Science.gov

Sample records for particle disease induced

  1. Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease

    PubMed Central

    Saber, Anne T; Jacobsen, Nicklas R; Jackson, Petra; Poulsen, Sarah Søs; Kyjovska, Zdenka O; Halappanavar, Sabina; Yauk, Carole L; Wallin, Håkan; Vogel, Ulla

    2014-01-01

    Inhalation of ambient and workplace particulate air pollution is associated with increased risk of cardiovascular disease. One proposed mechanism for this association is that pulmonary inflammation induces a hepatic acute phase response, which increases risk of cardiovascular disease. Induction of the acute phase response is intimately linked to risk of cardiovascular disease as shown in both epidemiological and animal studies. Indeed, blood levels of acute phase proteins, such as C-reactive protein and serum amyloid A, are independent predictors of risk of cardiovascular disease in prospective epidemiological studies. In this review, we present and review emerging evidence that inhalation of particles (e.g., air diesel exhaust particles and nanoparticles) induces a pulmonary acute phase response, and propose that this induction constitutes the causal link between particle inhalation and risk of cardiovascular disease. Increased levels of acute phase mRNA and proteins in lung tissues, bronchoalveolar lavage fluid and plasma clearly indicate pulmonary acute phase response following pulmonary deposition of different kinds of particles including diesel exhaust particles, nanoparticles, and carbon nanotubes. The pulmonary acute phase response is dose-dependent and long lasting. Conversely, the hepatic acute phase response is reduced relative to lung or entirely absent. We also provide evidence that pulmonary inflammation, as measured by neutrophil influx, is a predictor of the acute phase response and that the total surface area of deposited particles correlates with the pulmonary acute phase response. We discuss the implications of these findings in relation to occupational exposure to nanoparticles. How to cite this article: WIREs Nanomed Nanobiotechnol 2014, 6:517–531. doi: 10.1002/wnan.1279 PMID:24920450

  2. Venezuelan equine encephalitis replicon particles can induce rapid protection against foot-and-mouth disease virus.

    PubMed

    Diaz-San Segundo, Fayna; Dias, Camila C A; Moraes, Mauro P; Weiss, Marcelo; Perez-Martin, Eva; Owens, Gary; Custer, Max; Kamrud, Kurt; de los Santos, Teresa; Grubman, Marvin J

    2013-05-01

    We have previously shown that delivery of the porcine type I interferon gene (poIFN-?/?) with a replication-defective human adenovirus vector (adenovirus 5 [Ad5]) can sterilely protect swine challenged with foot-and-mouth disease virus (FMDV) 1 day later. However, the need of relatively high doses of Ad5 limits the applicability of such a control strategy in the livestock industry. Venezuelan equine encephalitis virus (VEE) empty replicon particles (VRPs) can induce rapid protection of mice against either homologous or, in some cases, heterologous virus challenge. As an alternative approach to induce rapid protection against FMDV, we have examined the ability of VRPs containing either the gene for green fluorescent protein (VRP-GFP) or poIFN-? (VRP-poIFN-?) to block FMDV replication in vitro and in vivo. Pretreatment of swine or bovine cell lines with either VRP significantly inhibited subsequent infection with FMDV as early as 6 h after treatment and for at least 120 h posttreatment. Furthermore, mice pretreated with either 10(7) or 10(8) infectious units of VRP-GFP and challenged with a lethal dose of FMDV 24 h later were protected from death. Protection was induced as early as 6 h after treatment and lasted for at least 48 h and correlated with induction of an antiviral response and production of IFN-?. By 6 h after treatment several genes were upregulated, and the number of genes and the level of induction increased at 24 h. Finally, we demonstrated that the chemokine IP-10, which is induced by IFN-? and VRP-GFP, is directly involved in protection against FMDV. PMID:23468490

  3. Unhealthy diet and ultrafine carbon black particles induce senescence and disease associated phenotypic changes.

    PubMed

    Büchner, Nicole; Ale-Agha, Niloofar; Jakob, Sascha; Sydlik, Ulrich; Kunze, Kerstin; Unfried, Klaus; Altschmied, Joachim; Haendeler, Judith

