control behavior and is frequently studied with saccadic eye movements. Contrary to frontal oculomotor areas, the role of the superior parietal lobe (SPL) in the executive control of saccades remains unknown. To explore the role of SPL networks in saccade control, we performed a saccadic search-step task while acquiring functional magnetic resonance imaging data for 41 participants. Psychophysiological interaction analyses assessed task-related differences in the effective connectivity of SPL with other brain regions during the inhibition and redirection of saccades. Results indicate an increased coupling of SPL with frontal, posterior, and striatal oculomotor areas for redirected saccades versus visually guided saccades. Saccade inhibition versus unsuccessful inhibition revealed an increased coupling of SPL with dorsolateral prefrontal cortex and anterior cingulate cortex. We discuss how these findings relate to ongoing debates about the implementation of executive control and conclude that early attentional control and rapid updating of saccade goals are important signals for executive control. PMID:27147827

  7. PKA phosphorylation redirects ERα to promoters of a unique gene set to induce tamoxifen resistance.

    Science.gov (United States)

    de Leeuw, R; Flach, K; Bentin Toaldo, C; Alexi, X; Canisius, S; Neefjes, J; Michalides, R; Zwart, W

    2013-07-25

    Protein kinase A (PKA)-induced estrogen receptor alpha (ERα) phosphorylation at serine residue 305 (ERαS305-P) can induce tamoxifen (TAM) resistance in breast cancer. How this phospho-modification affects ERα specificity and translates into TAM resistance is unclear. Here, we show that S305-P modification of ERα reprograms the receptor, redirecting it to new transcriptional start sites, thus modulating the transcriptome. By altering the chromatin-binding pattern, Ser305 phosphorylation of ERα translates into a 26-gene expression classifier that identifies breast cancer patients with a poor disease outcome after TAM treatment. MYC-target genes and networks were significantly enriched in this gene classifier that includes a number of selective targets for ERαS305-P. The enhanced expression of MYC increased cell proliferation in the presence of TAM. We demonstrate that activation of the PKA signaling pathway alters the transcriptome by redirecting ERα to new transcriptional start sites, resulting in altered transcription and TAM resistance.

  8. Redirection of Human Cancer Cells upon the Interaction with the Regenerating Mouse Mammary Gland Microenvironment

    Directory of Open Access Journals (Sweden)

    Sonia M. Rosenfield

    2013-01-01

    Full Text Available Tumorigenesis is often described as a result of accumulated mutations that lead to growth advantage and clonal expansion of mutated cells. There is evidence in the literature that cancer cells are influenced by the microenvironment. Our previous studies demonstrated that the mouse mammary gland is capable of redirecting mouse cells of non-mammary origins as well as Mouse Mammary Tumor Virus (MMTV-neu transformed cells toward normal mammary epithelial cell fate during gland regeneration. Interestingly, the malignant phenotype of MMTV-neu transformed cells was suppressed during serial transplantation experiments. Here, we discuss our studies that demonstrated the potential of the regenerating mouse mammary gland to redirect cancer cells of different species into a functional tumor-free mammary epithelial cell progeny. Immunochemistry for human specific CD133, mitochondria, cytokeratins as well as milk proteins and FISH for human specific probe identified human epithelial cell progeny in ducts, lobules, and secretory acini. Fluorescent In Situ Hybridization (FISH for human centromeric DNA and FACS analysis of propidium iodine staining excluded the possibility of mouse-human cell fusion. To our knowledge this is the first evidence that human cancer cells of embryonic or somatic origins respond to developmental signals generated by the mouse mammary gland microenvironment during gland regeneration in vivo.

  9. Changes in Effective Connectivity of the Superior Parietal Lobe during Inhibition and Redirection of Eye Movements

    Directory of Open Access Journals (Sweden)

    Susanne J. Asscheman

    2015-01-01

    Full Text Available Executive control is the ability to flexibly control behavior and is frequently studied with saccadic eye movements. Contrary to frontal oculomotor areas, the role of the superior parietal lobe (SPL in the executive control of saccades remains unknown. To explore the role of SPL networks in saccade control, we performed a saccadic search-step task while acquiring functional magnetic resonance imaging data for 41 participants. Psychophysiological interaction analyses assessed task-related differences in the effective connectivity of SPL with other brain regions during the inhibition and redirection of saccades. Results indicate an increased coupling of SPL with frontal, posterior, and striatal oculomotor areas for redirected saccades versus visually guided saccades. Saccade inhibition versus unsuccessful inhibition revealed an increased coupling of SPL with dorsolateral prefrontal cortex and anterior cingulate cortex. We discuss how these findings relate to ongoing debates about the implementation of executive control and conclude that early attentional control and rapid updating of saccade goals are important signals for executive control.

  10. Changes in Effective Connectivity of the Superior Parietal Lobe during Inhibition and Redirection of Eye Movements.

    Science.gov (United States)

    Asscheman, Susanne J; Thakkar, Katharine N; Neggers, Sebastiaan F W

    2015-01-01

    Executive control is the ability to flexibly control behavior and is frequently studied with saccadic eye movements. Contrary to frontal oculomotor areas, the role of the superior parietal lobe (SPL) in the executive control of saccades remains unknown. To explore the role of SPL networks in saccade control, we performed a saccadic search-step task while acquiring functional magnetic resonance imaging data for 41 participants. Psychophysiological interaction analyses assessed task-related differences in the effective connectivity of SPL with other brain regions during the inhibition and redirection of saccades. Results indicate an increased coupling of SPL with frontal, posterior, and striatal oculomotor areas for redirected saccades versus visually guided saccades. Saccade inhibition versus unsuccessful inhibition revealed an increased coupling of SPL with dorsolateral prefrontal cortex and anterior cingulate cortex. We discuss how these findings relate to ongoing debates about the implementation of executive control and conclude that early attentional control and rapid updating of saccade goals are important signals for executive control.

  11. Cellular Telephone

    Institute of Scientific and Technical Information of China (English)

    杨周

    1996-01-01

    Cellular phones, used in automobiles, airliners, and passenger trains, are basically low-power radiotelephones. Calls go through radio transmitters that are located within small geographical units called cells. Because each cell’s signals are too weak to interfere with those of other cells operating on the same fre-

  12. Photobiomodulation on alcohol induced dysfunction

    Science.gov (United States)

    Yang, Zheng-Ping; Liu, Timon C.; Zhang, Yan; Wang, Yan-Fang

    2007-05-01

    Alcohol, which is ubiquitous today, is a major health concern. Its use was already relatively high among the youngest respondents, peaked among young adults, and declined in older age groups. Alcohol is causally related to more than 60 different medical conditions. Overall, 4% of the global burden of disease is attributable to alcohol, which accounts for about as much death and disability globally as tobacco and hypertension. Alcohol also promotes the generation of reactive oxygen species (ROS) and/or interferes with the body's normal defense mechanisms against these compounds through numerous processes, particularly in the liver. Photobiomodulation (PBM) is a cell-specific effect of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems. The cellular effects of both alcohol and LIL are ligand-independent so that PBM might rehabilitate alcohol induced dysfunction. The PBM on alcohol induced human neutrophil dysfunction and rat chronic atrophic gastritis, the laser acupuncture on alcohol addiction, and intravascular PBM on alcoholic coma of patients and rats have been observed. The endonasal PBM (EPBM) mediated by Yangming channel, autonomic nervous systems and blood cells is suggested to treat alcohol induced dysfunction in terms of EPBM phenomena, the mechanism of alcohol induced dysfunction and our biological information model of PBM. In our opinion, the therapeutic effects of PBM might also be achieved on alcoholic myopathy.

  13. Genetics and Epigenetics of Chronic Allograft Dysfunction in Kidney Transplants.

    Science.gov (United States)

    Zununi Vahed, Sepideh; Samadi, Nasser; Mostafidi, Elmira; Ardalan, Mohammad Reza; Omidi, Yadollah

    2016-01-01

    Chronic allograft dysfunction is the most common cause of allograft lost. Chronic allograft dysfunction happens as a result of complex interactions at the molecular and cellular levels. Genetic and environmental factors both influence the evolution and progression of the chronic allograft dysfunction. Epigenetic modification could be considered as a therapeutically modifiable element to pause the fibrosis process through novel strategies. In this review, the PubMed database was searched for English-language articles on these new areas.

  14. [Senescence and cellular immortality].

    Science.gov (United States)

    Trentesaux, C; Riou, J-F

    2010-11-01

    Senescence was originally described from the observation of the limited ability of normal cells to grow in culture, and may be generated by telomere erosion, accumulation of DNA damages, oxidative stress and modulation of oncogenes or tumor suppressor genes. Senescence corresponds to a cellular response aiming to control tumor progression by limiting cell proliferation and thus constitutes an anticancer barrier. Senescence is observed in pre-malignant tumor stages and disappears from malignant tumors. Agents used in standard chemotherapy also have the potential to induce senescence, which may partly explain their therapeutic activities. It is possible to restore senescence in tumors using targeted therapies that triggers telomere dysfunction or reactivates suppressor genes functions, which are essential for the onset of senescence.

  15. Redirection of the Reaction Specificity of a Thermophilic Acetolactate Synthase toward Acetaldehyde Formation.

    Directory of Open Access Journals (Sweden)

    Maria Cheng

    Full Text Available Acetolactate synthase and pyruvate decarboxylase are thiamine pyrophosphate-dependent enzymes that convert pyruvate into acetolactate and acetaldehyde, respectively. Although the former are encoded in the genomes of many thermophiles and hyperthermophiles, the latter has been found only in mesophilic organisms. In this study, the reaction specificity of acetolactate synthase from Thermus thermophilus was redirected to catalyze acetaldehyde formation to develop a thermophilic pyruvate decarboxylase. Error-prone PCR and mutant library screening led to the identification of a quadruple mutant with 3.1-fold higher acetaldehyde-forming activity than the wild-type. Site-directed mutagenesis experiments revealed that the increased activity of the mutant was due to H474R amino acid substitution, which likely generated two new hydrogen bonds near the thiamine pyrophosphate-binding site. These hydrogen bonds might result in the better accessibility of H+ to the substrate-cofactor-enzyme intermediate and a shift in the reaction specificity of the enzyme.

  16. Asteroid Redirect Mission - Next Major stepping-stone to Human Exploration of NEOs and beyond

    Science.gov (United States)

    Sanchez, Natalia

    2016-07-01

    In response to NASA's Asteroid Initiative, an Asteroid Redirect and Robotic Mission (ARRM) is being studied by a NASA cohort, led by JPL, to enable the capture a multi-ton boulder from the surface of a Near-Earth Asteroid and return it to cislunar space for subsequent human and robotic exploration. The mission would boost our understanding of NEOs and develop technological capabilities for Planetary Defense, shall a NEO come up on a collision course. The benefits of this mission can extend our capabilities to explore farther into space, as well as create a new commercial sector in Space Mining, which would make materials in Space available for our use. ARRM would leverage and advance current knowledge of higher-efficiency propulsion systems with a new Solar Electric Propulsion demonstration (similar to that on the Dawn spacecraft) to be incorporated into future Mars Missions.

  17. Application of Artificial Vision in flow redirection during filling of Liquid Composite Molding processes

    Science.gov (United States)

    Montés, N.; Sanchez, F.; García, J. A.; Falcó, A.; Tornero, J.; Chinesta, F.

    2007-04-01

    The control techniques applied in Liquid Composite Molding processes have been extensively worked out by many different research groups abroad. In this work, the original use of artificial vision technology in order to redirect the flow path during mold filling appears as a major objective of online control strategy. In this study, a process performance index developed in a previous work is used to define the mold gate opening sequence. The Vacuum Assisted Resin Transfer Molding (VARTM) and Vacuum Assisted Resin Infusion (VARI) have been selected as the main processes of study. The expert system will make use of numerical simulation in order to obtain a previous physical understanding of the flow behaviour in different manufacturing conditions. Some examples of the installation are presented and discussed.

  18. Posterior Tibial Tendon Dysfunction

    Science.gov (United States)

    .org Posterior Tibial Tendon Dysfunction Page ( 1 ) Posterior tibial tendon dysfunction is one of the most common problems of the foot and ankle. It occurs when the posterior tibial tendon becomes inflamed or torn. As a result, the ...

  19. Female Sexual Dysfunction

    Science.gov (United States)

    ... Endocrinologist Search Featured Resource Menopause Map™ View Female Sexual Dysfunction February 2012 Download PDFs English Espanol Editors ... Resources Mayo Clinic Cleveland Clinic What is female sexual dysfunction (FSD)? Many women have a low sex ...

  20. Formulation Assessment and Support Team (FAST) for the Asteroid Redirect Mission (ARM)

    Science.gov (United States)

    Mazanek, Daniel D.; Abell, Paul; Reeves, David M.; NASA Asteroid Redirect Mission (ARM) Formulation Assessment and Support Team (FAST)

    2016-10-01

    The Formulation Assessment and Support Team (FAST) for the Asteroid Redirect Mission (ARM) was a two-month effort, chartered by NASA, to provide timely inputs for mission requirement formulation in support of the Asteroid Redirect Robotic Mission (ARRM) Requirements Closure Technical Interchange Meeting held December 15-16, 2015. Additionally, the FAST was tasked with developing an initial list of potential mission investigations and providing input on potential hosted payloads and partnerships. The FAST explored several aspects of potential science benefits and knowledge gain from the ARM. Expertise from the science, engineering, and technology communities was represented in exploring lines of inquiry related to key characteristics of the ARRM reference target asteroid (2008 EV5) for engineering design purposes. Specific areas of interest included target origin, spatial distribution and size of boulders, surface geotechnical properties, boulder physical properties, and considerations for boulder handling, crew safety, and containment. In order to increase knowledge gain potential from the mission, opportunities for partnerships and accompanying payloads that could be provided by domestic and international partners were also investigated. The ARM FAST final report was publicly released on February 18, 2016 and represents the FAST's final product. The report and associated public comments are being used to support mission requirements formulation and serve as an initial inquiry to the science and engineering communities relating to the characteristics of the ARRM reference target asteroid. This report also provides a suggested list of potential investigations sorted and grouped based on their likely benefit to ARM and potential relevance to NASA science and exploration goals. These potential investigations could be conducted to reduce mission risks and increase knowledge return in the areas of science, planetary defense, asteroid resources and in-situ resource

  1. Exposure of clinical MRSA heterogeneous strains to β-lactams redirects metabolism to optimize energy production through the TCA cycle.

    Directory of Open Access Journals (Sweden)

    Mignon A Keaton

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA has emerged as one of the most important pathogens both in health care and community-onset infections. The prerequisite for methicillin resistance is mecA, which encodes a β-lactam-insensitive penicillin binding protein PBP2a. A characteristic of MRSA strains from hospital and community associated infections is their heterogeneous expression of resistance to β-lactam (HeR in which only a small portion (≤ 0.1% of the population expresses resistance to oxacillin (OXA ≥ 10 µg/ml, while in other isolates, most of the population expresses resistance to a high level (homotypic resistance, HoR. The mechanism associated with heterogeneous expression requires both increase expression of mecA and a mutational event that involved the triggering of a β-lactam-mediated SOS response and related lexA and recA genes. In the present study we investigated the cellular physiology of HeR-MRSA strains during the process of β-lactam-mediated HeR/HoR selection at sub-inhibitory concentrations by using a combinatorial approach of microarray analyses and global biochemical profiling employing gas chromatography/mass spectrometry (GC/MS and liquid chromatography/mass spectrometry (LC/MS to investigate changes in metabolic pathways and the metabolome associated with β-lactam-mediated HeR/HoR selection in clinically relevant heterogeneous MRSA. We found unique features present in the oxacillin-selected SA13011-HoR derivative when compared to the corresponding SA13011-HeR parental strain that included significant increases in tricarboxyl citric acid (TCA cycle intermediates and a concomitant decrease in fermentative pathways. Inactivation of the TCA cycle enzyme cis-aconitase gene in the SA13011-HeR strain abolished β-lactam-mediated HeR/HoR selection demonstrating the significance of altered TCA cycle activity during the HeR/HoR selection. These results provide evidence of both the metabolic cost and the

  2. Overexpression of cellular prion protein (PrP(C)) prevents cognitive dysfunction and apoptotic neuronal cell death induced by amyloid-β (Aβ₁₋₄₀) administration in mice.

    Science.gov (United States)

    Rial, D; Piermartiri, T C; Duarte, F S; Tasca, C I; Walz, R; Prediger, R D

    2012-07-26

    The cellular prion protein (PrP(C)) is a neuronal-anchored glycoprotein that has been associated with several functions in the CNS such as synaptic plasticity, learning and memory and neuroprotection. There is great interest in understanding the role of PrP(C) in the deleterious effects induced by the central accumulation of amyloid-β (Aβ) peptides, a pathological hallmark of Alzheimer's disease, but the existent results are still controversial. Here we compared the effects of a single intracerebroventricular (i.c.v.) injection of aggregated Aβ(1-40) peptide (400pmol/mouse) on the spatial learning and memory performance as well as hippocampal cell death biomarkers in adult wild type (Prnp(+/+)), PrP(C) knockout (Prnp(0/0)) and the PrP(C) overexpressing Tg-20 mice. Tg-20 mice, which present a fivefold increase in PrP(C) expression in comparison to wild type mice, were resistant to the Aβ(1-40)-induced spatial learning and memory impairments as indicated by reduced escape latencies to find the platform and higher percentage of time spent in the correct quadrant during training and probe test sessions of the water maze task. The protection against Aβ(1-40)-induced cognitive impairments observed in Tg-20 mice was accompanied by a significant decrease in the hippocampal expression of the activated caspase-3 protein and Bax/Bcl-2 ratio as well as reduced hippocampal cell damage assessed by MTT and propidium iodide incorporation assays. These findings indicate that the overexpression of PrP(C) prevents Aβ(1-40)-induced spatial learning and memory deficits in mice and that this response is mediated, at least in part, by the modulation of programed cell death pathways. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Effector memory and central memory NY-ESO-1-specific re-directed T cells for treatment of multiple myeloma.

    Science.gov (United States)

    Schuberth, P C; Jakka, G; Jensen, S M; Wadle, A; Gautschi, F; Haley, D; Haile, S; Mischo, A; Held, G; Thiel, M; Tinguely, M; Bifulco, C B; Fox, B A; Renner, C; Petrausch, U

    2013-04-01

    The cancer-testis antigen NY-ESO-1 is a potential target antigen for immune therapy expressed in a subset of patients with multiple myeloma. We generated chimeric antigen receptors (CARs) recognizing the immunodominant NY-ESO-1 peptide 157-165 in the context of HLA-A*02:01 to re-direct autologous CD8(+) T cells towards NY-ESO-1(+) myeloma cells. These re-directed T cells specifically lysed NY-ESO-1(157-165)/HLA-A*02:01-positive cells and secreted IFNγ. A total of 40% of CCR7(-) re-directed T cells had an effector memory phenotype and 5% a central memory phenotype. Based on CCR7 cell sorting, effector and memory CAR-positive T cells were separated and CCR7(+) memory cells demonstrated after antigen-specific re-stimulation downregulation of CCR7 as sign of differentiation towards effector cells accompanied by an increased secretion of memory signature cytokines such as IL-2. To evaluate NY-ESO-1 as potential target antigen, we screened 78 bone marrow biopsies of multiple myeloma patients where NY-ESO-1 protein was found to be expressed by immunohistochemistry in 9.7% of samples. Adoptively transferred NY-ESO-1-specific re-directed T cells protected mice against challenge with endogenously NY-ESO-1-positive myeloma cells in a xenograft model. In conclusion, re-directed effector- and central memory T cells specifically recognized NY-ESO-1(157-165)/ HLA-A*02:01-positive cells resulting in antigen-specific functionality in vitro and in vivo.

  4. Mitochondrial Dysfunction in Lysosomal Storage Disorders

    Directory of Open Access Journals (Sweden)

    Mario de la Mata

    2016-10-01

    Full Text Available Lysosomal storage diseases (LSDs describe a heterogeneous group of rare inherited metabolic disorders that result from the absence or loss of function of lysosomal hydrolases or transporters, resulting in the progressive accumulation of undigested material in lysosomes. The accumulation of substances affects the function of lysosomes and other organelles, resulting in secondary alterations such as impairment of autophagy, mitochondrial dysfunction, inflammation and apoptosis. LSDs frequently involve the central nervous system (CNS, where neuronal dysfunction or loss results in progressive neurodegeneration and premature death. Many LSDs exhibit signs of mitochondrial dysfunction, which include mitochondrial morphological changes, decreased mitochondrial membrane potential (ΔΨm, diminished ATP production and increased generation of reactive oxygen species (ROS. Furthermore, reduced autophagic flux may lead to the persistence of dysfunctional mitochondria. Gaucher disease (GD, the LSD with the highest prevalence, is caused by mutations in the GBA1 gene that results in defective and insufficient activity of the enzyme β-glucocerebrosidase (GCase. Decreased catalytic activity and/or instability of GCase leads to accumulation of glucosylceramide (GlcCer and glucosylsphingosine (GlcSph in the lysosomes of macrophage cells and visceral organs. Mitochondrial dysfunction has been reported to occur in numerous cellular and mouse models of GD. The aim of this manuscript is to review the current knowledge and implications of mitochondrial dysfunction in LSDs.

  5. Redirecting Seismic Waves with Metamaterials and Sub-wavelength Scatterers for Protection of Critical Infrastructure

    Science.gov (United States)

    Liberman, V.; Haupt, R.; Rothschild, M.

    2016-12-01

    Each year, on average a major magnitude-8 earthquake strikes somewhere in the world. Furthermore, in several areas in the U.S. there is a rapidly growing number of industry induced earthquakes, albeit of lower magnitude. Both types of earthquakes can cause damage to critical structures from nuclear power plants to pipelines and dams. Here we propose a novel concept to redirect and attenuate the ground motion of earthquake surface waves by implementing an engineered seismic cloaking barrier around high value structures. These barriers employ seismic metamaterials. Metamaterials are media with sub-wavelength structures which possess unique wave manipulation properties not obtained with conventional media. When applied to seismic phenomena, metamaterial structures allow elastic wave re-direction and attenuation on length scales much smaller than the wavelength. Although sub-wavelength acoustic Helmholtz resonators have been suggested previously, they have significant limitations due to the large impedance mismatch between the soil and the resonator, and the fundamental inability of acoustic resonators to attenuate shear waves. In contrast, we propose an array of sub-wavelength scattering borehole barriers with an appropriate tilt, designed to form subwavelength apertures. We design arrays of such boreholes or wedges to form keep-out zones where substantial reduction of seismic energy occurs due to efficient scattering of the surface waves or, potentially, attenuation of the energy through coupling it to a viscous medium. The performance of such borehole arrays is studied with full 3D simulations with both spectral-element and finite-element codes in a supercomputing environment. Assuming a far field excitation source at realistic earthquake frequencies, the hole size, spacing, and tilt angle are optimized. Then, table-top frequency-scaled system measurements and analysis are performed and validated with simulations. This material is based upon work supported under Air

  6. Numerical and Experimental Study of Wake Redirection Techniques in a Boundary Layer Wind Tunnel

    Science.gov (United States)

    Wang, J.; Foley, S.; Nanos, E. M.; Yu, T.; Campagnolo, F.; Bottasso, C. L.; Zanotti, A.; Croce, A.

    2017-05-01

    The aim of the present paper is to validate a wind farm LES framework in the context of two distinct wake redirection techniques: yaw misalignment and individual cyclic pitch control. A test campaign was conducted using scaled wind turbine models in a boundary layer wind tunnel, where both particle image velocimetry and hot-wire thermo anemometers were used to obtain high quality measurements of the downstream flow. A LiDAR system was also employed to determine the non-uniformity of the inflow velocity field. A high-fidelity large-eddy simulation lifting-line model was used to simulate the aerodynamic behavior of the system, including the geometry of the wind turbine nacelle and tower. A tuning-free Lagrangian scale-dependent dynamic approach was adopted to improve the sub-grid scale modeling. Comparisons with experimental measurements are used to systematically validate the simulations. The LES results are in good agreement with the PIV and hot-wire data in terms of time-averaged wake profiles, turbulence intensity and Reynolds shear stresses. Discrepancies are also highlighted, to guide future improvements.

  7. Viroid RNA redirects host DNA ligase 1 to act as an RNA ligase.

    Science.gov (United States)

    Nohales, María-Ángeles; Flores, Ricardo; Daròs, José-Antonio

    2012-08-21

    Viroids are a unique class of noncoding RNAs: composed of only a circular, single-stranded molecule of 246-401 nt, they manage to replicate, move, circumvent host defenses, and frequently induce disease in higher plants. Viroids replicate through an RNA-to-RNA rolling-circle mechanism consisting of transcription of oligomeric viroid RNA intermediates, cleavage to unit-length strands, and circularization. Though the host RNA polymerase II (redirected to accept RNA templates) mediates RNA synthesis and a type-III RNase presumably cleavage of Potato spindle tuber viroid (PSTVd) and closely related members of the family Pospiviroidae, the host enzyme catalyzing the final circularization step, has remained elusive. In this study we propose that PSTVd subverts host DNA ligase 1, converting it to an RNA ligase, for the final step. To support this hypothesis, we show that the tomato (Solanum lycopersicum L.) DNA ligase 1 specifically and efficiently catalyzes circularization of the genuine PSTVd monomeric linear replication intermediate opened at position G95-G96 and containing 5'-phosphomonoester and 3'-hydroxyl terminal groups. Moreover, we also show a decreased PSTVd accumulation and a reduced ratio of monomeric circular to total monomeric PSTVd forms in Nicotiana benthamiana Domin plants in which the endogenous DNA ligase 1 was silenced. Thus, in a remarkable example of parasitic strategy, viroids reprogram for their replication the template and substrate specificity of a DNA-dependent RNA polymerase and a DNA ligase to act as RNA-dependent RNA polymerase and RNA ligase, respectively.

  8. EGOLOGY: psychological spatial breakthrough for social redirection--multidisciplinary spatial focus for individuals/humankind

    Science.gov (United States)

    Thompson, Robert A.

    1991-08-01

    Every age is marked by its physical tools. But today''s Space Age is unique because it is the spatial vantage itself which becomes a tool. It is a mental breakthrough, permitting us to contrast our outward-looking dreams with an inward-focused reality that can psychologically redirect the future for humankind. As the spatial perspective moves our eye from the surface of the earth to a remote point above its surface, our earth-based myopia disappears. We see all former parameters simultaneously, far out as well as close up. Physical differences are minimized, only natural demarcations remain, while similarities and interconnections abound. With the evolution of the Space Age this new awareness stimulated first the ecological movement, raising public consciousness about the physical environment, and then socially about human rights worldwide. From this intellectual quantum jump we realized that planetary interconnections permeated earth''s biosphere and on into the physical-chemical core. Like the ecological shell that identified ecology as the dynamic balance of all organisms interacting with their thermodynamic energy environment, a new outer shell, an egological one, or egoshell, is now needed to deal with multidisciplinary informational dynamics socially (acquisition for educational dissemination and perceptual workplace use). Individuals within their total spatial environment--the conceptual energy/human resource balance identified as EGOLOGY--would then be able to network society, inspiring mental fitness for an individual enlightenment to occur.

  9. Accordance of Light Scattering from Design and De-Facto Variants of a Daylight Redirecting Component

    Directory of Open Access Journals (Sweden)

    Andreas Noback

    2016-08-01

    Full Text Available For the systematic development of a small-scale daylight-redirecting louver system the impact of manufacturing on light scattering characteristics has to be quantified, localized and understood. In this research, the accordance of the measured scattering distributions of a de-facto production sample V1 with the computed predictions based on its design geometry V2 are quantified for selected incident light directions. A metric describing the global accordance of distributions is adapted to quantify their overall difference. A novel metric of local accordance allows further analysis. A particular low global accordance between V1 and V2 is found for an incident elevation θ i = 35 ∘ . To test the hypothesis that this result can be explained by observed geometric deviations, a simulation model V3 replicating these is compared to the design. The hypothesis is supported by the resulting high degree of accordance. The low local accordance for individual outgoing light directions indicates geometric non-uniformity of the sample V1. This method has been found useful for product development and quality assurance. Beyond their application in the proposed method, global and local accordance have potential applications in all fields of light scattering measurements.

  10. Logistics Needs for Potential Deep Space Mission Scenarios Post Asteroid Redirect Crewed Mission

    Science.gov (United States)

    Lopez, Pedro, Jr.; Shultz, Eric; Mattfeld, Bryan; Stromgren, Chel; Goodliff, Kandyce

    2015-01-01

    The Asteroid Redirect Mission (ARM) is currently being explored as the next step towards deep space human exploration, with the ultimate goal of reaching Mars. NASA is currently investigating a number of potential human exploration missions, which will progressively increase the distance and duration that humans spend away from Earth. Missions include extended human exploration in cis-lunar space which, as conceived, would involve durations of around 60 days, and human missions to Mars, which are anticipated to be as long as 1000 days. The amount of logistics required to keep the crew alive and healthy for these missions is significant. It is therefore important that the design and planning for these missions include accurate estimates of logistics requirements. This paper provides a description of a process and calculations used to estimate mass and volume requirements for crew logistics, including consumables, such as food, personal items, gasses, and liquids. Determination of logistics requirements is based on crew size, mission duration, and the degree of closure of the environmental control life support system (ECLSS). Details are provided on the consumption rates for different types of logistics and how those rates were established. Results for potential mission scenarios are presented, including a breakdown of mass and volume drivers. Opportunities for mass and volume reduction are identified, along with potential threats that could possibly increase requirements.

  11. Relative Terrain Imaging Navigation (RETINA) Tool for the Asteroid Redirect Robotic Mission (ARRM)

    Science.gov (United States)

    Wright, Cinnamon A.; Van Eepoel, John; Liounis, Andrew; Shoemaker, Michael; DeWeese, Keith; Getzandanner, Kenneth

    2016-01-01

    As a part of the NASA initiative to collect a boulder off of an asteroid and return it to Lunar orbit, the Satellite Servicing Capabilities Office (SSCO) and NASA GSFC are developing an on-board relative terrain imaging navigation algorithm for the Asteroid Redirect Robotic Mission (ARRM). After performing several flybys and dry runs to verify and refine the shape, spin, and gravity models and obtain centimeter level imagery, the spacecraft will descend to the surface of the asteroid to capture a boulder and return it to Lunar Orbit. The algorithm implements Stereophotoclinometry methods to register landmarks with images taken onboard the spacecraft, and use these measurements to estimate the position and orientation of the spacecraft with respect to the asteroid. This paper will present an overview of the ARRM GN&C system and concept of operations as well as a description of the algorithm and its implementation. These techniques will be demonstrated for the descent to the surface of the proposed asteroid of interest, 2008 EV5, and preliminary results will be shown.

  12. Redirected charge transport arising from diazonium grafting of carbon coated LiFePO4.

    Science.gov (United States)

    Madec, L; Seid, K A; Badot, J-C; Humbert, B; Moreau, P; Dubrunfaut, O; Lestriez, B; Guyomard, D; Gaubicher, J

    2014-11-07

    The morphological and the electrical properties of carbon coated LiFePO4 (LFPC) active material functionalized by 4-ethynylbenzene tetrafluoroboratediazonium salt were investigated. For this purpose, FTIR, Raman, XPS, High Resolution Transmission Electron Microscopy (HRTEM) and Broadband Dielectric Spectroscopy (BDS) were considered. Electronic conductivities of LFPC samples at room temperature were found to decrease in a large frequency range upon simple immersion in polar solvents and to decrease further upon functionalization. Due to their high dipole moment, strongly physisorbed molecules detected by XPS likely add barriers to electron hopping. Significant alteration of the carbon coating conductivity was only observed, however, upon functionalization. This effect is most presumably associated with an increase in the sp(3) content determined by Raman spectroscopy, which is a strong indication of the formation of a covalent bond between the organic layer and the carbon coating. In this case, the electron flux appears to be redirected and relayed by short-range (intra chain) and long-range (inter chain) electron transport through molecular oligomers anchored at the LFPC surface. The latter are controlled by tunnelling and slightly activated hopping, which enable higher conductivity at low temperature (T LiFePO4. XPS and HRTEM images allow a clear correlation of these findings with the island type oligomeric structure of grafted molecules.

  13. SOX2 redirects the developmental fate of the intestinal epithelium toward a premature gastric phenotype

    Institute of Scientific and Technical Information of China (English)

    Lalini Raghoebir; Dick Tibboel; Ron Smits; Robbert J. Rottier; Elvira RM. Bakker; Jason C. Mills; Sigrid Swagemakers; Marjon Buscop-van Kempen; Anne Boerema-de Munck; Siska Driegen; Dies Meijer; Frank Grosveld

    2012-01-01

    Various factors play an essential role in patterning the digestive tract.During development,Sox2 and Cdx2 are exclusively expressed in the anterior and the posterior parts of the primitive gut,respectively.However,it is unclear whether these transcription factors influence each other in determining specification of the na(i)ve gut endoderm.We therefore investigated whether Sox2 redirects the fate of the prospective intestinal part of the primitive gut.Ectopic expression of Sox2 in the posterior region of the primitive gut caused anteriorization of the gut toward a gastric-like phenotype.Sox2 activated the foregut transcriptional program,in spite of sustained co-expression of endogenous Cdx2.However,binding of Cdx2 to its genomic targets and thus its transcriptional activity was strongly reduced.Recent findings indicate that endodermal Cdx2 is required to initiate the intestinal program and to suppress anterior cell fate.Our findings suggest that reduced Cdx2 expression by itself is not sufficient to cause anteriorization,but that Sox2 expression is also required.Moreover,it indicates that the balance between Sox2 and Cdx2 function is essential for proper specification of the primitive gut and that Sox2 may overrule the initial patterning of the primitive gut,emphasizing the plasticity of the primitive gut.

  14. Application of a Novel Long-Reach Manipulator Concept to Asteroid Redirect Missions

    Science.gov (United States)

    Dorsey, John T.; Doggett, William R.; Jones, Thomas C.; King, Bruce D.

    2015-01-01

    A high priority mission currently being formulated by NASA is to capture all or part of an asteroid and return it to cis-lunar space for examination by an astronaut crew. Two major mission architectures are currently being considered: in the first (Mission Concept A), a spacecraft would rendezvous and capture an entire free flying asteroid (up to 14 meters in diameter), and in the second (Mission Concept B), a spacecraft would rendezvous with a large asteroid (which could include one of the Martian moons) and retrieve a boulder (up to 4 meters in diameter). A critical element of the mission is the system that will capture the asteroid or boulder material, enclose it and secure it for the return flight. This paper describes the design concepts, concept of operations, structural sizing and masses of capture systems that are based on a new and novel Tendon- Actuated Lightweight In-Space MANipulator (TALISMAN) general-purpose robotic system. Features of the TALISMAN system are described and the status of its technology development is summarized. TALISMAN-based asteroid material retrieval system concepts and concepts-of-operations are defined for each asteroid mission architecture. The TALISMAN-based capture systems are shown to dramatically increase operational versatility while reducing mission risk. Total masses of TALISMAN-based systems are presented, reinforcing the mission viability of using a manipulator-based approach for the asteroid redirect mission.

  15. Constraining eye movement when redirecting walking trajectories alters turning control in healthy young adults.

    Science.gov (United States)

    Pradeep Ambati, V N; Murray, Nicholas G; Saucedo, Fabricio; Powell, Douglas W; Reed-Jones, Rebecca J

    2013-05-01

    Humans use a specific steering synergy, where the eyes and head lead rotation to the new direction, when executing a turn or change in direction. Increasing evidence suggests that eye movement is critical for turning control and that when the eyes are constrained, or participants have difficulties making eye movements, steering control is disrupted. The purpose of the current study was to extend previous research regarding eye movements and steering control to a functional walking and turning task. This study investigated eye, head, trunk, and pelvis kinematics of healthy young adults during a 90° redirection of walking trajectory under two visual conditions: Free Gaze (the eyes were allowed to move naturally in the environment), and Fixed Gaze (participants were required to fixate the eyes on a target in front). Results revealed significant differences in eye, head, and trunk coordination between Free Gaze and Fixed Gaze conditions (p segments moved together with no significant differences between segment onset times. In addition, the sequence of segment rotation during Fixed Gaze suggested a bottom-up postural perturbation control strategy in place of top-down steering control seen in Free Gaze. The results of this study support the hypothesis that eye movement is critical for the release of the steering synergy for turning control.

  16. Asteroid Impact and Deflection Assessment mission: the Double Asteroid Redirection Test (DART)

    Science.gov (United States)

    Cheng, A.; Michel, P.

    2015-10-01

    The Asteroid Impact & Deflection Assessment (AIDA) mission will be the first space experiment to demonstrate asteroid impact hazard mitigation by using a kinetic impactor. AIDA is a joint ESA-NASA cooperative project, which includes the ESA Asteroid Impact Mission (AIM) rendezvous spacecraft and the NASA Double Asteroid Redirection Test (DART) mission. The AIDA target is the near-Earth binary asteroid 65803 Didymos, which will make an unusually close approach to Earth in October, 2022. The ~300-kg DART spacecraft is designed to impact the Didymos secondary at 6.5 km/s and demonstrate the ability to modify its trajectory through momentum transfer. The primary goals of AIDA are (i) to investigate the binary near-Earth asteroid (65803) Didymos, (ii) to demonstrate asteroid deflection by kinetic impact and to characterize the deflection. The primary DART objectives are to demonstrate a hypervelocity impact on the Didymos moon and to determine the resulting deflection from ground-based observatories. The DART impact on the Didymos secondary will cause a measurable change in the orbital period of the binary.

  17. Modeling cognitive dysfunction in neurofibromatosis-1.

    Science.gov (United States)

    Diggs-Andrews, Kelly A; Gutmann, David H

    2013-04-01

    Cognitive dysfunction, including significant impairments in learning, behavior, and attention, is found in over 10% of children in the general population. However, in the common inherited cancer predisposition syndrome, neurofibromatosis type 1 (NF1), the prevalence of these cognitive deficits approaches 70%. As a monogenic disorder, NF1 provides a unique genetic tool to identify and dissect mechanistically the molecular and cellular bases underlying cognitive dysfunction. In this review, we discuss Nf1 fly and mouse systems that mimic many of the cognitive abnormalities seen in children with NF1. Further, we describe discoveries from these models that have uncovered defects in the regulation of Ras activity, cAMP generation, and dopamine homeostasis as key mechanisms important for cognitive dysfunction in children with NF1.

  18. Libraries Can Make Open Access Happen Today by Simply Redirecting Subscription Funds: An Update on the SCOAP3 Initiative

    CERN Document Server

    Gentil-Beccot, Anne

    2008-01-01

    This article reviews the SCOAP3 initiative which aims to redirect the subscription funds used for the core journals in High Energy Physics, to make them Open Access. This model re-interprets the role of librarians in the Open Access debate. As they are the pivot of the current system, by keeping the lifeblood of scientific information flowing to their scientists, the authors argue that they are the best placed to make it change and take advantage of it.

  19. Deceived by stripes: conspicuous patterning on vital anterior body parts can redirect predatory strikes to expendable posterior organs.

    Science.gov (United States)

    Murali, Gopal; Kodandaramaiah, Ullasa

    2016-06-01

    Conspicuous coloration, which presumably makes prey more visible to predators, has intrigued researchers for long. Contrastingly coloured, conspicuous striped patterns are common among lizards and other animals, but their function is not well known. We propose and test a novel hypothesis, the 'redirection hypothesis', wherein longitudinal striped patterns, such as those found on the anterior body parts of most lacertilians, redirect attacks away from themselves during motion towards less vulnerable posterior parts, for example, the autotomous tail. In experiments employing human 'predators' attacking virtual prey on a touchscreen, we show that longitudinal striped patterns on the anterior half of prey decreased attacks to the anterior and increased attacks to the posterior. The position of stripes mattered-they worked best when they were at the anterior. By employing an adaptive psychophysical procedure, we show that prey with striped patterning are perceived to move slower, offering a mechanistic explanation for the redirective effect. In summary, our results suggest that the presence of stripes on the body (i.e. head and trunk) of lizards in combination with caudal autotomy can work as an effective anti-predator strategy during motion.

  20. Exodus: redirecting Genesis for solar wind observations 4-8 million km from Earth

    Science.gov (United States)

    Steinberg, J.; Barraclough, B.; Gosling, J.; Reisenfeld, D.; Wiens, R.; Liewer, P.; Murphy, N.

    2003-04-01

    Genesis is an ongoing NASA Discovery mission designed to collect samples of the solar wind at L1 and return them to Earth for analysis. After the return capsule is dropped off in September, 2004, the spacecraft, with its in situ solar wind ion and electron spectrometers, is available to perform a new solar wind mission. Spacecraft capabilities, including ample remaining Dv, allow it to achieve and maintain a distant retrograde orbit, a heliocentric orbit in which the spacecraft spends a significant amount of time ˜0.025 AU upstream and downstream of Earth (˜2.5x the Earth-L1 distance). From this orbit Genesis observations may be used, together with those from available L1 spacecraft, to compare solar wind parameters across important spatial scales. The multi-point collaborative studies will uniquely allow us to understand the propagation and evolution of solar wind plasma, as well as the internal spatial structure of large solar wind transients, for spacecraft separation distances of 0.025 to 0.05 AU. Such separation distances are significantly greater than can be attained between any pair of current and proposed satellites in Earth or in L1 halo orbits. At the same time the separations will be small enough to allow confident tracking of particular solar wind structures between spacecraft. In addition to groundbreaking science, the Genesis spacecraft would be a pathfinder for potential future space weather sentinels. We present a proposal to redirect the Genesis spacecraft after its prime mission is complete, and create a new, inexpensive mission: EXODUS.

  1. Light redirecting system using sine-wave based panels for dense urban areas

    Science.gov (United States)

    Mohamed, Mohamed W. N.; Mashaly, Islam A.; Mohamed, Osama N.; El-Henawy, Sally I.; Galal, Ola; Taha, Iman; Nassar, Khaled; Safwat, Amr M. E.

    2014-09-01

    Cities and towns around the world are becoming more condensed due to the shrinking amount of buildable areas, which significantly reduces the amount of light that occupants have access to. This lack of natural lighting results in health, safety and quality of life degradation. This paper presents a new technique of transmitting sunlight downward into narrow alleys and streets, by using a daylighting guiding acrylic panel that is capable of changing the direction and distribution of the incident light. The core of the proposed daylight guidance system is made up of light transmission panels with high quality. The corrugations have sine wave shaped cross-section so that the panel functions as an optical diffuser perpendicular to the direction of sunlight propagation. The day lighting system consists of the corrugated panels and a lattice frame, which supports the panel. The proposed system is to be mounted on the building roof facing the sun so as to redirect the incident sunlight downward into the narrow alleys or streets. Since building sizes and orientations are different the frame is arranged such that substantially deep light penetration and high luminance level can be achieved. Simulation results show that the proposed panel improves the illuminance values by more than 200% and 400% in autumn and winter, respectively, provides fan-out angle that exceeds 80° for certain solar altitudes and the transmitted power percentage varies from 40% to 90% as the solar altitude varies from 10° to 80°. Experimental results are in a good agreement with the simulations.

  2. Acute stimulation of glucose influx upon mitoenergetic dysfunction requires LKB1, AMPK, Sirt2 and mTOR-RAPTOR

    NARCIS (Netherlands)

    Liemburg-Apers, D.C.; Wagenaars, J.A.L.; Smeitink, J.A.M.; Willems, P.H.G.M.; Koopman, W.J.H.

    2016-01-01

    Mitochondria play a central role in cellular energy production, and their dysfunction can trigger a compensatory increase in glycolytic flux to sustain cellular ATP levels. Here, we studied the mechanism of this homeostatic phenomenon in C2C12 myoblasts. Acute (30 min) mitoenergetic dysfunction indu

  3. Oxidative stress, mitochondrial dysfunction and the mitochondria theory of aging.

    Science.gov (United States)

    Kong, Yahui; Trabucco, Sally E; Zhang, Hong

    2014-01-01

    Aging is characterized by a progressive decline in cellular function, organismal fitness and increased risk of age-associated diseases and death. One potential cause of aging is the progressive accumulation of dysfunctional mitochondria and oxidative damage with age. Considerable efforts have been made in our understanding of the role of mitochondrial dysfunction and oxidative stress in aging and age-associated diseases. This chapter outlines the interplay between oxidative stress and mitochondrial dysfunction, and discusses their impact on senescence, cell death, stem cell function, age-associated diseases and longevity.

  4. Neuroanatomy and Physiology of Brain Dysfunction in Sepsis.

    Science.gov (United States)

    Mazeraud, Aurelien; Pascal, Quentin; Verdonk, Franck; Heming, Nicholas; Chrétien, Fabrice; Sharshar, Tarek

    2016-06-01

    Sepsis-associated encephalopathy (SAE), a complication of sepsis, is often complicated by acute and long-term brain dysfunction. SAE is associated with electroencephalogram pattern changes and abnormal neuroimaging findings. The major processes involved are neuroinflammation, circulatory dysfunction, and excitotoxicity. Neuroinflammation and microcirculatory alterations are diffuse, whereas excitotoxicity might occur in more specific structures involved in the response to stress and the control of vital functions. A dysfunction of the brainstem, amygdala, and hippocampus might account for the increased mortality, psychological disorders, and cognitive impairment. This review summarizes clinical and paraclinical features of SAE and describes its mechanisms at cellular and structural levels.

  5. Generation and preclinical characterization of an NKp80-Fc fusion protein for redirected cytolysis of natural killer (NK) cells against leukemia.

    Science.gov (United States)

    Deng, Gang; Zheng, Xiaodong; Zhou, Jing; Wei, Haiming; Tian, Zhigang; Sun, Rui

    2015-09-11

    The capacity of natural killer (NK) cells to mediate Fc receptor-dependent effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), largely contributes to their clinical application. Given that activation-induced C-type lectin (AICL), an identified ligand for the NK-activating receptor NKp80, is frequently highly expressed on leukemia cells, the lack of therapeutic AICL-specific antibodies limits clinical application. Here we explore a strategy to reinforce NK anti-leukemia reactivity by combining targeting AICL-expressing leukemia cells with the induction of NK cell ADCC using NKp80-Fc fusion proteins. The NKp80-Fc fusion protein we generated bound specifically to leukemia cells in an AICL-specific manner. Cell binding assays between NK and leukemia cells showed that NKp80-Fc significantly increased NK target cell conjugation. In functional analyses, treatment with NKp80-Fc clearly induced the ADCC effect of NK cells. NKp80-Fc not only promoted NK-mediated leukemia cell apoptosis in the early stage of cell conjugation but also enhanced NK cell degranulation and cytotoxicity activity in the late stage. The bifunctional NKp80-Fc could redirect NK cells toward leukemia cells and triggered NK cell killing in vitro. Moreover, NKp80-Fc enhanced the lysis of NK cells against tumors in leukemia xenograft non-obese diabetic/severe combined immunodeficiency mice. Taken together, our results demonstrate that NKp80-Fc potently amplifies NK cell anti-leukemia effects in vitro and in vivo through induction of the NK cell ADCC effect. This method could potentially be useful for molecular targeted therapy, and the fusion proteins may be a promising drug for immunotherapy of leukemia. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Endothelial dysfunction in diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Hadi AR Hadi

    2008-01-01

    Full Text Available Hadi AR Hadi, Jassim Al SuwaidiDepartment of Cardiology and Cardiovascular Surgery, Hamad General Hospital – Hamad Medical Corporation, Doha, State of Qatar; Department of Cardioscience, Sheikh Khalifa Medical City, Abu Dhabi, UAEAbstract: Diabetes mellitus is associated with an increased risk of cardiovascular disease, even in the presence of intensive glycemic control. Substantial clinical and experimental evidence suggest that both diabetes and insulin resistance cause a combination of endothelial dysfunctions, which may diminish the anti-atherogenic role of the vascular endothelium. Both insulin resistance and endothelial dysfunction appear to precede the development of overt hyperglycemia in patients with type 2 diabetes. Therefore, in patients with diabetes or insulin resistance, endothelial dysfunction may be a critical early target for preventing atherosclerosis and cardiovascular disease. Microalbuminuria is now considered to be an atherosclerotic risk factor and predicts future cardiovascular disease risk in diabetic patients, in elderly patients, as well as in the general population. It has been implicated as an independent risk factor for cardiovascular disease and premature cardiovascular mortality for patients with type 1 and type 2 diabetes mellitus, as well as for patients with essential hypertension. A complete biochemical understanding of the mechanisms by which hyperglycemia causes vascular functional and structural changes associated with the diabetic milieu still eludes us. In recent years, the numerous biochemical and metabolic pathways postulated to have a causal role in the pathogenesis of diabetic vascular disease have been distilled into several unifying hypotheses. The role of chronic hyperglycemia in the development of diabetic microvascular complications and in neuropathy has been clearly established. However, the biochemical or cellular links between elevated blood glucose levels, and the vascular lesions remain

  7. Mitochondrial dysfunctions in Parkinson's disease.

    Science.gov (United States)

    Gautier, C A; Corti, O; Brice, A

    2014-05-01

    Neurodegenerative disorders (ND) include a wide spectrum of diseases characterized by progressive neuronal dysfunctions or degeneration. With an estimated cost of 135 billion € in 2010 in the European Union (Olesen et al., 2012), they put an enormous economic as well as social burden on modern societies. Hence, they have been the subject of a huge amount of research for the last fifty years. For many of these diseases, our understanding of their profound causes is incomplete and this hinders the discovery of efficient therapies. ND form a highly heterogeneous group of diseases affecting various neuronal subpopulations reflecting different origins and different pathological mechanisms. However, some common themes in the physiopathology of these disorders are emerging. There is growing evidence that mitochondrial dysfunctions play a pivotal role at some point in the course of neurodegeneration. In some cases (e.g. Alzheimer's disease, amyotrophic lateral sclerosis), impairment of mitochondrial functions probably occurs late in the course of the disease. In a subset of ND, current evidence suggests that mitochondrial dysfunctions play a more seminal role in neuronal demise. Parkinson's disease (PD) presents one of the strongest cases based in part on post-mortem studies that have shown mitochondrial impairment (e.g. reduced complex I activity) and oxidative damage in idiopathic PD brains. The occurrence of PD is largely sporadic, but clinical syndromes resembling sporadic PD have been linked to specific environmental insults or to mutations in at least 5 distinct genes (α-synuclein, parkin, DJ-1, PINK1 and LRRK2). It is postulated that the elucidation of the pathogenic mechanisms underlying the selective dopaminergic degeneration in familial and environmental Parkinsonism should provide important clues to the pathogenic mechanisms responsible for idiopathic PD. Hence, numerous cellular and animal models of the disease have been generated that mimic these

  8. Chronic pelvic floor dysfunction.

    Science.gov (United States)

    Hartmann, Dee; Sarton, Julie

    2014-10-01

    The successful treatment of women with vestibulodynia and its associated chronic pelvic floor dysfunctions requires interventions that address a broad field of possible pain contributors. Pelvic floor muscle hypertonicity was implicated in the mid-1990s as a trigger of major chronic vulvar pain. Painful bladder syndrome, irritable bowel syndrome, fibromyalgia, and temporomandibular jaw disorder are known common comorbidities that can cause a host of associated muscular, visceral, bony, and fascial dysfunctions. It appears that normalizing all of those disorders plays a pivotal role in reducing complaints of chronic vulvar pain and sexual dysfunction. Though the studies have yet to prove a specific protocol, physical therapists trained in pelvic dysfunction are reporting success with restoring tissue normalcy and reducing vulvar and sexual pain. A review of pelvic anatomy and common findings are presented along with suggested physical therapy management.

  9. Female Sexual Dysfunction

    Science.gov (United States)

    ... to be comfortable with your sexuality, improve your self-esteem and accept your body. Try practicing these healthy ... mayoclinic.org/diseases-conditions/female-sexual-dysfunction/basics/definition/CON-20027721 . Mayo Clinic Footer Legal Conditions and ...

  10. Spinal Cord Dysfunction (SCD)

    Data.gov (United States)

    Department of Veterans Affairs — The Spinal Cord Dysfunction (SCD) module supports the maintenance of local and national registries for the tracking of patients with spinal cord injury and disease...

  11. Basal ganglia dysfunction

    Science.gov (United States)

    ... ganglia dysfunction. They include: Dystonia (muscle tone problems) Huntington disease (disorder in which nerve cells in certain parts ... ed. Philadelphia, PA: Elsevier Mosby; 2013:chap 20. Review Date 5/30/2016 Updated by: Amit M. ...

  12. Sexual Dysfunction in Women

    OpenAIRE

    Brown, Pamela

    1989-01-01

    Sexual dysfunction takes place in the context of women's lives and affects their sexuality and self-esteem. Awareness of these influences are vital to the management of the dysfunction and the promotion of positive sexuality. The family physician's contribution to both the prevention and management of sexual concerns includes an awareness of societal influences and facilitation of a woman's sense of her own power and control over her life.

  13. Enhanced Gravity Tractor Derived from the Asteroid Redirect Mission for Deflecting Hypothetical Asteroid 2017 PDC

    Science.gov (United States)

    Mazanek, Daniel D.; Reeves, David M.; Abell, Paul A.; Shen, Haijun; Qu, Min

    2017-01-01

    The Asteroid Redirect Mission (ARM) concept would robotically visit a hazardous-size near-Earth asteroid (NEA) with a rendezvous spacecraft, collect a multi-ton boulder and regolith samples from its surface, demonstrate an innovative planetary defense technique known as the Enhanced Gravity Tractor (EGT), and return the asteroidal material to a stable orbit around the Moon, allowing astronauts to explore the returned material in the mid-2020s. Launch of the robotic vehicle to rendezvous with the ARM reference target, NEA (341843) 2008 EV5, would occur in late 2021 [1,2]. The robotic segment of the ARM concept uses a 40 kW Solar Electric Propulsion (SEP) system with a specific impulse (Isp) of 2600 s, and would provide the first ever demonstration of the EGT technique on a hazardous-size asteroid and validate one method of collecting mass in-situ. The power, propellant, and thrust capability of the ARM robotic spacecraft can be scaled from a 40 kW system to 150 kW and 300 kW, which represent a likely future power level progression. The gravity tractor technique uses the gravitational attraction of a station-keeping spacecraft with the asteroid to provide a velocity change and gradually alter the trajectory of the asteroid. EGT utilizes a spacecraft with a high-efficiency propulsion system, such as Solar Electric Propulsion (SEP), along with mass collected in-situ to augment the mass of the spacecraft, thereby increasing the gravitational force between the objects [3]. As long as the spacecraft has sufficient thrust and propellant capability, the EGT force is only limited by the amount of in-situ mass collected and can be increased several orders of magnitude compared to the traditional gravity tractor technique in which only the spacecraft mass is used to generate the gravitational attraction force. This increase in available force greatly reduces the required deflection time. The collected material can be a single boulder, multiple boulders, regolith, or a

  14. Re-directed T cells for the treatment of fibroblast activation protein (FAP-positive malignant pleural mesothelioma (FAPME-1

    Directory of Open Access Journals (Sweden)

    Petrausch Ulf

    2012-12-01

    Full Text Available Abstract Background Asbestos is the main cause of MPM in industrialized countries. Even since asbestos is banned in most developed countries, the peak wave of MPM incidence is anticipated for the next years due to the long latency of asbestos induced MPM. MPM patients not eligible for surgical procedures like decortication or pleuro-pneumectomie have a median survival of 12 months with palliative chemotherapy. Therefore, new therapeutic approaches are of crucial need in this clinical situation. Methods/design This is a phase I trial for patients with malignant pleural mesothelioma with pleural effusion testing the safety of a fixed single dose of 1x106 adoptively transferred FAP-specific re-directed T cells given directly in the pleural effusion. Lymphocytes will be taken 21 days before transfer from peripheral blood. CD8 positive T cells will be isolated and re-programmed by retroviral transfer of a chimeric antigen receptor recognizing FAP which serves as target structure in MPM. At day 0 of the protocol, re-directed T cells will be injected in the pleural effusion and patients will be monitored for 48h under intermediate care conditions. AE, SAE, SADR and SUSAR will be monitored for 35 days and evaluated by an independent safety board to define any dose limiting toxicity (DLT. No further patient can be treated before the previous patient passed day 14 after T cell transfer. The protocol will be judged as save when no DLT occurred in the first 3 patients, or 1 DLT in 6 patients. Secondary objectives are feasibility and immune monitoring. Discussion Adoptive T cell transfer is a new and rapidly expanding branch of immunotherapies focusing on cancer treatment. Recently, objective responses could be observed in patients with chronic lymphatic leukemia treated with adoptively transferred CD19-specific re-directed T cells. The choice of the target antigen determines the possible on-target off-tissue toxicity of such approaches. There are reports of

  15. Finding and characterizing candidate targets for the Asteroid Redirect Mission (ARM)

    Science.gov (United States)

    Chodas, P.

    2014-07-01

    NASA's proposed Asteroid Redirect Mission (ARM) leverages key on-going activities in Human Exploration and Space Technology to advance NASA's goals in these areas. One primary objective of ARM would be to develop and demonstrate a high-power Solar Electric Propulsion (SEP) vehicle which would have the capability of moving significant amounts of mass around the solar system. SEP would be a key technology for robust future missions to deep space destinations, possibly including human missions to asteroids or to Mars. ARM would use the SEP vehicle to redirect up to hundreds of tons of material from a near-Earth asteroid into a stable lunar orbit, where a crew flying in an Orion vehicle would rendezvous and dock with it. The crew would perform an extra-vehicular activity (EVA), sample the material, and bring it back to the Earth; follow-on visits would also be possible. Two ARM mission concepts are being studied: one is to go to a small 4-10-meter-diameter asteroid, capture the entire asteroid and guide it into lunar orbit; the other is to go to a large 100-500 meter asteroid, remove a 1-10 meter boulder, and bring the boulder back into lunar orbit. A planetary defense demonstration could be included under either concept. Although some candidate targets are already known for both mission concepts, an observation campaign has been organized to identify more mission candidates. This campaign naturally leverages off of NASA's NEO Observations Program. Enhancements to asteroid search capabilities which will come online soon should increase the discovery rates for ARM candidates and hazardous asteroids alike. For the small-asteroid ARM concept, candidate targets must be smaller than about 12 meters, must follow Earth-like orbits and must naturally approach the Earth closely in the early 2020s, providing the opportunity for a low-velocity capture into the Earth/Moon system. About a dozen candidates are known with absolute magnitudes in the right range and with orbits

  16. Acute mixed cellular and humoral rejection of renal allograft with leucopenia.

    Science.gov (United States)

    Agarwal, D K; Hota, J K; Malhotra, V

    2011-08-01

    Diagnosis and management of acute renal allograft dysfunction often pose challenge to nephrologists during practice. Acute rejection is a major cause of acute graft dysfunction but is rare in patients with leucopenia. Acute rejection can have either humoral or cellular components or sometimes mixed components. Mixed acute cellular and humoral rejection often present as steroid resistant rejection. Here we report a patient with live related renal transplant recipient with acute graft dysfunction with leucopenia who was found to have mixed acute cellular and humoral rejection.

  17. Cellular circadian clocks in mood disorders.

    Science.gov (United States)

    McCarthy, Michael J; Welsh, David K

    2012-10-01

    Bipolar disorder (BD) and major depressive disorder (MDD) are heritable neuropsychiatric disorders associated with disrupted circadian rhythms. The hypothesis that circadian clock dysfunction plays a causal role in these disorders has endured for decades but has been difficult to test and remains controversial. In the meantime, the discovery of clock genes and cellular clocks has revolutionized our understanding of circadian timing. Cellular circadian clocks are located in the suprachiasmatic nucleus (SCN), the brain's primary circadian pacemaker, but also throughout the brain and peripheral tissues. In BD and MDD patients, defects have been found in SCN-dependent rhythms of body temperature and melatonin release. However, these are imperfect and indirect indicators of SCN function. Moreover, the SCN may not be particularly relevant to mood regulation, whereas the lateral habenula, ventral tegmentum, and hippocampus, which also contain cellular clocks, have established roles in this regard. Dysfunction in these non-SCN clocks could contribute directly to the pathophysiology of BD/MDD. We hypothesize that circadian clock dysfunction in non-SCN clocks is a trait marker of mood disorders, encoded by pathological genetic variants. Because network features of the SCN render it uniquely resistant to perturbation, previous studies of SCN outputs in mood disorders patients may have failed to detect genetic defects affecting non-SCN clocks, which include not only mood-regulating neurons in the brain but also peripheral cells accessible in human subjects. Therefore, reporters of rhythmic clock gene expression in cells from patients or mouse models could provide a direct assay of the molecular gears of the clock, in cellular clocks that are likely to be more representative than the SCN of mood-regulating neurons in patients. This approach, informed by the new insights and tools of modern chronobiology, will allow a more definitive test of the role of cellular circadian clocks

  18. Voiding dysfunction - A review

    Directory of Open Access Journals (Sweden)

    Sripathi V

    2005-01-01

    Full Text Available In a child who is toilet trained the sudden onset of daytime wetting with frequency or urgency is alarming to the parents. Initially this subject was subdivided into a number of descriptive clinical conditions which led to a lot of confusion in recognition and management. Subsequently, the term elimination dysfunction was coined by Stephen Koff to emphasise the association between recurrent urinary infection, wetting, constipation and bladder overactivity. From a urodynamic point of view, in voiding dysfunction, there is either detrusor overactivity during bladder filling or dyssynergic action between the detrusor and the external sphincter during voiding. Identifying a given condition as a ′filling phase dysfunction′ or ′voiding phase dysfunction′ helps to provide appropriate therapy. Objective clinical criteria should be used to define voiding dysfunction. These include bladder wall thickening, large capacity bladder and infrequent voiding, bladder trabeculation and spinning top deformity of the urethra and a clinically demonstrated Vincent′s curtsy. The recognition and treatment of constipation is central to the adequate treatment of voiding dysfunction. Transcutaneous electric nerve stimuation for the treatment of detrusor overactivity, biofeedback with uroflow EMG to correct dyssynergic voiding, and behavioral therapy all serve to correct voiding dysfunction in its early stages. In established neurogenic bladder disease the use of Botulinum Toxin A injections into the detrusor or the external sphincter may help in restoring continence especially in those refractory to drug therapy. However in those children in whom the upper tracts are threatened, augmentation of the bladder may still be needed.

  19. α-Defensin HD5 Inhibits Human Papillomavirus 16 Infection via Capsid Stabilization and Redirection to the Lysosome

    Directory of Open Access Journals (Sweden)

    Mayim E. Wiens

    2017-01-01

    Full Text Available α-Defensins are an important class of abundant innate immune effectors that are potently antiviral against a number of nonenveloped viral pathogens; however, a common mechanism to explain their ability to block infection by these unrelated viruses is lacking. We previously found that human defensin 5 (HD5 blocks a critical host-mediated proteolytic processing step required for human papillomavirus (HPV infection. Here, we show that bypassing the requirement for this cleavage failed to abrogate HD5 inhibition. Instead, HD5 altered HPV trafficking in the cell. In the presence of an inhibitory concentration of HD5, HPV was internalized and reached the early endosome. The internalized capsid became permeable to antibodies and proteases; however, HD5 prevented dissociation of the viral capsid from the genome, reduced viral trafficking to the trans-Golgi network, redirected the incoming viral particle to the lysosome, and accelerated the degradation of internalized capsid proteins. This mechanism is equivalent to the mechanism by which HD5 inhibits human adenovirus. Thus, our data support capsid stabilization and redirection to the lysosome during infection as a general antiviral mechanism of α-defensins against nonenveloped viruses.

  20. α-Defensin HD5 Inhibits Human Papillomavirus 16 Infection via Capsid Stabilization and Redirection to the Lysosome

    Science.gov (United States)

    Wiens, Mayim E.

    2017-01-01

    ABSTRACT α-Defensins are an important class of abundant innate immune effectors that are potently antiviral against a number of nonenveloped viral pathogens; however, a common mechanism to explain their ability to block infection by these unrelated viruses is lacking. We previously found that human defensin 5 (HD5) blocks a critical host-mediated proteolytic processing step required for human papillomavirus (HPV) infection. Here, we show that bypassing the requirement for this cleavage failed to abrogate HD5 inhibition. Instead, HD5 altered HPV trafficking in the cell. In the presence of an inhibitory concentration of HD5, HPV was internalized and reached the early endosome. The internalized capsid became permeable to antibodies and proteases; however, HD5 prevented dissociation of the viral capsid from the genome, reduced viral trafficking to the trans-Golgi network, redirected the incoming viral particle to the lysosome, and accelerated the degradation of internalized capsid proteins. This mechanism is equivalent to the mechanism by which HD5 inhibits human adenovirus. Thus, our data support capsid stabilization and redirection to the lysosome during infection as a general antiviral mechanism of α-defensins against nonenveloped viruses. PMID:28119475

  1. Asteroid Redirect Crewed Mission Space Suit and EVA System Architecture Trade Study

    Science.gov (United States)

    Blanco, Raul A.; Bowie, Jonathan T.; Watson, Richard D.; Sipila, Stephanie A.

    2014-01-01

    The Asteroid Redirect Crewed Mission (ARCM) requires a Launch/Entry/Abort (LEA) suit capability and short duration Extra Vehicular Activity (EVA) capability for Orion. The EVAs will involve a two-person crew for approximately four hours. Currently, two EVAs are planned with one contingency EVA in reserve. Providing this EVA capability is very challenging due to system level constraints and a new and unknown environment. The goal of the EVA architecture for ARCM is one that builds upon previously developed technologies and lessons learned, and that accomplishes the ARCM mission while providing a stepping stone to future missions and destinations. The primary system level constraints are to 1) minimize system mass and volume and 2) minimize the interfacing impacts to the baseline Orion design. In order to minimize the interfacing impacts and to not perturb the baseline Orion schedule, the concept of adding "kits" to the baseline system is proposed. These kits consist of: an EVA kit (converts LEA suit to EVA suit), EVA Servicing and Recharge Kit (provides suit consumables), the EVA Tools, Translation Aids & Sample Container Kit (the tools and mobility aids to complete the tasks), the EVA Communications Kit (interface between the EVA radio and the MPCV), and the Cabin Repress Kit (represses the MPCV between EVAs). This paper will focus on the trade space, analysis, and testing regarding the space suit (pressure garment and life support system). Historical approaches and lessons learned from all past EVA operations were researched. Previous and current, successfully operated EVA hardware and high technology readiness level (TRL) hardware were evaluated, and a trade study was conducted for all possible pressure garment and life support options. Testing and analysis was conducted and a recommended EVA system architecture was proposed. Pressure garment options that were considered for this mission include the currently in-use ISS EVA Mobility Unit (EMU), all variations of

  2. Monitoring Stroke Progression: In Vivo Imaging of Cortical Perfusion, Blood—Brain Barrier Permeability and Cellular Damage in the Rat Photothrombosis Model

    National Research Council Canada - National Science Library

    Schoknecht, Karl; Prager, Ofer; Vazana, Udi; Kamintsky, Lyn; Harhausen, Denise; Zille, Marietta; Figge, Lena; Chassidim, Yoash; Schellenberger, Eyk; Kovács, Richard; Heinemann, Uwe; Friedman, Alon

    2014-01-01

    .... Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis...

  3. Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type- and insult-dependent manner and follow expression of p16

    National Research Council Canada - National Science Library

    Kosar, Martin; Bartkova, Jirina; Hubackova, Sona; Hodny, Zdenek; Lukas, Jiri; Bartek, Jiri

    2011-01-01

    Cellular senescence, an irreversible proliferation arrest evoked by stresses such as oncogene activation, telomere dysfunction, or diverse genotoxic insults, has been implicated in tumor suppression and aging...

  4. Neurogenic voiding dysfunction.

    Science.gov (United States)

    Georgopoulos, Petros; Apostolidis, Apostolos

    2017-05-01

    This review aims to analyze and discuss all recently published articles associated with neurogenic voiding discussion providing readers with the most updated knowledge and trigger for further research. They include the proposal of a novel classification system for the pathophysiology of neurogenic lower urinary tract dysfunction (NLUTD) which combines neurological defect in a distinct anatomic location, and data on bowel dysfunction, autonomic dysreflexia and urine biomarkers; review of patient-reported outcome measures in NLUTD; review of the criteria for the diagnosis of clinically significant urinary infections; novel research findings on the pathophysiology of NLUTD; and review of data on minimally and more invasive treatments. Despite the extended evidence base on NLUTD, there is a paucity of high-quality new research concerning voiding dysfunction as opposed to storage problems. The update aims to inform clinicians about new developments in clinical practice, as well as ignite discussion for further clinical and basic research in the aforementioned areas of NLUTD.

  5. Biology of Sexual Dysfunction

    Directory of Open Access Journals (Sweden)

    Anil Kumar Mysore Nagaraj

    2009-05-01

    Full Text Available Sexual activity is a multifaceted activity, involving complex interactions between the nervous system, the endocrine system, the vascular system and a variety of structures that are instrumental in sexual excitement, intercourse and satisfaction. Sexual function has three components i.e., desire, arousal and orgasm. Many sexual dysfunctions can be categorized according to the phase of sexual response that is affected. In actual clinical practice however, sexual desire, arousal and orgasmic difficulties more often than not coexist, suggesting an integration of phases. Sexual dysfunction can result from a wide variety of psychological and physiological causes including derangements in the levels of sex hormones and neurotrensmitters. This review deals with the biology of different phases of sexual function as well as implications of hormones and neurotransmitters in sexual dysfunction

  6. Diastolic dysfunction in cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Wiese, Signe Skovgaard; Halgreen, Hanne

    2016-01-01

    Development of esophageal varices, ascites, and hepatic nephropathy is among the major complications of cirrhosis. The presence of cirrhotic cardiomyopathy, which includes a left ventricular diastolic dysfunction (DD), seems to deteriorate the course of the disease and the prognosis. Increased st...

  7. Female sexual dysfunction

    DEFF Research Database (Denmark)

    Giraldi, Annamaria; Wåhlin-Jacobsen, Sarah

    2016-01-01

    Female sexual dysfunction (FSD) is a controversial condition, which has prompted much debate regarding its aetiology, components, and even its existence. Our inability to work together as clinicians, psychologists, patients, and advocates hinders our understanding of FSD, and we will only improve...

  8. Mitochondrial Dysfunction in Cancer

    Directory of Open Access Journals (Sweden)

    Michelle L Boland

    2013-12-01

    Full Text Available A mechanistic understanding of how mitochondrial dysfunction contributes to cell growth and tumorigenesis is emerging beyond Warburg as an area of research that is under-explored in terms of its significance for clinical management of cancer. Work discussed in this review focuses less on the Warburg effect and more on mitochondria and how dysfunctional mitochondria modulate cell cycle, gene expression, metabolism, cell viability and other more conventional aspects of cell growth and stress responses. There is increasing evidence that key oncogenes and tumor suppressors modulate mitochondrial dynamics through important signaling pathways and that mitochondrial mass and function vary between tumors and individuals but the sigificance of these events for cancer are not fully appreciated. We explore the interplay between key molecules involved in mitochondrial fission and fusion and in apoptosis, as well as in mitophagy, biogenesis and spatial dynamics and consider how these distinct mechanisms are coordinated in response to physiological stresses such as hypoxia and nutrient deprivation. Importantly, we examine how deregulation of these processes in cancer has knockon effects for cell proliferation and growth. Scientifically, there is also scope for defining what mitochondria dysfunction is and here we address the extent to which the functional consequences of such dysfunction can be determined and exploited for cancer diagnosis and treatment.

  9. Shared Parenting Dysfunction.

    Science.gov (United States)

    Turkat, Ira Daniel

    2002-01-01

    Joint custody of children is the most prevalent court ordered arrangement for families of divorce. A growing body of literature indicates that many parents engage in behaviors that are incompatible with shared parenting. This article provides specific criteria for a definition of the Shared Parenting Dysfunction. Clinical aspects of the phenomenon…

  10. Flat Cellular (UMTS) Networks

    NARCIS (Netherlands)

    Bosch, H.G.P.; Samuel, L.G.; Mullender, S.J.; Polakos, P.; Rittenhouse, G.

    2007-01-01

    Traditionally, cellular systems have been built in a hierarchical manner: many specialized cellular access network elements that collectively form a hierarchical cellular system. When 2G and later 3G systems were designed there was a good reason to make system hierarchical: from a cost-perspective i

  11. Cognitive dysfunction after cardiovascular surgery

    DEFF Research Database (Denmark)

    Funder, K S; Steinmetz, J; Rasmussen, L S

    2009-01-01

    This review describes the incidence, risk factors, and long-term consequences of cognitive dysfunction after cardiovascular surgery. Postoperative cognitive dysfunction (POCD) is increasingly being recognized as an important complication, especially in the elderly. A highly sensitive neuropsychol...

  12. Microvascular dysfunction: an emerging pathway in the pathogenesis of obesity-related insulin resistance.

    Science.gov (United States)

    Muris, Dennis M J; Houben, Alfons J H M; Schram, Miranda T; Stehouwer, Coen D A

    2013-03-01

    The prevalence of type 2 diabetes mellitus (T2DM) and its major risk factor, obesity, has reached epidemic proportions in Western society. How obesity leads to insulin resistance and subsequent T2DM is incompletely understood. It has been established that insulin can redirect blood flow in skeletal muscle from non-nutritive to nutritive capillary networks, without increasing total blood flow. This results in a net increase of the overall number of perfused nutritive capillary networks and thereby increases insulin-mediated glucose uptake by skeletal muscle. This process, referred to as functional (nutritive) capillary recruitment, has been shown to be endothelium-dependent and to require activation of the phosphatidylinositol-kinase (PI3K) pathway in the endothelial cell. Several studies have demonstrated that these processes are impaired in states of microvascular dysfunction. In obesity, changes in several adipokines are likely candidates to influence insulin signaling pathways in endothelial cells, thereby causing microvascular dysfunction. Microvascular dysfunction, in turn, impairs the timely access of glucose and insulin to their target tissues, and may therefore be an additional cause of insulin resistance. Thus, microvascular dysfunction may be a key feature in the development of obesity-related insulin resistance. In the present review, we will discuss the evidence for this emerging role for the microcirculation as a possible link between obesity and insulin resistance.

  13. Cellular membrane collapse by atmospheric-pressure plasma jet

    Science.gov (United States)

    Kim, Kangil; Jun Ahn, Hak; Lee, Jae-Hyeok; Kim, Jae-Ho; Sik Yang, Sang; Lee, Jong-Soo

    2014-01-01

    Cellular membrane dysfunction caused by air plasma in cancer cells has been studied to exploit atmospheric-pressure plasma jets for cancer therapy. Here, we report that plasma jet treatment of cervical cancer HeLa cells increased electrical conductivity across the cellular lipid membrane and caused simultaneous lipid oxidation and cellular membrane collapse. We made this finding by employing a self-manufactured microelectrode chip. Furthermore, increased roughness of the cellular lipid membrane and sequential collapse of the membrane were observed by atomic force microscopy following plasma jet treatment. These results suggest that the cellular membrane catastrophe occurs via coincident altered electrical conductivity, lipid oxidation, and membrane roughening caused by an atmospheric-pressure plasma jet, possibly resulting in cellular vulnerability to reactive species generated from the plasma as well as cytotoxicity to cancer cells.

  14. Cellular membrane collapse by atmospheric-pressure plasma jet

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kangil; Sik Yang, Sang, E-mail: jsjlee@ajou.ac.kr, E-mail: ssyang@ajou.ac.kr [Department of Electrical and Computer Engineering, Ajou University, Suwon 443-749 (Korea, Republic of); Jun Ahn, Hak; Lee, Jong-Soo, E-mail: jsjlee@ajou.ac.kr, E-mail: ssyang@ajou.ac.kr [Department of Biological Sciences, Ajou University, Suwon 443-749 (Korea, Republic of); Lee, Jae-Hyeok; Kim, Jae-Ho [Department of Molecular Science and Technology, Ajou University, Suwon 443-749 (Korea, Republic of)

    2014-01-06

    Cellular membrane dysfunction caused by air plasma in cancer cells has been studied to exploit atmospheric-pressure plasma jets for cancer therapy. Here, we report that plasma jet treatment of cervical cancer HeLa cells increased electrical conductivity across the cellular lipid membrane and caused simultaneous lipid oxidation and cellular membrane collapse. We made this finding by employing a self-manufactured microelectrode chip. Furthermore, increased roughness of the cellular lipid membrane and sequential collapse of the membrane were observed by atomic force microscopy following plasma jet treatment. These results suggest that the cellular membrane catastrophe occurs via coincident altered electrical conductivity, lipid oxidation, and membrane roughening caused by an atmospheric-pressure plasma jet, possibly resulting in cellular vulnerability to reactive species generated from the plasma as well as cytotoxicity to cancer cells.

  15. What Is a Dysfunctional School?

    Science.gov (United States)

    Bergman, M. M.

    2013-01-01

    Whether or not a school is dysfunctional depends largely on how dysfunctionality in schools is defined and measured. Dysfunctionality, as any construct, is subject to definition and interpretation, and it is thus always marked by perspectivism. But regardless of the definition games occasionally played by academics, some form of reality takes…

  16. Lesson Nine Sinus node dysfunction

    Institute of Scientific and Technical Information of China (English)

    鲁端; 吴文烈

    2004-01-01

    @@ Sinus node dysfunction most often is found in the elderly as an isolated phenomenon. Although interruption of the blood supply to the sinus node may produce dysfunction, the correlation between obstruction of the sinus node artery and clinical evidence of sinus node dysfunction is poor.

  17. An Evaluation of Navigational Ability Comparing Redirected Free Exploration with Distractors to Walking-in-Place and Joystick Locomotion Interfaces.

    Science.gov (United States)

    Peck, Tabitha C; Fuchs, Henry; Whitton, Mary C

    2011-03-19

    We report on a user study evaluating Redirected Free Exploration with Distractors (RFED), a large-scale, real-walking, locomotion interface, by comparing it to Walking-in-Place (WIP) and Joystick (JS), two common locomotion interfaces. The between-subjects study compared navigation ability in RFED, WIP, and JS interfaces in VEs that are more than two times the dimensions of the tracked space. The interfaces were evaluated based on navigation and wayfinding metrics and results suggest that participants using RFED were significantly better at navigating and wayfinding through virtual mazes than participants using walking-in-place and joystick interfaces. Participants traveled shorter distances, made fewer wrong turns, pointed to hidden targets more accurately and more quickly, and were able to place and label targets on maps more accurately. Moreover, RFED participants were able to more accurately estimate VE size.

  18. Technology Development of Automated Rendezvous and Docking/Capture Sensors and Docking Mechanism for the Asteroid Redirect Crewed Mission

    Science.gov (United States)

    Hinkel, Heather; Strube, Matthew; Zipay, John J.; Cryan, Scott

    2016-01-01

    This paper will describe the technology development efforts NASA has underway for Automated Rendezvous and Docking/Capture (AR&D/C) sensors and a docking mechanism and the challenges involved. The paper will additionally address how these technologies will be extended to other missions requiring AR&D/C whether robotic or manned. NASA needs AR&D/C sensors for both the robotic and crewed segments of the Asteroid Redirect Mission (ARM). NASA recently conducted a commonality assessment of the concept of operations for the robotic Asteroid Redirect Vehicle (ARV) and the crewed mission segment using the Orion spacecraft. The commonality assessment also considered several future exploration and science missions requiring an AR&D/C capability. Missions considered were asteroid sample return, satellite servicing, and planetary entry, descent, and landing. This assessment determined that a common sensor suite consisting of one or more visible wavelength cameras, a three-dimensional LIDAR along with long-wavelength infrared cameras for robustness and situational awareness could be used on each mission to eliminate the cost of multiple sensor developments and qualifications. By choosing sensor parameters at build-time instead of at design-time and, without having to requalify flight hardware, a specific mission can design overlapping bearing, range, relative attitude, and position measurement availability to suit their mission requirements with minimal non-recurring engineering costs. The resulting common sensor specification provides the union of all performance requirements for each mission and represents an improvement over the current systems used for AR&D/C today. These sensor specifications are tightly coupled to the docking system capabilities and requirements for final docking conditions. The paper will describe NASA's efforts to develop a standard docking system for use across NASA human spaceflight missions to multiple destinations. It will describe the current

  19. The cone dysfunction syndromes

    Science.gov (United States)

    Aboshiha, Jonathan; Dubis, Adam M; Hardcastle, Alison J; Michaelides, Michel

    2016-01-01

    The cone dysfunction syndromes are a heterogeneous group of inherited, predominantly stationary retinal disorders characterised by reduced central vision and varying degrees of colour vision abnormalities, nystagmus and photophobia. This review details the following conditions: complete and incomplete achromatopsia, blue-cone monochromatism, oligocone trichromacy, bradyopsia and Bornholm eye disease. We describe the clinical, psychophysical, electrophysiological and imaging findings that are characteristic to each condition in order to aid their accurate diagnosis, as well as highlight some classically held notions about these diseases that have come to be challenged over the recent years. The latest data regarding the genetic aetiology and pathological changes observed in the cone dysfunction syndromes are discussed, and, where relevant, translational avenues of research, including completed and anticipated interventional clinical trials, for some of the diseases described herein will be presented. Finally, we briefly review the current management of these disorders. PMID:25770143

  20. Dysfunctional Uterine Bleeding

    OpenAIRE

    1987-01-01

    Dysfunctional uterine bleeding (DUB) is defined as abnormal uterine bleeding that results from an ovarian endocrinopathy. It may be associated with ovulatory and anovulatory cycles. The diagnosis of DUB depends on a thorough history and physical examination to exclude organic disorders. In older women, endometrial biopsy should be done before starting therapy. The treatment depends on an understanding of the menstrual cycle. In less urgent cases, anovulatory cycles are managed using progester...

  1. Biology of Sexual Dysfunction

    OpenAIRE

    MN, Anil Kumar; Pai, NB; Rao, S; Rao, TSS; Goyal, N.

    2009-01-01

    Sexual activity is a multifaceted activity, involving complex interactions between the nervous system, the endocrine system, the vascular system and a variety of structures that are instrumental in sexual excitement, intercourse and satisfaction. Sexual function has three components i.e., desire, arousal and orgasm. Many sexual dysfunctions can be categorized according to the phase of sexual response that is affected. In actual clinical practice however, sexual desire, arousal and orgasmic di...

  2. Male Gender Role Dysfunction

    OpenAIRE

    Daig, Isolde

    2010-01-01

    Background: Men have a higher alcohol and cigarette consumption than women, they use more drugs, they have twice as high a suicide rate and only a minority of men attend on preventive medical checkups. Hypotheses: The central questions of the present study pertained to the identification of dysfunctional aspects of a male self concept and the possible correlations with risk behaviour of men in different age stages. One possible explanation for this high risk behaviour may be higher mascul...

  3. Thyroid dysfunction and subfertility.

    Science.gov (United States)

    Cho, Moon Kyoung

    2015-12-01

    The thyroid hormones act on nearly every cell in the body. Moreover, the thyroid gland continuously interacts with the ovaries, and the thyroid hormones are involved in almost all phases of reproduction. Thyroid dysfunctions are relatively common among women of reproductive age, and can affect fertility in various ways, resulting in anovulatory cycles, high prolactin levels, and sex hormone imbalances. Undiagnosed and untreated thyroid disease can be a cause of subfertility. Subclinical hypothyroidism (SCH), also known as mild thyroid failure, is diagnosed when peripheral thyroid hormone levels are within the normal reference laboratory range, but serum thyroid-stimulating hormone levels are mildly elevated. Thyroid autoimmunity (TAI) is characterized by the presence of anti-thyroid antibodies, which include anti-thyroperoxidase and anti-thyroglobulin antibodies. SCH and TAI may remain latent, asymptomatic, or even undiagnosed for an extended period. It has also been demonstrated that controlled ovarian hyperstimulation has a significant impact on thyroid function, particularly in women with TAI. In the current review, we describe the interactions between thyroid dysfunctions and subfertility, as well as the proper work-up and management of thyroid dysfunctions in subfertile women.

  4. Sexual dysfunction with antihypertensive drugs.

    Science.gov (United States)

    Prisant, L M; Carr, A A; Bottini, P B; Solursh, D S; Solursh, L P

    1994-04-11

    The relationship of antihypertensive drugs have a long history of association with sexual dysfunction; however, this relationship is poorly documented. There appears to be a higher rate of sexual dysfunction in untreated hypertensive men compared with normotensive men. Sexual dysfunction increases with age and is associated with physical and emotional symptoms. There are few studies assessing sexual dysfunction with female and African-American hypertensive patients. Sexual dysfunction is associated with impairment of quality of life and noncompliance. Since group data may hide individual drug effects, baseline data should be collected on all patients before initiating therapy with any antihypertensive agent. Although questionnaires may not provide objective information on sexual dysfunction, the response rate to direct questioning may be less than the response rate on a questionnaire and may be affected by the gender or race of the interviewer. Research protocols using a double-blind, placebo-controlled design should assess sexual dysfunction in men and women in a standardized fashion.

  5. Senescence-associated intrinsic mechanisms of osteoblast dysfunctions

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Trinquier, Anne Marie-Pierre Emilie

    2011-01-01

    -related osteoblast dysfunction is the main cause of age-related bone loss in both men and women beyond the fifth decade and results from two groups of pathogenic mechanisms: extrinsic mechanisms that are mediated by age-related changes in bone microenvironment including changes in levels of hormones and growth...... factors, and intrinsic mechanisms caused by the osteoblast cellular senescence. The aim of this review is to provide a summary of the intrinsic senescence mechanisms affecting osteoblastic functions and how they can be targeted in order to abolish age-related osteoblastic dysfunction and bone loss...

  6. Acidosis induces reprogramming of cellular metabolism to mitigate oxidative stress

    Science.gov (United States)

    2013-01-01

    Background A variety of oncogenic and environmental factors alter tumor metabolism to serve the distinct cellular biosynthetic and bioenergetic needs present during oncogenesis. Extracellular acidosis is a common microenvironmental stress in solid tumors, but little is known about its metabolic influence, particularly when present in the absence of hypoxia. In order to characterize the extent of tumor cell metabolic adaptations to acidosis, we employed stable isotope tracers to examine how acidosis impacts glucose, glutamine, and palmitate metabolism in breast cancer cells exposed to extracellular acidosis. Results Acidosis increased both glutaminolysis and fatty acid β-oxidation, which contribute metabolic intermediates to drive the tricarboxylic acid cycle (TCA cycle) and ATP generation. Acidosis also led to a decoupling of glutaminolysis and novel glutathione (GSH) synthesis by repressing GCLC/GCLM expression. We further found that acidosis redirects glucose away from lactate production and towards the oxidative branch of the pentose phosphate pathway (PPP). These changes all serve to increase nicotinamide adenine dinucleotide phosphate (NADPH) production and counter the increase in reactive oxygen species (ROS) present under acidosis. The reduced novel GSH synthesis under acidosis may explain the increased demand for NADPH to recycle existing pools of GSH. Interestingly, acidosis also disconnected novel ribose synthesis from the oxidative PPP, seemingly to reroute PPP metabolites to the TCA cycle. Finally, we found that acidosis activates p53, which contributes to both the enhanced PPP and increased glutaminolysis, at least in part, through the induction of G6PD and GLS2 genes. Conclusions Acidosis alters the cellular metabolism of several major metabolites, which induces a significant degree of metabolic inflexibility. Cells exposed to acidosis largely rely upon mitochondrial metabolism for energy generation to the extent that metabolic intermediates are

  7. Diabetic bladder dysfunction

    Institute of Scientific and Technical Information of China (English)

    Guiming Liu; Firouz Daneshgari

    2014-01-01

    Objective To review studies on diabetic bladder dysfunction (DBD),a common and bothersome complication of diabetes mellitus.Data sources We performed a search of the English literature through PubMed.The key words used were "diabetes" and "bladder dysfunction" or "cystopathy".Our own data and perspective are included in the discussion.Study selection Studies containing data relevant to DBD were selected.Because of the limited length of this article,we also referenced reviews that contain comprehensive amalgamations of relevant literature.Results The classic symptoms of DBD are decreased bladder sensation,increased bladder capacity,and impaired bladder emptying with resultant elevated post-void residual urine.However,recent clinical and experimental evidence indicate a strong presence of storage problems such as urge incontinence in diabetes.Recent studies of DBD in animal models of type 1 diabetes have revealed temporal effects of diabetes,causing an early phase of compensatory bladder function and a later phase of decompensated bladder function.The pathophysiology of DBD is multifactorial,including disturbances of the detrusor,urothelium,autonomic nerves,and urethra.Polyuria and hyperglycemia play important but distinctive roles in induction of bladder dysfunction in type 1 diabetes.Polyuria causes significant bladder hypertrophy in the early stage of diabetes,whereas oxidative stress in the bladder caused by chronic hyperglycemia may play an important role in the late stage failure of bladder function.Conclusions DBD includes time-dependent and mixed manifestations.The pathological alterations include muscle,nerve,and urothelium.Polyuria and hyperglycemia independently contribute to the pathogenesis of DBD.Treatments for DBD are limited.Future clinical studies on DBD in type 1 and type 2 diabetes should be investigated separately.Animal studies of DBD in type 2 diabetes are needed,from the natural history to mechanisms.Further understanding of the molecular

  8. Mitochondrial dysfunction in autism.

    Science.gov (United States)

    Legido, Agustín; Jethva, Reena; Goldenthal, Michael J

    2013-09-01

    Using data of the current prevalence of autism as 200:10,000 and a 1:2000 incidence of definite mitochondrial (mt) disease, if there was no linkage of autism spectrum disorder (ASD) and mt disease, it would be expected that 1 in 110 subjects with mt disease would have ASD and 1 in 2000 individuals with ASD would have mt disease. The co-occurrence of autism and mt disease is much higher than these figures, suggesting a possible pathogenetic relationship. Such hypothesis was initially suggested by the presence of biochemical markers of abnormal mt metabolic function in patients with ASD, including elevation of lactate, pyruvate, or alanine levels in blood, cerebrospinal fluid, or brain; carnitine level in plasma; and level of organic acids in urine, and by demonstrating impaired mt fatty acid β-oxidation. More recently, mtDNA genetic mutations or deletions or mutations of nuclear genes regulating mt function have been associated with ASD in patients or in neuropathologic studies on the brains of patients with autism. In addition, the presence of dysfunction of the complexes of the mt respiratory chain or electron transport chain, indicating abnormal oxidative phosphorylation, has been reported in patients with ASD and in the autopsy samples of brains. Possible pathogenetic mechanisms linking mt dysfunction and ASD include mt activation of the immune system, abnormal mt Ca(2+) handling, and mt-induced oxidative stress. Genetic and epigenetic regulation of brain development may also be disrupted by mt dysfunction, including mt-induced oxidative stress. The role of the purinergic system linking mt dysfunction and ASD is currently under investigation. In summary, there is genetic and biochemical evidence for a mitochondria (mt) role in the pathogenesis of ASD in a subset of children. To determine the prevalence and type of genetic and biochemical mt defects in ASD, there is a need for further research using the latest genetic technology such as next

  9. Depression and erectile dysfunction.

    Science.gov (United States)

    Makhlouf, Antoine; Kparker, Ashay; Niederberger, Craig S

    2007-11-01

    Depression and erectile dysfunction (ED) clearly are associated. Although urologists and psychiatrists have long recognized that antidepressant medications affect erectile function negatively, the interplay between the two conditions remains underappreciated. Psychiatrists may be reluctant to question a patient in detail about ED, and urologists seldom perform a formal assessment of the presence of depression in patients who have ED. This article gives a quick overview of the relationship between these two conditions and provides the clinician with the knowledge required to effectively manage ED with comorbid depression.

  10. Mitochondrial dysfunction in myofibrillar myopathy.

    Science.gov (United States)

    Vincent, Amy E; Grady, John P; Rocha, Mariana C; Alston, Charlotte L; Rygiel, Karolina A; Barresi, Rita; Taylor, Robert W; Turnbull, Doug M

    2016-10-01

    Myofibrillar myopathies (MFM) are characterised by focal myofibrillar destruction and accumulation of myofibrillar elements as protein aggregates. They are caused by mutations in the DES, MYOT, CRYAB, FLNC, BAG3, DNAJB6 and ZASP genes as well as other as yet unidentified genes. Previous studies have reported changes in mitochondrial morphology and cellular positioning, as well as clonally-expanded, large-scale mitochondrial DNA (mtDNA) deletions and focal respiratory chain deficiency in muscle of MFM patients. Here we examine skeletal muscle from patients with desmin (n = 6), ZASP (n = 1) and myotilin (n = 2) mutations and MFM protein aggregates, to understand how mitochondrial dysfunction may contribute to the underlying mechanisms causing disease pathology. We have used a validated quantitative immunofluorescent assay to study respiratory chain protein levels, together with oxidative enzyme histochemistry and single cell mitochondrial DNA analysis, to examine mitochondrial changes. Results demonstrate a small number of clonally-expanded mitochondrial DNA deletions, which we conclude are due to both ageing and disease pathology. Further to this we report higher levels of respiratory chain complex I and IV deficiency compared to age matched controls, although overall levels of respiratory deficient muscle fibres in patient biopsies are low. More strikingly, a significantly higher percentage of myofibrillar myopathy patient muscle fibres have a low mitochondrial mass compared to controls. We concluded this is mechanistically unrelated to desmin and myotilin protein aggregates; however, correlation between mitochondrial mass and muscle fibre area is found. We suggest this may be due to reduced mitochondrial biogenesis in combination with muscle fibre hypertrophy.

  11. Microfluidic Devices for the Measurement of Cellular Secretion

    Science.gov (United States)

    Schrell, Adrian M.; Mukhitov, Nikita; Yi, Lian; Wang, Xue; Roper, Michael G.

    2016-06-01

    The release of chemical information from cells and tissues holds the key to understanding cellular behavior and dysfunction. The development of methodologies that can measure cellular secretion in a time-dependent fashion is therefore essential. Often these measurements are made difficult by the high-salt conditions of the cellular environment, the presence of numerous other secreted factors, and the small mass samples that are produced when frequent sampling is used to resolve secretory dynamics. In this review, the methods that we have developed for measuring hormone release from islets of Langerhans are dissected to illustrate the practical difficulties of studying cellular secretions. Other methods from the literature are presented that provide alternative approaches to particularly challenging areas of monitoring cellular secretion. The examples presented in this review serve as case studies and should be adaptable to other cell types and systems for unique applications.

  12. Reversible quantum cellular automata

    CERN Document Server

    Schumacher, B

    2004-01-01

    We define quantum cellular automata as infinite quantum lattice systems with discrete time dynamics, such that the time step commutes with lattice translations and has strictly finite propagation speed. In contrast to earlier definitions this allows us to give an explicit characterization of all local rules generating such automata. The same local rules also generate the global time step for automata with periodic boundary conditions. Our main structure theorem asserts that any quantum cellular automaton is structurally reversible, i.e., that it can be obtained by applying two blockwise unitary operations in a generalized Margolus partitioning scheme. This implies that, in contrast to the classical case, the inverse of a nearest neighbor quantum cellular automaton is again a nearest neighbor automaton. We present several construction methods for quantum cellular automata, based on unitaries commuting with their translates, on the quantization of (arbitrary) reversible classical cellular automata, on quantum c...

  13. Vascular dysfunction in preeclampsia.

    Science.gov (United States)

    Brennan, Lesley J; Morton, Jude S; Davidge, Sandra T

    2014-01-01

    Preeclampsia is a complex disorder which affects an estimated 5% of all pregnancies worldwide. It is diagnosed by hypertension in the presence of proteinuria after the 20th week of pregnancy and is a prominent cause of maternal morbidity and mortality. As delivery is currently the only known treatment, preeclampsia is also a leading cause of preterm delivery. Preeclampsia is associated with maternal vascular dysfunction, leading to serious cardiovascular risk both during and following pregnancy. Endothelial dysfunction, resulting in increased peripheral resistance, is an integral part of the maternal syndrome. While the cause of preeclampsia remains unknown, placental ischemia resulting from aberrant placentation is a fundamental characteristic of the disorder. Poor placentation is believed to stimulate the release of a number of factors including pro- and antiangiogenic factors and inflammatory activators into the maternal systemic circulation. These factors are critical mediators of vascular function and impact the endothelium in distinctive ways, including enhanced endothelial oxidative stress. The mechanisms of action and the consequences on the maternal vasculature will be discussed in this review.

  14. Empirical assessment of a prismatic daylight-redirecting window film in a full-scale office testbed

    Energy Technology Data Exchange (ETDEWEB)

    Thanachareonkit, Anothai; Lee, Eleanor S.; McNeil, Andrew

    2013-08-31

    Daylight redirecting systems with vertical windows have the potential to offset lighting energy use in deep perimeter zones. Microstructured prismatic window films can be manufactured using low-cost, roll-to-roll fabrication methods and adhered to the inside surface of existing windows as a retrofit measure or installed as a replacement insulating glass unit in the clerestory portion of the window wall. A clear film patterned with linear, 50-250 micrometer high, four-sided asymmetrical prisms was fabricated and installed in the south-facing, clerestory low-e, clear glazed windows of a full-scale testbed facility. Views through the film were distorted. The film was evaluated in a sunny climate over a two-year period to gauge daylighting and visual comfort performance. The daylighting aperture was small (window-towall ratio of 0.18) and the lower windows were blocked off to isolate the evaluation to the window film. Workplane illuminance measurements were made in the 4.6 m (15 ft) deep room furnished as a private office. Analysis of discomfort glare was conducted using high dynamic range imaging coupled with the evalglare software tool, which computes the daylight glare probability and other metrics used to evaluate visual discomfort. The window film was found to result in perceptible levels of discomfort glare on clear sunny days from the most conservative view point in the rear of the room looking toward the window. Daylight illuminance levels at the rear of the room were significantly increased above the reference window condition, which was defined as the same glazed clerestory window but with an interior Venetian blind (slat angle set to the cut-off angle), for the equinox to winter solstice period on clear sunny days. For partly cloudy and overcast sky conditions, daylight levels were improved slightly. To reduce glare, the daylighting film was coupled with a diffusing film in an insulating glazing unit. The diffusing film retained the directionality of the

  15. Heterogeneous cellular networks

    CERN Document Server

    Hu, Rose Qingyang

    2013-01-01

    A timely publication providing coverage of radio resource management, mobility management and standardization in heterogeneous cellular networks The topic of heterogeneous cellular networks has gained momentum in industry and the research community, attracting the attention of standardization bodies such as 3GPP LTE and IEEE 802.16j, whose objectives are looking into increasing the capacity and coverage of the cellular networks. This book focuses on recent progresses,  covering the related topics including scenarios of heterogeneous network deployment, interference management i

  16. Impaired glycogen synthase activity and mitochondrial dysfunction in skeletal muscle

    DEFF Research Database (Denmark)

    Højlund, Kurt; Beck-Nielsen, Henning

    2006-01-01

    expression analysis and proteomics have pointed to abnormalities in mitochondrial oxidative phosphorylation and cellular stress in muscle of type 2 diabetic subjects, and recent work suggests that impaired mitochondrial activity is another early defect in the pathogenesis of type 2 diabetes. This review...... will discuss the latest advances in the understanding of the molecular mechanisms underlying insulin resistance in human skeletal muscle in type 2 diabetes with focus on possible links between impaired glycogen synthase activity and mitochondrial dysfunction....

  17. Molecular basis of telomere dysfunction in human genetic diseases.

    Science.gov (United States)

    Sarek, Grzegorz; Marzec, Paulina; Margalef, Pol; Boulton, Simon J

    2015-11-01

    Mutations in genes encoding proteins required for telomere structure, replication, repair and length maintenance are associated with several debilitating human genetic disorders. These complex telomere biology disorders (TBDs) give rise to critically short telomeres that affect the homeostasis of multiple organs. Furthermore, genome instability is often a hallmark of telomere syndromes, which are associated with increased cancer risk. Here, we summarize the molecular causes and cellular consequences of disease-causing mutations associated with telomere dysfunction.

  18. Cellular Senescence: A Translational Perspective

    Directory of Open Access Journals (Sweden)

    James L. Kirkland

    2017-07-01

    Full Text Available Cellular senescence entails essentially irreversible replicative arrest, apoptosis resistance, and frequently acquisition of a pro-inflammatory, tissue-destructive senescence-associated secretory phenotype (SASP. Senescent cells accumulate in various tissues with aging and at sites of pathogenesis in many chronic diseases and conditions. The SASP can contribute to senescence-related inflammation, metabolic dysregulation, stem cell dysfunction, aging phenotypes, chronic diseases, geriatric syndromes, and loss of resilience. Delaying senescent cell accumulation or reducing senescent cell burden is associated with delay, prevention, or alleviation of multiple senescence-associated conditions. We used a hypothesis-driven approach to discover pro-survival Senescent Cell Anti-apoptotic Pathways (SCAPs and, based on these SCAPs, the first senolytic agents, drugs that cause senescent cells to become susceptible to their own pro-apoptotic microenvironment. Several senolytic agents, which appear to alleviate multiple senescence-related phenotypes in pre-clinical models, are beginning the process of being translated into clinical interventions that could be transformative.

  19. Embryonic stem cells are redirected to non-tumorigenic epithelial cell fate by interaction with the mammary microenvironment.

    Directory of Open Access Journals (Sweden)

    Corinne A Boulanger

    Full Text Available Experiments were conducted to redirect mouse Embryonic Stem (ES cells from a tumorigenic phenotype to a normal mammary epithelial phenotype in vivo. Mixing LacZ-labeled ES cells with normal mouse mammary epithelial cells at ratios of 1:5 and 1:50 in phosphate buffered saline and immediately inoculating them into epithelium-divested mammary fat pads of immune-compromised mice accomplished this. Our results indicate that tumorigenesis occurs only when normal mammary ductal growth is not achieved in the inoculated fat pads. When normal mammary gland growth occurs, we find ES cells (LacZ+ progeny interspersed with normal mammary cell progeny in the mammary epithelial structures. We demonstrate that these progeny, marked by LacZ expression, differentiate into multiple epithelial subtypes including steroid receptor positive luminal cells and myoepithelial cells indicating that the ES cells are capable of epithelial multipotency in this context but do not form teratomas. In addition, in secondary transplants, ES cell progeny proliferate, contribute apparently normal mammary progeny, maintain their multipotency and do not produce teratomas.

  20. Embryonic stem cells are redirected to non-tumorigenic epithelial cell fate by interaction with the mammary microenvironment.

    Science.gov (United States)

    Boulanger, Corinne A; Bruno, Robert D; Mack, David L; Gonzales, Monica; Castro, Nadia P; Salomon, David S; Smith, Gilbert H

    2013-01-01

    Experiments were conducted to redirect mouse Embryonic Stem (ES) cells from a tumorigenic phenotype to a normal mammary epithelial phenotype in vivo. Mixing LacZ-labeled ES cells with normal mouse mammary epithelial cells at ratios of 1:5 and 1:50 in phosphate buffered saline and immediately inoculating them into epithelium-divested mammary fat pads of immune-compromised mice accomplished this. Our results indicate that tumorigenesis occurs only when normal mammary ductal growth is not achieved in the inoculated fat pads. When normal mammary gland growth occurs, we find ES cells (LacZ+) progeny interspersed with normal mammary cell progeny in the mammary epithelial structures. We demonstrate that these progeny, marked by LacZ expression, differentiate into multiple epithelial subtypes including steroid receptor positive luminal cells and myoepithelial cells indicating that the ES cells are capable of epithelial multipotency in this context but do not form teratomas. In addition, in secondary transplants, ES cell progeny proliferate, contribute apparently normal mammary progeny, maintain their multipotency and do not produce teratomas.

  1. Progressive posterior cortical dysfunction

    Directory of Open Access Journals (Sweden)

    Fábio Henrique de Gobbi Porto

    Full Text Available Abstract Progressive posterior cortical dysfunction (PPCD is an insidious syndrome characterized by prominent disorders of higher visual processing. It affects both dorsal (occipito-parietal and ventral (occipito-temporal pathways, disturbing visuospatial processing and visual recognition, respectively. We report a case of a 67-year-old woman presenting with progressive impairment of visual functions. Neurologic examination showed agraphia, alexia, hemispatial neglect (left side visual extinction, complete Balint's syndrome and visual agnosia. Magnetic resonance imaging showed circumscribed atrophy involving the bilateral parieto-occipital regions, slightly more predominant to the right . Our aim was to describe a case of this syndrome, to present a video showing the main abnormalities, and to discuss this unusual presentation of dementia. We believe this article can contribute by improving the recognition of PPCD.

  2. Cycling and erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Ina Šibli

    2015-01-01

    Full Text Available Abstract: For many years medical studies have implicated bicycle riding is causing erectile dysfunction (ED in association with higher perineal pressure. This review focuses upon epidemiological studies assesing the impact of cycling on ED, pathogenesis of ED in cyclists  as well as on research considering changes of perineal pressure, hemodynamics, and nerve conduction when cycling. Investigestors were also interested in different saddle sizes, materials and geometry and also in the impact of saddle and riders position on changes to the perineum. Research on female cyclists is very limited but indicates similar genitourinary disorders as in male cyclists. We also review  research on preventative and therapeutic options regarding bicycle riding and ED.

  3. Dysfunctional anger and sexual violence.

    Science.gov (United States)

    Ahmed, A G

    2014-06-01

    Sexual offenses with or without aggression attract attention from the popular media and the scientific community. Empirical research suggests a relationship between anger and sexual violence. This article describes the key themes of dysfunctional anger and sexual violence, and how dysfunctional anger relates to sexual fantasies, sexual offending, and sexual recidivism. The implications of the findings for clinical practice and future research are discussed.

  4. Defining sphincter of oddi dysfunction

    DEFF Research Database (Denmark)

    Funch-Jensen, P

    1996-01-01

    Sphincter of Oddi (SO) dysmotility may give rise to pain. The golden standard for the demonstration of SO dysfunction is endoscopic manometry. A number of abnormalities are observed in patients with postcholecystectomy pain and in patients with idiopathic recurrent pancreatitis. Criteria for defi...... for defining SO dysfunction and the possible mechanisms for the precipitation of pain are discussed....

  5. Bladder Dysfunction and Vesicoureteral Reflux

    Directory of Open Access Journals (Sweden)

    Ulla Sillén

    2008-01-01

    Full Text Available In this overview the influence of functional bladder disturbances and of its treatment on the resolution of vesicoureteral reflux (VUR in children is discussed. Historically both bladder dysfunction entities, the overactive bladder (OAB and the dysfunctional voiding (DV, have been described in conjunction with VUR. Treatment of the dysfunction was also considered to influence spontaneous resolution in a positive way. During the last decades, however, papers have been published which could not support these results. Regarding the OAB, a prospective study with treatment of the bladder overactivity with anticholinergics, did not influence spontaneous resolution rate in children with a dysfunction including also the voiding phase, DV and DES (dysfunctional elimination syndrome, most studies indicate a negative influence on the resolution rate of VUR in children, both before and after the age for bladder control, both with and without treatment. However, a couple of uncontrolled studies indicate that there is a high short-term resolution rate after treatment with flow biofeedback. It should be emphasized that the voiding phase dysfunctions (DV and DES are more severe than the genuine filling phase dysfunction (OAB, with an increased frequency of UTI and renal damage in the former groups. To be able to answer the question if treatment of bladder dysfunction influence the resolution rate of VUR in children, randomized controlled studies must be performed.

  6. Modeling cellular systems

    CERN Document Server

    Matthäus, Franziska; Pahle, Jürgen

    2017-01-01

    This contributed volume comprises research articles and reviews on topics connected to the mathematical modeling of cellular systems. These contributions cover signaling pathways, stochastic effects, cell motility and mechanics, pattern formation processes, as well as multi-scale approaches. All authors attended the workshop on "Modeling Cellular Systems" which took place in Heidelberg in October 2014. The target audience primarily comprises researchers and experts in the field, but the book may also be beneficial for graduate students.

  7. Epigenetics and Cellular Metabolism

    OpenAIRE

    Wenyi Xu; Fengzhong Wang; Zhongsheng Yu; Fengjiao Xin

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the proce...

  8. Nanostructured cellular networks.

    Science.gov (United States)

    Moriarty, P; Taylor, M D R; Brust, M

    2002-12-01

    Au nanocrystals spin-coated onto silicon from toluene form cellular networks. A quantitative statistical crystallography analysis shows that intercellular correlations drive the networks far from statistical equilibrium. Spin-coating from hexane does not produce cellular structure, yet a strong correlation is retained in the positions of nanocrystal aggregates. Mechanisms based on Marangoni convection alone cannot account for the variety of patterns observed, and we argue that spinodal decomposition plays an important role in foam formation.

  9. Muscle dysfunction in cancer patients

    DEFF Research Database (Denmark)

    Christensen, Jesper Frank; Jones, L W; Andersen, J L

    2014-01-01

    implications of muscle dysfunction in cancer patients. The efficacy of exercise training to prevent and/or mitigate cancer-related muscle dysfunction is also discussed. DESIGN: We identified 194 studies examining muscular outcomes in cancer patients by searching PubMed and EMBASE databases. RESULTS: Muscle...... dysfunction is evident across all stages of the cancer trajectory. The causes of cancer-related muscle dysfunction are complex, but may involve a wide range of tumor-, therapy- and/or lifestyle-related factors, depending on the clinical setting of the individual patient. The main importance of muscle...... dysfunction in cancer patients lies in the correlation to vital clinical end points such as cancer-specific and all-cause mortality, therapy complications and quality of life (QoL). Such associations strongly emphasize the need for effective therapeutic countermeasures to be developed and implemented...

  10. The weal and woe of costimulation in the adoptive therapy of cancer with chimeric antigen receptor (CAR)-redirected T cells.

    Science.gov (United States)

    Hombach, A A; Holzinger, A; Abken, H

    2013-08-01

    Adoptive cell therapy has shown impressive efficacy to combat cancer in early phase clinical trials, in particular when T cells engineered to specifically target tumor cells were applied. The patient's T cells are genetically equipped with a chimeric antigen receptor (CAR) which allows them to be redirected in a predefined manner towards virtually any target; by using an antibody-derived domain for binding, CAR T cells can be redirected in a major histocompatibility complex (MHC) dependent and independent fashion. The CAR also provides the stimuli required to induce and maintain T cell activation. Recent clinical data sustain the notion that strong costimulation in conjunction with the primary activation signal is crucial for lasting therapeutic efficacy of CAR T cells. However, costimulation is a double-edged sword and the impact of the individual costimuli to optimize T cell activation is still under debate; some general rules are emerging. The review summarizes how costimulation modulates, improves and prolongs the redirected anti-tumor T cell response and how the same costimulatory signals may contribute to unintended side effects including "cytokine storm" and T cell repression. Upcoming strategies to break the activation/repression circle by using CAR's with modified costimulatory signals are also discussed.

  11. Portal authentication HTTP redirection using netfilter NFQUEUE%利用netfilter NFQUEUE实现网关认证的HTTP重定向

    Institute of Scientific and Technical Information of China (English)

    张焕杰; 夏玉良

    2014-01-01

    利用netfilter的NFQUEUE机制,将未认证用户的TCP 80端口流量发送至用户态进程redir_http,redir_http使用原始套接字发送应答数据分组,在用户态实现HTTP重定向功能。这种实现方法既保证了重定向的高性能,又能避免Linux内核中的繁琐程序开发,降低程序开发复杂度,提高系统运行的稳定性。%When using portal for user authentication, unauthorized user's HTTP access should be redirected to portal login page to help user do authentication.Using netfilter NFQUEUE target send unauthorized user TCP port 80 packets to user-space program redir_http. Redir_http will send IP reply packets to user do HTTP redirection with the help of raw socket. Using NFQUEUE can ensures high performance redirection, avoid troublesome development in the Linux ker-nel,simplify application development and improve system stability.

  12. Nonalcoholic fatty liver disease and mitochondrial dysfunction

    Institute of Scientific and Technical Information of China (English)

    Yongzhong Wei; R Scott Rector; John P Thyfault; Jamal A Ibdah

    2008-01-01

    Nonalcoholic fatty liver disease (NAFLD) includes hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis,and cirrhosis. NAFLD is the most common liver disorder in the United States and worldwide. Due to the rapid rise of the metabolic syndrome, the prevalence of NAFLD has recently dramatically increased and will continue to increase. NAFLD has also the potential to progress to hepatocellular carcinoma (HCC) or liver failure. NAFLD is strongly linked to caloric overconsumption, physical inactivity, insulin resistance and genetic factors. Although significant progress in understanding the pathogenesis of NAFLD has been achieved in years, the primary metabolic abnormalities leading to lipid accumulation within hepatocytes has remained poorly understood.Mitochondria are critical metabolic organelles serving as "cellular power plants". Accumulating evidence indicate that hepatic mitochondrial dysfunction is crucial to the pathogenesis of NAFLD. This review is focused on the significant role of mitochondria in the development of NAFLD.

  13. Dysfunctional HCN ion channels in neurological diseases.

    Science.gov (United States)

    DiFrancesco, Jacopo C; DiFrancesco, Dario

    2015-01-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed as four different isoforms (HCN1-4) in the heart and in the central and peripheral nervous systems. HCN channels are activated by membrane hyperpolarization at voltages close to resting membrane potentials and carry the hyperpolarization-activated current, dubbed If (funny current) in heart and Ih in neurons. HCN channels contribute in several ways to neuronal activity and are responsible for many important cellular functions, including cellular excitability, generation, and modulation of rhythmic activity, dendritic integration, transmission of synaptic potentials, and plasticity phenomena. Because of their role, defective HCN channels are natural candidates in the search for potential causes of neurological disorders in humans. Several data, including growing evidence that some forms of epilepsy are associated with HCN mutations, support the notion of an involvement of dysfunctional HCN channels in different experimental models of the disease. Additionally, some anti-epileptic drugs are known to modify the activity of the Ih current. HCN channels are widely expressed in the peripheral nervous system and recent evidence has highlighted the importance of the HCN2 isoform in the transmission of pain. HCN channels are also present in the midbrain system, where they finely regulate the activity of dopaminergic neurons, and a potential role of these channels in the pathogenesis of Parkinson's disease has recently emerged. The function of HCN channels is regulated by specific accessory proteins, which control the correct expression and modulation of the neuronal Ih current. Alteration of these proteins can severely interfere with the physiological channel function, potentially predisposing to pathological conditions. In this review we address the present knowledge of the association between HCN dysfunctions and neurological diseases, including clinical, genetic, and physiopathological

  14. Dysfunctional HCN ion channels in neurological diseases

    Directory of Open Access Journals (Sweden)

    Jacopo C. DiFrancesco

    2015-03-01

    Full Text Available Hyperpolarization-activated cyclic nucleotide-gated (HCN channels are expressed as four different isoforms (HCN1-4 in the heart and in the central and peripheral nervous systems. HCN channels are activated by membrane hyperpolarization at voltages close to resting membrane potentials and carry the hyperpolarization-activated current, dubbed If (funny current in heart and Ih in neurons. HCN channels contribute in several ways to neuronal activity and are responsible for many important cellular functions, including cellular excitability, generation and modulation of rhythmic activity, dendritic integration, transmission of synaptic potentials and plasticity phenomena. Because of their role, defective HCN channels are natural candidates in the search for potential causes of neurological disorders in humans. Several data, including growing evidence that some forms of epilepsy are associated with HCN mutations, support the notion of an involvement of dysfunctional HCN channels in different experimental models of the disease. Additionally, some anti-epileptic drugs are known to modify the activity of the Ih current. HCN channels are widely expressed in the peripheral nervous system and recent evidence has highlighted the importance of the HCN2 isoform in the transmission of pain. HCN channels are also present in the midbrain system, where they finely regulate the activity of dopaminergic neurons, and a potential role of these channels in the pathogenesis of Parkinson’s disease has recently emerged. The function of HCN channels is regulated by specific accessory proteins, which control the correct expression and modulation of the neuronal Ih current. Alteration of these proteins can severely interfere with the physiological channel function, potentially predisposing to pathological conditions. In this review we address the present knowledge of the association between HCN dysfunctions and neurological diseases, including clinical, genetic and

  15. Protective role of melatonin in mitochondrial dysfunction and related disorders.

    Science.gov (United States)

    Paradies, Giuseppe; Paradies, Valeria; Ruggiero, Francesca M; Petrosillo, Giuseppe

    2015-06-01

    Mitochondria are the powerhouse of the eukaryotic cell through their use of oxidative phosphorylation to generate ATP. Mitochondrial dysfunction is considered an important contributing factor in a variety of physiopathological situations such as aging, heart ischemia/reperfusion injury, diabetes and several neurodegenerative and cardiovascular diseases, as well as in cell death. Increased formation of reactive oxygen species, altered respiratory chain complexes activity and opening of the mitochondrial permeability transition pore have been suggested as possible factors responsible for impaired mitochondrial function. Therefore, preventing mitochondrial dysfunction could be an effective therapeutic strategy against cellular degenerative processes. Cardiolipin is a unique phospholipid located at the level of inner mitochondrial membrane where it plays an important role in mitochondrial bioenergetics, as well as in cell death. Cardiolipin abnormalities have been associated with mitochondrial dysfunction in a variety of pathological conditions and aging. Melatonin, the major secretory product of the pineal gland, is a well-known antioxidant agent and thus an effective protector of mitochondrial bioenergetic function. Melatonin was reported to prevent mitochondrial dysfunction from oxidative damage by preserving cardiolipin integrity, and this may explain, at least in part, the beneficial effect of this compound in mitochondrial physiopathology. In this article, mechanisms through which melatonin exerts its protective role in mitochondrial dysfunction and related disorders are reviewed.

  16. Mitochondrial dysfunction in ataxia-telangiectasia.

    Science.gov (United States)

    Valentin-Vega, Yasmine A; Maclean, Kirsteen H; Tait-Mulder, Jacqueline; Milasta, Sandra; Steeves, Meredith; Dorsey, Frank C; Cleveland, John L; Green, Douglas R; Kastan, Michael B

    2012-02-09

    Ataxia-telangiectasia mutated (ATM) plays a central role in DNA damage responses, and its loss leads to development of T-cell malignancies. Here, we show that ATM loss also leads to intrinsic mitochondrial abnormalities in thymocytes, including elevated reactive oxygen species, increased aberrant mitochondria, high cellular respiratory capacity, and decreased mitophagy. A fraction of ATM protein is localized in mitochondria, and it is rapidly activated by mitochondrial dysfunction. Unexpectedly, allelic loss of the autophagy regulator Beclin-1 significantly delayed tumor development in ATM-null mice. This effect was not associated with rescue of DNA damage signaling but rather with a significant reversal of the mitochondrial abnormalities. These data support a model in which ATM plays direct roles in modulating mitochondrial homeostasis and suggest that mitochondrial dysfunction and associated increases in mitochondrial reactive oxygen species contribute to the cancer-prone phenotype observed in organisms lacking ATM. Thus, ataxia-telangiectasia should be considered, at least in part, as a mitochondrial disease.

  17. Iatrogenic causes of salivary gland dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Schubert, M.M.; Izutsu, K.T.

    1987-02-01

    Saliva is important for maintaining oral health and function. There are instances when medical therapy is intended to decrease salivary flow, such as during general anesthesia, but most instances of iatrogenic salivary gland dysfunction represent untoward or unavoidable side-effects. The clinical expression of the salivary dysfunction can range from very minor transient alteration in saliva flow to a total loss of salivary function. The most common forms of therapy that interfere with salivation are drug therapies, cancer therapies (radiation or chemotherapy), and surgical therapy. These therapies can affect salivation by a number of different mechanisms that include: disruption of autonomic nerve function related to salivation, interference with acinar or ductal cell functions related to salivation, cytotoxicity, indirect effects (vasoconstriction/dilation, fluid and electrolyte balance, etc.), and physical trauma to salivary glands and nerves. A wide variety of drugs is capable of increasing or decreasing salivary flow by mimicking autonomic nervous system actions or by directly acting on cellular processes necessary for salivation: drugs can also indirectly affect salivation by altering fluid and electrolyte balance or by affecting blood flow to the glands. Ionizing radiation can cause permanent damage to salivary glands, damage that is manifest as acinar cell destruction with subsequent atrophy and fibrosis of the glands. Cancer chemotherapy can cause changes in salivation, but the changes are usually much less severe and only transient. Finally, surgical and traumatic injuries interfere with salivation because of either disruption of gland innervation or gross physical damage (or removal) of glandular tissue (including ducts).

  18. Targeting synaptic dysfunction in Alzheimer's disease therapy.

    Science.gov (United States)

    Nisticò, Robert; Pignatelli, Marco; Piccinin, Sonia; Mercuri, Nicola B; Collingridge, Graham

    2012-12-01

    In the past years, major efforts have been made to understand the genetics and molecular pathogenesis of Alzheimer's disease (AD), which has been translated into extensive experimental approaches aimed at slowing down or halting disease progression. Advances in transgenic (Tg) technologies allowed the engineering of different mouse models of AD recapitulating a range of AD-like features. These Tg models provided excellent opportunities to analyze the bases for the temporal evolution of the disease. Several lines of evidence point to synaptic dysfunction as a cause of AD and that synapse loss is a pathological correlate associated with cognitive decline. Therefore, the phenotypic characterization of these animals has included electrophysiological studies to analyze hippocampal synaptic transmission and long-term potentiation, a widely recognized cellular model for learning and memory. Transgenic mice, along with non-Tg models derived mainly from exogenous application of Aβ, have also been useful experimental tools to test the various therapeutic approaches. As a result, numerous pharmacological interventions have been reported to attenuate synaptic dysfunction and improve behavior in the different AD models. To date, however, very few of these findings have resulted in target validation or successful translation into disease-modifying compounds in humans. Here, we will briefly review the synaptic alterations across the different animal models and we will recapitulate the pharmacological strategies aimed at rescuing hippocampal plasticity phenotypes. Finally, we will highlight intrinsic limitations in the use of experimental systems and related challenges in translating preclinical studies into human clinical trials.

  19. TOWARD THE QUESTION OF ISCHEMIC MYOCARDIAL DYSFUNCTION

    Directory of Open Access Journals (Sweden)

    V. V. Kalyuzhin

    2014-01-01

    Full Text Available The authors of the review have analyzed papers published on the problem of ischemic myocardial dysfunction. They begin with a definition of the term “ischemia” (derived from two Greek words: ischō, meaning to hold back, and haima, meaning blood - a condition at which the arterial blood flow is insufficient to provide enough oxygen to prevent intracellular respiration from shifting from the aerobic to the anaerobic form. The poor rate of ATP generation from this process causes a decrease in cellular ATP, a concomitant rise in ADP, and ultimately, to depression inotropic (systolic and lusitropic (diastolic function of the affected segments of the myocardium. But with such simplicity of basic concepts, the consequences of ischemia so diverse. Influence of an ischemia on myocardial function so unequally at different patients, which is almost impossible to find two identical cases (as in the case of fingerprints. It depends on the infinite variety of lesions of coronary arteries, reperfusion (time and completeness of restoration of blood flow and reactions of a myocardium which, apparently, has considerable flexibility in its response. Ischemic myocardial dysfunction includes a number of discrete states, such as acute left ventricular failure in angina, acute myocardial infarction, ischemic cardiomyopathy, stunning, hibernation, pre- and postconditioning. There are widely differing underlying pathophysiologic states. The possibility exists that several of these states can coexist.

  20. How do yeast sense mitochondrial dysfunction?

    Directory of Open Access Journals (Sweden)

    Dmitry A. Knorre

    2016-09-01

    Full Text Available Apart from energy transformation, mitochondria play important signaling roles. In yeast, mitochondrial signaling relies on several molecular cascades. However, it is not clear how a cell detects a particular mitochondrial malfunction. The problem is that there are many possible manifestations of mitochondrial dysfunction. For example, exposure to the specific antibiotics can either decrease (inhibitors of respiratory chain or increase (inhibitors of ATP-synthase mitochondrial transmembrane potential. Moreover, even in the absence of the dysfunctions, a cell needs feedback from mitochondria to coordinate mitochondrial biogenesis and/or removal by mitophagy during the division cycle. To cope with the complexity, only a limited set of compounds is monitored by yeast cells to estimate mitochondrial functionality. The known examples of such compounds are ATP, reactive oxygen species, intermediates of amino acids synthesis, short peptides, Fe-S clusters and heme, and also the precursor proteins which fail to be imported by mitochondria. On one hand, the levels of these molecules depend not only on mitochondria. On the other hand, these substances are recognized by the cytosolic sensors which transmit the signals to the nucleus leading to general, as opposed to mitochondria-specific, transcriptional response. Therefore, we argue that both ways of mitochondria-to-nucleus communication in yeast are mostly (if not completely unspecific, are mediated by the cytosolic signaling machinery and strongly depend on cellular metabolic state.

  1. CMVpp65 Vaccine Enhances the Antitumor Efficacy of Adoptively Transferred CD19-Redirected CMV-Specific T Cells.

    Science.gov (United States)

    Wang, Xiuli; Wong, ChingLam W; Urak, Ryan; Mardiros, Armen; Budde, Lihua E; Chang, Wen-Chung; Thomas, Sandra H; Brown, Christine E; La Rosa, Corinna; Diamond, Don J; Jensen, Michael C; Nakamura, Ryotaro; Zaia, John A; Forman, Stephen J

    2015-07-01

    T cells engineered with chimeric antigen receptors (CAR) recognizing CD19 can induce complete remission of B-cell malignancies in clinical trials; however, in some disease settings, CAR therapy confers only modest clinical benefit due to attenuated persistence of CAR T cells. The purpose of this study was to enhance persistence and augment the antitumor activity of adoptively transferred CD19CAR T cells by restimulating CAR(+) T cells through an endogenous cytomegalovirus (CMV)-specific T-cell receptor. CMV-specific T cells from CMV seropositive healthy donors were selected after stimulation with pp65 protein and transduced with clinical-grade lentivirus expressing the CD19R:CD28:ζ/EGFRt CAR. The resultant bispecific T cells, targeting CMV and CD19, were expanded via CD19 CAR-mediated signals using CD19-expressing cells. The bispecific T cells proliferated vigorously after engagement with either endogenous CMVpp65 T-cell receptors or engineered CD19 CARs, exhibiting specific cytolytic activity and IFNγ secretion. Upon adoptive transfer into immunodeficient mice bearing human lymphomas, the bispecific T cells exhibited proliferative response and enhanced antitumor activity following CMVpp65 peptide vaccine administration. We have redirected CMV-specific T cells to recognize and lyse tumor cells via CD19CARs, while maintaining their ability to proliferate in response to CMV antigen stimulation. These results illustrate the clinical applications of CMV vaccine to augment the antitumor activity of adoptively transferred CD19CAR T cells in patients with B-cell malignancies. ©2015 American Association for Cancer Research.

  2. [Female sexual dysfunction].

    Science.gov (United States)

    Luria, Mijal

    2009-09-01

    Female sexual problems are common, frequently overlooked and have a significant impact on the lives of women. Research in the last decade has brought to the understanding and recognition of a number of standpoints, mainly the broad range of normative function. In 2003, the American Urological Association Foundation convened an international committee of experts in the field of women's sexuality, to reconsider the existing definitions of women's sexual dysfunction. Based on the circular response cycle developed by Basson, the group emphasized motivations that might move a woman from being sexually "neutral" to making a decision to be sexual with her partner, as a normative alternative to the need for spontaneous sexual desire as the trigger for sexual behavior. Etiology may stem from medical as well as psychological factors, thus assessment must include a complete evaluation. Treatment includes psycho-education, improvement of interpersonal communication, cognitive behavioral treatment and elucidation and treatment of medical problems, if necessary. Several pharmacological treatments are under investigation, with modest results and uncertainties about their long term safety. This review presents the female sexual response as it is understood today and the current diagnostic and therapeutic understandings and directions.

  3. [Hypothalamic dysfunction in obesity].

    Science.gov (United States)

    van de Sande-Lee, Simone; Velloso, Licio A

    2012-08-01

    Obesity, defined as abnormal or excessive fat accumulation that may impair life quality, is one of the major public health problems worldwide. It results from an imbalance between food intake and energy expenditure. The control of energy balance in animals and humans is performed by the central nervous system (CNS) by means of neuroendocrine connections, in which circulating peripheral hormones, such as leptin and insulin, provide signals to specialized neurons of the hypothalamus reflecting body fat stores, and induce appropriate responses to maintain the stability of these stores. The majority of obesity cases are associated with central resistance to both leptin and insulin actions. In experimental animals, high-fat diets can induce an inflammatory process in the hypothalamus, which impairs leptin and insulin intracellular signaling pathways, and results in hyperphagia, decreased energy expenditure and, ultimately, obesity. Recent evidence obtained from neuroimaging studies and assessment of inflammatory markers in the cerebrospinal fluid of obese subjects suggests that similar alterations may be also present in humans. In this review, we briefly present the mechanisms involved with the loss of homeostatic control of energy balance in animal models of obesity, and the current evidence of hypothalamic dysfunction in obese humans.

  4. [Thyroid dysfunction during pregnancy].

    Science.gov (United States)

    Díez, Juan J; Iglesias, Pedro; Donnay, Sergio

    2015-10-21

    Recent clinical practice guidelines on thyroid dysfunction and pregnancy have changed health care provided to pregnant women, although their recommendations are under constant revision. Trimester- and area-specific reference ranges for serum thyroid-stimulating hormone are required for proper diagnosis of hypothyroidism and hyperthyroidism. There is no doubt on the need of therapy for overt hypothyroidism, while therapy for subclinical hypothyroidism is controversial. Further research is needed to settle adverse effects of isolated hypothyroxinemia and thyroid autoimmunity. Differentiation between hyperthyroidism due to Graves' disease and the usually self-limited gestational transient thyrotoxicosis is critical. It is also important to recognize risk factors for postpartum thyroiditis. Supplementation with iodine is recommended to maintain adequate iodine nutrition during pregnancy and avoid serious consequences in offspring. Controversy remains about universal screening for thyroid disease during pregnancy or case-finding in high-risk women. Opinions of some scientific societies and recent cost-benefit studies favour universal screening. Randomized controlled studies currently under development should reduce the uncertainties that still remain in this area. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  5. Multiple organ dysfunction syndrome.

    Science.gov (United States)

    Ramírez, Michelle

    2013-01-01

    Initially known as multiple system organ failure, the term multiple organ dysfunction syndrome (MODS) was first described in the 1960s in adults with bleeding, respiratory failure, and sepsis. It is defined as "the development of potentially reversible physiologic derangement involving two or more organ systems not involved in the disorder that resulted in ICU admission, and arising in the wake of a potentially life threatening physiologic insult."(3) There are many risk factors predisposing to MODS; however, the most common risk factors are shock due to any cause, sepsis, and tissue hypoperfusion. A dysregulated immune response, or immuneparalysis, in which the homeostasis between pro-inflammatory and anti-inflammatory reaction is lost is thought to be key in the development of MODS. The clinical course and evolution of MODS is dependent on a combination of acquired and genetic factors. There are several nonspecific therapies for the prevention and resolution of MODS, mostly care is supportive. Mortality from MODS in septic pediatric patients varies between 11% and 54%. © 2013 Published by Mosby, Inc.

  6. Markers of erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Kelvin P Davies

    2008-01-01

    Full Text Available With the development and marketing of oral pharmacotherapy that is both noninvasive and successful in treating erectile dysfunction (ED, the quest to identify markers of organic ED lost ground. Indeed, the multi-factorial nature of ED may have led many researchers to conclude that searching for a universal marker of ED was futile. However, the realization that ED is strongly correlated with the overall health of men, and may act as a predictor for the development of cardiovascular disease (CVD and diabetes, has stimulated interest in identifying genes that can distinguish organic ED. In addition, the potential ability to suggest to the patient that ED is reversible (i.e., psychogenic with a simple test would be of significance to both the physician and patient, as well as for reimbursement issues for therapy by insurance companies. Such a marker may also act as a non-subjective measure of the degree of ED and the efficacy of treatment. This review discusses the importance of identifying such markers and recent work identifying potential markers in human patients.

  7. DIASTOLIC DYSFUNCTION: A REVIEW

    Directory of Open Access Journals (Sweden)

    Rajat

    2016-01-01

    Full Text Available INTRODUCTION Diastolic heart failure is an underestimated pathology. Epidemiological and clinical studies suggest that HF with a preserved ejection fraction will become the more common form of HF which clinicians will encounter. Symptomatic treatment focuses on the reduction in pulmonary congestion and the improvement in LV filling. Specific treatment is actually lacking, but encouraging data are emerging concerning the use of renin–angiotensin–aldosterone axis blockers, nitric oxide donors, or, very recently, new agents specifically targeting actin–myosin cross-bridges. It is generally considered to have a somewhat better prognosis than systolic HF, but frequency of hospitalizations is comparable in systolic and diastolic HF. 1 Despite the recognition of its importance, definition and diagnostic criteria of diastolic dysfunction and diastolic HF remain controversial. AIMS AND OBJECTIVES This review focus of definition, diagnosis and management of diastolic heart failure with it prognosis. MATERIAL AND METHODS We have studied various guidelines, articles, reviews using given keywords, along with our experience in management of diastolic heart failure in 2015. The articles and the references were reviewed keeping in mind about the simplified management offered to the patient.

  8. Psychoanalysis: a dysfunctional family?

    Science.gov (United States)

    Grosskurth, P

    1998-01-01

    The discussion opens with an account of the author's mother's bizarre family in which a strong, charismatic grandmother maintained absolute control over her large family by encouraging a neurotic dependence in them through daily reports of their complaints. Getting interested in psychoanalysis in an effort to understand the dynamics of this dysfunctional family, the author, a biographer, turned to the study of Melanie Klein, becoming entranced by her ideas. Her research also revealed how Klein had discouraged her followers from developing ideas that diverged in any way from her own. Her portrait of the pioneer analyst provoked intense indignation. A similar pattern of absolute loyalty to his person and theories was to be found in Freud's Secret Committee, formed primarily as a means of getting rid of Jung who had been showing disturbing signs of independence. When Ferenczi and Rank began to pursue independent lines of enquiry in their work, they too were though to be undermining the foundations of classical psychoanalysis. Finally, the author concludes that though there have been sorry incidents in psychoanalysis, we should be mature enough to accept both the contributions of the early pioneers and the realizations that new ideas must be permitted to evolve.

  9. Endothelial dysfunction: EDCF revisited

    Institute of Scientific and Technical Information of China (English)

    PAUL M Vanhoutte

    2008-01-01

    Endothelial cells can initiate contraction (constriction) of the vascular smooth muscle cells that surround them. Such endothelium-dependent, acute increases in contractile tone can be due to the withdrawal of the production of nitric oxide, to the production of vasoconstrictor peptides (angiotensin Ⅱ, endothelin-1), to the formation of oxygen-derived free radicals(superoxide anions) and/or the release of vasoconstrictor metabolites of arachidonic acid. The latter have been termed endothelium-derived contracting factor (EDCF) as they can contribute to moment-to-moment changes in contractile activity of the underlying vascular smooth muscle cells. To judge from animal experiments, EDCF-mediated responses are exacerbated when the production of nitric oxide is impaired as well as by aging, spontaneous hypertension and diabetes. To judge from human studies, they contribute to the blunting of endothelium-dependent vasodilatations in aged subjects and essential hypertensive patients. Since EDCF causes vasoconstriction by activation of the TP-receptors on the vascular smooth muscle cells, selective antagonists at these receptors prevent endothelium-dependent contractions, and curtail the endothelial dysfunction in hypertension and diabetes.

  10. [Characteristics of postpartum thyroid dysfunction].

    Science.gov (United States)

    Argatska, A; Nonchev, B; Obretsova, M; Pehlivanov, B

    2015-01-01

    The risk factors and mechanisms for the development of postpartum thyroid dysfunction have been widely discussed. However data on patients suffered spontaneous or induced abortion during early pregnancy are scarce. To reveal the characteristics of thyroid dysfunction in women after an abortion in the first trimester of pregnancy. A total of 28 women (18 euthyroid, 10 with thyroid dysfunction), mean age 30.46 ± 1.01 years following abortion in the first trimester have been included in the study. Thyroid-stimulating hormone (TSH), free triiodthyronine (FT3), free thyroxine (FT4), thyreoglobulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb) were measured and ultrasound assessment of the thyroid was performed 3 and 9 months after the interruption of pregnancy. Hypothyroidism was found in 6 of the women with thyroid dysfunction and thyrotoxicosis--in 4. Clinical features of thyroid dysfunction were observed in 3 patients while in the remaining 7 cases, diagnosis was made on the basis of hormonal levels. Positive titers of thyroid autoantibodies were detected in the majority of the cases with functional disordes. In 6 patients thyroid dysfunction was transient and in 4 hormonal abnormalities persisted on by the 9th month after the abortion. The comparative analysis showed that the volume of the thyroid gland and the degree of hypoehogenicity were significantly higher in patients with thyroid dysfunction compared to euthyroid women. Thyroid dysfunction after abortion in the first trimester is mainly of autoimmune pathogenesis and its characteristics do not differ from those of postpartum thyroiditis. In the majority of patients these disorders are subclinical and may remain unrecognized. A close active follow up of patients at increased risk of functional thyroid disorders after an abortion is required in order to prevent morbidity and identify the cases developing permanent thyroid dysfunction.

  11. Sacroiliac joint dysfunction in athletes.

    Science.gov (United States)

    Brolinson, P Gunnar; Kozar, Albert J; Cibor, Greg

    2003-02-01

    The sacroiliac (SI) joint is a common source of low back pain in the general population. Because it is the link between the lower extremities and the spine, it sustains even higher loads during athletic activity, predisposing athletes to a greater probability of joint dysfunction and pain. The diagnosis and treatment of SI joint dysfunction remains controversial, due to complex anatomy and biomechanics, and a lack of universally accepted nomenclature and terminology, consistently reliable clinical tests and imaging studies, and consistently effective treatments. This article clarifies these issues by presenting a model of SI joint anatomy and function, a systematic approach to the diagnosis of dysfunction, and a comprehensive treatment plan.

  12. Strapping for temporomandibular joint dysfunction

    Directory of Open Access Journals (Sweden)

    Babu Abraham

    2008-01-01

    Full Text Available Temporomandibular joint dysfunction (TMJD is a common problem seen in many of the dental clinics. Management of this depends on an accurate diagnosis of the cause for the TMJD. Physical therapy and rehabilitation play a vital role in the management of these dysfunctions. Physical therapy is useful in treating post-traumatic stiffness of the TMJ while strapping of the TMJ for a dysfunction along with conventional physical therapy is of benefit in terms of reduction in click, decrease in pain, and an improvement in function.

  13. Strapping for temporomandibular joint dysfunction.

    Science.gov (United States)

    Babu, Abraham Samuel; John, Sandhya Mary; Unni, Amith

    2008-01-01

    Temporomandibular joint dysfunction (TMJD) is a common problem seen in many of the dental clinics. Management of this depends on an accurate diagnosis of the cause for the TMJD. Physical therapy and rehabilitation play a vital role in the management of these dysfunctions. Physical therapy is useful in treating post-traumatic stiffness of the TMJ while strapping of the TMJ for a dysfunction along with conventional physical therapy is of benefit in terms of reduction in click, decrease in pain, and an improvement in function.

  14. Architected Cellular Materials

    Science.gov (United States)

    Schaedler, Tobias A.; Carter, William B.

    2016-07-01

    Additive manufacturing enables fabrication of materials with intricate cellular architecture, whereby progress in 3D printing techniques is increasing the possible configurations of voids and solids ad infinitum. Examples are microlattices with graded porosity and truss structures optimized for specific loading conditions. The cellular architecture determines the mechanical properties and density of these materials and can influence a wide range of other properties, e.g., acoustic, thermal, and biological properties. By combining optimized cellular architectures with high-performance metals and ceramics, several lightweight materials that exhibit strength and stiffness previously unachievable at low densities were recently demonstrated. This review introduces the field of architected materials; summarizes the most common fabrication methods, with an emphasis on additive manufacturing; and discusses recent progress in the development of architected materials. The review also discusses important applications, including lightweight structures, energy absorption, metamaterials, thermal management, and bioscaffolds.

  15. Cellular structural biology.

    Science.gov (United States)

    Ito, Yutaka; Selenko, Philipp

    2010-10-01

    While we appreciate the complexity of the intracellular environment as a general property of every living organism, we collectively lack the appropriate tools to analyze protein structures in a cellular context. In-cell NMR spectroscopy represents a novel biophysical tool to investigate the conformational and functional characteristics of biomolecules at the atomic level inside live cells. Here, we review recent in-cell NMR developments and provide an outlook towards future applications in prokaryotic and eukaryotic cells. We hope to thereby emphasize the usefulness of in-cell NMR techniques for cellular studies of complex biological processes and for structural analyses in native environments. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. Cellular blue naevus

    Directory of Open Access Journals (Sweden)

    Mittal R

    2001-01-01

    Full Text Available A 31-year-old man had asymptomatic, stationary, 1.5X2 cm, shiny, smooth, dark blue nodule on dorsum of right hand since 12-14 years. In addition he had developed extensive eruption of yellow to orange papulonodular lesions on extensors of limbs and buttocks since one and half months. Investigations confirmed that yellow papules were xanthomatosis and he had associated diabetes mellitus and hyperlipidaemia. Biopsy of blue nodule confirmed the clinical diagnosis of cellular blue naevus. Cellular blue naevus is rare and its association with xanthomatosis and diabetes mellitus were interesting features of above patients which is being reported for its rarity.

  17. Cognitive dysfunction in spinocerebellar ataxias

    Directory of Open Access Journals (Sweden)

    Helio Afonso Ghizoni Teive

    Full Text Available Abstract Spinocerebellar ataxias (SCAs comprise a heterogeneous group of complex neurodegenerative diseases, characterized by the presence of progressive cerebellar ataxia, associated or otherwise with ophthalmoplegia, pyramidal signs, extrapyramidal features, pigmentary retinopathy, peripheral neuropathy, cognitive dysfunction and dementia. Objective: To verify the presence of cognitive dysfunction among the main types of SCA described in the literature. Methods: the review was conducted using the search system of the PUBMED and OMIM databases. Results: Cognitive dysfunction occurs in a considerable proportion of SCA, particularly in SCA 3, which is the most frequent form of SCA worldwide. Dementia has been described in several other types of SCA such as SCA 2, SCA 17 and DRPLA. Mental retardation is a specific clinical feature of SCA 13. Conclusions: The role of the cerebellum in cognitive functions has been observed in different types of SCAs which can manifest varying degrees of cognitive dysfunction, dementia and mental retardation.

  18. Executive Dysfunction in Geriatric Depression

    National Research Council Canada - National Science Library

    Lockwood, Kathryn A; Alexopoulos, George S; van Gorp, Wilfred G

    2002-01-01

    OBJECTIVE: The purpose of this study was to characterize the neuropsychological presentation of geriatric depression and to determine whether depression-related executive dysfunction is more pronounced during advanced age. METHOD...

  19. Thyroid dysfunction and pregnancy outcomes

    Science.gov (United States)

    Nazarpour, Sima; Ramezani Tehrani, Fahimeh; Simbar, Masoumeh; Azizi, Fereidoun

    2015-01-01

    Background: Pregnancy has a huge impact on the thyroid function in both healthy women and those that have thyroid dysfunction. The prevalence of thyroid dysfunction in pregnant women is relatively high. Objective: The objective of this review was to increase awareness and to provide a review on adverse effect of thyroid dysfunction including hyperthyroidism, hypothyroidism and thyroid autoimmune positivity on pregnancy outcomes. Materials and Methods: In this review, Medline, Embase and the Cochrane Library were searched with appropriate keywords for relevant English manuscript. We used a variety of studies, including randomized clinical trials, cohort (prospective and retrospective), case-control and case reports. Those studies on thyroid disorders among non-pregnant women and articles without adequate quality were excluded. Results: Overt hyperthyroidism and hypothyroidism has several adverse effects on pregnancy outcomes. Overt hyperthyroidism was associated with miscarriage, stillbirth, preterm delivery, intrauterine growth retardation, low birth weight, preeclampsia and fetal thyroid dysfunction. Overt hypothyroidism was associated with abortion, anemia, pregnancy-induced hypertension, preeclampsia, placental abruption, postpartum hemorrhage, premature birth, low birth weight, intrauterine fetal death, increased neonatal respiratory distress and infant neuro developmental dysfunction. However the adverse effect of subclinical hypothyroidism, and thyroid antibody positivity on pregnancy outcomes was not clear. While some studies demonstrated higher chance of placental abruption, preterm birth, miscarriage, gestational hypertension, fetal distress, severe preeclampsia and neonatal distress and diabetes in pregnant women with subclinical hypothyroidism or thyroid autoimmunity; the other ones have not reported these adverse effects. Conclusion: While the impacts of overt thyroid dysfunction on feto-maternal morbidities have been clearly identified and its long

  20. Thyroid dysfunction and pregnancy outcomes

    Directory of Open Access Journals (Sweden)

    Sima Nazarpour

    2015-07-01

    Full Text Available Background: Pregnancy has a huge impact on the thyroid function in both healthy women and those that have thyroid dysfunction. The prevalence of thyroid dysfunction in pregnant women is relatively high. Objective: The objective of this review was to increase awareness and to provide a review on adverse effect of thyroid dysfunction including hyperthyroidism, hypothyroidism and thyroid autoimmune positivity on pregnancy outcomes. Materials and Methods: In this review, Medline, Embase and the Cochrane Library were searched with appropriate keywords for relevant English manuscript. We used a variety of studies, including randomized clinical trials, cohort (prospective and retrospective, case-control and case reports. Those studies on thyroid disorders among non-pregnant women and articles without adequate quality were excluded. Results: Overt hyperthyroidism and hypothyroidism has several adverse effects on pregnancy outcomes. Overt hyperthyroidism was associated with miscarriage, stillbirth, preterm delivery, intrauterine growth retardation, low birth weight, preeclampsia and fetal thyroid dysfunction. Overt hypothyroidism was associated with abortion, anemia, pregnancy-induced hypertension, preeclampsia, placental abruption, postpartum hemorrhage, premature birth, low birth weight, intrauterine fetal death, increased neonatal respiratory distress and infant neuro developmental dysfunction. However the adverse effect of subclinical hypothyroidism, and thyroid antibody positivity on pregnancy outcomes was not clear. While some studies demonstrated higher chance of placental abruption, preterm birth, miscarriage, gestational hypertension, fetal distress, severe preeclampsia and neonatal distress and diabetes in pregnant women with subclinical hypothyroidism or thyroid autoimmunity; the other ones have not reported these adverse effects. Conclusion: While the impacts of overt thyroid dysfunction on feto-maternal morbidities have been clearly

  1. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

  2. Electromagnetic cellular interactions.

    Science.gov (United States)

    Cifra, Michal; Fields, Jeremy Z; Farhadi, Ashkan

    2011-05-01

    Chemical and electrical interaction within and between cells is well established. Just the opposite is true about cellular interactions via other physical fields. The most probable candidate for an other form of cellular interaction is the electromagnetic field. We review theories and experiments on how cells can generate and detect electromagnetic fields generally, and if the cell-generated electromagnetic field can mediate cellular interactions. We do not limit here ourselves to specialized electro-excitable cells. Rather we describe physical processes that are of a more general nature and probably present in almost every type of living cell. The spectral range included is broad; from kHz to the visible part of the electromagnetic spectrum. We show that there is a rather large number of theories on how cells can generate and detect electromagnetic fields and discuss experimental evidence on electromagnetic cellular interactions in the modern scientific literature. Although small, it is continuously accumulating. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Cellular rehabilitation of photobiomodulation

    Science.gov (United States)

    Liu, Timon Cheng-Yi; Yuan, Jian-Qin; Wang, Yan-Fang; Xu, Xiao-Yang; Liu, Song-Hao

    2007-05-01

    Homeostasis is a term that refers to constancy in a system. A cell in homeostasis normally functions. There are two kinds of processes in the internal environment and external environment of a cell, the pathogenic processes (PP) which disrupts the old homeostasis (OH), and the sanogenetic processes (SP) which restores OH or establishes a new homeostasis (NH). Photobiomodualtion (PBM), the cell-specific effects of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems, is a kind of modulation on PP or SP so that there is no PBM on a cell in homeostasis. There are two kinds of pathways mediating PBM, the membrane endogenetic chromophores mediating pathways which often act through reactive oxygen species, and membrane proteins mediating pathways which often enhance cellular SP so that it might be called cellular rehabilitation. The cellular rehabilitation of PBM will be discussed in this paper. It is concluded that PBM might modulate the disruption of cellular homeostasis induced by pathogenic factors such as toxin until OH has been restored or NH has been established, but can not change homeostatic processes from one to another one.

  4. Cellular Response to Irradiation

    Institute of Scientific and Technical Information of China (English)

    LIU Bo; YAN Shi-Wei

    2011-01-01

    To explore the nonlinear activities of the cellular signaling system composed of one transcriptional arm and one protein-interaction arm, we use an irradiation-response module to study the dynamics of stochastic interactions.It is shown that the oscillatory behavior could be described in a unified way when the radiation-derived signal and noise are incorporated.

  5. Mitochondrial dysfunction in cancer

    Directory of Open Access Journals (Sweden)

    Kinga Księżakowska-Łakoma

    2014-05-01

    Full Text Available Mitochondria are semi-autonomous organelles of eukaryotic cells. They perform crucial functions such as generating most of the cellular energy through the oxidative phosphorylation (OXPHOS system and some other metabolic processes. In addition, mitochondria are involved in regulation of cell death and reactive oxygen species (ROS generation. Also, mitochondria play important roles in carcinogenesis via altering energy metabolism, resistance to apoptosis, increase of production of ROS and mtDNA (mitochondrial genome changes. Studies have suggested that aerobic glycolysis is high in malignant tumors. Probably, it correlates with high glucose intake of cancerous tissues. This observation is contrary to Warburg’s theory that the main way of energy generation in cancer cells is non-oxidative glycolysis. Further studies have suggested that in tumor cells both oxidative phosphorylation and glycolysis were active at various rates. An increase of intracellular oxidative stress induces damage of cellular structure and somatic mutations. Further studies confirmed that permanent activity of oxidative stress and the influence of chronic inflammation damage the healthy neighboring epithelium and may lead to carcinogenesis. For instance, chronic inflammato­ry bowel disease could be related to high risk of colon adenocarcinoma. The data have shown a role of ROS generation, mtDNA or nDNA alterations and abnormal apoptotic machinery in endometrial cancer progress. Recent studies suggest that mtDNA mutations might play a potential role in endometrial cancer progress and indicate an increase of mitochondrial biogenesis in this cancer. The investigators suggested that MtCOI and MtND6 alteration has an influence on assembly of respiratory complexes in endometrial cancer. In many human cancers, there is a deregulation of the balance between cell growth and death. The tumor cells can avoid apoptosis through a loss of balance between anti- and pro

  6. Daylight Redirecting Window Films

    Science.gov (United States)

    2013-09-01

    a range of solar altitudes but their effectiveness has not been proven. Even more complex solutions involve roof mounted, sun tracking heliostats ...electricity rates and climate (range of 3-35 years). NPV was positive and SIR ranged from 1.4 to 2.58 Potential to reduce lighting energy use...and more cheerful. E. It was necessary to position an optically diffusing surface in front of microstructured film adhered to the glazing surface to

  7. Endothelial dysfunction in morbid obesity.

    Science.gov (United States)

    Mauricio, Maria Dolores; Aldasoro, Martin; Ortega, Joaquin; Vila, José María

    2013-01-01

    Morbid obesity is a chronic multifunctional disease characterized by an accumulation of fat. Epidemiological studies have shown that obesity is associated with cardiovascular and metabolic disorders. Endothelial dysfunction, as defined by an imbalance between relaxing and contractile endothelial factors, plays a central role in the pathogenesis of these cardiometabolic diseases. Diminished bioavailability of nitric oxide (NO) contributes to endothelial dysfunction and impairs endothelium- dependent vasodilatation. But this is not the only mechanism that drives to endothelial dysfunction. Obesity has been associated with a chronic inflammatory process, atherosclerosis, and oxidative stress. Moreover levels of asymmetrical dimethyl-L-arginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (eNOS), are elevated in obesity. On the other hand, increasing prostanoid-dependent vasoconstriction and decreasing vasodilator prostanoids also lead to endothelial dysfunction in obesity. Other mechanisms related to endothelin-1 (ET-1) or endothelium derived hyperpolarizing factor (EDHF) have been proposed. Bariatric surgery (BS) is a safe and effective means to achieve significant weight loss, but its use is limited only to patients with severe obesity including morbid obesity. BS also proved efficient in endothelial dysfunction reduction improving cardiovascular and metabolic comorbidities associated with morbid obesity such as diabetes, coronary artery disease, nonalcoholic fatty liver disease and cancer. This review will provide a brief overview of the mechanisms that link obesity with endothelial dysfunction, and how weight loss is a cornerstone treatment for cardiovascular comorbidities obesity-related. A better understanding of the mechanisms of obesity-induced endothelial dysfunction may help develop new therapeutic strategies to reduce cardiovascular morbidity and mortality.

  8. Molecular and Cellular Signaling

    CERN Document Server

    Beckerman, Martin

    2005-01-01

    A small number of signaling pathways, no more than a dozen or so, form a control layer that is responsible for all signaling in and between cells of the human body. The signaling proteins belonging to the control layer determine what kinds of cells are made during development and how they function during adult life. Malfunctions in the proteins belonging to the control layer are responsible for a host of human diseases ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. Molecular and Cellular Signaling provides an introduction to molecular and cellular signaling in biological systems with an emphasis on the underlying physical principles. The text is aimed at upper-level undergraduates, graduate students and individuals in medicine and pharmacology interested in broadening their understanding of how cells regulate and coordinate their core activities and how diseases ...

  9. Epidemiology and care of female sexual dysfunction

    OpenAIRE

    McCool, Megan Elizabeth

    2017-01-01

    Sexual dysfunction can have a negative impact on the well-being of an individual. For women, sexual dysfunction encompasses sexual interest / arousal disorder, female orgasmic disorder and genitopelvic pain / penetration disorder. Although sexual dysfunction has been identified as a significant public health problem, research on sexual dysfunction has primarily focused on men rather than women. Comprehensive epidemiological data on female sexual dysfunction and information on current levels o...

  10. Inflammation and cardiac dysfunction during sepsis, muscular dystrophy, and myocarditis

    Directory of Open Access Journals (Sweden)

    Ying Li

    2013-12-01

    Full Text Available Inflammation plays an important role in cardiac dysfunction under different situations. Acute systemic inflammation occurring in patients with severe burns, trauma, and inflammatory diseases causes cardiac dysfunction, which is one of the leading causes of mortality in these patients. Acute sepsis decreases cardiac contractility and impairs myocardial compliance. Chronic inflammation such as that occurring in Duchenne muscular dystropshy and myocarditis may cause adverse cardiac remodeling including myocyte hypertrophy and death, fibrosis, and altered myocyte function. However, the underlying cellular and molecular mechanisms for inflammatory cardiomyopathy are still controversial probably due to multiple factors involved. Potential mechanisms include the change in circulating blood volume; a direct inhibition of myocyte contractility by cytokines (tumor necrosis factor (TNF-a, interleukin (IL-1b; abnormal nitric oxide and reactive oxygen species (ROS signaling; mitochondrial dysfunction; abnormal excitation-contraction coupling; and reduced calcium sensitivity at the myofibrillar level and blunted b-adrenergic signaling. This review will summarize recent advances in diagnostic technology, mechanisms, and potential therapeutic strategies for inflammation-induced cardiac dysfunction.

  11. NASA's Asteroid Redirect Mission: A Robotic Boulder Capture Option for Science, Human Exploration, Resource Utilization, and Planetary Defense

    Science.gov (United States)

    Abell, P.; Nuth, J.; Mazanek, D.; Merrill, R.; Reeves, D.; Naasz, B.

    2014-01-01

    NASA is examining two options for the Asteroid Redirect Mission (ARM), which will return asteroid material to a Lunar Distant Retrograde Orbit (LDRO) using a robotic solar electric propulsion spacecraft, called the Asteroid Redirect Vehicle (ARV). Once the ARV places the asteroid material into the LDRO, a piloted mission will rendezvous and dock with the ARV. After docking, astronauts will conduct two extravehicular activities (EVAs) to inspect and sample the asteroid material before returning to Earth. One option involves capturing an entire small (4 - 10 m diameter) near-Earth asteroid (NEA) inside a large inflatable bag. However, NASA is also examining another option that entails retrieving a boulder (1 - 5 m) via robotic manipulators from the surface of a larger (100+ m) pre-characterized NEA. The Robotic Boulder Capture (RBC) option can leverage robotic mission data to help ensure success by targeting previously (or soon to be) well- characterized NEAs. For example, the data from the Japan Aerospace Exploration Agency's (JAXA) Hayabusa mission has been utilized to develop detailed mission designs that assess options and risks associated with proximity and surface operations. Hayabusa's target NEA, Itokawa, has been identified as a valid target and is known to possess hundreds of appropriately sized boulders on its surface. Further robotic characterization of additional NEAs (e.g., Bennu and 1999 JU3) by NASA's OSIRIS REx and JAXA's Hayabusa 2 missions is planned to begin in 2018. This ARM option reduces mission risk and provides increased benefits for science, human exploration, resource utilization, and planetary defense. Science: The RBC option is an extremely large sample-return mission with the prospect of bringing back many tons of well-characterized asteroid material to the Earth-Moon system. The candidate boulder from the target NEA can be selected based on inputs from the world-wide science community, ensuring that the most scientifically interesting

  12. Environment Aware Cellular Networks

    KAUST Repository

    Ghazzai, Hakim

    2015-02-01

    The unprecedented rise of mobile user demand over the years have led to an enormous growth of the energy consumption of wireless networks as well as the greenhouse gas emissions which are estimated currently to be around 70 million tons per year. This significant growth of energy consumption impels network companies to pay huge bills which represent around half of their operating expenditures. Therefore, many service providers, including mobile operators, are looking for new and modern green solutions to help reduce their expenses as well as the level of their CO2 emissions. Base stations are the most power greedy element in cellular networks: they drain around 80% of the total network energy consumption even during low traffic periods. Thus, there is a growing need to develop more energy-efficient techniques to enhance the green performance of future 4G/5G cellular networks. Due to the problem of traffic load fluctuations in cellular networks during different periods of the day and between different areas (shopping or business districts and residential areas), the base station sleeping strategy has been one of the main popular research topics in green communications. In this presentation, we present several practical green techniques that provide significant gains for mobile operators. Indeed, combined with the base station sleeping strategy, these techniques achieve not only a minimization of the fossil fuel consumption but also an enhancement of mobile operator profits. We start with an optimized cell planning method that considers varying spatial and temporal user densities. We then use the optimal transport theory in order to define the cell boundaries such that the network total transmit power is reduced. Afterwards, we exploit the features of the modern electrical grid, the smart grid, as a new tool of power management for cellular networks and we optimize the energy procurement from multiple energy retailers characterized by different prices and pollutant

  13. Mitochondrial Dysfunction: Different Routes to Alzheimer’s Disease Therapy

    Directory of Open Access Journals (Sweden)

    Pasquale Picone

    2014-01-01

    Full Text Available Mitochondria are dynamic ATP-generating organelle which contribute to many cellular functions including bioenergetics processes, intracellular calcium regulation, alteration of reduction-oxidation potential of cells, free radical scavenging, and activation of caspase mediated cell death. Mitochondrial functions can be negatively affected by amyloid β peptide (Aβ, an important component in Alzheimer’s disease (AD pathogenesis, and Aβ can interact with mitochondria and cause mitochondrial dysfunction. One of the most accepted hypotheses for AD onset implicates that mitochondrial dysfunction and oxidative stress are one of the primary events in the insurgence of the pathology. Here, we examine structural and functional mitochondrial changes in presence of Aβ. In particular we review data concerning Aβ import into mitochondrion and its involvement in mitochondrial oxidative stress, bioenergetics, biogenesis, trafficking, mitochondrial permeability transition pore (mPTP formation, and mitochondrial protein interaction. Moreover, the development of AD therapy targeting mitochondria is also discussed.

  14. An Endotoxin Tolerance Signature Predicts Sepsis and Organ Dysfunction at Initial Clinical Presentation

    Directory of Open Access Journals (Sweden)

    Olga M. Pena

    2014-11-01

    Interpretation: Our data support an updated model of sepsis pathogenesis in which endotoxin tolerance-mediated immune dysfunction (cellular reprogramming is present throughout the clinical course of disease and related to disease severity. Thus endotoxin tolerance might offer new insights guiding the development of new therapies and diagnostics for early sepsis.

  15. Obesity and pelvic floor dysfunction.

    Science.gov (United States)

    Ramalingam, Kalaivani; Monga, Ash

    2015-05-01

    Obesity is associated with a high prevalence of pelvic floor disorders. Patients with obesity present with a range of urinary, bowel and sexual dysfunction problems as well as uterovaginal prolapse. Urinary incontinence, faecal incontinence and sexual dysfunction are more prevalent in patients with obesity. Uterovaginal prolapse is also more common than in the non-obese population. Weight loss by surgical and non-surgical methods plays a major role in the improvement of these symptoms in such patients. The treatment of symptoms leads to an improvement in their quality of life. However, surgical treatment of these symptoms may be accompanied by an increased risk of complications in obese patients. A better understanding of the mechanism of obesity-associated pelvic floor dysfunction is essential.

  16. Vocal cord dysfunction in children.

    Science.gov (United States)

    Noyes, Blakeslee E; Kemp, James S

    2007-06-01

    Vocal cord dysfunction is characterised by paradoxical vocal cord adduction that occurs during inspiration, resulting in symptoms of dyspnoea, wheeze, chest or throat tightness and cough. Although the condition is well described in children and adults, confusion with asthma often triggers the use of an aggressive treatment regimen directed against asthma. The laryngoscopic demonstration of vocal cord adduction during inspiration has been considered the gold standard for the diagnosis of vocal cord dysfunction, but historical factors and pulmonary function findings may provide adequate clues to the correct diagnosis. Speech therapy, and in some cases psychological counselling, is often beneficial in this disorder. The natural course and prognosis of vocal cord dysfunction are still not well described in adults or children.

  17. Sexual dysfunctions in psoriatic patients

    Directory of Open Access Journals (Sweden)

    Maria Isabela Sarbu

    2015-04-01

    Full Text Available Psoriasis is a chronic, immune-mediated disorder with a worldwide occurrence characterized by well-defined infiltrated erythematous papules and plaques, covered by silvery white or yellowish scales. It is a physically, socially and emotionally invalidating disorder that affects 1-2% of the population. Sexual health is an important part of general health and sexual dysfunctions can negatively affect self-esteem, confidence, interpersonal relationships and the quality of life. Dermatology Life Quality Index (DLQI, Psoriasis Disability Index (PDI and the Impact of Psoriasis on Quality of Life (IPSO questionnaire are all questionnaires used to assess the quality of life of patients with psoriasis and each has one question regarding sexual dysfunction. Several scales were also designed to particularly assess sexual satisfaction in men and women. The aim of this paper is to perform an overview of the existing studies on sexual dysfunction in psoriatic patients.

  18. Hypercholesterolemia increases plasma saturated and n-6 fatty acids altering prostaglandin homeostasis and promotes endothelial dysfunction in rabbits.

    Science.gov (United States)

    Medina, M; Alberto, M R; Sierra, L; Van Nieuwenhove, C; Saad, S; Isla, M I; Jerez, S

    2014-07-01

    The present study evaluated the plasma fatty acid levels and the vascular prostaglandin (PG) release in a rabbit model of early hypercholesterolemia with endothelial dysfunction. Rabbits were fed either a control diet (CD) or a diet containing 1 % cholesterol (HD) for 5-6 weeks. The level of fatty acids was measured in plasma. The levels of PG and nitric oxide (NO) released from the aorta were also determined. Vascular morphology of the aorta was characterized by intima and media thickness measurements. The rabbits fed with HD had higher levels of arachidonic acid (ARA) and lower levels of oleic acid. The linoleic acid level was unchanged. PGI(2) and NO were diminished and PGF(2α) levels, the PGI(2)/TXA(2) ratio and the intima/media ratio were increased in rabbits fed with HD. In conclusion, feeding HD for a short period increased ARA plasma levels and unbalanced release of vasodilator/vasoconstrictor PG redirected the pathway to vasoconstrictor metabolite release. These lipid metabolism alterations in addition to the reduced NO levels and the moderate changes in the vascular morphology contributed to the endothelial dysfunction in this animal model. Therefore, the present findings support the importance of early correction or prevention of high cholesterol levels to disrupt the endothelial dysfunction process that leads to cardiovascular disease.

  19. Mitochondrial and Ubiquitin Proteasome System Dysfunction in Ageing and Disease: Two Sides of the Same Coin?

    Directory of Open Access Journals (Sweden)

    Jaime M. Ross

    2015-08-01

    Full Text Available Mitochondrial dysfunction and impairment of the ubiquitin proteasome system have been described as two hallmarks of the ageing process. Additionally, both systems have been implicated in the etiopathogenesis of many age-related diseases, particularly neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. Interestingly, these two systems are closely interconnected, with the ubiquitin proteasome system maintaining mitochondrial homeostasis by regulating organelle dynamics, the proteome, and mitophagy, and mitochondrial dysfunction impairing cellular protein homeostasis by oxidative damage. Here, we review the current literature and argue that the interplay of the two systems should be considered in order to better understand the cellular dysfunction observed in ageing and age-related diseases. Such an approach may provide valuable insights into molecular mechanisms underlying the ageing process, and further discovery of treatments to counteract ageing and its associated diseases. Furthermore, we provide a hypothetical model for the heterogeneity described among individuals during ageing.

  20. Thyroid Dysfunction and its Management

    Directory of Open Access Journals (Sweden)

    Supriya Agnihotri

    2016-09-01

    Full Text Available The focus of the present review article is on thyroid dysfunctions which can be hypo or hyper thyroidism. Along with the ongoing allopathic treatment options, one can go for the alternative therapies or natural cures. Various nutritional supplements including iodine, botanicals like guggul and many more play an effective role in the management of thyroid dysfunction apart from the pharmaceuticals like synthetic T3 and T4 hormones and procaine thyroid. Along with these, homeopathy and yoga are equally important. The discussion suggests and emphasizes the importance of improving the lifestyle and nutritional diet; and further providing spiritual support along with natural thyroid medication.

  1. Does stress induce bowel dysfunction?

    Science.gov (United States)

    Chang, Yu-Ming; El-Zaatari, Mohamad; Kao, John Y

    2014-08-01

    Psychological stress is known to induce somatic symptoms. Classically, many gut physiological responses to stress are mediated by the hypothalamus-pituitary-adrenal axis. There is, however, a growing body of evidence of stress-induced corticotrophin-releasing factor (CRF) release causing bowel dysfunction through multiple pathways, either through the HPA axis, the autonomic nervous systems, or directly on the bowel itself. In addition, recent findings of CRF influencing the composition of gut microbiota lend support for the use of probiotics, antibiotics, and other microbiota-altering agents as potential therapeutic measures in stress-induced bowel dysfunction.

  2. Cellular communication through light.

    Directory of Open Access Journals (Sweden)

    Daniel Fels

    Full Text Available Information transfer is a fundamental of life. A few studies have reported that cells use photons (from an endogenous source as information carriers. This study finds that cells can have an influence on other cells even when separated with a glass barrier, thereby disabling molecule diffusion through the cell-containing medium. As there is still very little known about the potential of photons for intercellular communication this study is designed to test for non-molecule-based triggering of two fundamental properties of life: cell division and energy uptake. The study was performed with a cellular organism, the ciliate Paramecium caudatum. Mutual exposure of cell populations occurred under conditions of darkness and separation with cuvettes (vials allowing photon but not molecule transfer. The cell populations were separated either with glass allowing photon transmission from 340 nm to longer waves, or quartz being transmittable from 150 nm, i.e. from UV-light to longer waves. Even through glass, the cells affected cell division and energy uptake in neighboring cell populations. Depending on the cuvette material and the number of cells involved, these effects were positive or negative. Also, while paired populations with lower growth rates grew uncorrelated, growth of the better growing populations was correlated. As there were significant differences when separating the populations with glass or quartz, it is suggested that the cell populations use two (or more frequencies for cellular information transfer, which influences at least energy uptake, cell division rate and growth correlation. Altogether the study strongly supports a cellular communication system, which is different from a molecule-receptor-based system and hints that photon-triggering is a fine tuning principle in cell chemistry.

  3. Redirection of client/server relationship of X Window system as a simple, low-cost, departmental picture archiving and communication system solution for nuclear medicine.

    Science.gov (United States)

    Datz, F L; Baune, D A; Christian, P E

    1994-08-01

    Picture archiving and communication systems (PACS) offer significant advantages over current film-management techniques. However, PACS are complex and expensive, factors that have limited their entry into the radiology and nuclear medicine communities. We present a simple, low-cost PACS solution that allows viewing of images from different computer systems by redirection of the X Window system. In this technique, multiple copies of the imaging software are remotely opened from generic UNIX workstations interfaced to the main computer system via Transmission Control Protocol/Internet Protocol over Ethernet. The X Window system that provides the windowing system for the main computer is redirected to the workstations' displays. With this technique, viewing and processing of images on a remote station is virtually identical to working at the main computer's console. The technique requires that the commercial imaging system's hardware, operating system, and imaging software support multiuser multitasking and the execution of multiple copies of its imaging software, and that they use X Windows as the graphical system. Advantages of the technique include low cost, ease of maintenance, ease of interconnecting different types of computers, the capacity to view images regardless of file format, and the capacity to both view and process images. The latter is a necessity for modalities such as nuclear medicine. A disadvantage of the technique is that the number of nodes that can be supported is limited.

  4. Immunology in the clinic review series; focus on cancer: double trouble for tumours: bi-functional and redirected T cells as effective cancer immunotherapies.

    Science.gov (United States)

    Marr, L A; Gilham, D E; Campbell, J D M; Fraser, A R

    2012-02-01

    Cancer is one of the most important pathological conditions facing mankind in the 21st century, and is likely to become the most important cause of death as improvements continue in health, diet and life expectancy. The immune response is responsible for controlling nascent cancer through immunosurveillance. If tumours escape this control, they can develop into clinical cancer. Although surgery and chemo- or radiotherapy have improved survival rates significantly, there is a drive to reharness immune responses to treat disease. As T cells are one of the key immune cells in controlling cancer, research is under way to enhance their function and improve tumour targeting. This can be achieved by transduction with tumour-specific T cell receptor (TCR) or chimaeric antigen receptors (CAR) to generate redirected T cells. Virus-specific cells can also be transduced with TCR or CAR to create bi-functional T cells with specificity for both virus and tumour. In this review we outline the development and optimization of redirected and bi-functional T cells, and outline the results from current clinical trials using these cells. From this we discuss the challenges involved in generating effective anti-tumour responses while avoiding concomitant damage to normal tissues and organs.

  5. On the rotation rates and axis ratios of the smallest known near-Earth asteroids---the archetypes of the Asteroid Redirect Mission targets

    CERN Document Server

    Hatch, Patrick

    2015-01-01

    NASA's Asteroid Redirect Mission (ARM) has been proposed with the aim to capture a small asteroid a few meters in size and redirect it into an orbit around the Moon. There it can be investigated at leisure by astronauts aboard an Orion or other spacecraft. The target for the mission has not yet been selected, and there are very few potential targets currently known. Though sufficiently small near-Earth asteroids (NEAs) are thought to be numerous, they are also difficult to detect and characterize with current observational facilities. Here we collect the most up-to-date information on the smallest known near-Earth asteroids to outline the properties of these small NEAs as currently understood, in order to examine what the eventual ARM target might be like. Observational biases certainly mean that our sample is not an ideal representation of the true population of small NEAs. However our sample is representative of the eventual target list for the ARM mission, which will be compiled under very similar observa...

  6. 虚拟机跨域迁移中的网络重定向模型%Network Redirection Model in Cross-domain Migration of Virtual Machine

    Institute of Scientific and Technical Information of China (English)

    刘进军; 徐志红; 赵生慧

    2012-01-01

    The network redirection model is proposed and cross-domain migration of Virtual Machine(VM) is achieved Local Area Network (LAN) or in Wide Area Network(WAN). With Address Resolution Protocol(ARP) synchronization, the unidirectional IP tunnel is quickly established between the source node and the migrated VM. The data is redirected to the VM. With dual IP stacks, all new requests are responded by the new IP and old sessions are maintained. Experimental results show that the model can effectively reduce the deployment time, optimize forwarding path, ' lower latency, achieve transparent cross-domain migration.%提出一个网络重定向模型,实现局域网或广域网环境下的虚拟机跨域迁移.利用地址解析协议同步策略,在源节点和迁移后的虚拟机之间快速建立单向IP隧道,将数据重定向至虚拟机.采用IP双栈方式,使虚拟机在保持原有会话的同时,通过新增IP响应所有新的连接请求.实验结果表明,该模型能减少部署时间,优化数据转发路径,降低响应延迟,实现跨域迁移.

  7. Failover in cellular automata

    CERN Document Server

    Kumar, Shailesh

    2010-01-01

    A cellular automata (CA) configuration is constructed that exhibits emergent failover. The configuration is based on standard Game of Life rules. Gliders and glider-guns form the core messaging structure in the configuration. The blinker is represented as the basic computational unit, and it is shown how it can be recreated in case of a failure. Stateless failover using primary-backup mechanism is demonstrated. The details of the CA components used in the configuration and its working are described, and a simulation of the complete configuration is also presented.

  8. Review of cellular mechanotransduction

    Science.gov (United States)

    Wang, Ning

    2017-06-01

    Living cells and tissues experience physical forces and chemical stimuli in the human body. The process of converting mechanical forces into biochemical activities and gene expression is mechanochemical transduction or mechanotransduction. Significant advances have been made in understanding mechanotransduction at the cellular and molecular levels over the last two decades. However, major challenges remain in elucidating how a living cell integrates signals from mechanotransduction with chemical signals to regulate gene expression and to generate coherent biological responses in living tissues in physiological conditions and diseases.

  9. Cellular automata: structures

    OpenAIRE

    Ollinger, Nicolas

    2002-01-01

    Jury : François Blanchard (Rapporteur), Marianne Delorme (Directeur), Jarkko Kari (Président), Jacques Mazoyer (Directeur), Dominique Perrin, Géraud Sénizergues (Rapporteur); Cellular automata provide a uniform framework to study an important problem of "complex systems" theory: how and why do system with a easily understandable -- local -- microscopic behavior can generate a more complicated -- global -- macroscopic behavior? Since its introduction in the 40s, a lot of work has been done to ...

  10. Mitochondrial dysfunction in DDR-related cancer predisposition syndromes.

    Science.gov (United States)

    Lyakhovich, Alex; Graifer, Dmitry; Stefanovie, Barbora; Krejci, Lumir

    2016-04-01

    Given the key role of mitochondria in various cellular events, it is not surprising that mitochondrial dysfunction (MDF) is seen in many pathological conditions, in particular cancer. The mechanisms defining MDF are not clearly understood and may involve genetic defects, misbalance of reactive oxygen species (ROS), impaired autophagy (mitophagy), acquired mutations in mitochondrial or nuclear DNA and inability of cells to cope with the consequences. The importance of MDF arises from its detection in the syndromes with defective DNA damage response (DDR) and cancer predisposition. Here, we will focus on the dual role of these syndromes in cancer predisposition and MDF with specific emphasis on impaired autophagy.

  11. Mitochondrial Dysfunction and Immune Cell Metabolism in Sepsis

    Science.gov (United States)

    2017-01-01

    Sepsis is a life threatening condition mediated by systemic infection, but also triggered by hemorrhage and trauma. These are significant causes of organ injury implicated in morbidity and mortality, as well as post-sepsis complications associated with dysfunction of innate and adaptive immunity. The role of cellular bioenergetics and loss of metabolic plasticity of immune cells is increasingly emerging in the pathogenesis of sepsis. This review describes mitochondrial biology and metabolic alterations of immune cells due to sepsis, as well as indicates plausible therapeutic opportunities.

  12. Role of Lipid Peroxidation-Derived α, β-Unsaturated Aldehydes in Vascular Dysfunction

    Directory of Open Access Journals (Sweden)

    Seung Eun Lee

    2013-01-01

    Full Text Available Vascular diseases are the most prominent cause of death, and inflammation and vascular dysfunction are key initiators of the pathophysiology of vascular disease. Lipid peroxidation products, such as acrolein and other α, β-unsaturated aldehydes, have been implicated as mediators of inflammation and vascular dysfunction. α, β-Unsaturated aldehydes are toxic because of their high reactivity with nucleophiles and their ability to form protein and DNA adducts without prior metabolic activation. This strong reactivity leads to electrophilic stress that disrupts normal cellular function. Furthermore, α, β-unsaturated aldehydes are reported to cause endothelial dysfunction by induction of oxidative stress, redox-sensitive mechanisms, and inflammatory changes such as induction of cyclooxygenase-2 and cytokines. This review provides an overview of the effects of lipid peroxidation products, α, β-unsaturated aldehydes, on inflammation and vascular dysfunction.

  13. Sepsis-induced brain dysfunction.

    Science.gov (United States)

    Adam, Nicolas; Kandelman, Stanislas; Mantz, Jean; Chrétien, Fabrice; Sharshar, Tarek

    2013-02-01

    Systemic infection is often revealed by or associated with brain dysfunction, which is characterized by alteration of consciousness, ranging from delirium to coma, seizure or focal neurological signs. Its pathophysiology involves an ischemic process, secondary to impairment of cerebral perfusion and its determinants and a neuroinflammatory process that includes endothelial activation, alteration of the blood-brain barrier and passage of neurotoxic mediators. Microcirculatory dysfunction is common to these two processes. This brain dysfunction is associated with increased mortality, morbidity and long-term cognitive disability. Its diagnosis relies essentially on neurological examination that can lead to specific investigations, including electrophysiological testing or neuroimaging. In practice, cerebrospinal fluid analysis is indisputably required when meningitis is suspected. Hepatic, uremic or respiratory encephalopathy, metabolic disturbances, drug overdose, sedative or opioid withdrawal, alcohol withdrawal delirium or Wernicke's encephalopathy are the main differential diagnoses. Currently, treatment consists mainly of controlling sepsis. The effects of insulin therapy and steroids need to be assessed. Various drugs acting on sepsis-induced blood-brain barrier dysfunction, brain oxidative stress and inflammation have been tested in septic animals but not yet in patients.

  14. Sweating dysfunction in Parkinson's disease

    NARCIS (Netherlands)

    Swinn, L; Schrag, A; Viswanathan, R; Lees, A; Quinn, N; Bloem, Bastiaan R.

    2003-01-01

    We sought to determine the prevalence and nature of sweating disturbances in patients with Parkinson's disease (PD), and investigated their correlation with other clinical features and with Quality of Life (QoL) measures. A questionnaire on symptoms and consequences of sweating dysfunction was compl

  15. Ageing with neurogenic bowel dysfunction

    DEFF Research Database (Denmark)

    Nielsen, S D; Faaborg, Pia Møller; Finnerup, Nanna Brix

    2017-01-01

    The aim of this longitudinal study with postal survey was to describe changes in the patterns of neurogenic bowel dysfunction and bowel management in a population of people with spinal cord injury (SCI) followed for two decades. In 1996, a validated questionnaire on bowel function was sent to the...

  16. Swallowing dysfunction in cancer patients

    NARCIS (Netherlands)

    Raber-Durlacher, J.E.; Brennan, M.T.; Verdonck- de Leeuw, I.M.; Gibson, R.J.; Eilers, J.G.; Waltimo, T.; Bots, C.P.; Michelet, M.; Sollecito, T.P.; Rouleau, T.S.; Sewnaik, A.; Bensadoun, R.J.; Fliedner, M.C.; Silverman, S.; Spijkervet, F.K.L.

    2012-01-01

    Purpose Dysphagia (swallowing dysfunction) is a debilitating, depressing, and potentially life-threatening complication in cancer patients that is likely underreported. The present paper is aimed to review relevant dysphagia literature between 1990 and 2010 with a focus on assessment tools, prevalen

  17. Swallowing dysfunction in cancer patients

    NARCIS (Netherlands)

    Raber-Durlacher, Judith E.; Brennan, Mike T.; Leeuw, Irma M. Verdonck-de; Gibson, Rachel J.; Eilers, June G.; Waltimo, Tuomas; Bots, Casper P.; Michelet, Marisol; Sollecito, Thomas P.; Rouleau, Tanya S.; Sewnaik, Aniel; Bensadoun, Rene-Jean; Fliedner, Monica C.; Silverman, Sol; Spijkervet, Fred K. L.

    Purpose Dysphagia (swallowing dysfunction) is a debilitating, depressing, and potentially life-threatening complication in cancer patients that is likely underreported. The present paper is aimed to review relevant dysphagia literature between 1990 and 2010 with a focus on assessment tools,

  18. Mitochondrial dysfunction and Huntington disease

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Huntington disease (HD) is a chronic autosomal-dominant neurodegenerative disease. The gene coding Huntingtin has been identified, but the pathogenic mechanisms of the disease are still not fully understood. This paper reviews the involvement of mitochondrial dysfunction in pathogenesis of HD.

  19. Cognitive dysfunction in senior pets.

    Science.gov (United States)

    Crowell-Davis, Sharon L

    2008-02-01

    Aging pets can experience declines in memory, learning, perception, and awareness. These pets may be disoriented, forget previously learned behaviors, develop new fears and anxiety, or change their interactions with people. When these changes are due to cognitive dysfunction, behavioral and environmental adjustments along with medical therapy can slow the progression and keep pets active longer.

  20. Assessing mitochondrial dysfunction in cells.

    Science.gov (United States)

    Brand, Martin D; Nicholls, David G

    2011-04-15

    Assessing mitochondrial dysfunction requires definition of the dysfunction to be investigated. Usually, it is the ability of the mitochondria to make ATP appropriately in response to energy demands. Where other functions are of interest, tailored solutions are required. Dysfunction can be assessed in isolated mitochondria, in cells or in vivo, with different balances between precise experimental control and physiological relevance. There are many methods to measure mitochondrial function and dysfunction in these systems. Generally, measurements of fluxes give more information about the ability to make ATP than do measurements of intermediates and potentials. For isolated mitochondria, the best assay is mitochondrial respiratory control: the increase in respiration rate in response to ADP. For intact cells, the best assay is the equivalent measurement of cell respiratory control, which reports the rate of ATP production, the proton leak rate, the coupling efficiency, the maximum respiratory rate, the respiratory control ratio and the spare respiratory capacity. Measurements of membrane potential provide useful additional information. Measurement of both respiration and potential during appropriate titrations enables the identification of the primary sites of effectors and the distribution of control, allowing deeper quantitative analyses. Many other measurements in current use can be more problematic, as discussed in the present review.

  1. Subclinical Thyroid Dysfunction and Fracture Risk

    DEFF Research Database (Denmark)

    Blum, Manuel R; Bauer, Douglas C; Collet, Tinh-Hai

    2015-01-01

    IMPORTANCE: Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. OBJECTIVE: To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. DATA SOURCES AND STUDY SELECTION: The databases of MEDLI...

  2. Autonomic dysfunction in cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

    Dümcke, Christine Winkler; Møller, Søren

    2008-01-01

    Liver cirrhosis and portal hypertension are frequently associated with signs of circulatory dysfunction and peripheral polyneuropathy, which includes defects of the autonomic nervous system. Autonomic dysfunction, which is seen in both alcoholic and non-alcoholic liver cirrhosis and increases...

  3. Endothelial dysfunction: the early predictor of atherosclerosis.

    Science.gov (United States)

    Mudau, Mashudu; Genis, Amanda; Lochner, Amanda; Strijdom, Hans

    2012-05-01

    Since the discovery in the 1980s that nitric oxide (NO) is in fact the elusive endothelium-derived relaxing factor, it has become evident that NO is not only a major cardiovascular signalling molecule, but that changes in its bioavailability are crucial in determining whether atherosclerosis will develop or not. Sustained high levels of harmful circulating stimuli associated with cardiovascular risk factors such as diabetes mellitus elicit responses in endothelial cells that appear sequentially, namely endothelial cell activation and endothelial dysfunction (ED). ED, characterised by reduced NO bioavailability, is now recognised by many as an early, reversible precursor of atherosclerosis. The pathogenesis of ED is multifactorial; however, oxidative stress appears to be the common underlying cellular mechanism in the ensuing loss of vaso-active, inflammatory, haemostatic and redox homeostasis in the body's vascular system. The role of ED as a pathophysiological link between early endothelial cell changes associated with cardiovascular risk factors and the development of ischaemic heart disease is of importance to basic scientists and clinicians alike.

  4. Engineering Cellular Metabolism.

    Science.gov (United States)

    Nielsen, Jens; Keasling, Jay D

    2016-03-10

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds, and pharmaceuticals. However, making cells into efficient factories is challenging because cells have evolved robust metabolic networks with hard-wired, tightly regulated lines of communication between molecular pathways that resist efforts to divert resources. Here, we will review the current status and challenges of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation.

  5. Cellular image classification

    CERN Document Server

    Xu, Xiang; Lin, Feng

    2017-01-01

    This book introduces new techniques for cellular image feature extraction, pattern recognition and classification. The authors use the antinuclear antibodies (ANAs) in patient serum as the subjects and the Indirect Immunofluorescence (IIF) technique as the imaging protocol to illustrate the applications of the described methods. Throughout the book, the authors provide evaluations for the proposed methods on two publicly available human epithelial (HEp-2) cell datasets: ICPR2012 dataset from the ICPR'12 HEp-2 cell classification contest and ICIP2013 training dataset from the ICIP'13 Competition on cells classification by fluorescent image analysis. First, the reading of imaging results is significantly influenced by one’s qualification and reading systems, causing high intra- and inter-laboratory variance. The authors present a low-order LP21 fiber mode for optical single cell manipulation and imaging staining patterns of HEp-2 cells. A focused four-lobed mode distribution is stable and effective in optical...

  6. Multiuser Cellular Network

    CERN Document Server

    Bao, Yi; Chen, Ming

    2011-01-01

    Modern radio communication is faced with a problem about how to distribute restricted frequency to users in a certain space. Since our task is to minimize the number of repeaters, a natural idea is enlarging coverage area. However, coverage has restrictions. First, service area has to be divided economically as repeater's coverage is limited. In this paper, our fundamental method is to adopt seamless cellular network division. Second, underlying physics content in frequency distribution problem is interference between two close frequencies. Consequently, we choose a proper frequency width of 0.1MHz and a relevantly reliable setting to apply one frequency several times. We make a few general assumptions to simplify real situation. For instance, immobile users yield to homogenous distribution; repeaters can receive and transmit information in any given frequency in duplex operation; coverage is mainly decided by antenna height. Two models are built up to solve 1000 users and 10000 users situations respectively....

  7. Resveratrol Attenuates Copper-Induced Senescence by Improving Cellular Proteostasis

    Science.gov (United States)

    2017-01-01

    Copper sulfate-induced premature senescence (CuSO4-SIPS) consistently mimetized molecular mechanisms of replicative senescence, particularly at the endoplasmic reticulum proteostasis level. In fact, disruption of protein homeostasis has been associated to age-related cell/tissue dysfunction and human disorders susceptibility. Resveratrol is a polyphenolic compound with proved antiaging properties under particular conditions. In this setting, we aimed to evaluate resveratrol ability to attenuate cellular senescence induction and to unravel related molecular mechanisms. Using CuSO4-SIPS WI-38 fibroblasts, resveratrol is shown to attenuate typical senescence alterations on cell morphology, senescence-associated beta-galactosidase activity, and cell proliferation. The mechanisms implicated in this antisenescence effect seem to be independent of senescence-associated genes and proteins regulation but are reliant on cellular proteostasis improvement. In fact, resveratrol supplementation restores copper-induced increased protein content, attenuates BiP level, and reduces carbonylated and polyubiquitinated proteins by autophagy induction. Our data provide compelling evidence for the beneficial effects of resveratrol by mitigating CuSO4-SIPS stressful consequences by the modulation of protein quality control systems. These findings highlight the importance of a balanced cellular proteostasis and add further knowledge on molecular mechanisms mediating resveratrol antisenescence effects. Moreover, they contribute to identifying specific molecular targets whose modulation will prevent age-associated cell dysfunction and improve human healthspan. PMID:28280523

  8. Resveratrol Attenuates Copper-Induced Senescence by Improving Cellular Proteostasis

    Directory of Open Access Journals (Sweden)

    Liliana Matos

    2017-01-01

    Full Text Available Copper sulfate-induced premature senescence (CuSO4-SIPS consistently mimetized molecular mechanisms of replicative senescence, particularly at the endoplasmic reticulum proteostasis level. In fact, disruption of protein homeostasis has been associated to age-related cell/tissue dysfunction and human disorders susceptibility. Resveratrol is a polyphenolic compound with proved antiaging properties under particular conditions. In this setting, we aimed to evaluate resveratrol ability to attenuate cellular senescence induction and to unravel related molecular mechanisms. Using CuSO4-SIPS WI-38 fibroblasts, resveratrol is shown to attenuate typical senescence alterations on cell morphology, senescence-associated beta-galactosidase activity, and cell proliferation. The mechanisms implicated in this antisenescence effect seem to be independent of senescence-associated genes and proteins regulation but are reliant on cellular proteostasis improvement. In fact, resveratrol supplementation restores copper-induced increased protein content, attenuates BiP level, and reduces carbonylated and polyubiquitinated proteins by autophagy induction. Our data provide compelling evidence for the beneficial effects of resveratrol by mitigating CuSO4-SIPS stressful consequences by the modulation of protein quality control systems. These findings highlight the importance of a balanced cellular proteostasis and add further knowledge on molecular mechanisms mediating resveratrol antisenescence effects. Moreover, they contribute to identifying specific molecular targets whose modulation will prevent age-associated cell dysfunction and improve human healthspan.

  9. COGNITIVE DYSFUNCTIONS IN DIABETIC POLYNEUROPATHY

    Directory of Open Access Journals (Sweden)

    Mirena Valkova

    2011-12-01

    Full Text Available Introduction: The objective of our study was to examine cognitive status, short – term memory, delayed recall and the retention of visual information in diabetics with polyneuropathy and to establish the impacts of some risk factors on cognitive performance.Contingent and methods: We assessed 47 diabetic patients with polyneuropathy, using the Mini Mental State Examination, 10 words test, the Benton visual retention test and the Hamilton scale.Results: Global cognitive dysfunction, decline in verbal memory and visual retention and tendency for depressive mood were observed. We found statistically significant interaction of ageing, sex, severity of pain, duration and late onset of diabetes mellitus (DM on cognitive functioning. Therapy association on cognition was not found.Conclusions: Our study confirms the hypothesis of global cognitive dysfunction, associated with diabetic polyneuropathy. The interactions of sex and pain severity require further study. We arise a hypothesis of asymmetrical brain injury in diabetics.

  10. Dysfunctional Reward Processing in Depression

    Science.gov (United States)

    Admon, Roee; Pizzagalli, Diego A.

    2015-01-01

    Anhedonia - diminished pleasure and/or decreased reactivity to pleasurable stimuli - is a core feature of depression that frequently persists after treatment. As a result, extensive effort has been directed towards characterizing the psychological and biological processes that mediate dysfunctional reward processing in depression. Reward processing can be parsed into sub-components that include motivation, reinforcement learning, and hedonic capacity, which, according to preclinical and neuroimaging evidence, involve partially dissociable brain systems. In line with this, recent findings indicate that behavioral impairments and neural abnormalities in depression vary across distinct reward-related constructs. Ultimately, improved understanding of precise reward-related dysfunctions in depression promises to improve diagnostic and therapeutic efforts in depression. PMID:26258159

  11. [Sexual dysfunction following pelvic surgery].

    Science.gov (United States)

    Hojo, K

    1997-11-01

    In male, sexual dysfunction was a common complication that occurred after radical pelvic surgery: radical protectomy, radical cysto-, prostatectomy. Upon the recent pelvic neuroanatomical findings and preservation of these nerves, it is now possible to perform successful cancer operation on the rectum, prostate or bladder with preservation of sexual function in the group of early cancer patients. Depending on the location and severity of these nerve injury, this could result in temporary or permanent erectile and ejaculation dysfunction. In female, the total hysterectomy for cervical cancer sacrifices or injuries the faculty of pregnancy or sexual intercourse. The oophorectomies causes a deficiency of female hormones. But recently the numbers of patients with a small or early stages cancer of uterine or ovary are increasing and we have become to be able to save the functions of these organs in many patients well with minimum local excision or partial resection of them.

  12. Neck pain causes respiratory dysfunction.

    Science.gov (United States)

    Kapreli, Eleni; Vourazanis, Evangelos; Strimpakos, Nikolaos

    2008-01-01

    This paper describes a presumptive mechanism for the development of changes in respiratory function due to chronic neck pain. The patient with neck pain presents a number of factors that could constitute a predisposition of leading to a respiratory dysfunction: (a) the decreased strength of deep neck flexors and extensors, (b) the hyperactivity and increased fatigability of superficial neck flexors, (c) the limitation of range of motion, (d) the decrease in proprioception and disturbances in neuromuscular control, (e) the existence of pain and (f) the psychosocial influence of dysfunction. The possible connection of neck pain and respiratory function could have a great impact on various clinical aspects notably patient assessment, rehabilitation and pharmacological prescription.

  13. Drug-induced sexual dysfunction.

    Science.gov (United States)

    Aldridge, S A

    1982-01-01

    Commonly used drugs that may cause sexual dysfunction are reviewed. The anatomy and physiology of the normal sexual response are reviewed. The influence of drugs on neurogenic, hormonal, and vascular mechanisms may result in diminished libido, impotence, ejaculatory and orgasmic difficulties, inhibited vaginal lubrication, menstrual irregularities, and gynecomastia in men or painful breast enlargement in women. Parasympatholytic agents, which interfere with cholinergic transmission, may affect erectile potency, while adrenergic inhibiting agents may interfere with ejaculatory control. Central nervous system depressants or sedating drugs, drugs producing hyperprolactinemia, and antiandrogenic drugs also may affect the normal sexual response. Drugs such as antihypertensive and antipsychotic agents may induce sexual dysfunction that can result in patient noncompliance. Usually, drug-induced side effects are reversible with discontinuation of the offending agent.

  14. Early detection of tubular dysfunction.

    Science.gov (United States)

    Piscator, M

    1991-11-01

    The determination of low-molecular-weight proteins in urine as a tool for early detection of damage to the proximal tubules is briefly discussed. Beta 2-microglobulin, retinol-binding protein and alpha 1-microglobulin are at present the most widely used markers for tubular dysfunction. The determination of beta 2-microglobulin has earlier been the method of choice, but due to its instability at low pH there are certain disadvantages. Available data indicate that alpha 1-microglobulin may replace beta 2-microglobulin for screening purposes. The low-molecular-weight proteins are at present the best markers for early detection of tubular dysfunction; other constituents are not as well suited for this, even if the determination of urine enzymes has its supporters.

  15. Insulin dysfunction and Tau pathology

    Directory of Open Access Journals (Sweden)

    Noura eEl Khoury

    2014-02-01

    Full Text Available The neuropathological hallmarks of Alzheimer's disease (AD include senile plaques of β-amyloid (Aβ peptides (a cleavage product of the Amyloid Precursor Protein, or APP and neurofibrillary tangles (NFT of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF. NFT pathology is important since it correlates with the degree of cognitive impairment in AD.Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99% is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease.Insulin dysfunction, manifested by diabetes mellitus (DM might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM and type 2 diabetes (T2DM are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment.Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting on Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia.

  16. Thyroid Dysfunction from Antineoplastic Agents

    Science.gov (United States)

    Larsen, P. Reed; Marqusee, Ellen

    2011-01-01

    Unlike cytotoxic agents that indiscriminately affect rapidly dividing cells, newer antineoplastic agents such as targeted therapies and immunotherapies are associated with thyroid dysfunction. These include tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-α, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide. Primary hypothyroidism is the most common side effect, although thyrotoxicosis and effects on thyroid-stimulating hormone secretion and thyroid hormone metabolism have also been described. Most agents cause thyroid dysfunction in 20%–50% of patients, although some have even higher rates. Despite this, physicians may overlook drug-induced thyroid dysfunction because of the complexity of the clinical picture in the cancer patient. Symptoms of hypothyroidism, such as fatigue, weakness, depression, memory loss, cold intolerance, and cardiovascular effects, may be incorrectly attributed to the primary disease or to the antineoplastic agent. Underdiagnosis of thyroid dysfunction can have important consequences for cancer patient management. At a minimum, the symptoms will adversely affect the patient’s quality of life. Alternatively, such symptoms can lead to dose reductions of potentially life-saving therapies. Hypothyroidism can also alter the kinetics and clearance of medications, which may lead to undesirable side effects. Thyrotoxicosis can be mistaken for sepsis or a nonendocrinologic drug side effect. In some patients, thyroid disease may indicate a higher likelihood of tumor response to the agent. Both hypothyroidism and thyrotoxicosis are easily diagnosed with inexpensive and specific tests. In many patients, particularly those with hypothyroidism, the treatment is straightforward. We therefore recommend routine testing for thyroid abnormalities in patients receiving these antineoplastic agents. PMID:22010182

  17. Thyroid dysfunction from antineoplastic agents.

    Science.gov (United States)

    Hamnvik, Ole-Petter Riksfjord; Larsen, P Reed; Marqusee, Ellen

    2011-11-02

    Unlike cytotoxic agents that indiscriminately affect rapidly dividing cells, newer antineoplastic agents such as targeted therapies and immunotherapies are associated with thyroid dysfunction. These include tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-α, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide. Primary hypothyroidism is the most common side effect, although thyrotoxicosis and effects on thyroid-stimulating hormone secretion and thyroid hormone metabolism have also been described. Most agents cause thyroid dysfunction in 20%-50% of patients, although some have even higher rates. Despite this, physicians may overlook drug-induced thyroid dysfunction because of the complexity of the clinical picture in the cancer patient. Symptoms of hypothyroidism, such as fatigue, weakness, depression, memory loss, cold intolerance, and cardiovascular effects, may be incorrectly attributed to the primary disease or to the antineoplastic agent. Underdiagnosis of thyroid dysfunction can have important consequences for cancer patient management. At a minimum, the symptoms will adversely affect the patient's quality of life. Alternatively, such symptoms can lead to dose reductions of potentially life-saving therapies. Hypothyroidism can also alter the kinetics and clearance of medications, which may lead to undesirable side effects. Thyrotoxicosis can be mistaken for sepsis or a nonendocrinologic drug side effect. In some patients, thyroid disease may indicate a higher likelihood of tumor response to the agent. Both hypothyroidism and thyrotoxicosis are easily diagnosed with inexpensive and specific tests. In many patients, particularly those with hypothyroidism, the treatment is straightforward. We therefore recommend routine testing for thyroid abnormalities in patients receiving these antineoplastic agents.

  18. Myofascial Pain Dysfunction Syndrome (MPDS)

    OpenAIRE

    2010-01-01

    Introduction: Myofascial Pain Dysfunction Syndrome (MPDS) is one of the most important causes of the orofacial pain. The main purpose of this study was to evaluate 40 related variables in this regard. Materials and Methods: Thirty nine patients with MPDS were evaluated in this study. Different factors including age, gender, occupation, marital status, sensitivity of masticatory muscles, maximum opening of the mouth, deviation, deflection, involvement of temporomandibular joint, habit, parafun...

  19. Hypnotic metaphor and sexual dysfunction.

    Science.gov (United States)

    Gilmore, L G

    1987-01-01

    Although hypnosis can be very effective in alleviating sexual problems, few sex therapists use hypnotic methods. This paper seeks to encourage a greater use of hypnosis among clinicians by presenting: a description of the new hypnosis exemplified in the work of Milton H. Erickson; an explanation of one of Erickson's most important and innovative methods, the use of multiple embedded metaphors; and case histories illustrating the application of hypnotic approaches to sexual dysfunction.

  20. Mitochondrial disease and endocrine dysfunction.

    Science.gov (United States)

    Chow, Jasmine; Rahman, Joyeeta; Achermann, John C; Dattani, Mehul T; Rahman, Shamima

    2017-02-01

    Mitochondria are critical organelles for endocrine health; steroid hormone biosynthesis occurs in these organelles and they provide energy in the form of ATP for hormone production and trafficking. Mitochondrial diseases are multisystem disorders that feature defective oxidative phosphorylation, and are characterized by enormous clinical, biochemical and genetic heterogeneity. To date, mitochondrial diseases have been found to result from >250 monogenic defects encoded across two genomes: the nuclear genome and the ancient circular mitochondrial genome located within mitochondria themselves. Endocrine dysfunction is often observed in genetic mitochondrial diseases and reflects decreased intracellular production or extracellular secretion of hormones. Diabetes mellitus is the most frequently described endocrine disturbance in patients with inherited mitochondrial diseases, but other endocrine manifestations in these patients can include growth hormone deficiency, hypogonadism, adrenal dysfunction, hypoparathyroidism and thyroid disease. Although mitochondrial endocrine dysfunction frequently occurs in the context of multisystem disease, some mitochondrial disorders are characterized by isolated endocrine involvement. Furthermore, additional monogenic mitochondrial endocrine diseases are anticipated to be revealed by the application of genome-wide next-generation sequencing approaches in the future. Understanding the mitochondrial basis of endocrine disturbance is key to developing innovative therapies for patients with mitochondrial diseases.

  1. A new glaucoma hypothesis: a role of glymphatic system dysfunction.

    Science.gov (United States)

    Wostyn, Peter; Van Dam, Debby; Audenaert, Kurt; Killer, Hanspeter Esriel; De Deyn, Peter Paul; De Groot, Veva

    2015-06-29

    In a recent review article titled "A new look at cerebrospinal fluid circulation", Brinker et al. comprehensively described novel insights from molecular and cellular biology as well as neuroimaging research, which indicate that cerebrospinal fluid (CSF) physiology is much more complex than previously believed. The glymphatic system is a recently defined brain-wide paravascular pathway for CSF and interstitial fluid exchange that facilitates efficient clearance of interstitial solutes, including amyloid-β, from the brain. Although further studies are needed to substantiate the functional significance of the glymphatic concept, one implication is that glymphatic pathway dysfunction may contribute to the deficient amyloid-β clearance in Alzheimer's disease. In this paper, we review several lines of evidence suggesting that the glymphatic system may also have potential clinical relevance for the understanding of glaucoma. As a clinically acceptable MRI-based approach to evaluate glymphatic pathway function in humans has recently been developed, a unique opportunity now exists to investigate whether suppression of the glymphatic system contributes to the development of glaucoma. The observation of a dysfunctional glymphatic system in patients with glaucoma would provide support for the hypothesis recently proposed by our group that CSF circulatory dysfunction may play a contributory role in the pathogenesis of glaucomatous damage. This would suggest a new hypothesis for glaucoma, which, just like Alzheimer's disease, might be considered then as an imbalance between production and clearance of neurotoxins, including amyloid-β.

  2. Redirection of the immune response to the functional catalytic domain of the cystein proteinase cruzipain improves protective immunity against Trypanosoma cruzi infection.

    Science.gov (United States)

    Cazorla, Silvia I; Frank, Fernanda M; Becker, Pablo D; Arnaiz, María; Mirkin, Gerardo A; Corral, Ricardo S; Guzmán, Carlos A; Malchiodi, Emilio L

    2010-07-01

    Despite the strong immune responses elicited after natural infection with Trypanosoma cruzi or vaccination against it, parasite survival suggests that these responses are insufficient or inherently inadequate. T. cruzi contains a major cystein proteinase, cruzipain, which has a catalytic N-terminal domain and a C-terminal extension. Immunizations that employed recombinant cruzipain or its N- and C-terminal domains allowed evaluation of the ability of cruzipain to circumvent responses against the catalytic domain. This phenomenon is not a property of the parasite but of cruzipain itself, because recombinant cruzipain triggers a response similar to that of cruzipain during natural or experimental infection. Cruzipain is not the only antigen with a highly immunogenic region of unknown function that somehow protects an essential domain for parasite survival. However, our studies show that this can be reverted by using the N-terminal domain as a tailored immunogen able to redirect host responses to provide enhanced protection.

  3. Young T cells age during a redirected anti-tumour attack: chimeric antigen receptor (CAR-provided dual costimulation is half the battle.

    Directory of Open Access Journals (Sweden)

    Andreas A Hombach

    2013-06-01

    Full Text Available Adoptive therapy with chimeric antigen receptor (CAR-redirected T cells showed spectacular efficacy in the treatment of leukaemia in recent early phase trials. Patient's T cells were ex vivo genetically engineered with a CAR, amplified and re-administered to the patient. While T cells mediating the primary response were predominantly of young effector and central memory phenotype, repetitive antigen engagement irreversible triggers T cell maturation leaving late memory cells with the KLRG-1+ CD57+ CD7- CCR7- phenotype in the long-term. These cells preferentially accumulate in the periphery, are hypo-responsive upon TCR engagement and prone to activation-induced cell death. A recent report indicates that those T cells can be rescued by CAR provided CD28 and OX40 (CD134 stimulation. We discuss the strategy with respect to prolong the anti-tumour response and to improve the over-all efficacy of adoptive cell therapy.

  4. Constitutive signaling from an engineered IL-7 receptor promotes durable tumor elimination by tumor redirected T-cells.

    Science.gov (United States)

    Shum, Thomas; Omer, Bilal; Tashiro, Haruko; Kruse, Robert L; Wagner, Dimitrios L; Parikh, Kathan; Yi, Zhongzhen; Sauer, Tim; Liu, Daofeng; Parihar, Robin; Castillo, Paul; Liu, Hao; Brenner, Malcolm K; Metelitsa, Leonid S; Gottschalk, Stephen; Rooney, Cliona M

    2017-08-22

    Successful adoptive T-cell immunotherapy of solid tumors will require improved expansion and cytotoxicity of tumor-directed T cells within tumors. Providing recombinant or transgenic cytokines may produce the desired benefits but are associated with significant toxicities, constraining clinical use. To circumvent this limitation, we constructed a constitutively signaling cytokine receptor, C7R, which potently triggers the IL-7 signaling axis but is unresponsive to extracellular cytokine. This strategy augments modified T-cell function following antigen exposure, but avoids stimulating bystander lymphocytes. Co-expressing the C7R with a tumor-directed chimeric antigen receptor (CAR) increased T-cell proliferation, survival, and anti-tumor activity during repeated exposure to tumor cells, without T cell dysfunction or autonomous T cell growth. Furthermore, C7R co-expressing CAR-T cells were active against metastatic neuroblastoma and orthotopic glioblastoma xenograft models even at cell doses that had been ineffective without C7R support. C7R may thus be able to enhance antigen-specific T-cell therapies against cancer. Copyright ©2017, American Association for Cancer Research.

  5. Human breast cancer cells are redirected to mammary epithelial cells upon interaction with the regenerating mammary gland microenvironment in-vivo.

    Science.gov (United States)

    Bussard, Karen M; Smith, Gilbert H

    2012-01-01

    Breast cancer is the second leading cause of cancer deaths in the United States. At present, the etiology of breast cancer is unknown; however the possibility of a distinct cell of origin, i.e. a cancer stem cell, is a heavily investigated area of research. Influencing signals from the tissue niche are known to affect stem cells. Literature has shown that cancer cells lose their tumorigenic potential and display 'normal' behavior when placed into 'normal' ontogenic environments. Therefore, it may be the case that the tissue microenvironment is able to generate signals to redirect cancer cell fate. Previously, we showed that pluripotent human embryonal carcinoma cells could be redirected by the regenerating mammary gland microenvironment to contribute epithelial progeny for 'normal' gland development in-vivo. Here, we show that that human metastatic, non-metastatic, and metastasis-suppressed breast cancer cells proliferate and contribute to normal mammary gland development in-vivo without tumor formation. Immunochemistry for human-specific mitochondria, keratin 8 and 14, as well as human-specific milk proteins (alpha-lactalbumin, impregnated transplant hosts) confirmed the presence of human cell progeny. Features consistent with normal mammary gland development as seen in intact hosts (duct, lumen formation, development of secretory acini) were recapitulated in both primary and secondary outgrowths from chimeric implants. These results suggest the dominance of the tissue microenvironment over cancer cell fate. This work demonstrates that cultured human breast cancer cells (metastatic and non-metastatic) respond developmentally to signals generated by the mouse mammary gland microenvironment during gland regeneration in-vivo.

  6. Human breast cancer cells are redirected to mammary epithelial cells upon interaction with the regenerating mammary gland microenvironment in-vivo.

    Directory of Open Access Journals (Sweden)

    Karen M Bussard

    Full Text Available Breast cancer is the second leading cause of cancer deaths in the United States. At present, the etiology of breast cancer is unknown; however the possibility of a distinct cell of origin, i.e. a cancer stem cell, is a heavily investigated area of research. Influencing signals from the tissue niche are known to affect stem cells. Literature has shown that cancer cells lose their tumorigenic potential and display 'normal' behavior when placed into 'normal' ontogenic environments. Therefore, it may be the case that the tissue microenvironment is able to generate signals to redirect cancer cell fate. Previously, we showed that pluripotent human embryonal carcinoma cells could be redirected by the regenerating mammary gland microenvironment to contribute epithelial progeny for 'normal' gland development in-vivo. Here, we show that that human metastatic, non-metastatic, and metastasis-suppressed breast cancer cells proliferate and contribute to normal mammary gland development in-vivo without tumor formation. Immunochemistry for human-specific mitochondria, keratin 8 and 14, as well as human-specific milk proteins (alpha-lactalbumin, impregnated transplant hosts confirmed the presence of human cell progeny. Features consistent with normal mammary gland development as seen in intact hosts (duct, lumen formation, development of secretory acini were recapitulated in both primary and secondary outgrowths from chimeric implants. These results suggest the dominance of the tissue microenvironment over cancer cell fate. This work demonstrates that cultured human breast cancer cells (metastatic and non-metastatic respond developmentally to signals generated by the mouse mammary gland microenvironment during gland regeneration in-vivo.

  7. Cellular bioluminescence imaging.

    Science.gov (United States)

    Welsh, David K; Noguchi, Takako

    2012-08-01

    Bioluminescence imaging of live cells has recently been recognized as an important alternative to fluorescence imaging. Fluorescent probes are much brighter than bioluminescent probes (luciferase enzymes) and, therefore, provide much better spatial and temporal resolution and much better contrast for delineating cell structure. However, with bioluminescence imaging there is virtually no background or toxicity. As a result, bioluminescence can be superior to fluorescence for detecting and quantifying molecules and their interactions in living cells, particularly in long-term studies. Structurally diverse luciferases from beetle and marine species have been used for a wide variety of applications, including tracking cells in vivo, detecting protein-protein interactions, measuring levels of calcium and other signaling molecules, detecting protease activity, and reporting circadian clock gene expression. Such applications can be optimized by the use of brighter and variously colored luciferases, brighter microscope optics, and ultrasensitive, low-noise cameras. This article presents a review of how bioluminescence differs from fluorescence, its applications to cellular imaging, and available probes, optics, and detectors. It also gives practical suggestions for optimal bioluminescence imaging of single cells.

  8. Cellular neurothekeoma with melanocytosis.

    Science.gov (United States)

    Wu, Ren-Chin; Hsieh, Yi-Yueh; Chang, Yi-Chin; Kuo, Tseng-Tong

    2008-02-01

    Cellular neurothekeoma (CNT) is a benign dermal tumor mainly affecting the head and neck and the upper extremities. It is characterized histologically by interconnecting fascicles of plump spindle or epithelioid cells with ample cytoplasm infiltrating in the reticular dermis. The histogenesis of CNT has been controversial, although it is generally regarded as an immature counterpart of classic/myxoid neurothekeoma, a tumor with nerve sheath differentiation. Two rare cases of CNT containing melanin-laden cells were described. Immunohistochemical study with NKI/C3, vimentin, epithelial membrane antigen, smooth muscle antigen, CD34, factor XIIIa, collagen type IV, S100 protein and HMB-45 was performed. Both cases showed typical growth pattern of CNT with interconnecting fascicles of epithelioid cells infiltrating in collagenous stroma. One of the nodules contained areas exhibiting atypical cytological features. Melanin-laden epithelioid or dendritic cells were diffusely scattered throughout one nodule, and focally present in the peripheral portion of the other nodule. Both nodules were strongly immunoreactive to NKI/C3 and vimentin, but negative to all the other markers employed. CNT harboring melanin-laden cells may pose diagnostic problems because of their close resemblance to nevomelanocytic lesions and other dermal mesenchymal tumors. These peculiar cases may also provide further clues to the histogenesis of CNT.

  9. Symptoms of Nerve Dysfunction After Hip Arthroscopy

    DEFF Research Database (Denmark)

    Dippmann, Christian; Thorborg, Kristian; Kraemer, Otto

    2014-01-01

    PURPOSE: The primary purpose of this study was to analyze the rate, pattern, and severity of symptoms of nerve dysfunction after hip arthroscopy (HA) by reviewing prospectively collected data. The secondary purpose was to study whether symptoms of nerve dysfunction were related to traction time...... year after HA concerning symptoms of nerve dysfunction, possible localization, and erectile dysfunction. Fifty patients participated and returned fully completed questionnaires. Patients reporting symptoms of nerve dysfunction 1 year after HA were re-examined. RESULTS: Twenty-three of 50 patients (46......%) reported symptoms of nerve dysfunction during the first week after HA; this was reduced to 14 patients (28%) after 6 weeks, 11 patients (22%) after 26 weeks, and 9 patients (18%) after 1 year. One patient experienced temporary erectile dysfunction. No difference in traction time between patients...

  10. Autonomic Nervous System Dysfunction in Parkinson's Disease.

    Science.gov (United States)

    Zesiewicz, Theresa A.; Baker, Matthew J.; Wahba, Mervat; Hauser, Robert A.

    2003-03-01

    Autonomic nervous system (ANS) dysfunction is common in Parkinson's disease (PD), affects 70% to 80% of patients, and causes significant morbidity and discomfort. Autonomic nervous system dysfunction symptoms in PD include sexual dysfunction, swallowing and gastrointestinal disorders, bowel and bladder abnormalities, sleep disturbances, and derangements of cardiovascular regulation, particularly, orthostatic hypotension. Autonomic nervous system dysfunction in PD may be caused by an underlying degenerative process that affects the autonomic ganglia, brainstem nuclei, and hypothalamic nuclei. Anti-parkinsonian medications can cause or worsen symptoms of ANS dysfunction. The care of a PD patient with ANS dysfunction relies on its recognition and directed treatment, including coordinated care between the neurologist and appropriate subspecialist. Pharmacotherapy may be useful to treat orthostasis, gastrointestinal, urinary, and sexual dysfunction.

  11. Therapeutic intervention at cellular quality control systems in Alzheimer's and Parkinson's diseases.

    Science.gov (United States)

    Arduino, Daniela M; Esteves, A Raquel; Silva, Diana F F; Martins-Branco, Diogo; Santos, Daniel; Pimentel, Diana F Gomes; Cardoso, Sandra M

    2011-01-01

    Cellular homeostasis relies on quality control systems so that damaged biologic structures are either repaired or degraded and entirely replaced by newly formed proteins or even organelles. The clearance of dysfunctional cellular structures in long-lived postmitotic cells, like neurons, is essential to eliminate, per example, defective mitochondria, lipofuscin-loaded lysosomes and oxidized proteins. Short-lived proteins are degraded mainly by proteases and proteasomes whether most long-lived proteins and all organelles are digested by autophagy in the lysosomes. Recently, it an interplay was established between the ubiquitin-proteasome system and macroautophagy, so that both degradative mechanisms compensate for each other. In this article we describe each of these clearance systems and their contribution to neuronal quality control. We will highlight some of the findings that provide evidence for the dysfunction of these systems in Alzheimer's and Parkinson's diseases. Ultimately, we provide an outline on potential therapeutic interventions based on the modulation of cellular degradative systems.

  12. Recent insights into the cellular biology of atherosclerosis.

    Science.gov (United States)

    Tabas, Ira; García-Cardeña, Guillermo; Owens, Gary K

    2015-04-13

    Atherosclerosis occurs in the subendothelial space (intima) of medium-sized arteries at regions of disturbed blood flow and is triggered by an interplay between endothelial dysfunction and subendothelial lipoprotein retention. Over time, this process stimulates a nonresolving inflammatory response that can cause intimal destruction, arterial thrombosis, and end-organ ischemia. Recent advances highlight important cell biological atherogenic processes, including mechanotransduction and inflammatory processes in endothelial cells, origins and contributions of lesional macrophages, and origins and phenotypic switching of lesional smooth muscle cells. These advances illustrate how in-depth mechanistic knowledge of the cellular pathobiology of atherosclerosis can lead to new ideas for therapy. © 2015 Tabas et al.

  13. Cellular and molecular biology of aging endothelial cells.

    Science.gov (United States)

    Donato, Anthony J; Morgan, R Garrett; Walker, Ashley E; Lesniewski, Lisa A

    2015-12-01

    Cardiovascular disease (CVD) is the leading cause of death in the United States and aging is a major risk factor for CVD development. One of the major age-related arterial phenotypes thought to be responsible for the development of CVD in older adults is endothelial dysfunction. Endothelial function is modulated by traditional CVD risk factors in young adults, but advancing age is independently associated with the development of vascular endothelial dysfunction. This endothelial dysfunction results from a reduction in nitric oxide bioavailability downstream of endothelial oxidative stress and inflammation that can be further modulated by traditional CVD risk factors in older adults. Greater endothelial oxidative stress with aging is a result of augmented production from the intracellular enzymes NADPH oxidase and uncoupled eNOS, as well as from mitochondrial respiration in the absence of appropriate increases in antioxidant defenses as regulated by relevant transcription factors, such as FOXO. Interestingly, it appears that NFkB, a critical inflammatory transcription factor, is sensitive to this age-related endothelial redox change and its activation induces transcription of pro-inflammatory cytokines that can further suppress endothelial function, thus creating a vicious feed-forward cycle. This review will discuss the two macro-mechanistic processes, oxidative stress and inflammation, that contribute to endothelial dysfunction with advancing age as well as the cellular and molecular events that lead to the vicious cycle of inflammation and oxidative stress in the aged endothelium. Other potential mediators of this pro-inflammatory endothelial phenotype are increases in immune or senescent cells in the vasculature. Of note, genomic instability, telomere dysfunction or DNA damage has been shown to trigger cell senescence via the p53/p21 pathway and result in increased inflammatory signaling in arteries from older adults. This review will discuss the current state

  14. Free fall and cellular automata

    Directory of Open Access Journals (Sweden)

    Pablo Arrighi

    2016-03-01

    Full Text Available Three reasonable hypotheses lead to the thesis that physical phenomena can be described and simulated with cellular automata. In this work, we attempt to describe the motion of a particle upon which a constant force is applied, with a cellular automaton, in Newtonian physics, in Special Relativity, and in General Relativity. The results are very different for these three theories.

  15. About Strongly Universal Cellular Automata

    Directory of Open Access Journals (Sweden)

    Maurice Margenstern

    2013-09-01

    Full Text Available In this paper, we construct a strongly universal cellular automaton on the line with 11 states and the standard neighbourhood. We embed this construction into several tilings of the hyperbolic plane and of the hyperbolic 3D space giving rise to strongly universal cellular automata with 10 states.

  16. Reactive Programming of Cellular Automata

    OpenAIRE

    Boussinot, Frédéric

    2004-01-01

    Implementation of cellular automata using reactive programming gives a way to code cell behaviors in an abstract and modular way. Multiprocessing also becomes possible. The paper describes the implementation of cellular automata with the reactive programming language LOFT, a thread-based extension of C. Self replicating loops considered in artificial life are coded to show the interest of the approach.

  17. Proximal tubular dysfunction as an indicator of chronic graft dysfunction

    Directory of Open Access Journals (Sweden)

    N.O.S. Câmara

    2009-03-01

    Full Text Available New strategies are being devised to limit the impact of renal sclerosis on graft function. Individualization of immunosuppression, specifically the interruption of calcineurin-inhibitors has been tried in order to promote better graft survival once chronic graft dysfunction has been established. However, the long-term impact of these approaches is still not totally clear. Nevertheless, patients at higher risk for tubular atrophy and interstitial fibrosis (TA/IF development should be carefully monitored for tubular function as well as glomerular performance. Since tubular-interstitial impairment is an early event in TA/IF pathogenesis and associated with graft function, it seems reasonable that strategies directed at assessing tubular structural integrity and function would yield important functional and prognostic data. The measurement of small proteins in urine such as α-1-microglobulin, N-acetyl-beta-D-glucosaminidase, alpha/pi S-glutathione transferases, β-2 microglobulin, and retinol binding protein is associated with proximal tubular cell dysfunction. Therefore, its straightforward assessment could provide a powerful tool in patient monitoring and ongoing clinical assessment of graft function, ultimately helping to facilitate longer patient and graft survival associated with good graft function.

  18. MIMO Communication for Cellular Networks

    CERN Document Server

    Huang, Howard; Venkatesan, Sivarama

    2012-01-01

    As the theoretical foundations of multiple-antenna techniques evolve and as these multiple-input multiple-output (MIMO) techniques become essential for providing high data rates in wireless systems, there is a growing need to understand the performance limits of MIMO in practical networks. To address this need, MIMO Communication for Cellular Networks presents a systematic description of MIMO technology classes and a framework for MIMO system design that takes into account the essential physical-layer features of practical cellular networks. In contrast to works that focus on the theoretical performance of abstract MIMO channels, MIMO Communication for Cellular Networks emphasizes the practical performance of realistic MIMO systems. A unified set of system simulation results highlights relative performance gains of different MIMO techniques and provides insights into how best to use multiple antennas in cellular networks under various conditions. MIMO Communication for Cellular Networks describes single-user,...

  19. Cellular automata analysis and applications

    CERN Document Server

    Hadeler, Karl-Peter

    2017-01-01

    This book focuses on a coherent representation of the main approaches to analyze the dynamics of cellular automata. Cellular automata are an inevitable tool in mathematical modeling. In contrast to classical modeling approaches as partial differential equations, cellular automata are straightforward to simulate but hard to analyze. In this book we present a review of approaches and theories that allow the reader to understand the behavior of cellular automata beyond simulations. The first part consists of an introduction of cellular automata on Cayley graphs, and their characterization via the fundamental Cutis-Hedlund-Lyndon theorems in the context of different topological concepts (Cantor, Besicovitch and Weyl topology). The second part focuses on classification results: What classification follows from topological concepts (Hurley classification), Lyapunov stability (Gilman classification), and the theory of formal languages and grammars (Kůrka classification). These classifications suggest to cluster cel...

  20. Drug addiction and sexual dysfunction.

    Science.gov (United States)

    Zaazaa, Adham; Bella, Anthony J; Shamloul, Rany

    2013-09-01

    This article attempts to review the most current and the well-established facts concerning drug addiction and sexual dysfunction. Surprisingly, even though alcohol is prevalent in many societies with many myths surrounding its sexual-enhancing effects, current scientific research cannot provide a solid conclusion on its effect on sexual function. Unfortunately, the same concept applies to tobacco smoking; however, most of the current knowledge tends to support the notion that it, indeed, can negatively affect sexual function. Similar ambiguities also prevail with substances of abuse.

  1. Endothelial dysfunction: a comprehensive appraisal

    Directory of Open Access Journals (Sweden)

    Vilariño Jorge O

    2006-02-01

    Full Text Available Abstract The endothelium is a thin monocelular layer that covers all the inner surface of the blood vessels, separating the circulating blood from the tissues. It is not an inactive organ, quite the opposite. It works as a receptor-efector organ and responds to each physical or chemical stimulus with the release of the correct substance with which it may maintain vasomotor balance and vascular-tissue homeostasis. It has the property of producing, independently, both agonistic and antagonistic substances that help to keep homeostasis and its function is not only autocrine, but also paracrine and endocrine. In this way it modulates the vascular smooth muscle cells producing relaxation or contraction, and therefore vasodilatation or vasoconstriction. The endothelium regulating homeostasis by controlling the production of prothrombotic and antithrombotic components, and fibrynolitics and antifibrynolitics. Also intervenes in cell proliferation and migration, in leukocyte adhesion and activation and in immunological and inflammatory processes. Cardiovascular risk factors cause oxidative stress that alters the endothelial cells capacity and leads to the so called endothelial "dysfunction" reducing its capacity to maintain homeostasis and leads to the development of pathological inflammatory processes and vascular disease. There are different techniques to evaluate the endothelium functional capacity, that depend on the amount of NO produced and the vasodilatation effect. The percentage of vasodilatation with respect to the basal value represents the endothelial functional capacity. Taking into account that shear stress is one of the most important stimulants for the synthesis and release of NO, the non-invasive technique most often used is the transient flow-modulate "endothelium-dependent" post-ischemic vasodilatation, performed on conductance arteries such as the brachial, radial or femoral arteries. This vasodilatation is compared with the

  2. Vaccination-related shoulder dysfunction.

    Science.gov (United States)

    Bodor, Marko; Montalvo, Enoch

    2007-01-08

    We present two cases of shoulder pain and weakness following influenza and pneumococcal vaccine injections provided high into the deltoid muscle. Based on ultrasound measurements, we hypothesize that vaccine injected into the subdeltoid bursa caused a periarticular inflammatory response, subacromial bursitis, bicipital tendonitis and adhesive capsulitis. Resolution of symptoms followed corticosteroid injections to the subacromial space, bicipital tendon sheath and glenohumeral joint, followed by physical therapy. We conclude that the upper third of the deltoid muscle should not be used for vaccine injections, and the diagnosis of vaccination-related shoulder dysfunction should be considered in patients presenting with shoulder pain following a vaccination.

  3. Multiple sclerosis and sexual dysfunction

    Institute of Scientific and Technical Information of China (English)

    Zhen-Ni Guo; Si-Yuan He; Hong-Liang Zhang; Jiang Wu; Yi Yang

    2012-01-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system characterized by episodic and progressive neurologic dysfunction resulting from inflammatory and autoimmune reactions.The underlying pathogenesis of MS remains largely unclear.However,it is currently accepted as a T cell-mediated autoimmune disease.Among other clinical manifestations,sexual dysfunction (SD) is a painful but still underreported and underdiagnosed symptom of the disorder.SD in MS patients may result from a complex set of conditions and may be associated with multiple anatomic,physiologic,biologic,medical and psychological factors.SD arises primarily from lesions affecting the neural pathways involved in physiologic function.In addition,psychological factors,the side effects of medications and physical symptoms such as fatigue,muscular weakness,menstrual changes,pain and concerns about bladder and bowel incontinence may also be involved.Since MS primarily affects young people,SD secondary to MS may have a great impact on quality of life.Thus,maintaining a healthy sexual life with MS is an important priority.The treatment of SD requires multidisciplinary teamwork and cooperation among specialists,individual patients,partners and the society.

  4. Mitochondrial dysfunction in heart failure.

    Science.gov (United States)

    Rosca, Mariana G; Hoppel, Charles L

    2013-09-01

    Heart failure (HF) is a complex chronic clinical syndrome. Energy deficit is considered to be a key contributor to the development of both cardiac and skeletal myopathy. In HF, several components of cardiac and skeletal muscle bioenergetics are altered, such as oxygen availability, substrate oxidation, mitochondrial ATP production, and ATP transfer to the contractile apparatus via the creatine kinase shuttle. This review focuses on alterations in mitochondrial biogenesis and respirasome organization, substrate oxidation coupled with ATP synthesis in the context of their contribution to the chronic energy deficit, and mechanical dysfunction of the cardiac and skeletal muscle in HF. We conclude that HF is associated with decreased mitochondrial biogenesis and function in both heart and skeletal muscle, supporting the concept of a systemic mitochondrial cytopathy. The sites of mitochondrial defects are located within the electron transport and phosphorylation apparatus and differ with the etiology and progression of HF in the two mitochondrial populations (subsarcolemmal and interfibrillar) of cardiac and skeletal muscle. The roles of adrenergic stimulation, the renin-angiotensin system, and cytokines are evaluated as factors responsible for the systemic energy deficit. We propose a cyclic AMP-mediated mechanism by which increased adrenergic stimulation contributes to the mitochondrial dysfunction.

  5. Insulin Resistance and Mitochondrial Dysfunction.

    Science.gov (United States)

    Gonzalez-Franquesa, Alba; Patti, Mary-Elizabeth

    2017-01-01

    Insulin resistance precedes and predicts the onset of type 2 diabetes (T2D) in susceptible humans, underscoring its important role in the complex pathogenesis of this disease. Insulin resistance contributes to multiple tissue defects characteristic of T2D, including reduced insulin-stimulated glucose uptake in insulin-sensitive tissues, increased hepatic glucose production, increased lipolysis in adipose tissue, and altered insulin secretion. Studies of individuals with insulin resistance, both with established T2D and high-risk individuals, have consistently demonstrated a diverse array of defects in mitochondrial function (i.e., bioenergetics, biogenesis and dynamics). However, it remains uncertain whether mitochondrial dysfunction is primary (critical initiating defect) or secondary to the subtle derangements in glucose metabolism, insulin resistance, and defective insulin secretion present early in the course of disease development. In this chapter, we will present the evidence linking mitochondrial dysfunction and insulin resistance, and review the potential for mitochondrial targets as a therapeutic approach for T2D.

  6. Mitochondrial dysfunction in cancer chemoresistance.

    Science.gov (United States)

    Guaragnella, Nicoletta; Giannattasio, Sergio; Moro, Loredana

    2014-11-01

    Mitochondrial dysfunction has been associated with cancer development and progression. Recent evidences suggest that pathogenic mutations or depletion of the mitochondrial genome can contribute to development of chemoresistance in malignant tumors. In this review we will describe the current knowledge on the role of mitochondrial dysfunction in the development of chemoresistance in cancer. We will also discuss the significance of this research topic in the context of development of more effective, targeted therapeutic modalities and diagnostic strategies for cancer patients, with a particular focus on the potential use of PARP inhibitors in cancer patients displaying mitochondrial DNA mutations. We will discuss recent studies highlighting the importance of the cross-talk between the tumor microenvironment and mitochondrial functionality in determining selective response to certain chemotherapeutic drugs. Finally, owing to the similarities between cancer and yeast cell metabolism, we will point out the use of yeast as a model system to study cancer-related genes and for anti-cancer drugs screening. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Apraxia and Motor Dysfunction in Corticobasal Syndrome

    OpenAIRE

    Burrell, James R.; Michael Hornberger; Steve Vucic; Kiernan, Matthew C.; Hodges, John R.

    2014-01-01

    Background: Corticobasal syndrome (CBS) is characterized by multifaceted motor system dysfunction and cognitive disturbance; distinctive clinical features include limb apraxia and visuospatial dysfunction. Transcranial magnetic stimulation (TMS) has been used to study motor system dysfunction in CBS, but the relationship of TMS parameters to clinical features has not been studied. The present study explored several hypotheses; firstly, that limb apraxia may be partly due to visuospatial impai...

  8. The treatment of autonomic dysfunction in tetanus

    Directory of Open Access Journals (Sweden)

    T van den Heever

    2017-07-01

    Full Text Available We report a case of generalised tetanus in a 50-year-old female patient after sustaining a wound to her right lower leg. She developed autonomic dysfunction, which included labile hypertension alternating with hypotension and sweating. The autonomic dysfunction was treated successfully with a combination of morphine sulphate infusion, magnesium sulphate, and clonidine. She also received adrenaline and phenylephrine infusions as needed for hypotension. We then discuss the pathophysiology, clinical features and treatment options of autonomic dysfunction.

  9. Multiple system atrophy and cognitive dysfunction

    Directory of Open Access Journals (Sweden)

    Sen-yang LANG

    2016-06-01

    Full Text Available As the survival of patients with multiple system atrophy (MSA is prolonged, patients may present cognitive dysfunction or even dementia in addition to autonomic dysfunction, damage of extrapyramidal system and cerebellar ataxia. This article made a brief summary on the research progress of MSA combined with cognitive dysfunction reported at home and abroad. DOI: 10.3969/j.issn.1672-6731.2016.06.003

  10. Cellular systems biology profiling applied to cellular models of disease.

    Science.gov (United States)

    Giuliano, Kenneth A; Premkumar, Daniel R; Strock, Christopher J; Johnston, Patricia; Taylor, Lansing

    2009-11-01

    Building cellular models of disease based on the approach of Cellular Systems Biology (CSB) has the potential to improve the process of creating drugs as part of the continuum from early drug discovery through drug development and clinical trials and diagnostics. This paper focuses on the application of CSB to early drug discovery. We discuss the integration of protein-protein interaction biosensors with other multiplexed, functional biomarkers as an example in using CSB to optimize the identification of quality lead series compounds.

  11. Role of microparticles in endothelial dysfunction and arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    Thomas; Helbing; Christoph; Olivier; Christoph; Bode; Martin; Moser; Philipp; Diehl

    2014-01-01

    Microparticles are small cell vesicles that can be released by almost all eukaryotic cells during cellular stress and cell activation. Within the last 1-2 decades it has been shown that microparticles are useful blood surrogate markers for different pathological conditions, such as vascular inflammation, coagulation and tumour diseases. Several studies have investigated the abundance of microparticles of different cellular origins in multiple cardiovascular diseases. It thereby has been shown that microparticles released by platelets, leukocytes and endothelial cells can be found in conditions of endothelial dysfunction, acute and chronic vascular inflammation and hypercoagulation. In addition to their function as surrogate markers, several studies indicate that circulating microparticles can fuse with distinct target cells, such as endothelial cells or leukocyte, and thereby deliver cellular components of their parental cells to the target cells. Hence, microparticles are a novel entity of circulating, paracrine, biological vectors which can influence the phenotype, the function and presumably even the transcriptome of their target cells.This review article aims to give a brief overview about the microparticle biology with a focus on endothelial activation and arterial hypertension. More detailed information about the role of microparticles in pathophysiology and disease can be found in already published work.

  12. Intestinal dysfunction associated with acute thoracolumbar fractures.

    Science.gov (United States)

    Peschiera, J L; Beerman, S P

    1990-03-01

    The frequency of intestinal dysfunction, particularly intestinal ileus, among patients with acute thoracolumbar fractures and no neurologic compromise was assessed. We reviewed the medical records of 70 patients who met specific criteria. Only four (6%) of these patients developed intestinal dysfunction, manifested by vomiting, abdominal distention, diminished bowel sounds, or an intestinal ileus documented by an abdominal roentgenogram. Conservative initial nutritional management of the patients did not reduce the incidence of intestinal dysfunction. This study suggests that patients with acute thoracolumbar fractures and no neurologic compromise are not at substantial risk of intestinal dysfunction and that nasogastric suction and restriction of oral intake are unnecessary in the initial management of these patients.

  13. Cardiovascular dysfunction in infants with neonatal encephalopathy.

    LENUS (Irish Health Repository)

    Armstrong, Katey

    2012-04-01

    Severe perinatal asphyxia with hypoxic ischaemic encephalopathy occurs in approximately 1-2\\/1000 live births and is an important cause of cerebral palsy and associated neurological disabilities in children. Multiorgan dysfunction commonly occurs as part of the asphyxial episode, with cardiovascular dysfunction occurring in up to a third of infants. This narrative paper attempts to review the literature on the importance of early recognition of cardiac dysfunction using echocardiography and biomarkers such as troponin and brain type natriuretic peptide. These tools may allow accurate assessment of cardiac dysfunction and guide therapy to improve outcome.

  14. The relationship between depression and erectile dysfunction.

    Science.gov (United States)

    Seidman, S N; Roose, S P

    2000-06-01

    Normal sexual function is a biopsychosocial process; sexual dysfunction almost always has organic and psychologic components, and it requires multidisciplinary, goal-directed evaluation and treatment. Factors such as aging, declining testosterone levels, medical illness, certain medications, and comorbid depressive illness can contribute to sexual dysfunction. Erectile dysfunction (ED) is the most common male sexual dysfunction encountered in the clinical setting. Comorbidity between ED and depressive illness is high, but the causal relationship is unclear, and likely bidirectional. In this article, we review the existing literature on the relationship between depression and ED.

  15. Skeletal Muscle and Lymphocyte Mitochondrial Dysfunctions in Septic Shock Trigger ICU-Acquired Weakness and Sepsis-Induced Immunoparalysis

    Directory of Open Access Journals (Sweden)

    Quentin Maestraggi

    2017-01-01

    Full Text Available Fundamental events driving the pathological processes of septic shock-induced multiorgan failure (MOF at the cellular and subcellular levels remain debated. Emerging data implicate mitochondrial dysfunction as a critical factor in the pathogenesis of sepsis-associated MOF. If macrocirculatory and microcirculatory dysfunctions undoubtedly participate in organ dysfunction at the early stage of septic shock, an intrinsic bioenergetic failure, sometimes called “cytopathic hypoxia,” perpetuates cellular dysfunction. Short-term failure of vital organs immediately threatens patient survival but long-term recovery is also severely hindered by persistent dysfunction of organs traditionally described as nonvital, such as skeletal muscle and peripheral blood mononuclear cells (PBMCs. In this review, we will stress how and why a persistent mitochondrial dysfunction in skeletal muscles and PBMC could impair survival in patients who overcome the first acute phase of their septic episode. First, muscle wasting protracts weaning from mechanical ventilation, increases the risk of mechanical ventilator-associated pneumonia, and creates a state of ICU-acquired muscle weakness, compelling the patient to bed. Second, failure of the immune system (“immunoparalysis” translates into its inability to clear infectious foci and predisposes the patient to recurrent nosocomial infections. We will finally emphasize how mitochondrial-targeted therapies could represent a realistic strategy to promote long-term recovery after sepsis.

  16. Skeletal Muscle and Lymphocyte Mitochondrial Dysfunctions in Septic Shock Trigger ICU-Acquired Weakness and Sepsis-Induced Immunoparalysis.

    Science.gov (United States)

    Maestraggi, Quentin; Lebas, Benjamin; Clere-Jehl, Raphaël; Ludes, Pierre-Olivier; Chamaraux-Tran, Thiên-Nga; Schneider, Francis; Diemunsch, Pierre; Geny, Bernard; Pottecher, Julien

    2017-01-01

    Fundamental events driving the pathological processes of septic shock-induced multiorgan failure (MOF) at the cellular and subcellular levels remain debated. Emerging data implicate mitochondrial dysfunction as a critical factor in the pathogenesis of sepsis-associated MOF. If macrocirculatory and microcirculatory dysfunctions undoubtedly participate in organ dysfunction at the early stage of septic shock, an intrinsic bioenergetic failure, sometimes called "cytopathic hypoxia," perpetuates cellular dysfunction. Short-term failure of vital organs immediately threatens patient survival but long-term recovery is also severely hindered by persistent dysfunction of organs traditionally described as nonvital, such as skeletal muscle and peripheral blood mononuclear cells (PBMCs). In this review, we will stress how and why a persistent mitochondrial dysfunction in skeletal muscles and PBMC could impair survival in patients who overcome the first acute phase of their septic episode. First, muscle wasting protracts weaning from mechanical ventilation, increases the risk of mechanical ventilator-associated pneumonia, and creates a state of ICU-acquired muscle weakness, compelling the patient to bed. Second, failure of the immune system ("immunoparalysis") translates into its inability to clear infectious foci and predisposes the patient to recurrent nosocomial infections. We will finally emphasize how mitochondrial-targeted therapies could represent a realistic strategy to promote long-term recovery after sepsis.

  17. DNA damage response inhibition at dysfunctional telomeres by modulation of telomeric DNA damage response RNAs.

    Science.gov (United States)

    Rossiello, Francesca; Aguado, Julio; Sepe, Sara; Iannelli, Fabio; Nguyen, Quan; Pitchiaya, Sethuramasundaram; Carninci, Piero; d'Adda di Fagagna, Fabrizio

    2017-02-27

    The DNA damage response (DDR) is a set of cellular events that follows the generation of DNA damage. Recently, site-specific small non-coding RNAs, also termed DNA damage response RNAs (DDRNAs), have been shown to play a role in DDR signalling and DNA repair. Dysfunctional telomeres activate DDR in ageing, cancer and an increasing number of identified pathological conditions. Here we show that, in mammals, telomere dysfunction induces the transcription of telomeric DDRNAs (tDDRNAs) and their longer precursors from both DNA strands. DDR activation and maintenance at telomeres depend on the biogenesis and functions of tDDRNAs. Their functional inhibition by sequence-specific antisense oligonucleotides allows the unprecedented telomere-specific DDR inactivation in cultured cells and in vivo in mouse tissues. In summary, these results demonstrate that tDDRNAs are induced at dysfunctional telomeres and are necessary for DDR activation and they validate the viability of locus-specific DDR inhibition by targeting DDRNAs.

  18. Therapeutic Strategies for Mitochondrial Dysfunction and Oxidative Stress in Age-Related Metabolic Disorders.

    Science.gov (United States)

    Bhatti, J S; Kumar, S; Vijayan, M; Bhatti, G K; Reddy, P H

    2017-01-01

    Mitochondria are complex, intercellular organelles present in the cells and are involved in multiple roles including ATP formation, free radicals generation and scavenging, calcium homeostasis, cellular differentiation, and cell death. Many studies depicted the involvement of mitochondrial dysfunction and oxidative damage in aging and pathogenesis of age-related metabolic disorders and neurodegenerative diseases. Remarkable advancements have been made in understanding the structure, function, and physiology of mitochondria in metabolic disorders such as diabetes, obesity, cardiovascular diseases, and stroke. Further, much progress has been done in the improvement of therapeutic strategies, including lifestyle interventions, pharmacological, and mitochondria-targeted therapeutic approaches. These strategies were mainly focused to reduce the mitochondrial dysfunction caused by oxidative stress and to retain the mitochondrial health in various diseases. In this chapter, we have highlighted the involvement of mitochondrial dysfunction in the pathophysiology of various disorders and recent progress in the development of mitochondria-targeted molecules as therapeutic measures for metabolic disorders.

  19. Oxidative stress action in cellular aging

    Directory of Open Access Journals (Sweden)

    Monique Cristine de Oliveira

    2010-12-01

    Full Text Available Various theories try to explain the biological aging by changing the functions and structure of organic systems and cells. During lifetime, free radicals in the oxidative stress lead to lipid peroxidation of cellular membranes, homeostasis imbalance, chemical residues formation, gene mutations in DNA, dysfunction of certain organelles, and the arise of diseases due to cell death and/or injury. This review describes the action of oxidative stress in the cells aging process, emphasizing the factors such as cellular oxidative damage, its consequences and the main protective measures taken to prevent or delay this process. Tests with antioxidants: vitamins A, E and C, flavonoids, carotenoids and minerals, the practice of caloric restriction and physical exercise, seeking the beneficial effects on human health, increasing longevity, reducing the level of oxidative stress, slowing the cellular senescence and origin of certain diseases, are discussed.Diferentes teorias tentam explicar o envelhecimento biológico através da alteração das funções e estrutura dos sistemas orgânicos e células. Ao longo da vida, os radicais livres presentes no estresse oxidativo conduzem à peroxidação dos lipídios das membranas celulares, desequilíbrio da homeostase, formação de resíduos químicos, mutações gênicas no DNA, disfunção de certas organelas, bem como ao surgimento de doenças devido à lesão e/ou morte celular. Nesta revisão descreve-se a ação do estresse oxidativo no processo de envelhecimento das células, enfatizando fatores como os danos oxidativos celulares, suas conseqüências e as principais medidas protetoras adotadas para se prevenir ou retardar este processo. Testes com antioxidantes: vitaminas A, E e C, flavonóides, carotenóides e minerais; a prática de restrição calórica e exercícios físicos, que buscam efeitos benéficos sobre a saúde humana, aumentando a longevidade, reduzindo o nível de estresse oxidativo

  20. A Course in Cellular Bioengineering.

    Science.gov (United States)

    Lauffenburger, Douglas A.

    1989-01-01

    Gives an overview of a course in chemical engineering entitled "Cellular Bioengineering," dealing with how chemical engineering principles can be applied to molecular cell biology. Topics used are listed and some key references are discussed. Listed are 85 references. (YP)

  1. Novel Materials for Cellular Nanosensors

    DEFF Research Database (Denmark)

    Sasso, Luigi

    The monitoring of cellular behavior is useful for the advancement of biomedical diagnostics, drug development and the understanding of a cell as the main unit of the human body. Micro- and nanotechnology allow for the creation of functional devices that enhance the study of cellular dynamics...... by providing platforms that offer biocompatible surfaces for the cell culturing in lab-on-chip devices integrated with optimized nanosensors with high specificities and sensitivities towards cellular analytes. In this project, novel materials were investigated with a focus on providing suitable surface...... modifications for electrochemical nanosensors for the detection of analytes released from cells. Two type of materials were investigated, each pertaining to the two different aspects of such devices: peptide nanostructures were studied for the creation of cellular sensing substrates that mimic in vivo surfaces...

  2. Temsirolimus Partially Rescues the Hutchinson-Gilford Progeria Cellular Phenotype

    Science.gov (United States)

    Gabriel, Diana; Gordon, Leslie B.

    2016-01-01

    Hutchinson-Gilford syndrome (HGPS, OMIM 176670, a rare premature aging disorder that leads to death at an average age of 14.7 years due to myocardial infarction or stroke, is caused by mutations in the LMNA gene. Lamins help maintain the shape and stability of the nuclear envelope in addition to regulating DNA replication, DNA transcription, proliferation and differentiation. The LMNA mutation results in the deletion of 50 amino acids from the carboxy-terminal region of prelamin A, producing the truncated, farnesylated protein progerin. The accumulation of progerin in HGPS nuclei causes numerous morphological and functional changes that lead to premature cellular senescence. Attempts to reverse this HGPS phenotype have identified rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), as a drug that is able to rescue the HGPS cellular phenotype by promoting autophagy and reducing progerin accumulation. Rapamycin is an obvious candidate for the treatment of HGPS disease but is difficult to utilize clinically. To further assess rapamycin’s efficacy with regard to proteostasis, mitochondrial function and the degree of DNA damage, we tested temsirolimus, a rapamycin analog with a more favorable pharmacokinetic profile than rapamycin. We report that temsirolimus decreases progerin levels, increases proliferation, reduces misshapen nuclei, and partially ameliorates DNA damage, but does not improve proteasome activity or mitochondrial dysfunction. Our findings suggest that future therapeutic strategies should identify new drug combinations and treatment regimens that target all the dysfunctional hallmarks that characterize HGPS cells. PMID:28033363

  3. Energy Landscape of Cellular Networks

    Science.gov (United States)

    Wang, Jin

    2008-03-01

    Cellular Networks are in general quite robust and perform their biological functions against the environmental perturbations. Progresses have been made from experimental global screenings, topological and engineering studies. However, there are so far few studies of why the network should be robust and perform biological functions from global physical perspectives. In this work, we will explore the global properties of the network from physical perspectives. The aim of this work is to develop a conceptual framework and quantitative physical methods to study the global nature of the cellular network. The main conclusion of this presentation is that we uncovered the underlying energy landscape for several small cellular networks such as MAPK signal transduction network and gene regulatory networks, from the experimentally measured or inferred inherent chemical reaction rates. The underlying dynamics of these networks can show bi-stable as well as oscillatory behavior. The global shapes of the energy landscapes of the underlying cellular networks we have studied are robust against perturbations of the kinetic rates and environmental disturbances through noise. We derived a quantitative criterion for robustness of the network function from the underlying landscape. It provides a natural explanation of the robustness and stability of the network for performing biological functions. We believe the robust landscape is a global universal property for cellular networks. We believe the robust landscape is a quantitative realization of Darwinian principle of natural selection at the cellular network level. It may provide a novel algorithm for optimizing the network connections, which is crucial for the cellular network design and synthetic biology. Our approach is general and can be applied to other cellular networks.

  4. Inside the Spiral of Dysfunction: The Personal Consequences of Working for a Dysfunctional Leader

    Science.gov (United States)

    Shuck, Brad; Rose, Kevin; Bergman, Matt

    2015-01-01

    Dysfunctional leaders suffocate others with coercive power and ego, are unpredictable, and often lack self-awareness about their dysfunction. Dysfunctional leaders are incredibly difficult to work with and can cause a series of cascading personal consequences for employees who work with them. This Perspectives in Human Resource Development essay…

  5. Diabetes and sexual dysfunction: current perspectives

    Directory of Open Access Journals (Sweden)

    Maiorino MI

    2014-03-01

    Full Text Available Maria Ida Maiorino,1 Giuseppe Bellastella,1 Katherine Esposito2 1Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Naples, Italy; 2Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy Abstract: Diabetes mellitus is one of the most common chronic diseases in nearly all countries. It has been associated with sexual dysfunction, both in males and in females. Diabetes is an established risk factor for sexual dysfunction in men, as a threefold increased risk of erectile dysfunction was documented in diabetic men, as compared with nondiabetic men. Among women, evidence regarding the association between diabetes and sexual dysfunction are less conclusive, although most studies have reported a higher prevalence of female sexual dysfunction in diabetic women as compared with nondiabetic women. Female sexual function appears to be more related to social and psychological components than to the physiological consequence of diabetes. Hyperglycemia, which is a main determinant of vascular and microvascular diabetic complications, may participate in the pathogenetic mechanisms of sexual dysfunction in diabetes. Moreover, diabetic people may present several clinical conditions, including hypertension, overweight and obesity, metabolic syndrome, cigarette smoking, and atherogenic dyslipidemia, which are themselves risk factors for sexual dysfunction, both in men and in women. The adoption of healthy lifestyles may reduce insulin resistance, endothelial dysfunction, and oxidative stress – all of which are desirable achievements in diabetic patients. Improved well-being may further contribute to reduce and prevent sexual dysfunction in both sexes. Keywords: diabetes mellitus, diabetes complications, erectile dysfunction, female sexual dysfunction, lifestyle changes

  6. Mathematical Modeling of Cellular Metabolism.

    Science.gov (United States)

    Berndt, Nikolaus; Holzhütter, Hermann-Georg

    2016-01-01

    Cellular metabolism basically consists of the conversion of chemical compounds taken up from the extracellular environment into energy (conserved in energy-rich bonds of organic phosphates) and a wide array of organic molecules serving as catalysts (enzymes), information carriers (nucleic acids), and building blocks for cellular structures such as membranes or ribosomes. Metabolic modeling aims at the construction of mathematical representations of the cellular metabolism that can be used to calculate the concentration of cellular molecules and the rates of their mutual chemical interconversion in response to varying external conditions as, for example, hormonal stimuli or supply of essential nutrients. Based on such calculations, it is possible to quantify complex cellular functions as cellular growth, detoxification of drugs and xenobiotic compounds or synthesis of exported molecules. Depending on the specific questions to metabolism addressed, the methodological expertise of the researcher, and available experimental information, different conceptual frameworks have been established, allowing the usage of computational methods to condense experimental information from various layers of organization into (self-) consistent models. Here, we briefly outline the main conceptual frameworks that are currently exploited in metabolism research.

  7. Environmental Enteric Dysfunction in Children.

    Science.gov (United States)

    Syed, Sana; Ali, Asad; Duggan, Christopher

    2016-07-01

    Diarrheal diseases are a major cause of childhood death in resource-poor countries, killing approximately 760,000 children younger than 5 years each year. Although deaths due to diarrhea have declined dramatically, high rates of stunting and malnutrition have persisted. Environmental enteric dysfunction (EED) is a subclinical condition caused by constant fecal-oral contamination with resultant intestinal inflammation and villous blunting. These histological changes were first described in the 1960s, but the clinical effect of EED is only just being recognized in the context of failure of nutritional interventions and oral vaccines in resource-poor countries. We review the existing literature regarding the underlying causes of and potential interventions for EED in children, highlighting the epidemiology, clinical and histologic classification of the entity, and discussing novel biomarkers and possible therapies. Future research priorities are also discussed.

  8. Olfactory dysfunction in Down's Syndrome.

    Science.gov (United States)

    Murphy, C; Jinich, S

    1996-01-01

    Down's Syndrome subjects over 40 years old show neuropathology similar to that of Alzheimer's disease. The olfactory system is particularly vulnerable in Alzheimer's disease, both anatomically and functionally. Several measures of sensory and cognitive functioning were studied in the older Down's Syndrome patient, with the hypothesis of significant olfactory dysfunction. Participants were 23 Down's subjects, and 23 controls. The Dementia Rating Scale showed mean scores of 103 for Down's subjects and 141 for controls. Down's subjects showed significant deficits in odor detection threshold, odor identification, and odor recognition memory. Normal performance in a taste threshold task, similar to the olfactory threshold task in subject demands, suggested that the Down's syndrome subjects' poor performance was not due to task demands. Deficits in olfaction may provide a sensitive and early indicator of the deterioration and progression of the brain in older subjects with Down's Syndrome.

  9. Muscle dysfunction in male hypogonadism.

    Science.gov (United States)

    Chauhan, A K; Katiyar, B C; Misra, S; Thacker, A K; Singh, N K

    1986-05-01

    Twenty-eight consecutive male patients with primary and secondary hypogonadism (14 each) were evaluated clinically and electrophysiologically for muscle dysfunction. Although generalised muscle weakness was initially reported by only 9 patients, on direct questioning, it was recorded in 19. Objective weakness was found in 13 patients and it involved both the proximal and distal limb muscles. Quantitative electromyography showed evidence of myopathy in the proximal muscle in 25 patients, i.e., reduced MUP duration and amplitude with increased polyphasia in the deltoid and the gluteus maximus. There were no denervation potentials. None of the patients showed clinical neuropathy or NCV abnormalities. Thus, the profile of muscle involvement in hypogonadism closely simulates limb-girdle muscular dystrophy and other endocrine myopathies. The incidence of muscle involvement was higher in secondary hypogonadism. Diminished androgens in primary hypogonadism and diminished growth hormone in the secondary hypogonadism are probably responsible for the myopathy.

  10. Animal models of erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Snehlata V Gajbhiye

    2015-01-01

    Full Text Available Animal models have contributed to a great extent to understanding and advancement in the field of sexual medicine. Many current medical and surgical therapies in sexual medicine have been tried based on these animal models. Extensive literature search revealed that the compiled information is limited. In this review, we describe various experimental models of erectile dysfunction (ED encompassing their procedures, variables of assessment, advantages and disadvantages. The search strategy consisted of review of PubMed based articles. We included original research work and certain review articles available in PubMed database. The search terms used were "ED and experimental models," "ED and nervous stimulation," "ED and cavernous nerve stimulation," "ED and central stimulation," "ED and diabetes mellitus," "ED and ageing," "ED and hypercholesteremia," "ED and Peyronie′s disease," "radiation induced ED," "telemetric recording," "ED and mating test" and "ED and non-contact erection test."

  11. Flibanserin for female sexual dysfunction.

    Science.gov (United States)

    Reviriego, C

    2014-08-01

    Hypoactive sexual desire disorder (HSDD) is the most commonly described form of female sexual dysfunction. There is currently no pharmacological therapy approved to treat HSDD, and therefore, there is an unmet medical need for the development of efficacious treatment alternatives. Flibanserin is a novel, non-hormonal drug for the treatment of HSDD in pre- and postmenopausal women, although the application submitted to the U.S. Food and Drug Administration by Sprout Pharmaceuticals is only for premenopausal women. Flibanserin works by correcting an imbalance of the levels of the neurotransmitters that affect sexual desire. More specifically, flibanserin increases dopamine and norepinephrine, both responsible for sexual excitement, and decreases serotonin, responsible for sexual inhibition. Clinically, flibanserin has exhibited some encouraging results in terms of its ability to increase the frequency of satisfying sexual events, and the intensity of sexual desire. However, adverse events such as dizziness, nausea, fatigue and somnolence, typical of a centrally acting drug, are also frequently related to flibanserin treatment.

  12. Coronary microvascular dysfunction: an update

    Science.gov (United States)

    Crea, Filippo; Camici, Paolo G.; Bairey Merz, Cathleen Noel

    2014-01-01

    Many patients undergoing coronary angiography because of chest pain syndromes, believed to be indicative of obstructive atherosclerosis of the epicardial coronary arteries, are found to have normal angiograms. In the past two decades, a number of studies have reported that abnormalities in the function and structure of the coronary microcirculation may occur in patients without obstructive atherosclerosis, but with risk factors or with myocardial diseases as well as in patients with obstructive atherosclerosis; furthermore, coronary microvascular dysfunction (CMD) can be iatrogenic. In some instances, CMD represents an epiphenomenon, whereas in others it is an important marker of risk or may even contribute to the pathogenesis of cardiovascular and myocardial diseases, thus becoming a therapeutic target. This review article provides an update on the clinical relevance of CMD in different clinical settings and also the implications for therapy. PMID:24366916

  13. Nutraceuticals, aging, and cognitive dysfunction.

    Science.gov (United States)

    Head, Elizabeth; Zicker, Steven C

    2004-01-01

    Decline in cognitive function that accompanies aging in dogs might have a biological basis, and many of the disorders associated with aging in canines might be preventable through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants might be one class of nutraceutical that benefits aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which can lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes might lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs; however, determining which compounds, combinations, dosage ranges, when to initiate intervention, and long-term effects constitute critical gaps in knowledge about this subject.

  14. Ambulatory anaesthesia and cognitive dysfunction

    DEFF Research Database (Denmark)

    Rasmussen, Lars S; Steinmetz, Jacob

    2015-01-01

    serious adverse outcomes, hence difficult to obtain sound scientific evidence for avoiding complications. RECENT FINDINGS: Few studies have assessed recovery of cognitive function after ambulatory surgery, but it seems that both propofol and modern volatile anaesthetics are rational choices for general...... anaesthesia in the outpatient setting. Cognitive complications such as delirium and postoperative cognitive dysfunction are less frequent in ambulatory surgery than with hospitalization. SUMMARY: The elderly are especially susceptible to adverse effects of the hospital environment such as immobilisation......, sleep deprivation, unfamiliar surroundings, and medication errors. Enhanced recovery programmes (fast-track regimens) may allow earlier discharge which is probably beneficial for the elderly. Frailty is becoming an increasingly important concept that needs to be clinically considered in elderly patients...

  15. Thyroid dysfunction in infertile women

    Directory of Open Access Journals (Sweden)

    S G Perminova

    2011-12-01

    Full Text Available Objective. To study the rate and structure of thyroid diseases in infertile women and to asses their reproductive system depending upon the thyroid pathology. Subjects and methods. The study was based on the results of screening of T status of 496 women with infertility (main group and 80 fertile women (control group. Traditional methods of diagnosis of infertility were used along with special methods of investigation including assessment of function and structure of T (TTH, fT4, fT3, AT-TPO, AT-rTTH, ultrasound examination of T, thin-niddle aspirational biopsy, scintigraphy of T. A complex evaluation of the reproductive system status in infertile women was done depending on the type of T pathology. Results. Infertile women were found to suffer from thyroid dysfunction 3.8 times as more often as fertile ones (48% and 12.5%, p <0.05. Its structure included mainly AT-TPO carrier phenomenon in combination with ultrasound markers of thyroid autoimmunity (24%, hypothyroidism following thyroid autoimmunity (9.4% demonstrating itself as clinical (0.8%, subclinical (8.6%, and euthyroid (7.8% goiters. The portion of women with infertility and hyperthyroidism was small (0.6%. An association of thyroid autoimmunity with idiopathic infertility, endometriosis, endocrine infertility was found. Conclusion. It is necessary to perform a screening assessment of the function and structure of T in infertile women within diagnostic search for the reasons of infertility and in-time correction of the revealed thyroid dysfunction.

  16. Test Performance Related Dysfunctional Beliefs

    Directory of Open Access Journals (Sweden)

    Recep TÜTÜNCÜ

    2012-11-01

    Full Text Available Objective: Examinations by using tests are very frequently used in educational settings and successful studying before the examinations is a complex matter to deal with. In order to understand the determinants of success in exams better, we need to take into account not only emotional and motivational, but also cognitive aspects of the participants such as dysfunctional beliefs. Our aim is to present the relationship between candidates’ characteristics and distorted beliefs/schemata just before an examination. Method: The subjects of the study were 30 female and 30 male physicians who were about to take the medical specialization exam (MSE in Turkey. Dysfunctional Attitude Scale (DAS and Young Schema Questionnaire Short Form (YSQ-SF were applied to the subjects. The statistical analysis was done using the F test, Mann-Whitney, Kruskal-Wallis, chi-square test and spearman’s correlation test. Results: It was shown that some of the DAS and YSQ-SF scores were significantly higher in female gender, in the group who could not pass the exam, who had repetitive examinations, who had their first try taking an examination and who were unemployed at the time of the examination. Conclusion: Our findings indicate that candidates seeking help before MSE examination could be referred for cognitive therapy or counseling even they do not have any psychiatric diagnosis due to clinically significant cognitive distortion. Measurement and treatment of cognitive distortions that have negative impact on MSE performance may improve the cost-effectiveness and mental well being of the young doctors.

  17. Vitamin A supplementation redirects the flow of retinyl esters from peripheral to central organs of neonatal rats raised under vitamin A-marginal conditions.

    Science.gov (United States)

    Hodges, Joanna K; Tan, Libo; Green, Michael H; Ross, A Catharine

    2017-05-01

    Background: Vitamin A (VA; retinol) supplementation is used to reduce child mortality in countries with high rates of malnutrition. Existing research suggests that neonates (esters (CM-REs), retinol bound to retinol-binding protein (RBP-ROH), and total retinol were estimated in WinSAAM software.Results: VA supplementation redirected the flow of CM-REs from peripheral to central organs and accumulated mainly in the liver. The RBP-ROH released from the liver was acquired mainly by the peripheral tissues but not retained efficiently, causing repeated recycling of retinol between plasma and tissues (541 compared with 5 times in the supplemented group and control group, respectively) and its rapid turnover in all organs, except the brain and white adipose tissue. Retinol stores in the liver lasted for ∼2 wk before being gradually transferred to other organs.Conclusions: VA supplementation administered in a single high dose during the first month after birth is readily acquired but not retained efficiently in peripheral tissues of neonatal rats, suggesting that a more frequent, lower-dose supplementation may be necessary to maintain steady VA concentrations in rapidly developing neonatal tissues. © 2017 American Society for Nutrition.

  18. A phase I clinical trial of adoptive transfer of folate receptor-alpha redirected autologous T cells for recurrent ovarian cancer

    Directory of Open Access Journals (Sweden)

    Kandalaft Lana E

    2012-08-01

    Full Text Available Abstract Purpose In spite of increased rates of complete response to initial chemotherapy, most patients with advanced ovarian cancer relapse and succumb to progressive disease. Rationale Genetically reprogrammed, patient-derived chimeric antigen receptor (CAR-T lymphocytes with the ability to recognize predefined surface antigens with high specificity in a non-MHC restricted manner have shown increasing anti-tumor efficacy in preclinical and clinical studies. Folate receptor-α (FRα is an ovarian cancer-specific tumor target; however, it is expressed at low levels in certain organs with risk for toxicity. Design Here we propose a phase I study testing the feasibility, safety and preliminary activity of FRα-redirected CAR-T cells bearing the CD137 (4-1BB costimulatory domain, administered after lymphodepletion for the treatment of recurrent ovarian cancer. A novel trial design is proposed that maximizes safety features. Innovation This design involves an initial accelerated dose escalation phase of FR-α CAR-T cells followed by a standard 3 + 3 escalation phase. A split-dose approach is proposed to mitigate acute adverse events. Furthermore, infusion of bulk untransduced autologous peripheral blood lymphocytes (PBL is proposed two days after CAR-T cell infusion at the lower dose levels of CAR-T cells, to suppress excessive expansion of CAR-T cells in vivo and mitigate toxicity.

  19. Immunotherapy of HCC metastases with autologous T cell receptor redirected T cells, targeting HBsAg in a liver transplant patient.

    Science.gov (United States)

    Qasim, Waseem; Brunetto, Maurizia; Gehring, Adam J; Xue, Shao-An; Schurich, Anna; Khakpoor, Atefeh; Zhan, Hong; Ciccorossi, Pietro; Gilmour, Kimberly; Cavallone, Daniela; Moriconi, Francesco; Farzhenah, Farzin; Mazzoni, Alessandro; Chan, Lucas; Morris, Emma; Thrasher, Adrian; Maini, Mala K; Bonino, Ferruccio; Stauss, Hans; Bertoletti, Antonio

    2015-02-01

    HBV-DNA integration frequently occurs in HBV-related hepatocellular carcinoma (HCC), but whether HBV antigens are expressed in HCC cells and can be targeted by immune therapeutic strategies remains controversial. Here, we first characterized HBV antigen expression in HCC metastases, occurring in a patient who had undergone liver transplantation for HBV-related HCC. We then deployed for the first time in HCC autologous T cells, genetically modified to express an HBsAg specific T cell receptor, as therapy against chemoresistant extrahepatic metastases. We confirmed that HBV antigens were expressed in HCC metastases (but not in the donor liver) and demonstrated that tumour cells were recognized in vivo by lymphocytes, engineered to express an HBV-specific T cell receptor (TCR). Gene-modified T cells survived, expanded and mediated a reduction in HBsAg levels without exacerbation of liver inflammation or other toxicity. Whilst clinical efficacy was not established in this subject with end-stage metastatic disease, we confirm the feasibility of providing autologous TCR-redirected therapy against HCC and advocate this strategy as a novel therapeutic opportunity in hepatitis B-associated malignancies.

  20. Treatment of Intracranial Aneurysms with Flow Re-direction Endoluminal Device - A Single Centre Experience with Short-term Follow-up Results

    Science.gov (United States)

    Chong, Wing Ho; Lam, Samuel Siu Kei; Siu, Jimmy Chi Wai; Tan, Chong Boon; Wong, Yiu Chung

    2017-01-01

    Purpose A flow diverter (FD) is an effective treatment option for intracranial aneurysms. The Flow Re-direction Endoluminal Device (FRED) is a relatively new flow diverter with a unique dual-layer design. We report our experience and short-term results with the FRED. Materials and Methods We did a retrospective review of all consecutive cases in which the FRED was used to treat intracranial aneurysms at a single institution from March 2014 till December 2015. Clinical parameters, aneurysm characteristics, technical results and short-term outcomes were reviewed. Results Eleven intracranial aneurysms were treated with the FRED in 11 patients. The technical device deployment success rate was 100%. Immediate reduction in intra-aneurysmal flow after deployment was noted in 10 cases. The aneurysm occlusion rate at 6 months was 75%. There was 1 complication of in-stent thrombosis immediately after deployment. There was no side branch occlusion, delayed aneurysm rupture, stroke, or intraparenchymal haemorrhage. There was no neurological deficit, morbidity, or mortality. Conclusion The FRED is a new FD. It has shown to be safe and effective in our series. The unique dual-layer design of the device renders it to have technical advantages over other FDs. The 6-month aneurysm occlusion rate and complication profile of FRED are similar to other FDs. PMID:28316865

  1. Metabolic Flux Redirection and Transcriptomic Reprogramming in the Albino Tea Cultivar ‘Yu-Jin-Xiang’ with an Emphasis on Catechin Production

    Science.gov (United States)

    Liu, Guo-Feng; Han, Zhuo-Xiao; Feng, Lin; Gao, Li-Ping; Gao, Ming-Jun; Gruber, Margaret Y.; Zhang, Zhao-Liang; Xia, Tao; Wan, Xiao-Chun; Wei, Shu

    2017-01-01

    In this study, shade-induced conversion from a young pale/yellow leaf phenotype to a green leaf phenotype was studied using metabolic and transcriptomic profiling and the albino cultivar ‘Yu-Jin-Xiang’ (‘YJX’) of Camellia sinensis for a better understanding of mechanisms underlying the phenotype shift and the altered catechin and theanine production. Shaded leaf greening resulted from an increase in leaf chlorophyll and carotenoid abundance and chloroplast development. A total of 1,196 differentially expressed genes (DEGs) were identified between the ‘YJX’ pale and shaded green leaves, and these DEGs affected ‘chloroplast organization’ and ‘response to high light’ besides many other biological processes and pathways. Metabolic flux redirection and transcriptomic reprogramming were found in flavonoid and carotenoid pathways of the ‘YJX’ pale leaves and shaded green leaves to different extents compared to the green cultivar ‘Shu-Cha-Zao’. Enhanced production of the antioxidant quercetin rather than catechin biosynthesis was correlated positively with the enhanced transcription of FLAVONOL SYNTHASE and FLAVANONE/FLAVONOL HYDROXYLASES leading to quercetin accumulation and negatively correlated to suppressed LEUCOANTHOCYANIDIN REDUCTASE, ANTHOCYANIDIN REDUCTASE and SYNTHASE leading to catechin biosynthesis. The altered levels of quercetin and catechins in ‘YJX’ will impact on its tea flavor and health benefits. PMID:28332598

  2. Metabolic Flux Redirection and Transcriptomic Reprogramming in the Albino Tea Cultivar 'Yu-Jin-Xiang' with an Emphasis on Catechin Production.

    Science.gov (United States)

    Liu, Guo-Feng; Han, Zhuo-Xiao; Feng, Lin; Gao, Li-Ping; Gao, Ming-Jun; Gruber, Margaret Y; Zhang, Zhao-Liang; Xia, Tao; Wan, Xiao-Chun; Wei, Shu

    2017-03-23

    In this study, shade-induced conversion from a young pale/yellow leaf phenotype to a green leaf phenotype was studied using metabolic and transcriptomic profiling and the albino cultivar 'Yu-Jin-Xiang' ('YJX') of Camellia sinensis for a better understanding of mechanisms underlying the phenotype shift and the altered catechin and theanine production. Shaded leaf greening resulted from an increase in leaf chlorophyll and carotenoid abundance and chloroplast development. A total of 1,196 differentially expressed genes (DEGs) were identified between the 'YJX' pale and shaded green leaves, and these DEGs affected 'chloroplast organization' and 'response to high light' besides many other biological processes and pathways. Metabolic flux redirection and transcriptomic reprogramming were found in flavonoid and carotenoid pathways of the 'YJX' pale leaves and shaded green leaves to different extents compared to the green cultivar 'Shu-Cha-Zao'. Enhanced production of the antioxidant quercetin rather than catechin biosynthesis was correlated positively with the enhanced transcription of FLAVONOL SYNTHASE and FLAVANONE/FLAVONOL HYDROXYLASES leading to quercetin accumulation and negatively correlated to suppressed LEUCOANTHOCYANIDIN REDUCTASE, ANTHOCYANIDIN REDUCTASE and SYNTHASE leading to catechin biosynthesis. The altered levels of quercetin and catechins in 'YJX' will impact on its tea flavor and health benefits.

  3. Sublingual immunization with recombinant adenovirus encoding SARS-CoV spike protein induces systemic and mucosal immunity without redirection of the virus to the brain

    Directory of Open Access Journals (Sweden)

    Shim Byoung-Shik

    2012-09-01

    Full Text Available Abstract Background Sublingual (s.l. administration of soluble protein antigens, inactivated viruses, or virus-like particles has been shown to induce broad immune responses in mucosal and extra-mucosal tissues. Recombinant replication-defective adenovirus vectors (rADVs infect mucosa surface and therefore can serve as a mucosal antigen delivery vehicle. In this study we examined whether s.l. immunization with rADV encoding spike protein (S (rADV-S of severe acute respiratory syndrome-associated coronavirus (SARS-CoV induces protective immunity against SARS-CoV and could serve as a safe mucosal route for delivery of rADV. Results Here, we show that s.l. administration of rADV-S induced serum SARS-CoV neutralizing and airway IgA antibodies in mice. These antibody responses are comparable to those induced by intranasal (i.n. administration. In addition, s.l. immunization induced antigen-specific CD8+ T cell responses in the lungs that are superior to those induced by intramuscular immunization. Importantly, unlike i.n. administration, s.l. immunization with rADV did not redirect the rADV vector to the olfactory bulb. Conclusion Our study indicates that s.l. immunization with rADV-S is safe and effective in induction of a broad spectrum of immune responses and presumably protection against infection with SARS-CoV.

  4. Redirected Primary Human Chimeric Antigen Receptor Natural Killer Cells As an “Off-the-Shelf Immunotherapy” for Improvement in Cancer Treatment

    Science.gov (United States)

    Oberschmidt, Olaf; Kloess, Stephan; Koehl, Ulrike

    2017-01-01

    Primary human natural killer (NK) cells recognize and subsequently eliminate virus infected cells, tumor cells, or other aberrant cells. However, cancer cells are able to develop tumor immune escape mechanisms to undermine this immune control. To overcome this obstacle, NK cells can be genetically modified to express chimeric antigen receptors (CARs) in order to improve specific recognition of cancer surface markers (e.g., CD19, CD20, and ErbB2). After target recognition, intracellular CAR domain signaling (CD3ζ, CD28, 4-1BB, and 2B4) leads to activation of PI3K or DNAX proteins (DAP10, DAP12) and finally to enhanced cytotoxicity, proliferation, and/or interferon γ release. This mini-review summarizes both the first preclinical trials with CAR-engineered primary human NK cells and the translational implications for “off-the-shelf immunotherapy” in cancer treatment. Signal transduction in NK cells as well as optimization of CAR signaling will be described, becoming more and more a focal point of interest in addition to redirected T cells. Finally, strategies to overcome off-target effects will be discussed in order to improve future clinical trials and to avoid attacking healthy tissues. PMID:28649246

  5. Understanding taste dysfunction in patients with cancer.

    Science.gov (United States)

    McLaughlin, Laura; Mahon, Suzanne M

    2012-04-01

    Taste dysfunction is a significant but underestimated issue for patients with cancer. Impaired taste results in changes in diet and appetite, early satiety, and impaired social interactions. Nurses can play a key role in educating patients and families on the pathophysiology of taste dysfunction by suggesting interventions to treat the consequences of taste dysfunction, when available, and offering psychosocial support as patients cope with this often devastating consequence of treatment. Taste recognition helps humans identify the nutritional quality of food and signals the digestive tract to begin secreting enzymes. Spoiled or tainted foods typically are recognized by their bad taste. Along with the other sensory systems, taste is crucial for helping patients treated for cancer feel normal. This article will review the anatomy and physiology of taste; define the different types of taste dysfunction, including the underlying pathophysiologic basis related to cancer treatment; and discuss potential nursing interventions to manage the consequences of taste dysfunction.

  6. Olfactory dysfunction in Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Zou YM

    2016-04-01

    Full Text Available Yong-ming Zou, Da Lu, Li-ping Liu, Hui-hong Zhang, Yu-ying Zhou Department of Neurology, Tianjin Huanhu Hospital, Tianjin, People’s Republic of China Abstract: Alzheimer’s disease (AD is a common neurodegenerative disorder with the earliest clinical symptom of olfactory dysfunction, which is a potential clinical marker for AD severity and progression. However, many questions remain unanswered. This article reviews relevant research on olfactory dysfunction in AD and evaluates the predictive value of olfactory dysfunction for the epidemiological, pathophysiological, and clinical features of AD, as well as for the conversion of cognitive impairment to AD. We summarize problems of existing studies and provide a useful reference for further studies in AD olfactory dysfunction and for clinical applications of olfactory testing. Keywords: olfactory dysfunction, Alzheimer’s disease, olfactory testing, progress

  7. Endothelial Dysfunction in Renal Failure: Current Update.

    Science.gov (United States)

    Radenkovic, Miroslav; Stojanovic, Marko; Prostran, Milica

    2016-01-01

    Endothelial dysfunction is principally characterized by impaired endothelium- dependent transduction mechanisms related to vascular relaxation, as an outcome of decreased release of endothelium-derived relaxing factors, mainly nitric oxide, as well as augmented oxidative stress, increased inflammation and predominance of vascular action produced by endothelium-derived contracting factors. Current data strongly suggest that pathological development of different types of kidney impairment with further progression to renal failure includes notable vascular changes associated with endothelial dysfunction. In accordance, this scientific field represents an advancing area of investigation, involving different biomarkers of endothelial dysfunction linked to renal impairment, as well as clinical findings with new information that can provide a more comprehensive understanding of the role of endothelial dysfunction in kidney disease. With regards to quoted facts, the aim of this article was to review the latest data related to endothelial dysfunction and renal failure by selection of relevant articles released from 2010 to 2015.

  8. Diastolic dysfunction in the critically ill patient.

    Science.gov (United States)

    Suárez, J C; López, P; Mancebo, J; Zapata, L

    2016-11-01

    Left ventricular diastolic dysfunction is a common finding in critically ill patients. It is characterized by a progressive deterioration of the relaxation and the compliance of the left ventricle. Two-dimensional and Doppler echocardiography is a cornerstone in its diagnosis. Acute pulmonary edema associated with hypertensive crisis is the most frequent presentation of diastolic dysfunction critically ill patients. Myocardial ischemia, sepsis and weaning failure from mechanical ventilation also may be associated with diastolic dysfunction. The treatment is based on the reduction of pulmonary congestion and left ventricular filling pressures. Some studies have found a prognostic role of diastolic dysfunction in some diseases such as sepsis. The present review aims to analyze thoroughly the echocardiographic diagnosis and the most frequent scenarios in critically ill patients in whom diastolic dysfunction plays a key role. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  9. Attachment, borderline personality, and romantic relationship dysfunction.

    Science.gov (United States)

    Hill, Jonathan; Stepp, Stephanie D; Wan, Ming Wai; Hope, Holly; Morse, Jennifer Q; Steele, Miriam; Steele, Howard; Pilkonis, Paul A

    2011-12-01

    Previous studies have implicated attachment and disturbances in romantic relationships as important indicators for Borderline Personality Disorder (BPD). The current research extends our current knowledge by examining the specific associations among attachment, romantic relationship dysfunction, and BPD, above and beyond the contribution of emotional distress and nonromantic interpersonal functioning in two distinct samples. Study 1 comprised a community sample of women (N = 58) aged 25-36. Study 2 consisted of a psychiatric sample (N = 138) aged 21-60. Results from both Study 1 and Study 2 demonstrated that (1) attachment was specifically related to BPD symptoms and romantic dysfunction, (2) BPD symptoms were specifically associated with romantic dysfunction, and (3) the association between attachment and romantic dysfunction was statistically mediated by BPD symptoms. The findings support specific associations among attachment, BPD symptoms, and romantic dysfunction.

  10. Hierarchical Cellular Structures in High-Capacity Cellular Communication Systems

    CERN Document Server

    Jain, R K; Agrawal, N K

    2011-01-01

    In the prevailing cellular environment, it is important to provide the resources for the fluctuating traffic demand exactly in the place and at the time where and when they are needed. In this paper, we explored the ability of hierarchical cellular structures with inter layer reuse to increase the capacity of mobile communication network by applying total frequency hopping (T-FH) and adaptive frequency allocation (AFA) as a strategy to reuse the macro and micro cell resources without frequency planning in indoor pico cells [11]. The practical aspects for designing macro- micro cellular overlays in the existing big urban areas are also explained [4]. Femto cells are inducted in macro / micro / pico cells hierarchical structure to achieve the required QoS cost effectively.

  11. Effect of agmatine on experimental vascular endothelial dysfunction.

    Science.gov (United States)

    Nader, M A; Gamiel, N M; El-Kashef, H; Zaghloul, M S

    2016-05-01

    This study was designed to investigate the effect of agmatine sulfate (AG, CAS2482-00-0) in nicotine (NIC)-induced vascular endothelial dysfunction (VED) in rabbits. NIC was administered to produce VED in rabbits with or without AG for 6 weeks. Serum lipid profile, serum thiobarbituric acid reactive substances, reduced glutathione, superoxide dismutase generation, serum nitrite/nitrate, serum vascular cellular adhesion molecule-1 (VCAM-1), and aortic nuclear factor κB (NF-κB) levels were analyzed.Treatment with AG markedly improves lipid profile and prevented NIC-induced VED and oxidative stress. The mechanism of AG in improving NIC-induced VED may be due to the significant reduction in serum VCAM-1 levels and aortic NF-κB. Thus, it may be concluded that AG reduces the oxidative stress, nitric oxide production, VCAM-1 levels, and aortic NF-κB expression, thereby consequently improving the integrity of vascular endothelium.

  12. TP53 dysfunction in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Lu, Ting-Xun; Young, Ken H; Xu, Wei; Li, Jian-Yong

    2016-01-01

    The aberrations of TP53 gene and dysregulation of the TP53 pathway are important in the pathogenesis of many human cancers, including malignant lymphomas, especially for diffuse large B cell lymphoma (DLBCL). By regulating many downstream target genes or molecules, TP53 governs major defenses against tumor growth and promotes cellular DNA repair, apoptosis, autophagy, cell cycle arrest, signaling, transcription, immune or inflammatory responses and metabolism. Dysfunction of TP53, including microRNA regulations, copy number alterations of TP53 pathway and TP53 itself, dysregulation of TP53 regulators, and somatic mutations by abnormal TP53 function modes, play an important role in lymphoma generation, progression and invasion. The role of TP53 in DLBCL has been widely explored recently. In this review, we summarized recent advances on different mechanisms of TP53 in DLBCL and new therapeutic approaches to overcome TP53 inactivation.

  13. Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong-Eun [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Woo, Seon Rang [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Kang, Chang-Mo [Laboratory of Cytogenetics and Tissue Regeneration, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Juhn, Kyoung-Mi; Ju, Yeun-Jin; Shin, Hyun-Jin; Joo, Hyun-Yoo; Park, Eun Ran; Park, In-chul; Hong, Sung Hee; Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Lee, Jung-Kee [Department of Life Science and Genetic Engineering, Paichai University, Daejeon 302-735 (Korea, Republic of); Kim, Hae Kwon [Department of Biotechnology, Seoul Woman' s University, Seoul 139-774 (Korea, Republic of); Cho, Myung-Haing [Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-74-2 (Korea, Republic of); Park, Gil Hong [Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Lee, Kee-Ho, E-mail: khlee@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2011-01-14

    Research highlights: {yields} Paclitaxel serves as a stimulator of chromosomal fusion in cells in which telomeres are dysfunctional. {yields} Typical fusions involve p-arms, but paclitaxel-induced fusions occur between both q- and p-arms. {yields} Paclitaxel-stimulated fusions in cells in which telomeres are dysfunctional evoke prolonged G2/M cell cycle arrest and delay multinucleation. {yields} Upon telomere erosion, paclitaxel promotes chromosomal instability and subsequent apoptosis. {yields} Chromosomal fusion enhances paclitaxel chemosensitivity under telomere dysfunction. -- Abstract: The anticancer effect of paclitaxel is attributable principally to irreversible promotion of microtubule stabilization and is hampered upon development of chemoresistance by tumor cells. Telomere shortening, and eventual telomere erosion, evoke chromosomal instability, resulting in particular cellular responses. Using telomerase-deficient cells derived from mTREC-/-p53-/- mice, here we show that, upon telomere erosion, paclitaxel propagates chromosomal instability by stimulating chromosomal end-to-end fusions and delaying the development of multinucleation. The end-to-end fusions involve both the p- and q-arms in cells in which telomeres are dysfunctional. Paclitaxel-induced chromosomal fusions were accompanied by prolonged G2/M cell cycle arrest, delayed multinucleation, and apoptosis. Telomere dysfunctional cells with mutlinucleation eventually underwent apoptosis. Thus, as telomere erosion proceeds, paclitaxel stimulates chromosomal fusion and instability, and both apoptosis and chemosensitization eventually develop.

  14. Prognosis of Different Cellular Generations

    Directory of Open Access Journals (Sweden)

    Preetish Ranjan

    2013-04-01

    Full Text Available Technological advancement in mobile telephony from 1G to 3G, 4G and 5G has a very axiomatic fact that made an entire world a global village. The cellular system employs a different design approach and technology that most commercial radio and television system use. In the cellular system, the service area is divided into cells and a transmitter is designed to serve an individual cell. The system seeks to make efficient use of available channels by using low-power transmitters to allow frequency reuse at a smaller distance. Maximizing the number of times each channel can be reused in a given geographical area is the key to an efficient cellular system design. During the past three decades, the world has seen significant changes in telecommunications industry. There have been some remarkable aspects to the rapid growth in wireless communications, as seen by the large expansion in mobile systems. This paper focuses on “Past, Present & Future of Cellular Telephony” and some light has been thrown upon the technologies of the cellular systems, namely 1G, 2G, 2.5G, 3G and future generations like 4G and 5G systems as well.

  15. Continuum representations of cellular solids

    Energy Technology Data Exchange (ETDEWEB)

    Neilsen, M.K.

    1993-09-01

    Cellular materials consist of interconnected struts or plates which form cells. The struts or plates are constructed from a variety of metals, polymers, ceramics and wood products. Cellular materials are often used in impact limiters for shipping containers to protect the contents from accidental impact events. These materials exhibit a variety of complex behavior when subjected to crushing loads. This research focuses on the development of continuum representations of cellular solids that can be used in the finite element analysis of shipping container accidents. A significant portion of this work is the development of a new methodology to relate localized deformations to appropriate constitutive descriptions. This methodology provides the insight needed to select constitutive descriptions for cellular solids that capture the localized deformations that are observed experimentally. Constitutive relations are developed for two different cellular materials, aluminum honeycomb and polyurethane foam. These constitutive relations are based on plasticity and continuum damage theories. Plasticity is used to describe the permanent deformation exhibited by both aluminum honeycomb and polyurethane foam. Continuum damage is needed to capture the change in elastic parameters due to cracking of the polyurethane cell wall materials. The new constitutive description of polyurethane foam is implemented in both static and dynamic finite element codes, and analytical and numerical predictions are compared with available experimental data.

  16. Classifying cellular automata using grossone

    Science.gov (United States)

    D'Alotto, Louis

    2016-10-01

    This paper proposes an application of the Infinite Unit Axiom and grossone, introduced by Yaroslav Sergeyev (see [7] - [12]), to the development and classification of one and two-dimensional cellular automata. By the application of grossone, new and more precise nonarchimedean metrics on the space of definition for one and two-dimensional cellular automata are established. These new metrics allow us to do computations with infinitesimals. Hence configurations in the domain space of cellular automata can be infinitesimally close (but not equal). That is, they can agree at infinitely many places. Using the new metrics, open disks are defined and the number of points in each disk computed. The forward dynamics of a cellular automaton map are also studied by defined sets. It is also shown that using the Infinite Unit Axiom, the number of configurations that follow a given configuration, under the forward iterations of cellular automaton maps, can now be computed and hence a classification scheme developed based on this computation.

  17. The role of neutrophils in immune dysfunction during severe inflammation.

    Science.gov (United States)

    Leliefeld, Pieter H C; Wessels, Catharina M; Leenen, Luke P H; Koenderman, Leo; Pillay, Janesh

    2016-03-23

    Critically ill post-surgical, post-trauma and/or septic patients are characterised by severe inflammation. This immune response consists of both a pro- and an anti-inflammatory component. The pro-inflammatory component contributes to (multiple) organ failure whereas occurrence of immune paralysis predisposes to infections. Strikingly, infectious complications arise in these patients despite the presence of a clear neutrophilia. We propose that dysfunction of neutrophils potentially increases the susceptibility to infections or can result in the inability to clear existing infections. Under homeostatic conditions these effector cells of the innate immune system circulate in a quiescent state and serve as the first line of defence against invading pathogens. In severe inflammation, however, neutrophils are rapidly activated, which affects their functional capacities, such as chemotaxis, phagocytosis, intra-cellular killing, NETosis, and their capacity to modulate adaptive immunity. This review provides an overview of the current understanding of neutrophil dysfunction in severe inflammation. We will discuss the possible mechanisms of downregulation of anti-microbial function, suppression of adaptive immunity by neutrophils and the contribution of neutrophil subsets to immune paralysis.

  18. Molecular profiling of mitochondrial dysfunction in Caenorhabditis elegans.

    Science.gov (United States)

    Polyak, Erzsebet; Zhang, Zhe; Falk, Marni J

    2012-01-01

    Cellular effects of primary mitochondrial dysfunction, as well as potential mitochondrial disease therapies, can be modeled in living animals such as the microscopic nematode, Caenorhabditis elegans. In particular, molecular analyses can provide substantial insight into the mechanism by which genetic and/or pharmacologic manipulations alter mitochondrial function. The relative expression of individual genes across both nuclear and mitochondrial genomes, as well as relative quantitation of mitochondrial DNA content, can be readily performed by quantitative real-time PCR (qRT-PCR) analysis of C. elegans. Additionally, microarray expression profiling offers a powerful tool by which to survey the global genetic consequences of various causes of primary mitochondrial dysfunction and potential therapeutic interventions at both the single gene and integrated pathway level. Here, we describe detailed protocols for RNA and DNA isolation from whole animal populations in C. elegans, qRT-PCR analysis of both nuclear and mitochondrial genes, and global nuclear genome expression profiling using the Affymetrix GeneChip C. elegans Genome Array.

  19. Mitochondrial dysfunction in schizophrenia: pathways, mechanisms and implications.

    Science.gov (United States)

    Rajasekaran, Ashwini; Venkatasubramanian, Ganesan; Berk, Michael; Debnath, Monojit

    2015-01-01

    Mitochondria play a critical role in regulating cellular functions including bioenergetics, calcium homeostasis, redox signalling, and apoptotic cell death. Mitochondria are also essential to many aspects of neurodevelopment and neuronal functions. However, mitochondrial impairment may affect bioenergetics in the developing brain and alter critical neuronal processes leading to neurodevelopmental abnormalities. Schizophrenia is a chronic and severe neuropsychiatric disorder of neurodevelopmental origin. Immuno-inflammatory pathway is one of the widely appreciated mechanisms that has consistently been implicated in the neurodevelopmental origin of schizophrenia. However, the source of inflammation and the underlying neurobiological mechanisms leading to schizophrenia are yet to be fully ascertained. Recent understanding reveals that perturbation of mitochondrial network dynamics might lead to various nervous system disorders with inflammatory pathologies. Mitochondrial deficit, altered redox balance and chronic low-grade inflammation are evident in schizophrenia. It is hypothesized that oxidative/nitrosative stress responses due to mitochondrial dysfunctions might activate immuno-inflammatory pathways and subsequently lead to neuroprogressive changes in schizophrenia. Herein, we summarise the current understanding of molecular links between mitochondrial dysfunctions and pathogenesis of schizophrenia based on evidence from genomics, proteomics and imaging studies, which together support a role for mitochondrial impairment in the pathogenetic pathways of schizophrenia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Most Do, but Some Do Not: CD4⁺CD25(-) T Cells, but Not CD4⁺CD25⁺ Treg Cells, Are Cytolytic When Redirected by a Chimeric Antigen Receptor (CAR).

    Science.gov (United States)

    Hombach, Andreas A; Abken, Hinrich

    2017-08-29

    Evidences are accumulating that CD4⁺ T cells can physiologically mediate antigen specific target cell lysis. By circumventing major histocompatibility complex (MHC)-restrictions through an engineered chimeric antigen receptor (CAR), CD4⁺ T cells lyse defined target cells as efficiently as do CD8⁺ T cells. However, the cytolytic capacity of redirected CD4⁺CD25(-) T cells, in comparison with CD4⁺CD25⁺ regulatory T (Treg) cells was so far not thoroughly defined. Treg cells require a strong CD28 signal together with CD3ζ for activation. We consequently used a CAR with combined CD28-CD3ζ signalling for redirecting CD4⁺CD25(-) T cells and CD4⁺CD25⁺ Treg cells from the same donor. CAR redirected activation of these T cell subsets and induced a distinct cytokine pattern with high IL-10 and a lack of IL-2 release by Treg cells. Despite strong antigen-specific activation, CAR Treg cells produced only weak target cell lysis, whereas CD4⁺CD25(-) CAR T cells were potent killers. Cytolysis did not correlate with the target cell sensitivity to Fas/FasL mediated killing; CD4⁺CD25(-) T cells upregulated perforin and granzyme B upon CAR activation, whereas Treg cells did less. The different cytolytic capacities of CAR redirected conventional CD4⁺ cells and Treg cells imply their use for different purposes in cell therapy.

  1. Lack of awareness of erectile dysfunction in many men with risk factors for erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Magee Michelle

    2010-11-01

    Full Text Available Abstract Background Men with erectile dysfunction often have concurrent medical conditions. Conversely, men with these conditions may also have underlying erectile dysfunction. The prevalence of unrecognized erectile dysfunction in men with comorbidities commonly associated with erectile dysfunction was determined in men invited to participate in a double-blind, randomized, placebo-controlled trial of sildenafil citrate. Methods Men ≥30 years old presenting with ≥1 erectile dysfunction risk factor (controlled hypertension, hypercholesterolemia, smoking, metabolic syndrome, stable coronary artery disease, diabetes, depression, lower urinary tract symptoms, obesity [body mass index ≥30 kg/m2] or waist circumference ≥40 inches, and not previously diagnosed with erectile dysfunction were evaluated. The screening question, "Do you have erectile dysfunction?," with responses of "no," "yes," and "unsure," and the Erectile Function domain of the International Index of Erectile Function (IIEF-EF were administered. Results Of 1084 men screened, 1053 answered the screening question and also had IIEF-EF scores. IIEF-EF scores indicating erectile dysfunction occurred in 71% (744/1053, of whom 54% (399/744 had moderate or severe erectile dysfunction. Of 139 answering "yes," 526 answering "unsure," and 388 answering "no," 96%, 90%, and 36%, respectively, had some degree of erectile dysfunction. The mean±SD (range number of risk factors was 2.9 ± 1.7 (3-8 in the "yes" group, 3.2 ± 1.7 (3-9 in the "unsure" group, and 2.6 ± 1.5 (2-8 in the "no" group. Conclusion Although awareness of having erectile dysfunction was low, most men with risk factors had IIEF-EF scores indicating erectile dysfunction. Erectile dysfunction should be suspected and assessed in men with risk factors, regardless of their apparent level of awareness of erectile dysfunction. Trial registration ClinicalTrials.gov Identifier NCT00343200.

  2. Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction.

    Directory of Open Access Journals (Sweden)

    Maria Giovanna Scioli

    Full Text Available Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery.We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS reduction, inducible nitric oxide synthase (iNOS and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF, placental growth factor (PlGF and reduction of NADPH-oxidase 4 (Nox4 expression. In serum-deprived human dermal microvascular endothelial cell cultures, PLC ameliorated endothelial dysfunction by increasing iNOS, PlGF, VEGF receptors 1 and 2 expression and NO level. In addition, PLC counteracted serum deprivation-induced impairment of mitochondrial β-oxidation, Nox4 and cellular adhesion molecule (CAM expression, ROS generation and leukocyte adhesion. Moreover, dermal microvascular endothelial cell dysfunction was prevented by Nox4 inhibition. Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction.PLC treatment improved rat skin flap viability, accelerated wound healing and dermal angiogenesis. The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction. Antioxidant therapy and

  3. Cellular models for Parkinson's disease.

    Science.gov (United States)

    Falkenburger, Björn H; Saridaki, Theodora; Dinter, Elisabeth

    2016-10-01

    Developing new therapeutic strategies for Parkinson's disease requires cellular models. Current models reproduce the two most salient changes found in the brains of patients with Parkinson's disease: The degeneration of dopaminergic neurons and the existence of protein aggregates consisting mainly of α-synuclein. Cultured cells offer many advantages over studying Parkinson's disease directly in patients or in animal models. At the same time, the choice of a specific cellular model entails the requirement to focus on one aspect of the disease while ignoring others. This article is intended for researchers planning to use cellular models for their studies. It describes for commonly used cell types the aspects of Parkinson's disease they model along with technical advantages and disadvantages. It might also be helpful for researchers from other fields consulting literature on cellular models of Parkinson's disease. Important models for the study of dopaminergic neuron degeneration include Lund human mesencephalic cells and primary neurons, and a case is made for the use of non-dopaminergic cells to model pathogenesis of non-motor symptoms of Parkinson's disease. With regard to α-synuclein aggregates, this article describes strategies to induce and measure aggregates with a focus on fluorescent techniques. Cellular models reproduce the two most salient changes of Parkinson's disease, the degeneration of dopaminergic neurons and the existence of α-synuclein aggregates. This article is intended for researchers planning to use cellular models for their studies. It describes for commonly used cell types and treatments the aspects of Parkinson's disease they model along with technical advantages and disadvantages. Furthermore, this article describes strategies to induce and measure aggregates with a focus on fluorescent techniques. This article is part of a special issue on Parkinson disease.

  4. Psychogenic erectile dysfunction. Classification and management.

    Science.gov (United States)

    Rosen, R C

    2001-05-01

    Psychogenic factors are involved alone or in combination with organic causes in a substantial number of cases of erectile dysfunction. Epidemiologic studies have implicated the role of depressed mood, loss of self-esteem, and other psychosocial stresses in the cause of erectile dysfunction. A new definition and classification of psychogenic erectile dysfunction has been proposed based on recent clinical and research findings. According to this new classification, psychogenic erectile dysfunction is categorized as generalized or situational type, with subcategories of each type proposed. Traditional treatment approaches for psychogenic erectile dysfunction have included anxiety reduction and desensitization procedures, cognitive-behavioral interventions, guided sexual stimulation techniques, and couples' or relationship counseling. Recently, these approaches increasingly have been combined with pharmacologic therapy such as sildenafil. Special situations have been identified in which combining psychosocial interventions with medical therapy is recommended. These situations include problems of sexual initiation, low sexual desire, other sexual dysfunctions, and significant couples' or relationship problems. More research is needed on the role of psychosocial interventions in the treatment of erectile dysfunction.

  5. Auditory Dysfunction in Patients with Cerebrovascular Disease

    Directory of Open Access Journals (Sweden)

    Sadaharu Tabuchi

    2014-01-01

    Full Text Available Auditory dysfunction is a common clinical symptom that can induce profound effects on the quality of life of those affected. Cerebrovascular disease (CVD is the most prevalent neurological disorder today, but it has generally been considered a rare cause of auditory dysfunction. However, a substantial proportion of patients with stroke might have auditory dysfunction that has been underestimated due to difficulties with evaluation. The present study reviews relationships between auditory dysfunction and types of CVD including cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, cerebrovascular malformation, moyamoya disease, and superficial siderosis. Recent advances in the etiology, anatomy, and strategies to diagnose and treat these conditions are described. The numbers of patients with CVD accompanied by auditory dysfunction will increase as the population ages. Cerebrovascular diseases often include the auditory system, resulting in various types of auditory dysfunctions, such as unilateral or bilateral deafness, cortical deafness, pure word deafness, auditory agnosia, and auditory hallucinations, some of which are subtle and can only be detected by precise psychoacoustic and electrophysiological testing. The contribution of CVD to auditory dysfunction needs to be understood because CVD can be fatal if overlooked.

  6. Cellular uptake of metallated cobalamins

    DEFF Research Database (Denmark)

    Tran, Mai Thanh Quynh; Stürup, Stefan; Lambert, Ian Henry

    2016-01-01

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN......(-) and H2O, respectively), were included as control samples. The results indicated that B12 derivatives delivered cisplatin to both cellular cytosol and nuclei with an efficiency of one third compared to the uptake of free cisplatin cis-[Pt(II)Cl2(NH3)2]. In addition, uptake of charged B12 derivatives...

  7. Cellular basis of Alzheimer's disease.

    Science.gov (United States)

    Bali, Jitin; Halima, Saoussen Ben; Felmy, Boas; Goodger, Zoe; Zurbriggen, Sebastian; Rajendran, Lawrence

    2010-12-01

    Alzheimer's disease (AD) is the most common form of neurodegenerative disease. A characteristic feature of the disease is the presence of amyloid-β (Aβ) which either in its soluble oligomeric form or in the plaque-associated form is causally linked to neurodegeneration. Aβ peptide is liberated from the membrane-spanning -amyloid precursor protein by sequential proteolytic processing employing β- and γ-secretases. All these proteins involved in the production of Aβ peptide are membrane associated and hence, membrane trafficking and cellular compartmentalization play important roles. In this review, we summarize the key cellular events that lead to the progression of AD.

  8. Mitochondrial dysfunction in neuromuscular disorders.

    Science.gov (United States)

    Katsetos, Christos D; Koutzaki, Sirma; Melvin, Joseph J

    2013-09-01

    This review deciphers aspects of mitochondrial (mt) dysfunction among nosologically, pathologically, and genetically diverse diseases of the skeletal muscle, lower motor neuron, and peripheral nerve, which fall outside the traditional realm of mt cytopathies. Special emphasis is given to well-characterized mt abnormalities in collagen VI myopathies (Ullrich congenital muscular dystrophy and Bethlem myopathy), megaconial congenital muscular dystrophy, limb-girdle muscular dystrophy type 2 (calpainopathy), centronuclear myopathies, core myopathies, inflammatory myopathies, spinal muscular atrophy, Charcot-Marie-Tooth neuropathy type 2, and drug-induced peripheral neuropathies. Among inflammatory myopathies, mt abnormalities are more prominent in inclusion body myositis and a subset of polymyositis with mt pathology, both of which are refractory to corticosteroid treatment. Awareness is raised about instances of phenotypic mimicry between cases harboring primary mtDNA depletion, in the context of mtDNA depletion syndrome, and established neuromuscular disorders such as spinal muscular atrophy. A substantial body of experimental work, derived from animal models, attests to a major role of mitochondria (mt) in the early process of muscle degeneration. Common mechanisms of mt-related cell injury include dysregulation of the mt permeability transition pore opening and defective autophagy. The therapeutic use of mt permeability transition pore modifiers holds promise in various neuromuscular disorders, including muscular dystrophies.

  9. Myofascial Pain Dysfunction Syndrome (MPDS

    Directory of Open Access Journals (Sweden)

    Hamed Mortazavi

    2010-10-01

    Full Text Available Introduction: Myofascial Pain Dysfunction Syndrome (MPDS is one of the most important causes of the orofacial pain. The main purpose of this study was to evaluate 40 related variables in this regard. Materials and Methods: Thirty nine patients with MPDS were evaluated in this study. Different factors including age, gender, occupation, marital status, sensitivity of masticatory muscles, maximum opening of the mouth, deviation, deflection, involvement of temporomandibular joint, habit, parafunction, malocclusion, neck pain, headache, earache and history of jaw involvement, etc were analyzed in this  evaluation. Results: In our study, 39 patients (32 females and 7 males, 20-40 years old, with the average age of 35 ± 13.32 years were studied. 51% were housewives and 74.4% were married. The most common involvements were Clicking (74.4%, pain in temporomandibular joint (54%, headache (46.2%, earache (41%, neck-pain (35.9%, trouble in the mouth opening (71.8%, malocclusion Class I (74.4%, cross bite and deep bite (25%, clenching (64.1% and involvement of masseter and lateral pterygoid muscle (84%. Conclusion: Since MPDS consists of variable symptoms, it might be very difficult to provide any definite diagnosis and treatment. Therefore the more the specialists extend their knowledge and information about this disorder, the more they will make the best decision in this regard.

  10. Polyphenols in preventing endothelial dysfunction

    Directory of Open Access Journals (Sweden)

    Sylwia Biegańska-Hensoldt

    2017-03-01

    Full Text Available One of the main causes of mortality in developed countries is atherosclerosis. The pathogenesis of atherosclerosis is associated with endothelial dysfunction. Consumption of food rich in natural antioxidants including polyphenols significantly improves endothelial cells functions.Polyphenols have a beneficial effect on the human body and play an important part in protecting the cardiovascular system. Polyphenols present in food have antioxidant, anti-inflammatory, antihypertensive, antithrombotic and antiproliferative properties. Catechins cause an increase in the activity of endothelial nitric oxide synthase (eNOS and increased production of nitric oxide (NO and decrease in blood pressure. Catechins also reduce platelet adhesion, lower the concentration of C-reactive protein and tumor necrosis factor alpha and interleukin-6. Resveratrol inhibits NADPH oxidase expression, increases the expression of eNOS and NO production as well as decreases the expression of proinflammatory cytokines, and also lowers the concentration of the soluble forms of adhesion molecules – sICAM-1 and sVCAM-1 in blood. Quercetin reduces the blood level of low density lipoprotein cholesterol, lowers blood pressure, reduces the concentration of C-reactive protein and F2-isoprostane level. Curcumin has antagonistic activity to homocysteine. Curcumin increases the expression of eNOS and reduces oxidative DNA damage in rat cardiomyocytes. Numerous attempts are taken for improving the bioavailability of polyphenols in order to increase their use in the body.

  11. Erectile dysfunction in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Imen Gorsane

    2016-01-01

    Full Text Available Erectile dysfunction (ED is a common problem seen among patients on hemodialysis (HD, but it is still a taboo subject in our country. The attention given to this sexual problem remained low, and the prevalence of ED among these patients has not been well characterized. We carried out this study in order to determine the prevalence and severity of ED in HD patients. We conducted a descriptive cross-sectional study in our HD unit in March 2013. ED was evaluated using the International Index Erection Function. Thirty patients with a mean age of 49.1 years were eligible for this study. The main causes of chronic kidney disease were hypertension (62.5% and diabetes (41.6%. The prevalence of ED was 80%, including 33.3% severe ED. Plasma levels of gonadotropins: luteinizing hormone (LH, follicule-stimulating hormone were in the standards except for one patient who had an elevated level of LH. Prolactin was elevated in four cases. ED was present in 8.4% of patients before the discovery of renal failure and in 91.6% of patients at the beginning of dialysis. For 19 patients (79.1%, the ED had increased during the dialysis sessions. A significant number of our HD patients presented with ED of varying degrees. Nephrologists should pay attention to the problem of ED in order to improve the quality of their life.

  12. Neurostimulation for Neurogenic Bowel Dysfunction

    Directory of Open Access Journals (Sweden)

    J. Worsøe

    2013-01-01

    Full Text Available Background. Loss of normal bowel function caused by nerve injury, neurological disease or congenital defects of the nervous system is termed neurogenic bowel dysfunction (NBD. It usually includes combinations of fecal incontinence, constipation, abdominal pain and bloating. When standard treatment of NBD fails surgical procedures are often needed. Neurostimulation has also been investigated, but no consensus exists about efficacy or clinical use. Methods. A systematic literature search of NBD treated by sacral anterior root stimulation (SARS, sacral nerve stimulation (SNS, peripheral nerve stimulation, magnetic stimulation, and nerve re-routing was made in Pubmed, Embase, Scopus, and the Cochrane Library. Results. SARS improves bowel function in some patients with complete spinal cord injury (SCI. Nerve re-routing is claimed to facilitate defecation through mechanical stimulation of dermatomes in patients with complete or incomplete SCI or myelomeningocele. SNS can reduce NBD in selected patients with a variety of incomplete neurological lesions. Peripheral stimulation using electrical stimulation or magnetic stimulation may represent non-invasive alternatives. Conclusion. Numerous methods of neurostimulation to treat NBD have been investigated in pilot studies or retrospective studies. Therefore, larger controlled trials with well-defined inclusion criteria and endpoints are recommended before widespread clinical use of neurostimulation against NBD.

  13. Sarcomere Dysfunction in Nemaline Myopathy.

    Science.gov (United States)

    de Winter, Josine M; Ottenheijm, Coen A C

    2017-01-01

    Nemaline myopathy (NM) is among the most common non-dystrophic congenital myopathies (incidence 1:50.000). Hallmark features of NM are skeletal muscle weakness and the presence of nemaline bodies in the muscle fiber. The clinical phenotype of NM patients is quite diverse, ranging from neonatal death to normal lifespan with almost normal motor function. As the respiratory muscles are involved as well, severely affected patients are ventilator-dependent. The mechanisms underlying muscle weakness in NM are currently poorly understood. Therefore, no therapeutic treatment is available yet.Eleven implicated genes have been identified: ten genes encode proteins that are either components of thin filament, or are thought to contribute to stability or turnover of thin filament proteins. The thin filament is a major constituent of the sarcomere, the smallest contractile unit in muscle. It is at this level of contraction - thin-thick filament interaction - where muscle weakness originates in NM patients.This review focusses on how sarcomeric gene mutations directly compromise sarcomere function in NM. Insight into the contribution of sarcomeric dysfunction to muscle weakness in NM, across the genes involved, will direct towards the development of targeted therapeutic strategies.

  14. Sleep apnoea and metabolic dysfunction

    Directory of Open Access Journals (Sweden)

    Maria R. Bonsignore

    2013-09-01

    Full Text Available Obstructive sleep apnoea (OSA is a highly prevalent condition often associated with central obesity. In the past few years, several studies have analysed the potential independent contribution of OSA to the pathogenesis of metabolic abnormalities, including type 2 diabetes, the metabolic syndrome and non-alcoholic fatty liver disease. New perspectives in OSA patient care have been opened by the promotion of lifestyle interventions, such as diet and exercise programmes that could improve both OSA and the metabolic profile. The rich clinical literature on this subject, together with the growing amount of data on pathophysiological mechanisms provided by animal studies using the chronic intermittent hypoxia model, urged the organising Committee of the Sleep and Breathing meeting to organise a session on sleep apnoea and metabolic dysfunction, in collaboration with the European Association for the Study of Diabetes. This review summarises the state-of-the-art lectures presented in the session, more specifically the relationship between OSA and diabetes, the role of OSA in the metabolic consequences of obesity, and the effects of lifestyle interventions on nocturnal respiratory disturbances and the metabolic profile in OSA patients.

  15. Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma

    NARCIS (Netherlands)

    van Baarle, D; Hovenkamp, E; Callan, M F; Wolthers, K C; Kostense, S; Tan, L C; Niesters, H G; Osterhaus, A D; McMichael, A J; van Oers, M H; Miedema, F

    2001-01-01

    Acquired immunodeficiency syndrome-related non-Hodgkin lymphomas (AIDS-NHL) are thought to arise because of loss of Epstein-Barr Virus (EBV)-specific cellular immunity. Here, an investigation was done to determine whether cellular immunity to EBV is lost because of physical loss or dysfunction of EB

  16. Erectile Dysfunction and Undiagnosed Diabetes, Hypertension, and Hypercholesterolemia

    National Research Council Canada - National Science Library

    Skeldon, Sean C; Detsky, Allan S; Goldenberg, S Larry; Law, Michael R

    2015-01-01

    .... Erectile dysfunction was determined by a single, validated survey question. We used logistic regression analyses to investigate the relationship between erectile dysfunction and undiagnosed hypertension, hypercholesterolemia, and diabetes...

  17. Male Sexual Dysfunction and Chronic Kidney Disease

    Science.gov (United States)

    Edey, Matthew M.

    2017-01-01

    Male sexual dysfunction is common in chronic kidney disease (CKD), particularly in end-stage renal disease. Historically, this cause of considerable morbidity has been under-reported and under-recognized. The ideal approach to diagnosis and management remains unclear due to a paucity of good quality data, but an understanding of the pathophysiology is necessary in order to address the burden of this important complication of CKD. This paper will review the endocrine dysfunction that occurs in renal disease, particularly the hypothalamic–pituitary–gonadal axis, discuss the causes of erectile dysfunction, infertility, and altered body image and libido in these patients and suggest appropriate treatment interventions. PMID:28382300

  18. Etiology and Management of Sexual Dysfunction

    Directory of Open Access Journals (Sweden)

    Narendra Kumar Muthugaduru Shivarudrappa

    2009-09-01

    Full Text Available Sexual dysfunction is the impairment or disruption of any of the three phases of normal sexual functioning, including loss of libido, impairment of physiological arousal and loss, delay or alteration of orgasm. Each one of these can be affected by an orchestra of factors like senility, medical and surgical illnesses, medications and drugs of abuse. Non-pharmacological therapy is the main stay in the treatment of sexual dysfunction and drugs are used as adjuncts for a quicker and better result. Management in many of the cases depends on the primary cause. Here is a review of the major etiological factors of sexual dysfunction and its management

  19. Sexual dysfunction within an adult developmental perspective.

    Science.gov (United States)

    Fagan, P J; Meyer, J K; Schmidt, C W

    1986-01-01

    The focus of this paper is on the adult who has adequately mastered the oedipal stage of psychosexual development and who presents with a sexual dysfunction. Drawing on the developmental sequence of Erik Erikson, the authors suggest that failure to address adequately an adult psychosocial crisis may result in sexual dysfunction. There may be both adult developmental deficits and regression to adolescent and adult stages previously negotiated. Both may be symptomatically represented by sexual dysfunction. The authors urge that the sexual and marital problems be evaluated within an adult developmental framework and that the therapy address the psychosocial issues which are appropriate to the developmental stage of the patient.

  20. Velo-pharyngeal dysfunction: Evaluation and management

    Directory of Open Access Journals (Sweden)

    Marsh Jeffrey

    2009-10-01

    Full Text Available Separation of the nasal and oral cavities by dynamic closure of the velo-pharyngeal port is necessary for normal speech and swallowing. Velo-pharyngeal dysfunction (VPD may either follow repair of a cleft palate or be independent of clefting. While the diagnosis of VPD is made by audiologic perceptual evaluation of speech, identification of the mechanism of the dysfunction requires instrumental visualization of the velo-pharyngeal port during specific speech tasks. Matching the specific intervention for management of VPD with the type of dysfunction, i.e. differential management for differential diagnosis, maximizes the result while minimizing the morbidity of the intervention.

  1. Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury

    Science.gov (United States)

    Sturdivant, Nasya M.; Smith, Sean G.; Ali, Syed F.; Wolchok, Jeffrey C.; Balachandran, Kartik

    2016-09-01

    Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a water channel protein, following brain injury. AZA is an antiepileptic drug that has been shown to inhibit AQP4 expression and in this study we investigate the drug as a therapeutic to mitigate the extent of mTBI induced cellular edema. We hypothesized that mTBI-mediated astrocyte dysfunction, initiated by increased intracellular volume, could be reduced when treated with AZA. We tested our hypothesis in a three-dimensional in vitro astrocyte model of mTBI. Samples were subject to no stretch (control) or one high-speed stretch (mTBI) injury. AQP4 expression was significantly increased 24 hours after mTBI. mTBI resulted in a significant increase in the cell swelling within 30 min of mTBI, which was significantly reduced in the presence of AZA. Cell death and expression of S100B was significantly reduced when AZA was added shortly before mTBI stretch. Overall, our data point to occurrence of astrocyte swelling immediately following mTBI, and AZA as a promising treatment to mitigate downstream cellular mortality.

  2. Advances in the cellular and molecular biology of angiogenesis.

    Science.gov (United States)

    Egginton, Stuart; Bicknell, Roy

    2011-12-01

    Capillaries have been recognized for over a century as one of the most important components in regulating tissue oxygen transport, and their formation or angiogenesis a pivotal element of tissue remodelling during development and adaptation. Clinical interest stems from observations that both excessive and inadequate vascular growth plays a major role in human diseases, and novel developments in treatments for cancer and eye disease increasingly rely on anti-angiogenic therapies. Although the discovery of VEGF (vascular endothelial growth factor) provided the first clue for specificity of signalling in endothelial cell activation, understanding the integrative response that drives angiogenesis requires a much broader perspective. The Advances in the Cellular and Molecular Biology of Angiogenesis meeting brought together researchers at the forefront of this rapidly moving field to provide an update on current understanding, and the most recent insights into molecular and cellular mechanisms of vascular growth. The plenary lecture highlighted the integrative nature of the angiogenic process, whereas invited contributions from basic and clinician scientists described fundamental mechanisms and disease-associated issues of blood vessel formation, grouped under a number of themes to aid discussion. These articles will appeal to academic, clinical and pharmaceutical scientists interested in the molecular and cellular basis of angiogenesis, their modulation or dysfunction in human diseases, and application of these findings towards translational medicine.

  3. Modulation of innate and adaptive cellular immunity relevant to HIV-1 vaccine design by seminal plasma.

    Science.gov (United States)

    Selva, Kevin J; Kent, Stephen J; Parsons, Matthew S

    2017-01-28

    Mucosal exposure to HIV-1 infection generally occurs in the presence of semen. Immunomodulation by seminal plasma is well described in the reproductive biology literature. Little is known, however, about the impact of seminal plasma on innate and adaptive anti-HIV-1 cellular immunity. The study investigated the effects of seminal plasma on immune responses considered important for prophylactic HIV-1 vaccine development, namely innate and adaptive cellular immunity mediated by natural killer (NK) cells and T cells, respectively. The ability of seminal plasma to modulate direct, antibody-dependent and cytokine-stimulated NK cell activation was assessed utilizing intracellular cytokine staining. Direct and antibody-dependent cellular cytotoxicity was assessed using lactate dehydrogenase release assays. The effects of seminal plasma on T-cell activation upon stimulation with staphylococcus enterotoxin B or HIV-1 Gag peptides were assessed by intracellular cytokine staining. The impact of seminal plasma on redirected cytolysis mediated by T cells was measured using lactate dehydrogenase release assays. Both direct and antibody-dependent NK cell activation were dramatically impaired by the presence of either HIV-1-uninfected or HIV-1-infected seminal plasma in a dose-dependent manner. Additionally, seminal plasma suppressed both direct and antibody-dependent NK cell-mediated cytolysis, including anti-HIV-1 antibody-dependent cytolysis of gp120-pulsed CEM.NKr-CCR5 cells. Finally, seminal plasma attenuated both HIV-1 Gag-specific and staphylococcus enterotoxin B-induced CTL activation. Semen contains potent immunosuppressors of both NK cell and CD8 T-cell-mediated anti-HIV-1 immune responses. This could impede attempts to provide vaccine-induced immunity to HIV-1.

  4. Redox control of cellular signalling

    NARCIS (Netherlands)

    Putker, M.

    2014-01-01

    Reactive oxygen species (ROS) are natural by-products of cellular energy production. Consequently, mammalian cells encounter them on a daily basis. Increased ROS levels are associated with the onset of cancer and accelerated ageing, and historically, ROS are therefore considered harmful molecules.

  5. On Cellular MIMO Channel Capacity

    Science.gov (United States)

    Adachi, Koichi; Adachi, Fumiyuki; Nakagawa, Masao

    To increase the transmission rate without bandwidth expansion, the multiple-input multiple-output (MIMO) technique has recently been attracting much attention. The MIMO channel capacity in a cellular system is affected by the interference from neighboring co-channel cells. In this paper, we introduce the cellular channel capacity and evaluate its outage capacity, taking into account the frequency-reuse factor, path loss exponent, standard deviation of shadowing loss, and transmission power of a base station (BS). Furthermore, we compare the cellular MIMO downlink channel capacity with those of other multi-antenna transmission techniques such as single-input multiple-output (SIMO) and space-time block coded multiple-input single-output (STBC-MISO). We show that the optimum frequency-reuse factor F that maximizes 10%-outage capacity is 3 and both 50%- and 90%-outage capacities is 1 irrespective of the type of multi-antenna transmission technique, where q%-outage capacity is defined as the channel capacity that gives an outage probability of q%. We also show that the cellular MIMO channel capacity is always higher than those of SIMO and STBC-MISO.

  6. Cellular uptake of metallated cobalamins

    DEFF Research Database (Denmark)

    Tran, MQT; Stürup, Stefan; Lambert, Ian H.;

    2016-01-01

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN(-...

  7. Telomere Dysfunction in Nonalcoholic Fatty Liver Disease and Cryptogenic Cirrhosis.

    Science.gov (United States)

    Laish, Ido; Mannasse-Green, Batya; Hadary, Ruth; Biron-Shental, Tal; Konikoff, Fred M; Amiel, Aliza; Kitay-Cohen, Yona

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC) are considered preneoplastic conditions that might progress to hepatocellular carcinoma. We evaluated parameters of telomere dysfunction in these patient groups to study the correlation between telomere length and the progression of NAFLD. We analyzed peripheral lymphocytes from 22 patients with NAFLD, 20 patients with CC, and 20 healthy, age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization, and cellular senescence was evaluated by the percentage of cells with senescence-associated heterochromatin foci. The expression of telomerase reverse transcriptase (hTERT) mRNA was measured using polymerase chain reaction, and telomere capture (TC) was assessed with 2 Cytocell probes, 15qter and 13qter. Shorter telomere length and increased cellular senescence was demonstrated in patients with NAFLD, compared to the CC patients and healthy controls. While hTERT mRNA was significantly decreased, TC was increased in CC patients, compared to the NAFLD group and healthy individuals. Thus, there is a correlation between hTERT mRNA expression and telomere length in patients with NAFLD, which might be related to associated metabolic disorders and the risk of malignant transformation. Patients with CC, on the contrary, elongate their telomeres through the TC mechanism.

  8. ATRX dysfunction induces replication defects in primary mouse cells.

    Directory of Open Access Journals (Sweden)

    David Clynes

    Full Text Available The chromatin remodeling protein ATRX, which targets tandem repetitive DNA, has been shown to be required for expression of the alpha globin genes, for proliferation of a variety of cellular progenitors, for chromosome congression and for the maintenance of telomeres. Mutations in ATRX have recently been identified in tumours which maintain their telomeres by a telomerase independent pathway involving homologous recombination thought to be triggered by DNA damage. It is as yet unknown whether there is a central underlying mechanism associated with ATRX dysfunction which can explain the numerous cellular phenomena observed. There is, however, growing evidence for its role in the replication of various repetitive DNA templates which are thought to have a propensity to form secondary structures. Using a mouse knockout model we demonstrate that ATRX plays a direct role in facilitating DNA replication. Ablation of ATRX alone, although leading to a DNA damage response at telomeres, is not sufficient to trigger the alternative lengthening of telomere pathway in mouse embryonic stem cells.

  9. ATRX dysfunction induces replication defects in primary mouse cells.

    Science.gov (United States)

    Clynes, David; Jelinska, Clare; Xella, Barbara; Ayyub, Helena; Taylor, Stephen; Mitson, Matthew; Bachrati, Csanád Z; Higgs, Douglas R; Gibbons, Richard J

    2014-01-01

    The chromatin remodeling protein ATRX, which targets tandem repetitive DNA, has been shown to be required for expression of the alpha globin genes, for proliferation of a variety of cellular progenitors, for chromosome congression and for the maintenance of telomeres. Mutations in ATRX have recently been identified in tumours which maintain their telomeres by a telomerase independent pathway involving homologous recombination thought to be triggered by DNA damage. It is as yet unknown whether there is a central underlying mechanism associated with ATRX dysfunction which can explain the numerous cellular phenomena observed. There is, however, growing evidence for its role in the replication of various repetitive DNA templates which are thought to have a propensity to form secondary structures. Using a mouse knockout model we demonstrate that ATRX plays a direct role in facilitating DNA replication. Ablation of ATRX alone, although leading to a DNA damage response at telomeres, is not sufficient to trigger the alternative lengthening of telomere pathway in mouse embryonic stem cells.

  10. Intraperitoneal delivery of a novel liposome-encapsulated paclitaxel redirects metabolic reprogramming and effectively inhibits cancer stem cells in Taxol(®)-resistant ovarian cancer.

    Science.gov (United States)

    Shen, Yao-An; Li, Wai-Hou; Chen, Po-Hung; He, Chun-Lin; Chang, Yen-Hou; Chuang, Chi-Mu

    2015-01-01

    Taxol(®) remained as the mainstay therapeutic agent in the treatment of ovarian cancer, however recurrence rate is still high. Cancer stem cells (CSCs) represent a subset of cells in the bulk of tumors and play a central role in inducing drug resistance and recurrence. Furthermore, cancer metabolism has been an area under intensive investigation, since accumulating evidence has shown that CSCs and cancer metabolism are closely linked, an effect named as metabolic reprogramming. In this work, we aimed to investigate the impacts of a novel liposome-encapsulated paclitaxel (Nano-Taxol) on the stemness phenotype and metabolic reprogramming. A paclitaxel-resistant cell line (TR) was established at first. Tumor growth was induced in the mice peritoneal cavity by inoculation of TR cells. A 2x2 factorial experiment was designed to test the therapeutic efficacy in which factor 1 represented the comparison of drugs (Taxol(®) versus Nano-Taxol), while factor 2 represented the delivery route (intravenous versus intraperitoneal delivery). In this work, we found that intraperitoneal delivery of Nano-Taxol redirects metabolic reprogramming, from glycolysis to oxidative phosphorylation, and effectively suppresses cancer stem cells. Also, intraperitoneal delivery of Nano-Taxol led to a significantly better control of tumor growth compared with intravenous delivery of Taxol(®) (current standard treatment). This translational research may serve as a novel pathway for the drug development of nanomedicine. In the future, this treatment modality may be extended to treat several relevant cancers that have been proved to be suitable for the loco-regional delivery of therapeutic agents, including colon cancer, gastric cancer, and pancreatic cancer.

  11. Redirected lysis of human melanoma cells by a MCSP/CD3-bispecific BiTE antibody that engages patient-derived T cells.

    Science.gov (United States)

    Torisu-Itakura, Hitoe; Schoellhammer, Hans F; Sim, Myung-Shin; Irie, Reiko F; Hausmann, Susanne; Raum, Tobias; Baeuerle, Patrick A; Morton, Donald L

    2011-10-01

    Melanoma-associated chondroitin sulfate proteoglycan (MCSP; also called HMW-MAA, CSPG4, NG2, MSK16, MCSPG, MEL-CSPG, or gp240) is a well characterized melanoma cell-surface antigen. In this study, a new bispecific T-cell engaging (BiTE) antibody that binds to MCSP and human CD3 (MCSP-BiTE) was tested for its cytotoxic activity against human melanoma cell lines. When unstimulated peripheral mononuclear blood cells (PBMCs) derived from healthy donors were cocultured with melanoma cells at effector:target ratios of 1:1, 1:5, or 1:10, and treated with MCSP-BiTE antibody at doses of 10, 100, or 1000 ng/mL, all MCSP-expressing melanoma cell lines (n=23) were lysed in a dose-dependent and effector:target ratio-dependent manner, whereas there was no cytotoxic activity against MCSP-negative melanoma cell lines (n=2). To investigate whether T cells from melanoma patients could act as effector cells, we cocultured unstimulated PBMCs with allogeneic melanoma cells from 13 patients (4 stage I/II, 3 stage III, and 6 stage IV) or with autologous melanoma cells from 2 patients (stage IV). Although cytotoxic activity varied, all 15 PBMC samples mediated significant redirected lysis by the BiTE antibody. When PBMC or CD8 T cells were prestimulated by anti-CD3 antibody OKT-3 and interleukin-2, the MCSP-BiTE concentrations needed for melanoma cell lysis decreased up to 1000-fold. As MCSP is expressed on most human melanomas, immunotherapy with MCSP/CD3-bispecific antibodies merits clinical investigation.

  12. Oral sensory dysfunction following radiotherapy.

    Science.gov (United States)

    Bearelly, Shethal; Wang, Steven J; Cheung, Steven W

    2017-10-01

    To assess differences in oral tactile sensation between subjects who have undergone radiation therapy (XRT) compared to healthy controls. Cross-sectional cohort comparison. Thirty-four subjects with a history of XRT were compared with 23 healthy controls. There was no difference in age (P = .23), but there were slightly more males in the XRT cohort (P = .03). The mean (standard deviation) time after XRT completion was 3.84 (4.84) years. Fifty-six percent of the XRT cohort received chemotherapy. Using our previously validated methodology to measure oral tactile sensory threshold quantitatively with Cheung-Bearelly monofilaments, sensory thresholds of four subsites (anterior tongue, buccal mucosa, posterior tongue, soft palate) were compared for the two cohorts. Site-by-site comparisons showed higher forces were required for stimulus detection at all four subsites among subjects in the XRT cohort compared to healthy controls. Mean force in grams for XRT versus control cohorts were: anterior tongue, 0.39 (1.0) versus 0.02 (0.01); buccal mucosa, 0.42 (0.95) versus 0.06 (0.05); posterior tongue, 0.76 (1.46) versus 0.10 (0.07); and soft palate, 0.86 (1.47) versus 0.08 (0.05) (P sensory dysfunction, manifested by increased tactile forces required for stimulus detection. The magnitude of sensory impairment is 18.7 dB. 3b. Laryngoscope, 127:2282-2286, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  13. Endocrine dysfunction in hereditary hemochromatosis.

    Science.gov (United States)

    Pelusi, C; Gasparini, D I; Bianchi, N; Pasquali, R

    2016-08-01

    Hereditary hemochromatosis (HH) is a genetic disorder of iron overload and subsequent organ damage. Five types of HH are known, classified by age of onset, genetic cause, clinical manifestations and mode of inheritance. Except for the rare form of juvenile haemochromatosis, symptoms do not usually appear until after decades of progressive iron loading and may be triggered by environmental and lifestyle factors. Despite the last decades discovery of genetic and phenotype diversity of HH, early studies showed a frequent involvement of the endocrine glands where diabetes and hypogonadism are the most common encountered endocrinopathies. The pathogenesis of diabetes is still relatively unclear, but the main mechanisms include the loss of insulin secretory capacity and insulin resistance secondary to liver damage. The presence of obesity and/or genetic predisposition may represent addictive risk factor for the development of this metabolic disease. Although old cases of primary gonad involvement are described, hypogonadism is mainly secondary to selective deposition of iron on the gonadotropin-producing cells of the pituitary gland, leading to hormonal impaired secretion. Cases of hypopituitarism or selected tropin defects, and abnormalities of adrenal, thyroid and parathyroid glands, even if rare, are reported. The prevalence of individual gland dysfunction varies enormously within studies for several bias due to small numbers of and selected cases analyzed, mixed genotypes and missing data on medical history. Moreover, in the last few years early screening and awareness of the disease among physicians have allowed hemochromatosis to be diagnosed in most cases at early stages when patients have no symptoms. Therefore, the clinical presentation of this disease has changed significantly and the recognized common complications are encountered less frequently. This review summarizes the current knowledge on HH-associated endocrinopathies.

  14. Temporomandibular dysfunction and headache disorder.

    Science.gov (United States)

    Speciali, José G; Dach, Fabíola

    2015-02-01

    It has been well established that primary headaches (especially migraine, chronic migraine, and tension-type headache) and temporomandibular dysfunction (TMD) are comorbid diseases, with the presence of one of them in a patient increasing the prevalence of the others. The relationship between the 2 diseases may involve the sharing of common physiopathological aspects. Studies about the treatment of this disease association have shown that a simultaneous therapeutic approach to the 2 diseases is more effective than the separate treatment of each. As a consequence, specialists in orofacial pain are now required to know the criteria for the diagnosis of headaches, and headache physicians are required to know the semiologic aspects of orofacial pain. Nevertheless, a headache may be attributed to TMD, instead be an association of 2 problems - TMD and primary headaches - in these cases a secondary headache, described in item 11.7 of the International Classification of Headache Disorders, is still a controversial topic. Attempts to determine the existence of this secondary headache with a specific or suggestive phenotype have been frustrated. The conclusion that can be reached based on the few studies published thus far is that this headache has a preferential unilateral or bilateral temporal location and migraine-like or tension-type headache-like clinical characteristics. In the present review, we will consider the main aspects of the TMD-headache relationship, that is, comorbidity of primary headaches and TMD and clinical aspects of the headaches attributed to TMD from the viewpoint of the International Headache Society and of a group of specialists in orofacial pain. This paper aims to explore our understanding of the association between TMD and headaches in general and migraine in particular.

  15. Erectile Dysfunction: Viagra and Other Oral Medications

    Science.gov (United States)

    ... loss or vision loss. Some men have had sudden loss of hearing or loss of vision after taking one of ... taking an oral erectile dysfunction medication and have sudden loss of hearing or vision, seek prompt medical attention. An erection ...

  16. Questionnaires for assessment of female sexual dysfunction

    DEFF Research Database (Denmark)

    Giraldi, Annamaria; Rellini, Alessandra; Pfaus, James G;

    2011-01-01

    There are many methods to evaluate female sexual function and dysfunction (FSD) in clinical and research settings, including questionnaires, structured interviews, and detailed case histories. Of these, questionnaires have become an easy first choice to screen individuals into different categories...

  17. Animal models of brain dysfunction in phenylketonuria

    NARCIS (Netherlands)

    Martynyuk, A. E.; van Spronsen, F. J.; Van der Zee, E. A.

    2010-01-01

    Phenylketonuria (PKU) is a metabolic disorder that results in significant brain dysfunction if untreated. Although phenylalanine restricted diets instituted at birth have clearly improved PKU outcomes, neuropsychological deficits and neurological changes still represent substantial problems. The spe

  18. Erectile Dysfunction: A Sign of Heart Disease?

    Science.gov (United States)

    ... High cholesterol. A high level of low-density lipoprotein (LDL, or "bad") cholesterol can lead to atherosclerosis. ... Erectile-Dysfunction-and-High-Blood-Pressure_UCM_301827_Article.jsp. Accessed July 8, 2015. Ma RCW, et ...

  19. Hyperemesis gravidarum and placental dysfunction disorders

    NARCIS (Netherlands)

    Koudijs, Heleen M; Savitri, Ary I; Browne, Joyce L; Amelia, Dwirani; Baharuddin, Mohammad; Grobbee, Diederick E; Uiterwaal, Cuno S P M

    2016-01-01

    BACKGROUND: Evidence about the consequence of hyperemesis gravidarum (HG) on pregnancy outcomes is still inconclusive. In this study, we evaluated if occurrence of hyperemesis gravidarum is associated with placental dysfunction disorders and neonatal outcomes. METHODS: A prospective cohort study was

  20. Sexual dysfunction in women with epilepsy.

    Science.gov (United States)

    Harden, Cynthia L

    2008-03-01

    Sexual dysfunction in women with epilepsy (WWE) is an important comorbidity. A significant minority of WWE have markedly decreased sexual interest and it appears that orgasmic dysfunction occurs more frequently in WWE than in control women. Enzyme-inducing antiepileptic drugs can adversely affect sexual functioning by decreasing bioactive testosterone levels. Temporal lobe epilepsy of right-sided versus left-sided origin may also be a risk factor for sexual dysfunction. In addition to these factors, emerging evidence suggests that the serotonin transporter protein is related to temporal lobe epilepsy and it is postulated that this transporter may play a role in altered sexual functioning in epilepsy, perhaps through the serotonergic effects of antiepileptic drugs (AEDs). Strategies for modifying the contributors to sexual dysfunction in WWE will be discussed as well as the role of the neurologist in initiating management of this challenging comorbidity.

  1. [Endothelial dysfunction in pathogenesis of duodenal ulcer].

    Science.gov (United States)

    Oparin, A G; Oparin, A A

    2002-01-01

    It is shown that in patients with ulcer associated with Helicobacter pylori (HP) there is a close correlation between the severity of the lesion of gastroduodenal protective mucous barrier and that of endothelial dysfunction manifesting in elevated level of endothelin-1, serum levels of TBK-active products, inhibition of blood flow and narrowing of the celiac trunk. The correlation becomes stronger with expanding contamination of gastroduodenal mucosa with HP. Thus, HP may participate in breaking the protective mucous barrier in endothelial dysfunction.

  2. Piracetam improves mitochondrial dysfunction following oxidative stress

    OpenAIRE

    2005-01-01

    Mitochondrial dysfunction including decrease of mitochondrial membrane potential and reduced ATP production represents a common final pathway of many conditions associated with oxidative stress, for example, hypoxia, hypoglycemia, and aging.Since the cognition-improving effects of the standard nootropic piracetam are usually more pronounced under such pathological conditions and young healthy animals usually benefit little by piracetam, the effect of piracetam on mitochondrial dysfunction fol...

  3. Trichotillomania In A Patient With Sexual Dysfunction

    Directory of Open Access Journals (Sweden)

    Aswathi Krishna

    2016-10-01

    Full Text Available Trichotillomania is a chronic psychiatric disorder characterized by pulling out one's own hair, which results in an obvious loss of hair. Hair pulling was first described in Henri Allopeau in 1889. The term "trichotillomania" comes from the Greek words "thrix" - hair, "tillein" - to pull and "Mania" madness or frenzy. 30 year old man presented with complaints of hairpulling behavior and associated erectile dysfunction. His hairpulling behavior improved on treating his sexual dysfunction.

  4. Functional and Dysfunctional rumination in alcohol dependence

    OpenAIRE

    Grynberg, Delphine; Briane, Yasmine; Timary, Philippe De; Maurage, Pierre; 16th International Society of Addiction Medicine Annual Meeting

    2014-01-01

    Previous findings have shown that rumination predicts alcohol abuse independently of depression. However, the literature does not inform about the relationships between alcohol dependence and functional and dysfunctional rumination. It has indeed been suggested that there exist a functional form of rumination(concrete thinking) and a dysfunctional form of rumination (abstract thinking). In this study, our aim is to evaluate if alcohol dependence is similarly associated with functional/constru...

  5. Eosinophilic gastroenteritis with ascites and hepatic dysfunction

    Institute of Scientific and Technical Information of China (English)

    Hai-Bo Zhou; Jin-Ming Chen; Qin Du

    2007-01-01

    Eosinophilic gastroenteritis is a rare gastrointestinal disorder with eosinophilic infiltration of the gastrointestinal wall and various gastrointestinal dysfunctions. Diagnosis requires a high index of suspicion and exclusion of various disorders that are associated with peripheral eosinophilia.We report a case of eosinophilic gastroenteritis, which had features of the predominant subserosal type presenting with ascites and hepatic dysfunction, and which responded to a course of low-dose steroid.

  6. SECONDARY MITOCHONDRIAL DYSFUNCTION IN ACUTE CORONARY SYNDROME

    Directory of Open Access Journals (Sweden)

    Y. A. Vasyuk

    2015-12-01

    Full Text Available So-called “metabolic” direction has been developing intensively during last decades. Its aim is the theoretical and practical analysis of the role of metabolic disorders in initiation and progression of many diseases. The pathogenic peculiarities of acute coronary syndrome (ACS which result in developing of secondary mitochondrial dysfunction are considered as a subject of this review. The methods of laboratory diagnosis of mitochondrial dysfunction and possibilities of its pharmaceutical correction in patients with ACS are reviewed.

  7. Endothelial dysfunction and inflammation in asymptomatic proteinuria

    OpenAIRE

    Paisley, K.E.; Beaman, M; Tooke, J. E.; Mohamed-Ali, V; Lowe, G. D. O.; Shore, A C

    2003-01-01

    Background. Proteinuria is associated with vascular risk and a systemic increase in vascular permeability. Endothelial dysfunction occurs early in atherosclerosis and modulates vascular permeability. Vascular risk and chronic inflammation are associated. This study investigates whether the increased vascular permeability in proteinuria reflects systemic endothelial dysfunction and chronic inflammation. Methods. Twenty-one patients with asymptomatic proteinuria (1.29 g/24 h; range 0.18 to 3.17...

  8. Temporomandibular Joint Dysfunction: A Dental Overview

    OpenAIRE

    Hillier, Clyde D.

    1985-01-01

    Temporomandibular joint dysfunction is common and often acutely painful. Because of the large and diverse symptom complex created by this disorder, patients frequently first seek relief from their physician rather than their dentist. In this article temporomandibular joint (TMJ) dysfunction is defined and the presenting signs and symptoms are discussed. Their etiology is described in relation to the anatomy of the temporomandibular joint. Examination techniques can help in the differential di...

  9. Cerebral energy metabolism during induced mitochondrial dysfunction

    DEFF Research Database (Denmark)

    Nielsen, T H; Bindslev, TT; Pedersen, S M

    2013-01-01

    In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes in...... in brain tissue oxygen tension (PbtO(2)) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets....

  10. Mechanisms of oxidative stress and vascular dysfunction

    Science.gov (United States)

    Nedeljkovic, Z; Gokce, N; Loscalzo, J

    2003-01-01

    The endothelium regulates vascular homoeostasis through local elaboration of mediators that modulate vascular tone, platelet adhesion, inflammation, fibrinolysis, and vascular growth. Impaired vascular function contributes to the pathogenesis of atherosclerosis and acute coronary syndromes. There is growing pathophysiological evidence that increased generation of reactive oxygen species and oxidative stress participates in proatherogenic mechanisms of vascular dysfunction and atherothrombosis. In this review, the role of oxidative stress in mechanisms of vascular dysfunction is discussed, and potential antioxidant strategies are reviewed. PMID:12743334

  11. Peri-operative cognitive dysfunction and protection

    DEFF Research Database (Denmark)

    Steinmetz, J; Rasmussen, L S

    2016-01-01

    Cognition may decline after surgery. Postoperative delirium, especially when hyperactive, may be easily recognised, whereas cognitive dysfunction is subtle and can only be detected using neuropsychological tests. The causes for these two conditions are largely unknown, although they share risk...... reduce the rate of delirium in the elderly, but in spite of promising findings in animal experiments, no intervention reduces postoperative cognitive dysfunction in humans....

  12. Thyroid hormone dysfunction during pregnancy: A review

    Science.gov (United States)

    Alemu, Aynadis; Terefe, Betelihem; Abebe, Molla; Biadgo, Belete

    2016-01-01

    Thyroid dysfunctions such as hypothyroidism, thyrotoxicosis and thyroid nodules may develop during pregnancy leading to abortion, placental abruptions, preeclampsia, preterm delivery and reduced intellectual function in the offspring. Epidemiological data have shown the significant role of maternal thyroid hormone in fetal neurologic development and maternal health. It has been suggested that the deleterious effects of thyroid dysfunction can also extend beyond pregnancy and delivery to affect neuro-intellectual development in the early life of the child. Pregnancy poses an important challenge to the maternal thyroid gland as hormone requirements are increased during gestation as a result of an increase in thyroid- binding globulin, the stimulatory effect of HCG on TSH receptors, and increased peripheral thyroid hormone requirements. Maternal thyroid dysfunction is associated with increased risk for early abortion, preterm delivery, neonatal morbidity and other obstetrical complications. Early diagnosis for thyroid dysfunction of pregnant women and treatment of thyroid dysfunction during pregnancy is important and cost effective to avoid both fetal and maternal complications secondary to thyroid dysfunction. Therefore the aim of this review was to assess the thyroid function changes occurring during pregnancy, the different disorders with their maternal and fetal implications, the laboratory diagnosis and the best ways of management of these conditions. PMID:27981252

  13. Vascular endothelial dysfunction and pharmacological treatment

    Institute of Scientific and Technical Information of China (English)

    Jin; Bo; Su

    2015-01-01

    The endothelium exerts multiple actions involving regulation of vascular permeability and tone, coagulation and fibrinolysis, inflammatory and immunological reactions and cell growth. Alterations of one or more such actions may cause vascular endothelial dysfunction. Different risk factors such as hypercholesterolemia, homocystinemia, hyperglycemia, hypertension, smo-king, inflammation, and aging contribute to the development of endothelial dysfunction. Mechanisms underlying endothelial dysfunction are multiple, including impaired endothelium-derived vasodilators, enhanced endothelium-derived vasoconstrictors, over production of reactive oxygen species and reactive nitrogen species, activation of inflammatory and immune reactions, and imbalance of coagulation and fibrinolysis. Endothelial dysfunction occurs in many cardiovascular diseases, which involves different mechanisms, depending on specific risk factors affecting the disease. Among these mechanisms, a reduction in nitric oxide(NO) bioavailability plays a central role in the development of endothelial dysfunction because NO exerts diverse physiological actions, including vasodilation, anti-inflammation, antiplatelet, antiproliferation and antimigration. Experimental and clinical studies have demonstrated that a variety of currently used or investigational drugs, such as angiotensin-converting enzyme inhibitors, angiotensin AT1 receptors blockers, angiotensin-(1-7), antioxidants, beta-blockers, calcium channel blockers, endothelial NO synthase enhancers, phosphodiesterase 5 inhibitors, sphingosine-1-phosphate and statins, exert endothelial protective effects. Due to the difference in mechanisms of action, these drugs need to be used according to specific mechanisms underlying endothelial dysfunction of the disease.

  14. The evolving role of the NAD+/nicotinamide metabolome in skin homeostasis, cellular bioenergetics, and aging.

    Science.gov (United States)

    Oblong, John E

    2014-11-01

    Human skin is exposed to daily environmental insults, particularly solar radiation, that triggers a range of molecular responses. These perturbations to the normal homeostatic state can lead to cellular dysfunction and, ultimately, impacts tissue integrity and accelerates skin aging (photoaging). One of the responses is increased oxidative stress which has been shown to disrupt cellular bioenergetics. This can be detected by depletion of the nucleotide energy metabolites NAD+ and ATP as both an acute transient decrease and, over time, a more permanent chronic reduction due in part to cumulative damage of mitochondria. NAD+ and its primary precursor nicotinamide have been known for some time to impact skin homeostasis based on linkages to dietary requirements, treatment of various inflammatory conditions, photoaging, and prevention of cancer. Cellular NAD+ pools are known to be lower in aged skin and treatment with nicotinamide is hypothesized to restore these levels, thereby mitigating cellular bioenergetics dysfunction. In dermal fibroblasts, nicotinamide is able to protect against oxidative stress to glycolysis, oxidative phosphorylation as well as increase mitochondrial efficiency via sirtuin-dependent selective mitophagy. Recent research has found that NAD+ cellular pools are more dynamic than previously thought, oscillating in tandem with free nicotinamide, and serves as a regulatory point and feedback loop in cellular metabolism regulation, maintenance of mitochondrial efficiency, and circadian rhythmicity. Since UV-induced oxidative stress in skin can disrupt these processes, continued molecular understanding of the role of NAD+ and nicotinamide in skin biology is important to identify interventions that would help maintain its normal homeostatic functions and efficient cellular bioenergetics.

  15. Immune Dysfunction in Tourette Syndrome

    Directory of Open Access Journals (Sweden)

    Ishraga Elamin

    2013-01-01

    Full Text Available The association between immunity and neurodevelopmental disorders has been extensively investigated in autism, suggesting a potential involvement of both cellular and humoral immunity in the establishment of synaptic connectivity modulation during development. A similar link has been proposed also for Tourette syndrome (TS, a complex, multifactorial disorder, in which the interplay between genetic, environmental, hormonal and immunological factors might be relevant. Lymphocyte subpopulation analysis in TS suggests a possible systemic activation of several T- and B-cell subtypes, whereas the observed decreased numbers of T regulatory lymphocytes might predispose to autoimmunity. Genes related to both cell- and antibody-mediated immune responses may be over-expressed at specific ages in youngsters with TS. Data from cytokine measurements and transcriptomics profiles in TS patients are coherent with the systemic immune activation detected by studies on lymphocyte subpopulations. Moreover, TS patients have exhibited IgG3 and IgA dysgammaglobulinemia, which might predispose to recurrent infections and autoimmunity. To date, the association between TS and autoantibodies has not been demonstrated. Interestingly, however, there is a higher degree of maternal family history of autoimmune diseases among TS patients. Finally, TS patients could be prone to allergic illnesses (asthma, atopic dermatitis, rhinitis, conjunctivitis, but more work is needed in this area.

  16. Dermatitis herpetiformis and neurological dysfunction.

    Science.gov (United States)

    Wills, A J; Turner, B; Lock, R J; Johnston, S L; Unsworth, D J; Fry, L

    2002-02-01

    Dermatitis herpetiformis and coeliac disease are gluten sensitive diseases, which have common immunopathological and genetic mechanisms. Neuropsychiatric complications have been reported in up to 26% of patients with coeliac disease. This is probably an overestimate, because of the chance associations with some common neurological conditions such as epilepsy. The pathogenesis is speculative but it has been postulated that gluten is neurotoxic possibly via immune mechanisms. The frequency of neurological dysfunction in patients with dermatitis herpetiformis has not been characterised. Patients with dermatitis herpetiformis might be expected to be particularly susceptible to neuronal damage as some continue to consume gluten when their dermatological symptoms are controlled by dapsone. Thirty five patients were recruited with dermatitis herpetiformis from dermatology clinics at St Mary's Hospital, London and Queen's Medical Centre, Nottingham and investigated for evidence of neurological abnormality. All patients underwent a full neurological examination and were asked about their neurological and general medical history by means of a structured questionnaire. Serum samples were taken and screened for the presence of anti-neuronal antibodies (anti-Hu and Yo) as well as anti-gliadin (IgA and G) anti-endomysial (IgA), and anti-tissue transglutaminase (IgA) antibodies. Neurophysiological tests were carried out where appropriate. Only two patients were identified with unexplained neurological abnormalities (one essential tremor, and one chorea). Two other patients had a history of migraine. The patient with chorea also had borderline/equivocally positive anti-Hu antibodies by immunofluorescence assay. All other samples were negative for anti-neuronal antibodies. Fifteen patients were positive for anti-gliadin antibodies (IgA and/or IgG), four for anti-endomysial antibodies (monkey oesophagus or umbilical cord), and six for anti-tissue transglutaminase antibodies. The

  17. Peroxisome Metabolism and Cellular Aging

    Science.gov (United States)

    Titorenko, Vladimir I.; Terlecky, Stanley R.

    2010-01-01

    The essential role of peroxisomes in fatty acid oxidation, anaplerotic metabolism, and hydrogen peroxide turnover is well established. Recent findings suggest these and other related biochemical processes governed by the organelle may also play a critical role in regulating cellular aging. The goal of this review is to summarize and integrate into a model, the evidence that peroxisome metabolism actually helps define the replicative and chronological age of a eukaryotic cell. In this model, peroxisomal reactive oxygen species (ROS) are seen as altering organelle biogenesis and function, and eliciting changes in the dynamic communication networks that exist between peroxisomes and other cellular compartments. At low levels, peroxisomal ROS activate an anti-aging program in the cell; at concentrations beyond a specific threshold, a pro-aging course is triggered. PMID:21083858

  18. Cellular proliferation and hypusine synthesis.

    Science.gov (United States)

    Torrelio, B M; Paz, M A; Gallop, P M

    1984-10-01

    Hypusine (N(-)-(4-amino-2-hydroxybutyl) lysine), a spermidine-dependent post-translational protein modification, is synthesized by various mammalian cells in culture. Experiments described in this paper demonstrated a relationship between rates of cellular growth and the synthesis of hypusine. Cells that divide at fast rates have a high rate of hypusine synthesis. In kinetic experiments, a positive relationship is evident between the rates of protein, DNA and hypusine synthesis. Cells seeded at high density, growing non-exponentially, synthesized less hypusine than logarithmically growing cells seeded at low density. Slowing the growth rate of cells by modification of the external milieu also results in a decreased rate of hypusine synthesis. These results provide additional evidence of the association of hypusine with cell proliferation in cultured cell lines and suggest a possible role for this unusual post-translational modification in the complex macromolecular events leading to cellular growth.

  19. Mitochondrial Dysfunction and Oxidative Stress in Asthma: Implications for Mitochondria-Targeted Antioxidant Therapeutics

    Directory of Open Access Journals (Sweden)

    P. Hemachandra Reddy

    2011-02-01

    Full Text Available Asthma is a complex, inflammatory disorder characterized by airflow obstruction of variable degrees, bronchial hyper-responsiveness, and airway inflammation. Asthma is caused by environmental factors and a combination of genetic and environmental stimuli. Genetic studies have revealed that multiple loci are involved in the etiology of asthma. Recent cellular, molecular, and animal-model studies have revealed several cellular events that are involved in the progression of asthma, including: increased Th2 cytokines leading to the recruitment of inflammatory cells to the airway, and an increase in the production of reactive oxygen species and mitochondrial dysfunction in the activated inflammatory cells, leading to tissue injury in the bronchial epithelium. Further, aging and animal model studies have revealed that mitochondrial dysfunction and oxidative stress are involved and play a large role in asthma. Recent studies using experimental allergic asthmatic mouse models and peripheral cells and tissues from asthmatic humans have revealed antioxidants as promising treatments for people with asthma. This article summarizes the latest research findings on the involvement of inflammatory changes, and mitochondrial dysfunction/oxidative stress in the development and progression of asthma. This article also addresses the relationship between aging and age-related immunity in triggering asthma, the antioxidant therapeutic strategies in treating people with asthma.

  20. Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress.

    Science.gov (United States)

    Akbar, Mohammed; Essa, Musthafa Mohamed; Daradkeh, Ghazi; Abdelmegeed, Mohamed A; Choi, Youngshim; Mahmood, Lubna; Song, Byoung-Joon

    2016-04-15

    Mitochondria are important for providing cellular energy ATP through the oxidative phosphorylation pathway. They are also critical in regulating many cellular functions including the fatty acid oxidation, the metabolism of glutamate and urea, the anti-oxidant defense, and the apoptosis pathway. Mitochondria are an important source of reactive oxygen species leaked from the electron transport chain while they are susceptible to oxidative damage, leading to mitochondrial dysfunction and tissue injury. In fact, impaired mitochondrial function is commonly observed in many types of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, alcoholic dementia, brain ischemia-reperfusion related injury, and others, although many of these neurological disorders have unique etiological factors. Mitochondrial dysfunction under many pathological conditions is likely to be promoted by increased nitroxidative stress, which can stimulate post-translational modifications (PTMs) of mitochondrial proteins and/or oxidative damage to mitochondrial DNA and lipids. Furthermore, recent studies have demonstrated that various antioxidants, including naturally occurring flavonoids and polyphenols as well as synthetic compounds, can block the formation of reactive oxygen and/or nitrogen species, and thus ultimately prevent the PTMs of many proteins with improved disease conditions. Therefore, the present review is aimed to describe the recent research developments in the molecular mechanisms for mitochondrial dysfunction and tissue injury in neurodegenerative diseases and discuss translational research opportunities.

  1. Contribution of mitochondria and endoplasmic reticulum dysfunction in insulin resistance: Distinct or interrelated roles?

    Science.gov (United States)

    Rieusset, J

    2015-11-01

    Mitochondria and the endoplasmic reticulum (ER) regulate numerous cellular processes, and are critical contributors to cellular and whole-body homoeostasis. More important, mitochondrial dysfunction and ER stress are both closely associated with hepatic and skeletal muscle insulin resistance, thereby playing crucial roles in altered glucose homoeostasis in type 2 diabetes mellitus (T2DM). The accumulated evidence also suggests a potential interrelationship between alterations in both types of organelles, as mitochondrial dysfunction could participate in activation of the unfolded protein response, whereas ER stress could influence mitochondrial function. The fact that mitochondria and the ER are physically and functionally interconnected via mitochondria-associated membranes (MAMs) supports their interrelated roles in the pathophysiology of T2DM. However, the mechanisms that coordinate the interplay between mitochondrial dysfunction and ER stress, and its relevance to the control of glucose homoeostasis, are still unknown. This review evaluates the involvement of mitochondria and ER independently in the development of peripheral insulin resistance, as well as their potential roles in the disruption of organelle crosstalk at MAM interfaces in the alteration of insulin signalling. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  2. Identification of Nonstationary Cellular Automata

    Institute of Scientific and Technical Information of China (English)

    AndrewI.Adamatzky

    1992-01-01

    The principal feature of nonstationary cellular automata(NCA) is that a local transitiol rule of each cell is changed at each time step depending on neighborhood configuration at previous time step.The identification problem for NCA is extraction of local transition rules and the establishment of mechanism for changing these rules using sequence of NCA configurations.We present serial and parallel algorithms for identification of NCA.

  3. CELLULAR INTERACTIONS MEDIATED BY GLYCONECTIDS

    OpenAIRE

    Popescu, O.; Sumanovski, L. T.; I. Checiu; Elisabeta Popescu; G. N. Misevic

    1999-01-01

    Cellular interactions involve many types of cell surface molecules and operate via homophilic and/or heterophilic protein-protein and protein-carbohydrate binding. Our investigations in different model-systems (marine invertebrates and mammals) have provided direct evidence that a novel class of primordial proteoglycans, named by us gliconectins, can mediate cell adhesion via a new alternative molecular mechanism of polyvalent carbohydrate-carbohydrate binding. Biochemical characterization of...

  4. Stochastic Nature in Cellular Processes

    Institute of Scientific and Technical Information of China (English)

    刘波; 刘圣君; 王祺; 晏世伟; 耿轶钊; SAKATA Fumihiko; GAO Xing-Fa

    2011-01-01

    The importance of stochasticity in cellular processes is increasingly recognized in both theoretical and experimental studies. General features of stochasticity in gene regulation and expression are briefly reviewed in this article, which include the main experimental phenomena, classification, quantization and regulation of noises. The correlation and transmission of noise in cascade networks are analyzed further and the stochastic simulation methods that can capture effects of intrinsic and extrinsic noise are described.

  5. Glycosylation regulates prestin cellular activity.

    Science.gov (United States)

    Rajagopalan, Lavanya; Organ-Darling, Louise E; Liu, Haiying; Davidson, Amy L; Raphael, Robert M; Brownell, William E; Pereira, Fred A

    2010-03-01

    Glycosylation is a common post-translational modification of proteins and is implicated in a variety of cellular functions including protein folding, degradation, sorting and trafficking, and membrane protein recycling. The membrane protein prestin is an essential component of the membrane-based motor driving electromotility changes (electromotility) in the outer hair cell (OHC), a central process in auditory transduction. Prestin was earlier identified to possess two N-glycosylation sites (N163, N166) that, when mutated, marginally affect prestin nonlinear capacitance (NLC) function in cultured cells. Here, we show that the double mutant prestin(NN163/166AA) is not glycosylated and shows the expected NLC properties in the untreated and cholesterol-depleted HEK 293 cell model. In addition, unlike WT prestin that readily forms oligomers, prestin(NN163/166AA) is enriched as monomers and more mobile in the plasma membrane, suggesting that oligomerization of prestin is dependent on glycosylation but is not essential for the generation of NLC in HEK 293 cells. However, in the presence of increased membrane cholesterol, unlike the hyperpolarizing shift in NLC seen with WT prestin, cells expressing prestin(NN163/166AA) exhibit a linear capacitance function. In an attempt to explain this finding, we discovered that both WT prestin and prestin(NN163/166AA) participate in cholesterol-dependent cellular trafficking. In contrast to WT prestin, prestin(NN163/166AA) shows a significant cholesterol-dependent decrease in cell-surface expression, which may explain the loss of NLC function. Based on our observations, we conclude that glycosylation regulates self-association and cellular trafficking of prestin(NN163/166AA). These observations are the first to implicate a regulatory role for cellular trafficking and sorting in prestin function. We speculate that the cholesterol regulation of prestin occurs through localization to and internalization from membrane microdomains by

  6. Cellular fiber–reinforced concrete

    OpenAIRE

    Isachenko S.; Kodzoev M.

    2016-01-01

    Methods disperse reinforcement of concrete matrix using polypropylene, glass, basalt and metal fibers allows to make the construction of complex configuration, solve the problem of frost products. Dispersed reinforcement reduces the overall weight of the structures. The fiber replaces the secondary reinforcement, reducing the volume of use of structural steel reinforcement. Cellular Fiber concretes are characterized by high-performance properties, especially increased bending strength and...

  7. Progress of cellular dedifferentiation research

    Institute of Scientific and Technical Information of China (English)

    LIU Hu-xian; HU Da-hai; JIA Chi-yu; FU Xiao-bing

    2006-01-01

    Differentiation, the stepwise specialization of cells, and transdifferentiation, the apparent switching of one cell type into another, capture much of the stem cell spotlight. But dedifferentiation, the developmental reversal of a cell before it reinvents itself, is an important process too. In multicellular organisms, cellular dedifferentiation is the major process underlying totipotency, regeneration and formation of new stem cell lineages. In humans,dedifferentiation is often associated with carcinogenesis.The study of cellular dedifferentiation in animals,particularly early events related to cell fate-switch and determination, is limited by the lack of a suitable,convenient experimental system. The classic example of dedifferentiation is limb and tail regeneration in urodele amphibians, such as salamanders. Recently, several investigators have shown that certain mammalian cell types can be induced to dedifferentiate to progenitor cells when stimulated with the appropriate signals or materials. These discoveries open the possibility that researchers might enhance the endogenous regenerative capacity of mammals by inducing cellular dedifferentiation in vivo.

  8. The insect cellular immune response

    Institute of Scientific and Technical Information of China (English)

    Michael R. Strand

    2008-01-01

    The innate immune system of insects is divided into humoral defenses that include the production of soluble effector molecules and cellular defenses like phagocytosis and encapsulation that are mediated by hemocytes. This review summarizes current understanding of the cellular immune response. Insects produce several terminally differentiated types of hemocytes that are distinguished by morphology, molecular and antigenic markers, and function. The differentiated hemocytes that circulate in larval or nymphal stage insects arise from two sources: progenitor cells produced during embryogenesis and mesodermally derived hematopoietic organs. Regulation of hematopoiesis and hemocyte differentiation also involves several different signaling pathways. Phagocytosis and encapsulation require that hemocytes first recognize a given target as foreign followed by activation of downstream signaling and effector responses. A number of humoral and cellular receptors have been identified that recognize different microbes and multicellular parasites. In turn, activation of these receptors stimulates a number of signaling pathways that regulate different hemocyte functions. Recent studies also identify hemocytes as important sources of a number of humoral effector molecules required for killing different foreign invaders.

  9. [Cellular phones and public health].

    Science.gov (United States)

    Leventhal, Alex; Karsenty, Eric; Sadetzki, Siegal

    2004-08-01

    The increased use of mobile cellular phone by the public is associated with a wave of contradictory reports about the possible health effects, due to the exposure of the users to electromagnetic non-ionizing radiation. This article reviews the state of the art of the present knowledge concerning the biological and medical effects of exposure to cellular phones, with an emphasis on its possible carcinogenic effect. Health conditions, which have been ascribed to the use of mobile phones mainly include some types of cancer and changes of brain activity. However, the balance of evidence from available studies has not yet supported these claims. Following the recommendation of special international expert committees, the IARC (International Association for Research on Cancer) is conducting a multi-center study to determine the possible effect of cellular phone use on brain and salivary gland tumors. Israel is one of the participants of this study. The only established health effect associated with the use of such technology is an increased risk for road accidents, unrelated to the amount of radiation emitted by phone. The challenge posed by this new technology to health authorities all over the world has lead to the definition of a new principle, the so-called "prudent avoidance", used as guidelines for the definition of an adequate public health policy. The public policy in Israel has used the prudent avoidance principles, while awaiting the results of the multi-national epidemiological studies.

  10. The Asteroid Redirect Mission (ARM)

    Science.gov (United States)

    Abell, P. A.; Mazanek, D. D.; Reeves, D. M.; Chodas, P. W.; Gates, M. M.; Johnson, L. N.; Ticker, R. L.

    2016-01-01

    To achieve its long-term goal of sending humans to Mars, the National Aeronautics and Space Administration (NASA) plans to proceed in a series of incrementally more complex human spaceflight missions. Today, human flight experience extends only to Low-Earth Orbit (LEO), and should problems arise during a mission, the crew can return to Earth in a matter of minutes to hours. The next logical step for human spaceflight is to gain flight experience in the vicinity of the Moon. These cis-lunar missions provide a "proving ground" for the testing of systems and operations while still accommodating an emergency return path to the Earth that would last only several days. Cis-lunar mission experience will be essential for more ambitious human missions beyond the Earth- Moon system, which will require weeks, months, or even years of transit time.

  11. Bladder Dysfunction and Urinary Incontinence

    Directory of Open Access Journals (Sweden)

    F. faizi

    2009-01-01

    Full Text Available   "nIn the name of God. Dear colleagues, ladies and gentlemen, it is a great honor to be here. Bladder dysfunction is serious enough to seek serious help. If you may know I am working in a private clinic which it is impossible to follow the patients so this lecture is based on unusual and rare cases who came to me. Bladder dysfunction (BD is common among 30% of young and old people who are suffering from it, however it is more common in old ages. According to a research, women are more involved as in men which prostate has a role is more common. The usual cases were: "n1. A young girl, aged 20, who had to wake up five times during the night to micturate. "n2. Also a lady said when I roll in bed I wet myself. "n3. A young lady who always had to use a pad. "n4. A man said I can’t use underground. "n5. I cannot go out since I have to micturate every hour. "n6. One said I have to wake up every hour at night. "n7. Young people say we have to micturate 3-4 times at night. "n8. A young man said as soon as I feel to micturate I empty my bladder before I’ve reached the WC and I wet myself to the ankle, how could I have a job? "n9. Some women wet themselves when they cough. "nIn order to know and diagnosis, the physiology of bladder function must be known. "nThe bladder is divided into two parts: "nThe Dom, which is innervated by Beta-Adrenergic. It relaxes the bladder in order to comply the urine. "nFrom the orifice of the urether and posterior ridge of the trigon to the bladder neck or internal sphincter. The prostatic urethra plays a major role in conti- nence. It has two parts,   "n1: From the bladder neck to V.M. this is enclaved by extension of detrusor muscles like a sleeve. These muscles contract during ejaculation to prevent retrograde ejaculation. "nDistal urethra from V.M. to the external sphincter which is covered by voluntary muscles. "nThe internal pressure of the urethra is higher than the bladder. If the pressure of the bladder rises

  12. Apraxia and motor dysfunction in corticobasal syndrome.

    Directory of Open Access Journals (Sweden)

    James R Burrell

    Full Text Available BACKGROUND: Corticobasal syndrome (CBS is characterized by multifaceted motor system dysfunction and cognitive disturbance; distinctive clinical features include limb apraxia and visuospatial dysfunction. Transcranial magnetic stimulation (TMS has been used to study motor system dysfunction in CBS, but the relationship of TMS parameters to clinical features has not been studied. The present study explored several hypotheses; firstly, that limb apraxia may be partly due to visuospatial impairment in CBS. Secondly, that motor system dysfunction can be demonstrated in CBS, using threshold-tracking TMS, and is linked to limb apraxia. Finally, that atrophy of the primary motor cortex, studied using voxel-based morphometry analysis (VBM, is associated with motor system dysfunction and limb apraxia in CBS. METHODS: Imitation of meaningful and meaningless hand gestures was graded to assess limb apraxia, while cognitive performance was assessed using the Addenbrooke's Cognitive Examination - Revised (ACE-R, with particular emphasis placed on the visuospatial subtask. Patients underwent TMS, to assess cortical function, and VBM. RESULTS: In total, 17 patients with CBS (7 male, 10 female; mean age 64.4+/- 6.6 years were studied and compared to 17 matched control subjects. Of the CBS patients, 23.5% had a relatively inexcitable motor cortex, with evidence of cortical dysfunction in the remaining 76.5% patients. Reduced resting motor threshold, and visuospatial performance, correlated with limb apraxia. Patients with a resting motor threshold <50% performed significantly worse on the visuospatial sub-task of the ACE-R than other CBS patients. Cortical function correlated with atrophy of the primary and pre-motor cortices, and the thalamus, while apraxia correlated with atrophy of the pre-motor and parietal cortices. CONCLUSIONS: Cortical dysfunction appears to underlie the core clinical features of CBS, and is associated with atrophy of the primary motor and

  13. Apraxia and motor dysfunction in corticobasal syndrome.

    Science.gov (United States)

    Burrell, James R; Hornberger, Michael; Vucic, Steve; Kiernan, Matthew C; Hodges, John R

    2014-01-01

    Corticobasal syndrome (CBS) is characterized by multifaceted motor system dysfunction and cognitive disturbance; distinctive clinical features include limb apraxia and visuospatial dysfunction. Transcranial magnetic stimulation (TMS) has been used to study motor system dysfunction in CBS, but the relationship of TMS parameters to clinical features has not been studied. The present study explored several hypotheses; firstly, that limb apraxia may be partly due to visuospatial impairment in CBS. Secondly, that motor system dysfunction can be demonstrated in CBS, using threshold-tracking TMS, and is linked to limb apraxia. Finally, that atrophy of the primary motor cortex, studied using voxel-based morphometry analysis (VBM), is associated with motor system dysfunction and limb apraxia in CBS. Imitation of meaningful and meaningless hand gestures was graded to assess limb apraxia, while cognitive performance was assessed using the Addenbrooke's Cognitive Examination - Revised (ACE-R), with particular emphasis placed on the visuospatial subtask. Patients underwent TMS, to assess cortical function, and VBM. In total, 17 patients with CBS (7 male, 10 female; mean age 64.4+/- 6.6 years) were studied and compared to 17 matched control subjects. Of the CBS patients, 23.5% had a relatively inexcitable motor cortex, with evidence of cortical dysfunction in the remaining 76.5% patients. Reduced resting motor threshold, and visuospatial performance, correlated with limb apraxia. Patients with a resting motor threshold apraxia correlated with atrophy of the pre-motor and parietal cortices. Cortical dysfunction appears to underlie the core clinical features of CBS, and is associated with atrophy of the primary motor and pre-motor cortices, as well as the thalamus, while apraxia correlates with pre-motor and parietal atrophy.

  14. Cellular communications a comprehensive and practical guide

    CERN Document Server

    Tripathi, Nishith

    2014-01-01

    Even as newer cellular technologies and standards emerge, many of the fundamental principles and the components of the cellular network remain the same. Presenting a simple yet comprehensive view of cellular communications technologies, Cellular Communications provides an end-to-end perspective of cellular operations, ranging from physical layer details to call set-up and from the radio network to the core network. This self-contained source forpractitioners and students represents a comprehensive survey of the fundamentals of cellular communications and the landscape of commercially deployed

  15. Ejaculatory dysfunction in the treatment of lower urinary tract symptoms

    OpenAIRE

    DeLay, Kenneth Jackson; Nutt,Max; McVary, Kevin T.

    2016-01-01

    The link between lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) and sexual dysfunction is well established. Sexual dysfunction can encompass both ejaculatory dysfunction (EjD) and erectile dysfunction (ED). Ejaculatory dysfunction can consist of premature ejaculation, delayed ejaculation, retrograde ejaculation, anejaculation, decreased force of ejaculation and pain upon ejaculation. The impact of different medical and surgical therapies on ejaculatory fun...

  16. Mitochondria-Targeted Antioxidant Prevents Cardiac Dysfunction Induced by Tafazzin Gene Knockdown in Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Quan He

    2014-01-01

    Full Text Available Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress.

  17. Pathophysiology of muscle dysfunction in COPD.

    Science.gov (United States)

    Gea, Joaquim; Agustí, Alvar; Roca, Josep

    2013-05-01

    Muscle dysfunction often occurs in patients with chronic obstructive pulmonary disease (COPD) and may involve both respiratory and locomotor (peripheral) muscles. The loss of strength and/or endurance in the former can lead to ventilatory insufficiency, whereas in the latter it limits exercise capacity and activities of daily life. Muscle dysfunction is the consequence of complex interactions between local and systemic factors, frequently coexisting in COPD patients. Pulmonary hyperinflation along with the increase in work of breathing that occur in COPD appear as the main contributing factors to respiratory muscle dysfunction. By contrast, deconditioning seems to play a key role in peripheral muscle dysfunction. However, additional systemic factors, including tobacco smoking, systemic inflammation, exercise, exacerbations, nutritional and gas exchange abnormalities, anabolic insufficiency, comorbidities and drugs, can also influence the function of both respiratory and peripheral muscles, by inducing modifications in their local microenvironment. Under all these circumstances, protein metabolism imbalance, oxidative stress, inflammatory events, as well as muscle injury may occur, determining the final structure and modulating the function of different muscle groups. Respiratory muscles show signs of injury as well as an increase in several elements involved in aerobic metabolism (proportion of type I fibers, capillary density, and aerobic enzyme activity) whereas limb muscles exhibit a loss of the same elements, injury, and a reduction in fiber size. In the present review we examine the current state of the art of the pathophysiology of muscle dysfunction in COPD.

  18. Involvement of lysosomal dysfunction in autophagosome accumulation and early pathologies in adipose tissue of obese mice.

    Science.gov (United States)

    Mizunoe, Yuhei; Sudo, Yuka; Okita, Naoyuki; Hiraoka, Hidenori; Mikami, Kentaro; Narahara, Tomohiro; Negishi, Arisa; Yoshida, Miki; Higashibata, Rikako; Watanabe, Shukoh; Kaneko, Hiroki; Natori, Daiki; Furuichi, Takuma; Yasukawa, Hiromine; Kobayashi, Masaki; Higami, Yoshikazu

    2017-04-03

    Whether obesity accelerates or suppresses autophagy in adipose tissue is still debatable. To clarify dysregulation of autophagy and its role in pathologies of obese adipose tissue, we focused on lysosomal function, protease maturation and activity, both in vivo and in vitro. First, we showed that autophagosome formation was accelerated, but autophagic clearance was impaired in obese adipose tissue. We also found protein and activity levels of CTSL (cathepsin L) were suppressed in obese adipose tissue, while the activity of CTSB (cathepsin B) was significantly enhanced. Moreover, cellular senescence and inflammasomes were activated in obese adipose tissue. In 3T3L1 adipocytes, downregulation of CTSL deteriorated autophagic clearance, upregulated expression of CTSB, promoted cellular senescence and activated inflammasomes. Upregulation of CTSB promoted additional activation of inflammasomes. Therefore, we suggest lysosomal dysfunction observed in obese adipose tissue leads to lower autophagic clearance, resulting in autophagosome accumulation. Simultaneously, lysosomal abnormalities, including deteriorated CTSL function and compensatory activation of CTSB, caused cellular senescence and inflammasome activation. Our findings strongly suggest lysosomal dysfunction is involved in early pathologies of obese adipose tissue.

  19. The Yeast Retrograde Response as a Model of Intracellular Signaling of Mitochondrial Dysfunction

    Directory of Open Access Journals (Sweden)

    S. Michal eJazwinski

    2012-05-01

    Full Text Available Mitochondrial dysfunction activates intracellular signaling pathways that impact yeast longevity, and the best known of these pathways is the retrograde response. More recently, similar responses have been discerned in other systems, from invertebrates to human cells. However, the identity of the signal transducers is either unknown or apparently diverse, contrasting with the well-established signaling module of the yeast retrograde response. On the other hand, it has become equally clear that several other pathways and processes interact with the retrograde response, embedding it in a network responsive to a variety of cellular states. An examination of this network supports the notion that the master regulator NFkB aggregated a variety of mitochondria-related cellular responses at some point in evolution and has become the retrograde transcription factor. This has significant consequences for how we view some of the deficits associated with aging, such as inflammation. The support for NFkB as the retrograde response transcription factor is not only based on functional analyses. It is bolstered by the fact that NFkB can regulate Myc-Max, which is activated in human cells with dysfunctional mitochondria and impacts cellular metabolism. Myc-Max is homologous to the yeast retrograde response transcription factor Rtg1-Rtg3. Further research will be needed to disentangle the pro-aging from the anti-aging effects of NFkB. Interestingly, this is also a challenge for the complete understanding of the yeast retrograde response.

  20. Glutathione in Cellular Redox Homeostasis: Association with the Excitatory Amino Acid Carrier 1 (EAAC1

    Directory of Open Access Journals (Sweden)

    Koji Aoyama

    2015-05-01

    Full Text Available Reactive oxygen species (ROS are by-products of the cellular metabolism of oxygen consumption, produced mainly in the mitochondria. ROS are known to be highly reactive ions or free radicals containing oxygen that impair redox homeostasis and cellular functions, leading to cell death. Under physiological conditions, a variety of antioxidant systems scavenge ROS to maintain the intracellular redox homeostasis and normal cellular functions. This review focuses on the antioxidant system’s roles in maintaining redox homeostasis. Especially, glutathione (GSH is the most important thiol-containing molecule, as it functions as a redox buffer, antioxidant, and enzyme cofactor against oxidative stress. In the brain, dysfunction of GSH synthesis leading to GSH depletion exacerbates oxidative stress, which is linked to a pathogenesis of aging-related neurodegenerative diseases. Excitatory amino acid carrier 1 (EAAC1 plays a pivotal role in neuronal GSH synthesis. The regulatory mechanism of EAAC1 is also discussed.

  1. Mitochondrial Oxidative Stress due to Complex I Dysfunction Promotes Fibroblast Activation and Melanoma Cell Invasiveness

    Directory of Open Access Journals (Sweden)

    Maria Letizia Taddei

    2012-01-01

    Full Text Available Increased ROS (cellular reactive oxygen species are characteristic of both fibrosis and tumour development. ROS induce the trans-differentiation to myofibroblasts, the activated form of fibroblasts able to promote cancer progression. Here, we report the role of ROS produced in response to dysfunctions of mitochondrial complex I, in fibroblast activation and in tumour progression. We studied human fibroblasts with mitochondrial dysfunctions of complex I, leading to hyperproduction of ROS. We demonstrated that ROS level produced by the mutated fibroblasts correlates with their activation. The increase of ROS in these cells provides a greater ability to remodel the extracellular matrix leading to an increased motility and invasiveness. Furthermore, we evidentiated that in hypoxic conditions these fibroblasts cause HIF-1α stabilization and promote a proinvasive phenotype of human melanoma cells through secretion of cytokines. These data suggest a possible role of deregulated mitochondrial ROS production in fibrosis evolution as well as in cancer progression and invasion.

  2. Game of Life Cellular Automata

    CERN Document Server

    Adamatzky, Andrew

    2010-01-01

    In the late 1960s, British mathematician John Conway invented a virtual mathematical machine that operates on a two-dimensional array of square cell. Each cell takes two states, live and dead. The cells' states are updated simultaneously and in discrete time. A dead cell comes to life if it has exactly three live neighbours. A live cell remains alive if two or three of its neighbours are alive, otherwise the cell dies. Conway's Game of Life became the most programmed solitary game and the most known cellular automaton. The book brings together results of forty years of study into computational

  3. Repaglinide at a cellular level

    DEFF Research Database (Denmark)

    Krogsgaard Thomsen, M; Bokvist, K; Høy, M

    2002-01-01

    To investigate the hormonal and cellular selectivity of the prandial glucose regulators, we have undertaken a series of experiments, in which we characterised the effects of repaglinide and nateglinide on ATP-sensitive potassium ion (KATP) channel activity, membrane potential and exocytosis in rat...... pancreatic alpha-cells and somatotrophs. We found a pharmacological dissociation between the actions on KATP channels and exocytosis and suggest that compounds that, unlike repaglinide, have direct stimulatory effects on exocytosis in somatotrophs and alpha- and beta-cells, such as sulphonylureas...... and nateglinide, may have a clinically undesirable general stimulatory effect on cells within the endocrine system....

  4. ING proteins in cellular senescence.

    Science.gov (United States)

    Menéndez, Camino; Abad, María; Gómez-Cabello, Daniel; Moreno, Alberto; Palmero, Ignacio

    2009-05-01

    Cellular senescence is an effective anti-tumor barrier that acts by restraining the uncontrolled proliferation of cells carrying potentially oncogenic alterations. ING proteins are putative tumor suppressor proteins functionally linked to the p53 pathway and to chromatin regulation. ING proteins exert their tumor-protective action through different types of responses. Here, we review the evidence on the participation of ING proteins, mainly ING1 and ING2, in the implementation of the senescent response. The currently available data support an important role of ING proteins as regulators of senescence, in connection with the p53 pathway and chromatin organization.

  5. Cellular automata a parallel model

    CERN Document Server

    Mazoyer, J

    1999-01-01

    Cellular automata can be viewed both as computational models and modelling systems of real processes. This volume emphasises the first aspect. In articles written by leading researchers, sophisticated massive parallel algorithms (firing squad, life, Fischer's primes recognition) are treated. Their computational power and the specific complexity classes they determine are surveyed, while some recent results in relation to chaos from a new dynamic systems point of view are also presented. Audience: This book will be of interest to specialists of theoretical computer science and the parallelism challenge.

  6. Cellular immune responses to HIV

    Science.gov (United States)

    McMichael, Andrew J.; Rowland-Jones, Sarah L.

    2001-04-01

    The cellular immune response to the human immunodeficiency virus, mediated by T lymphocytes, seems strong but fails to control the infection completely. In most virus infections, T cells either eliminate the virus or suppress it indefinitely as a harmless, persisting infection. But the human immunodeficiency virus undermines this control by infecting key immune cells, thereby impairing the response of both the infected CD4+ T cells and the uninfected CD8+ T cells. The failure of the latter to function efficiently facilitates the escape of virus from immune control and the collapse of the whole immune system.

  7. CELLULAR AUTOMATA AND COMPUTER GRAPHICS

    Directory of Open Access Journals (Sweden)

    Şen ÇAKIR

    1999-01-01

    Full Text Available Cellular Automata (CA are simple mathematical systems which provide models for a variety of physical processes. They show how minute changes and simple rules lead to enormous changes in the behaviour of a system. They can also be used as computer graphics tools to produce a rich reservoir of interesting figures. In recent years, CA have attracked the attention of many scientists. Today, CA are used in many fields from ecology to image processing. In this paper, it is shown that a large number of complex and interesting patterns can be created with relatively simple CA rules.

  8. Pelvic radiotherapy and sexual dysfunction in women

    DEFF Research Database (Denmark)

    Jensen, Pernille Tine; Froeding, Ligita Paskeviciute

    2015-01-01

    of life (QOL) issues; sexual functioning has proved to be one of the most important aspects of concern in long-term survivors. METHODS: An updated literature search in PubMed was performed on pelvic radiotherapy and female sexual functioning/dysfunction. Studies on gynaecological, urological...... and gastrointestinal cancers were included. The focus was on the period from 2010 to 2014, on studies using PROs, on potential randomized controlled trials (RCTs) where female sexual dysfunction (FSD) at least constituted a secondary outcome, and on studies reporting from modern radiotherapy modalities. RESULTS...... during the next five years. Several newer studies confirm that health care professionals are still reluctant to discuss treatment induced sexual dysfunction with patients. CONCLUSIONS: Pelvic radiotherapy has a persistent deteriorating effect on the vaginal mucosa impacting negatively on the sexual...

  9. Pain related sexual dysfunction after inguinal herniorrhaphy

    DEFF Research Database (Denmark)

    Aasvang, Eske Kvanner; Møhl, Bo; Bay-Nielsen, Morten

    2006-01-01

    To determine the incidence of pain related sexual dysfunction 1 year after inguinal herniorrhaphy and to assess the impact pain has on sexual function. In contrast to the well-described about 10% risk of chronic wound related pain after inguinal herniorrhaphy, chronic genital pain, dysejaculation......, and sexual dysfunction have only been described sporadically. The aim was therefore to describe these symptoms in a questionnaire study. A nationwide detailed questionnaire study in September 2004 of pain related sexual dysfunction in all men aged 18-40 years undergoing inguinal herniorrhaphy between October...... 2002 and June 2003 (n=1015) based upon the nationwide Danish Hernia Database collaboration. The response rate was 68.4%. Combined frequent and moderate or severe pain from the previous hernia site during activity was reported by 187 patients (18.4%). Pain during sexual activity was reported by 224...

  10. Stent graft placement for dysfunctional arteriovenous grafts

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Gyeong Sik [Dept. of Radiology, CHA Bundang Medical Center, College of Medicine, CHA University, Seongnam (Korea, Republic of); Shin, Byung Seok; Ohm, Joon Young; Ahn, Moon Sang [Chungnam National University Hospital, Daejeon (Korea, Republic of)

    2015-07-15

    This study aimed to evaluate the usefulness and outcomes of stent graft use in dysfunctional arteriovenous grafts. Eleven patients who underwent stent graft placement for a dysfunctional hemodialysis graft were included in this retrospective study. Expanded polytetrafluoroethylene covered stent grafts were placed at the venous anastomosis site in case of pseudoaneurysm, venous laceration, elastic recoil or residual restenosis despite the repeated angioplasty. The patency of the arteriovenous graft was evaluated using Kaplan-Meier analysis. Primary and secondary mean patency was 363 days and 741 days. Primary patency at 3, 6, and 12 months was 82%, 73%, and 32%, respectively. Secondary patency at the 3, 6, 12, 24, and 36 months was improved to 91%, 82%, 82%, 50%, and 25%, respectively. Fractures of the stent graft were observed in 2 patients, but had no effect on the patency. Stent graft placement in dysfunctional arteriovenous graft is useful and effective in prolonging graft patency.

  11. DELINQUENT BEHAVIOUR OF CHILDREN FROM DYSFUNCTIONAL FAMILIES

    Directory of Open Access Journals (Sweden)

    Sandra Bateva

    2014-12-01

    Full Text Available The subject of my research in the paper are the children from dysfunctional families, primarily their delinquent behavior, education and moral, actually, who takes care of them and who undertakes the family roles and whether this care is sufficient for building these personalities.This research approaches towards the study of the delinquent behavior of children from dysfunctional families. It examines to what extent the educational level of parents, the material condition, the health condition, the leisure time, the average monthly income of the family, the available permanent goods, the educational resources, the social communications within the very family, all affect the delinquent behavior of children from dysfunctional families. 

  12. Inherited Causes of Exocrine Pancreatic Dysfunction

    Directory of Open Access Journals (Sweden)

    Peter R Durie

    1997-01-01

    Full Text Available The exocrine pancreas is functionally immature at birth. Protease function is probably adequate, but lipase activity approximates 5% to 10% of adult values in the newborn and remains low in infancy. Pancreatic amylase secretion is essentially absent at birth and remains low through the first years of life. Functional disturbances of the exocrine pancreas are less frequent in childhood than in adult life. Causes of pancreatic dysfunction in childhood can be divided in two general categories: hereditary conditions, which directly affect the pancreas; and acquired disorders, in which loss of pancreatic function is a secondary phenomenon. Most inherited causes of pancreatic dysfunction are due to a generalized disorder. Cystic fibrosis is, by far, the most common inherited cause of disturbed pancreatic function among Caucasian children. All other inherited causes of exocrine pancreatic dysfunction (eg, Johanson-Blizzard syndrome are uncommon or rare.

  13. AB271. Sexual dysfunction in chronic prostatitis

    Science.gov (United States)

    Cho, In-Rae

    2016-01-01

    Chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS), or NIH category III prostatitis, is a clinical syndrome characterized by genital/ pelvic pain and lower urinary tract symptoms in the absence of urinary tract infection. CPPS is the most common prostatic disease in men younger than 50 years of age and the third most common in men older than 50 years of age. CP/CPPS is a complex entity with unclear etiology. Many articles reported that the high percentage of patients with CP/CPPS had sexual dysfunction. The most common symptoms of sexual dysfunction in chronic prostatitis patients are erectile dysfunction (ED), painful ejaculation and premature ejaculation. So we will discuss about ED and ejaculation problems in CP/CPPS patients.

  14. Effectiveness of tolterodine in nonneurogenic voiding dysfunction.

    Science.gov (United States)

    Babu, Ramesh

    2006-11-01

    The efficacy of tolterodine was analysed in children with non-neurogenic voiding dysfunction, using dysfunctional voiding symptom score (DVSS). Of 44 patients (mean age 9.3 yrs; M:F = 25:19), 36 received long acting tolterodine tartrate at a dose of 2mg OD and 8 at a dose of 4mg OD. The mean (SD) DVSS before and after the treatment was 17.1 (2.8) and 12.0 (2.4). There was a significant improvement in the mean DVSS score at the end of the treatment (Students t test P tolterodine is effective in children with voiding dysfunction. The single daily dose has good compliance and minimal side effect profile.

  15. Dialogue between endoplasmic reticulum and mitochondria as a key actor of vascular dysfunction associated to metabolic disorders.

    Science.gov (United States)

    Safiedeen, Zainab; Andriantsitohaina, Ramaroson; Martinez, M Carmen

    2016-08-01

    Metabolic syndrome due to its association with increased risk of cardiovascular diseases and cardiac mortality, comprises a cluster of metabolic abnormalities such as central obesity, hyperglycemia, dyslipidemia, and hypertension. Recent studies have shown that metabolic syndrome patients exhibit impaired nitric oxide-mediated vasodilatation leading to endothelial dysfunction in addition to insulin resistance. Interestingly, development and maintenance of the unfolded protein response of the endoplasmic reticulum stress revealed a surprisingly direct link with metabolic syndrome and endothelial dysfunction. On the other hand, in metabolic disorders, interaction between endoplasmic reticulum and mitochondria is mandatory for the generation of mitochondrial oxidative stress and perturbation of mitochondrial function accounting, at least in part, for vascular dysfunction. Herein, we review the impact of the dialogue between endoplasmic reticulum and mitochondria in modulating the cellular signals governing vascular alterations associated to metabolic disorders.

  16. 5G Ultra-Dense Cellular Networks

    OpenAIRE

    Ge, Xiaohu; Tu, Song; Mao, Guoqiang; Wang, Cheng-xiang; Han, Tao

    2015-01-01

    Traditional ultra-dense wireless networks are recommended as a complement for cellular networks and are deployed in partial areas, such as hotspot and indoor scenarios. Based on the massive multiple-input multi-output (MIMO) antennas and the millimeter wavecommunication technologies, the 5G ultra-dense cellular network is proposed to deploy in overall cellular scenarios. Moreover, a distribution network architecture is presented for 5G ultra-dense cellular networks. Furthermore, the backhaul ...

  17. Unexplained Graft Dysfunction after Heart Transplantation—Role of Novel Molecular Expression Test Score and QTc-Interval: A Case Report

    Directory of Open Access Journals (Sweden)

    Khurram Shahzad

    2010-01-01

    Full Text Available In the current era of immunosuppressive medications there is increased observed incidence of graft dysfunction in the absence of known histological criteria of rejection after heart transplantation. A noninvasive molecular expression diagnostic test was developed and validated to rule out histological acute cellular rejection. In this paper we present for the first time, longitudinal pattern of changes in this novel diagnostic test score along with QTc-interval in a patient who was admitted with unexplained graft dysfunction. Patient presented with graft failure with negative findings on all known criteria of rejection including acute cellular rejection, antibody mediated rejection and cardiac allograft vasculopathy. The molecular expression test score showed gradual increase and QTc-interval showed gradual prolongation with the gradual decline in graft function. This paper exemplifies that in patients presenting with unexplained graft dysfunction, GEP test score and QTc-interval correlate with the changes in the graft function.

  18. TAp63γ demethylation regulates protein stability and cellular distribution during neural stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Maria B Fonseca

    Full Text Available p63 is a close relative of the p53 tumor suppressor and transcription factor that modulates cell fate. The full-length isoform of p63, containing a transactivation (TA domain (TAp63 is an essential proapoptotic protein in neural development. The role of p63 in epithelial development is also well established; however, its precise function during neural differentiation remains largely controversial. Recently, it has been demonstrated that several conserved elements of apoptosis are also integral components of cellular differentiation; p53 directly interacts with key regulators of neurogenesis. The aim of this study was to evaluate the role of p63 during mouse neural stem cell (NSC differentiation and test whether the histone H3 lysine 27-specific demethylase JMJD3 interacts with p63 to redirect NSCs to neurogenesis. Our results showed that JMJD3 and TAp63γ are coordinately regulated to establish neural-specific gene expression programs in NSCs undergoing differentiation. JMJD3 overexpression increased TAp63γ levels in a demethylase activity-dependent manner. Importantly, overexpression of TAp63γ increased β-III tubulin whereas downregulation of TAp63γ by specific p63 siRNA decreased β-III tubulin. Immunoprecipitation assays demonstrated direct interaction between TAp63γ and JMJD3, and modulation of TAp63γ methylation status by JMJD3-demethylase activity. Importantly, the demethylase activity of JMJD3 influenced TAp63γ protein stabilization and cellular distribution, as well as TAp63γ-regulated neurogenesis. These findings clarify the role of p63 in adult neural progenitor cells and reveal TAp63γ as a direct target for JMJD3-mediated neuronal commitment.

  19. [Urinary tract dysfunction in older patients].

    Science.gov (United States)

    Verdejo, Carlos; Méndez, Santiago; Salinas, Jesús

    2016-11-18

    Urinary tract dysfunction in older patients has a multifactorial aetiology and is not a uniform clinical condition. Changes due to physiological ageing as well as comorbidity and polypharmacy, can produce several dynamic conditions such as urinary incontinence and urinary retention. Lower urinary tract symptoms increase with age in both sexes and are a major problem in older patients due to their medical and psychosocial consequences. For these reasons, in assessing urinary dysfunction in older patients, we should consider external circumstances such as polypharmacy, poor mobility, affective and cognitive disorders and also accessibility to housing. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  20. Sexual Dysfunction Due to Psychotropic Medications.

    Science.gov (United States)

    Clayton, Anita H; Alkis, Andrew R; Parikh, Nishant B; Votta, Jennifer G

    2016-09-01

    Sexual functioning is important to assess in patients with psychiatric illness as both the condition and associated treatment may contribute to sexual dysfunction (SD). Antidepressant medications, mood stabilizers, antipsychotics, and antianxiety agents may be associated with SD related to drug mechanism of action. Sexual adverse effects may be related to genetic risk factors, impact on neurotransmitters and hormones, and psychological elements. Effective strategies to manage medication-induced sexual dysfunction are initial choice of a drug unlikely to cause SD, switching to a different medication, and adding an antidote to reverse SD. Appropriate interventions should be determined on a clinical case-by-case basis.

  1. The female athlete triad and endothelial dysfunction.

    Science.gov (United States)

    Lanser, Erica M; Zach, Karie N; Hoch, Anne Z

    2011-05-01

    A tremendous increase in the number of female athletes of all ages and abilities has occurred in the past 35 years. In general, sports and athletic competition produce healthier and happier women. However, explosion in participation has revealed clear gender-specific injuries and medical conditions unique to the female athlete. This article focuses on the latest advances in our knowledge of the female athlete triad and the relationship between athletic-associated amenorrhea and endothelial dysfunction. Treatment of vascular dysfunction with folic acid is also discussed.

  2. Mitochondrial dysfunction underlying outer retinal diseases

    DEFF Research Database (Denmark)

    Lefevere, Evy; Toft-Kehler, Anne Katrine; Vohra, Rupali

    2017-01-01

    Dysfunction of photoreceptors, retinal pigment epithelium (RPE) or both contribute to the initiation and progression of several outer retinal disorders. Disrupted Müller glia function might additionally subsidize to these diseases. Mitochondrial malfunctioning is importantly associated with outer...... retina pathologies, which can be classified as primary and secondary mitochondrial disorders. This review highlights the importance of oxidative stress and mitochondrial DNA damage, underlying outer retinal disorders. Indeed, the metabolically active photoreceptors/RPE are highly prone to these hallmarks...... of mitochondrial dysfunction, indicating that mitochondria represent a weak link in the antioxidant defenses of outer retinal cells....

  3. Liver dysfunction and anti-thyroid therapy

    Directory of Open Access Journals (Sweden)

    Danae A Papachristos

    2015-01-01

    Full Text Available Thioamides have been used in the management of hyperthyroidism for over 50 years. Liver dysfunction is a rare but important side effect associated with their use. Recently, cases of liver failure associated with propylthiouracil have prompted the Federal Drug Administration to issue a Boxed Warning to the label of propylthiouracil regarding its risk of potentially fatal liver injury and acute liver failure in adults and children. Herein, we present a case to underline the importance of recognising the similar potential for severe hepatic dysfunction with the use of other thioamides.

  4. Lithocholic bile acid accumulated in yeast mitochondria orchestrates a development of an anti-aging cellular pattern by causing age-related changes in cellular proteome.

    Science.gov (United States)

    Beach, Adam; Richard, Vincent R; Bourque, Simon; Boukh-Viner, Tatiana; Kyryakov, Pavlo; Gomez-Perez, Alejandra; Arlia-Ciommo, Anthony; Feldman, Rachel; Leonov, Anna; Piano, Amanda; Svistkova, Veronika; Titorenko, Vladimir I

    2015-01-01

    We have previously revealed that exogenously added lithocholic bile acid (LCA) extends the chronological lifespan of the yeast Saccharomyces cerevisiae, accumulates in mitochondria and alters mitochondrial membrane lipidome. Here, we use quantitative mass spectrometry to show that LCA alters the age-related dynamics of changes in levels of many mitochondrial proteins, as well as numerous proteins in cellular locations outside of mitochondria. These proteins belong to 2 regulons, each modulated by a different mitochondrial dysfunction; we call them a partial mitochondrial dysfunction regulon and an oxidative stress regulon. We found that proteins constituting these regulons (1) can be divided into several "clusters", each of which denotes a distinct type of partial mitochondrial dysfunction that elicits a different signaling pathway mediated by a discrete set of transcription factors; (2) exhibit 3 different patterns of the age-related dynamics of changes in their cellular levels; and (3) are encoded by genes whose expression is regulated by the transcription factors Rtg1p/Rtg2p/Rtg3p, Sfp1p, Aft1p, Yap1p, Msn2p/Msn4p, Skn7p and Hog1p, each of which is essential for longevity extension by LCA. Our findings suggest that LCA-driven changes in mitochondrial lipidome alter mitochondrial proteome and functionality, thereby enabling mitochondria to operate as signaling organelles that orchestrate an establishment of an anti-aging transcriptional program for many longevity-defining nuclear genes. Based on these findings, we propose a model for how such LCA-driven changes early and late in life of chronologically aging yeast cause a stepwise development of an anti-aging cellular pattern and its maintenance throughout lifespan.

  5. Cellular functions of the microprocessor.

    Science.gov (United States)

    Macias, Sara; Cordiner, Ross A; Cáceres, Javier F

    2013-08-01

    The microprocessor is a complex comprising the RNase III enzyme Drosha and the double-stranded RNA-binding protein DGCR8 (DiGeorge syndrome critical region 8 gene) that catalyses the nuclear step of miRNA (microRNA) biogenesis. DGCR8 recognizes the RNA substrate, whereas Drosha functions as an endonuclease. Recent global analyses of microprocessor and Dicer proteins have suggested novel functions for these components independent of their role in miRNA biogenesis. A HITS-CLIP (high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation) experiment designed to identify novel substrates of the microprocessor revealed that this complex binds and regulates a large variety of cellular RNAs. The microprocessor-mediated cleavage of several classes of RNAs not only regulates transcript levels, but also modulates alternative splicing events, independently of miRNA function. Importantly, DGCR8 can also associate with other nucleases, suggesting the existence of alternative DGCR8 complexes that may regulate the fate of a subset of cellular RNAs. The aim of the present review is to provide an overview of the diverse functional roles of the microprocessor.

  6. Melanoma screening with cellular phones.

    Directory of Open Access Journals (Sweden)

    Cesare Massone

    Full Text Available BACKGROUND: Mobile teledermatology has recently been shown to be suitable for teledermatology despite limitations in image definition in preliminary studies. The unique aspect of mobile teledermatology is that this system represents a filtering or triage system, allowing a sensitive approach for the management of patients with emergent skin diseases. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigated the feasibility of teleconsultation using a new generation of cellular phones in pigmented skin lesions. 18 patients were selected consecutively in the Pigmented Skin Lesions Clinic of the Department of Dermatology, Medical University of Graz, Graz (Austria. Clinical and dermoscopic images were acquired using a Sony Ericsson with a built-in two-megapixel camera. Two teleconsultants reviewed the images on a specific web application (http://www.dermahandy.net/default.asp where images had been uploaded in JPEG format. Compared to the face-to-face diagnoses, the two teleconsultants obtained a score of correct telediagnoses of 89% and of 91.5% reporting the clinical and dermoscopic images, respectively. CONCLUSIONS/SIGNIFICANCE: The present work is the first study performing mobile teledermoscopy using cellular phones. Mobile teledermatology has the potential to become an easy applicable tool for everyone and a new approach for enhanced self-monitoring for skin cancer screening in the spirit of the eHealth program of the European Commission Information for Society and Media.

  7. Melanoma screening with cellular phones.

    Science.gov (United States)

    Massone, Cesare; Hofmann-Wellenhof, Rainer; Ahlgrimm-Siess, Verena; Gabler, Gerald; Ebner, Christoph; Soyer, H Peter

    2007-05-30

    Mobile teledermatology has recently been shown to be suitable for teledermatology despite limitations in image definition in preliminary studies. The unique aspect of mobile teledermatology is that this system represents a filtering or triage system, allowing a sensitive approach for the management of patients with emergent skin diseases. In this study we investigated the feasibility of teleconsultation using a new generation of cellular phones in pigmented skin lesions. 18 patients were selected consecutively in the Pigmented Skin Lesions Clinic of the Department of Dermatology, Medical University of Graz, Graz (Austria). Clinical and dermoscopic images were acquired using a Sony Ericsson with a built-in two-megapixel camera. Two teleconsultants reviewed the images on a specific web application (http://www.dermahandy.net/default.asp) where images had been uploaded in JPEG format. Compared to the face-to-face diagnoses, the two teleconsultants obtained a score of correct telediagnoses of 89% and of 91.5% reporting the clinical and dermoscopic images, respectively. The present work is the first study performing mobile teledermoscopy using cellular phones. Mobile teledermatology has the potential to become an easy applicable tool for everyone and a new approach for enhanced self-monitoring for skin cancer screening in the spirit of the eHealth program of the European Commission Information for Society and Media.

  8. Cellular automata modelling of SEIRS

    Institute of Scientific and Technical Information of China (English)

    Liu Quan-Xing; Jin Zhen

    2005-01-01

    In this paper the SEIRS epidemic spread is analysed, and a two-dimensional probability cellular automata model for SEIRS is presented. Each cellular automation cell represents a part of the population that may be found in one of five states of individuals: susceptible, exposed (or latency), infected, immunized (or recovered) and death. Here studied are the effects of two cases on the epidemic spread. i.e. the effects of non-segregation and segregation on the latency and the infected of population. The conclusion is reached that the epidemic will persist in the case of non-segregation but it will decrease in the case of segregation. The proposed model can serve as a basis for the development of algorithms to simulate real epidemics based on real data. Last we find the density series of the exposed and the infected will fluctuate near a positive equilibrium point, when the constant for the immunized is less than its corresponding constant τ0. Our theoretical results are verified by numerical simulations.

  9. Redox regulation of SIRT1 in inflammation and cellular senescence.

    Science.gov (United States)

    Hwang, Jae-woong; Yao, Hongwei; Caito, Samuel; Sundar, Isaac K; Rahman, Irfan

    2013-08-01

    Sirtuin 1 (SIRT1) regulates inflammation, aging (life span and health span), calorie restriction/energetics, mitochondrial biogenesis, stress resistance, cellular senescence, endothelial functions, apoptosis/autophagy, and circadian rhythms through deacetylation of transcription factors and histones. SIRT1 level and activity are decreased in chronic inflammatory conditions and aging, in which oxidative stress occurs. SIRT1 is regulated by a NAD(+)-dependent DNA repair enzyme, poly(ADP-ribose) polymerase-1 (PARP1), and subsequent NAD(+) depletion by oxidative stress may have consequent effects on inflammatory and stress responses as well as cellular senescence. SIRT1 has been shown to undergo covalent oxidative modifications by cigarette smoke-derived oxidants/aldehydes, leading to posttranslational modifications, inactivation, and protein degradation. Furthermore, oxidant/carbonyl stress-mediated reduction of SIRT1 leads to the loss of its control on acetylation of target proteins including p53, RelA/p65, and FOXO3, thereby enhancing the inflammatory, prosenescent, and apoptotic responses, as well as endothelial dysfunction. In this review, the mechanisms of cigarette smoke/oxidant-mediated redox posttranslational modifications of SIRT1 and its roles in PARP1 and NF-κB activation, and FOXO3 and eNOS regulation, as well as chromatin remodeling/histone modifications during inflammaging, are discussed. Furthermore, we have also discussed various novel ways to activate SIRT1 either directly or indirectly, which may have therapeutic potential in attenuating inflammation and premature senescence involved in chronic lung diseases.

  10. REDOX REGULATION OF SIRT1 IN INFLAMMATION AND CELLULAR SENESCENCE

    Science.gov (United States)

    Hwang, Jae-woong; Yao, Hongwei; Caito, Samuel; Sundar, Isaac K.; Rahman, Irfan

    2013-01-01

    Sirtuin1 (SIRT1) regulates inflammation, aging (lifespan and healthspan), calorie restriction/energetics, mitochondrial biogenesis, stress resistance, cellular senescence, endothelial functions, apoptosis/autophagy, and circadian rhythms through deacetylation of transcription factors and histones. SIRT1 level and activity are decreased in chronic inflammatory conditions and aging where oxidative stress occurs. SIRT1 is regulated by a NAD+-dependent DNA repair enzyme poly(ADP-ribose)-polymerase-1 (PARP-1), and subsequent NAD+ depletion by oxidative stresses may have consequent effects on inflammatory and stress responses as well as cellular senescence. SIRT1 has been shown to undergo covalent oxidative modifications by cigarette smoke-derived oxidants/aldehydes, leading to post-translational modifications, inactivation, and protein degradation. Furthermore, oxidant/carbonyl stress-mediated reduction of SIRT1 leads to the loss of its control on acetylation of target proteins including p53, RelA/p65 and FOXO3, thereby enhancing the inflammatory, pro-senescent and apoptotic responses, as well as endothelial dysfunction. In this review, the mechanisms of cigarette smoke/oxidant-mediated redox post-translational modifications of SIRT1 and its role in PARP1, NF-κB activation, FOXO3 and eNOS regulation, as well as chromatin remodeling/histone modifications during inflammaging are discussed. Furthermore, we also discussed various novel ways to activate SIRT1 either directly or indirectly, which may have therapeutic potential in attenuating inflammation and premature senescence involved in chronic lung diseases. PMID:23542362

  11. Mitochondria-specific accumulation of amyloid β induces mitochondrial dysfunction leading to apoptotic cell death.

    Science.gov (United States)

    Cha, Moon-Yong; Han, Sun-Ho; Son, Sung Min; Hong, Hyun-Seok; Choi, Young-Ju; Byun, Jayoung; Mook-Jung, Inhee

    2012-01-01

    Mitochondria are best known as the essential intracellular organelles that host the homeostasis required for cellular survival, but they also have relevance in diverse disease-related conditions, including Alzheimer's disease (AD). Amyloid β (Aβ) peptide is the key molecule in AD pathogenesis, and has been highlighted in the implication of mitochondrial abnormality during the disease progress. Neuronal exposure to Aβ impairs mitochondrial dynamics and function. Furthermore, mitochondrial Aβ accumulation has been detected in the AD brain. However, the underlying mechanism of how Aβ affects mitochondrial function remains uncertain, and it is questionable whether mitochondrial Aβ accumulation followed by mitochondrial dysfunction leads directly to neuronal toxicity. This study demonstrated that an exogenous Aβ(1-42) treatment, when applied to the hippocampal cell line of mice (specifically HT22 cells), caused a deleterious alteration in mitochondria in both morphology and function. A clathrin-mediated endocytosis blocker rescued the exogenous Aβ(1-42)-mediated mitochondrial dysfunction. Furthermore, the mitochondria-targeted accumulation of Aβ(1-42) in HT22 cells using Aβ(1-42) with a mitochondria-targeting sequence induced the identical morphological alteration of mitochondria as that observed in the APP/PS AD mouse model and exogenous Aβ(1-42)-treated HT22 cells. In addition, subsequent mitochondrial dysfunctions were demonstrated in the mitochondria-specific Aβ(1-42) accumulation model, which proved indistinguishable from the mitochondrial impairment induced by exogenous Aβ(1-42)-treated HT22 cells. Finally, cellular toxicity was directly induced by mitochondria-targeted Aβ(1-42) accumulation, which mimics the apoptosis process in exogenous Aβ(1-42)-treated HT22 cells. Taken together, these results indicate that mitochondria-targeted Aβ(1-42) accumulation is the necessary and sufficient condition for Aβ-mediated mitochondria impairments, and leads

  12. Procalcitonin Impairs Liver Cell Viability and Function In Vitro: A Potential New Mechanism of Liver Dysfunction and Failure during Sepsis?

    Science.gov (United States)

    Ehler, Johannes; Wagner, Nana-Maria

    2017-01-01

    Purpose. Liver dysfunction and failure are severe complications of sepsis and result in poor outcome and increased mortality. The underlying pathologic mechanisms of hepatocyte dysfunction and necrosis during sepsis are only incompletely understood. Here, we investigated whether procalcitonin, a biomarker of sepsis, modulates liver cell function and viability. Materials and Methods. Employing a previously characterized and patented biosensor system evaluating hepatocyte toxicity in vitro, human hepatocellular carcinoma cells (HepG2/C3A) were exposed to 0.01–50 ng/mL procalcitonin for 2 × 72 h and evaluated for proliferation, necrosis, metabolic activity, cellular integrity, microalbumin synthesis, and detoxification capacity. Acetaminophen served as positive control. For further standardization, procalcitonin effects were confirmed in a cellular toxicology assay panel employing L929 fibroblasts. Data were analyzed using ANOVA/Tukey's test. Results. Already at concentrations as low as 0.25 ng/mL, procalcitonin induced HepG2/C3A necrosis (P < 0.05) and reduced metabolic activity, cellular integrity, synthesis, and detoxification capacity (all P < 0.001). Comparable effects were obtained employing L929 fibroblasts. Conclusion. We provide evidence for procalcitonin to directly impair function and viability of human hepatocytes and exert general cytotoxicity in vitro. Therapeutical targeting of procalcitonin could thus display a novel approach to reduce incidence of liver dysfunction and failure during sepsis and lower morbidity and mortality of septic patients. PMID:28255555

  13. De Novo ACTA2 Mutation Causes a Novel Syndrome of Multisystemic Smooth Muscle Dysfunction

    Science.gov (United States)

    Milewicz, Dianna M.; Østergaard, John R.; Ala-Kokko, Leena M.; Khan, Nadia; Grange, Dorothy K.; Mendoza-Londono, Roberto; Bradley, Timothy J.; Olney, Ann Haskins; Adès, Lesley; Maher, Joseph F.; Guo, Dongchuan; Buja, L. Maximilian; Kim, Dong; Hyland, James C.; Regalado, Ellen S.

    2011-01-01

    Smooth muscle cells (SMCs) contract to perform many physiological functions, including regulation of blood flow and pressure in arteries, contraction of the pupils, peristalsis of the gut and voiding of the bladder. SMC lineage in these organs is characterized by cellular expression of the SMC isoform of α-actin, encoded by the ACTA2 gene. We report here on a unique and de novo mutation in ACTA2, R179H, that causes a syndrome characterized by dysfunction of SMCs throughout the body, leading to aortic and cerebrovascular disease, fixed dilated pupils, hypotonic bladder, malrotation and hypoperistalsis of the gut and pulmonary hypertension. PMID:20734336

  14. Ubiquitin-proteasome system in cardiac dysfunction

    OpenAIRE

    Mearini, Giulia; Schlossarek, Saskia; Willis, Monte S.; Carrier, Lucie

    2008-01-01

    Ubiquitin-proteasome system in cardiac dysfunction correspondance: Corresponding author. Tel.: +49 40 42803 7208; fax: +49 40 42803 5925. (Carrier, Lucie) (Carrier, Lucie) Institute of Experimental and Clinical Pharmacology and Toxicology--> , University Medical Center Hamburg-Eppendorf--> , Hamburg--> - GERMANY (Mearini, Giulia) Institute of Experimental and Clinical Pharmacology and...

  15. Cycloserine induced psychosis with hepatic dysfunction

    Directory of Open Access Journals (Sweden)

    Vishal R Tandon

    2015-01-01

    Full Text Available With the increase in the cases of multidrug resistance tuberculosis, second line anti-tubercular drugs like the cycloserine are being prescribed frequently. Isoniazid and ethambutol are reported to cause psychosis like state; however, few reports of cycloserine induced psychosis are available. To the best of our knowledge, this is the first case of cycloserine induced psychosis with hepatic dysfunction.

  16. Intestinal microcirculatory dysfunction and neonatal necrotizing enterocolitis

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong-yi; WANG Fang; FENG Jie-xiong

    2013-01-01

    Objective Based on the observation that coagulation necrosis occurs in the majority of neonatal necrotizing enterocolitis (NEC) patients,it is clear that intestinal ischemia is a contributing factor to the pathogenesis of NEC.However,the published studies regarding the role of intestinal ischemia in NEC are controversial.The aim of this paper is to review the current studies regarding intestinal microcirculatory dysfunction and NEC,and try to elucidate the exact role of intestinal microcirculatory dysfunction in NEC.Data sources The studies cited in this review were mainly obtained from articles listed in Medline and PubMed.The search terms used were "intestinal microcirculatory dysfunction" and "neonatal necrotizing enterocolitis".Study selection Mainly original milestone articles and critical reviews written by major pioneer investigators in the field were selected.Results Immature regulatory control of mesentery circulation makes the neonatal intestinal microvasculature vulnerable.When neonates are subjected to stress,endothelial cell dysfunction occurs and results in vasoconstriction of arterioles,inflammatory cell infiltration and activation in venules,and endothelial barrier disruption in capillaries.The compromised vasculature increases circulation resistance and therefore decreases intestinal perfusion,and may eventually progress to intestinal necrosis.Conclusion Intestinal ischemia plays an important role through the whole course of NEC.New therapeutic agents targeting intestinal ischemia,like HB-EGF,are promising therapeutic agents for the treatment of NEC.

  17. New Diagnostic Terminology for Minimal Brain Dysfunction.

    Science.gov (United States)

    Shaywitz, Bennett A.; And Others

    1979-01-01

    Minimal brain dysfunction has been redefined by the American Psychological Association as attention deficit disorder (ADD) and subdivided into categories with and without hyperactivity. The revised 'Diagnostic and Statistical Manual' (DSM III) is now undergoing field trials. Journal Availability: C. V. Mosby Company, 11830 Westline Industrial…

  18. Early diastolic filling dynamics in diastolic dysfunction

    Directory of Open Access Journals (Sweden)

    Crean Peter A

    2003-07-01

    Full Text Available Abstract Background The aim of the study was to determine the relationship between the rate of peak early mitral inflow velocity and the peak early diastolic mitral annular tissue velocities in normal controls and to compare them with subjects with diastolic dysfunction. Methods The relationship between early passive diastolic transmitral flow and peak early mitral annular velocity in the normal and in diastolic dysfunction was studied. Two groups comprising 22 normal controls and 25 patients with diastolic dysfunction were studied. Results Compared with the normal group, those with diastolic dysfunction had a lower E/A ratio (0.7 ± 0.2 vs. 1.9 ± 0.5, p 2 vs. 871 ± 128.1 cm/sec2, p Conclusions This investigation provides information on the acceleration of early diastolic filling and its relationship to mitral annular peak tissue velocity (Ea recorded by Doppler tissue imaging. It supports not only the premise that recoil is an important mechanism for rapid early diastolic filling but also the existence of an early diastolic mechanism in normal.

  19. Acute lung injury induces cardiovascular dysfunction

    DEFF Research Database (Denmark)

    Suda, Koichi; Tsuruta, Masashi; Eom, Jihyoun

    2011-01-01

    Acute lung injury (ALI) is associated with systemic inflammation and cardiovascular dysfunction. IL-6 is a biomarker of this systemic response and a predictor of cardiovascular events, but its possible causal role is uncertain. Inhaled corticosteroids and long-acting β2 agonists (ICS/LABA) down...

  20. Lower urinary tract dysfunction in children

    NARCIS (Netherlands)

    Klijn, AJ

    2016-01-01

    Lower urinary tract dysfunction in children can have many faces. It can present with incontinenece for urine, urinary tract infections or even constipation or loosing stools. All kinds of factors influencing the function of the pelvic floor muscle tension can have an impact on the lower urinary trac