    2013-01-01

    Diet and pollution are environmental factors known to compromise "healthy aging" of the cardiovascular and respiratory systems. The molecular consequences of this permanent burden in these cells are still unknown. Therefore, this study investigates the impact of unhealthy diet on aging-related signaling pathways of human, primary cardiovascular cells and of airborne particles on lung epithelial and human endothelial cells. Nutrition health reports have shown that the diet in industrialized countries contains more than 100mg/dl low density lipoprotein (LDL) and a high fraction of added sugars, especially fructose. Several studies demonstrated that ultrafine particles can enter the circulation and thus may interact with endothelial cells directly. Both, dietary compounds and pollution derived particles, have been shown to increase the risk for cardiovascular diseases. To simulate an unhealthy diet, we supplemented cell culture media of human primary endothelial cells, smooth muscle cells and cardiomyocytes with LDL and replaced 1/3 of glucose with fructose. We observed hypertrophy in cardiomyocytes, enhanced proliferation in smooth muscle cells and increased senescence, loss of endothelial nitric oxide synthase and increased nuclear FoxO3A in endothelial cells. With respect to pollution we have used ultrafine carbon black particles (ufCB), one of the major constituents of industrial and exhaust emissions, in concentrations our lungs and vessels are constantly exposed to. These concentrations of ufCB increased reactive oxygen species in lung epithelial and vascular endothelial cells and reduced the S-NO content, a marker for NO-bioavailability, in endothelial cells. NO increases activation of Telomerase Reverse Transcriptase (TERT), an enzyme essential for telomere maintenance. TERT is required for proper endothelial cell function and is inactivated by Src kinase under conditions of oxidative stress. ufCB significantly increased Src kinase activation and reduced Telomerase activity in endothelial and lung epithelial cells. As a consequence, ufCB increased senescence of endothelial cells. To investigate whether ufCB show also effects in vivo, we instilled ufCB in concentrations not inducing inflammation into mice. Indeed, eNOS expression was reduced in the abdominal aorta of animals treated with ufCB. Thus, a combination of fructose and LDL in the diet and ufCB, as a major constituent of air pollution, seem to accelerate respiratory and cardiovascular cellular changes, which may compromise "healthy aging" and can lead to cardiovascular and pulmonary diseases. PMID:22507566

  4. Particles causing lung disease.

    PubMed Central

    Kilburn, K H

    1984-01-01

    The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response, appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. The insidious and probably most important human lung disease due to particles is bronchiolar obstruction and obliteration, producing progressive impairment of air flow. The responsible particle is the complex combination of poorly digestive lipids and complex carbohydrates with active chemicals which we call cigarette smoke. More research is needed to perfect, correct and quantify our preliminary picture of the pathogenesis of lung disease by particles, but a useful start has been made. Images FIGURE 1. PMID:6376114

  5. Particles causing lung disease

    SciTech Connect

    Kilburn, K.H.

    1984-04-01

    The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. 164 references, 1 figure, 2 tables.

  6. Toxicity of Mineral Dusts and a Proposed Mechanism for the Pathogenesis of Particle-Induced Lung Diseases

    NASA Technical Reports Server (NTRS)

    Lam, C.-W.; Zeidler-Erdely, P.; Scully, R.R.; Meyers, V.; Wallace, W.; Hunter, R.; Renne, R.; McCluskey, R.; Castranova, V.; Barger, M.; Meighan, T.; James, J.T.

    2015-01-01

    Humans will set foot on the moon again. The lunar surface has been bombarded for 4 billion years by micrometeoroids and cosmic radiation, creating a layer of fine dust having a potentially reactive particle surface. To investigate the impact of surface reactivity (SR) on the toxicity of particles, and in particular, lunar dust (LD), we ground 2 Apollo 14 LD samples to increase their SR and compare their toxicity with those of unground LD, TiO2 and quartz. Intratracheally instilled at 0, 1, 2.5, or 7.5 mg/rat, all dusts caused dose-dependent increases in pulmonary lesions, and enhancement of biomarkers of toxicity assessed in bronchoalveolar lavage fluids (BALF). The toxicity of LD was greater than that of TiO2 but less than that of quartz. Three LDs differed 14-fold in SR but were equally toxic; quartz had the lowest SR but was most toxic. These results show no correlation between particle SR and toxicity. Often pulmonary toxicity of a dust can be attributed to oxidative stress (OS). We further observed dose-dependent and dustcytotoxicity- dependent increases in neutrophils. The oxidative content per BALF cell was also directly proportional to both the dose and cytotoxicity of the dusts. Because neutrophils are short-lived and release of oxidative contents after they die could initiate and promote a spectrum of lesions, we postulate a general mechanism for the pathogenesis of particle-induced diseases in the lung that involves chiefly neutrophils, the source of persistent endogenous OS. This mechanism explains why one dust (e.g., quartz or nanoparticles) is more toxic than another (e.g., micrometer-sized TiO2), why dust-induced lesions progress with time, and why lung cancer occurs in rats but not in mice and hamsters exposed to the same duration and concentration of dust.

  7. Newcastle Disease Virus Vector Producing Human Norovirus-Like Particles Induces Serum, Cellular, and Mucosal Immune Responses in Mice

    PubMed Central

    Kim, Shin-Hee; Chen, Shun; Jiang, Xi; Green, Kim Y.

    2014-01-01

    ABSTRACT Human norovirus infection is the most common cause of viral gastroenteritis worldwide. Development of an effective vaccine is required for reducing norovirus outbreaks. The inability to grow human norovirus in cell culture has hindered the development of live-attenuated vaccines. To overcome this obstacle, we generated a recombinant Newcastle disease virus (rNDV)-vectored experimental norovirus vaccine by expressing the capsid protein (VP1) of norovirus strain VA387. We compared two different NDV vectors, a conventional rNDV vector and a modified rNDV vector, for their efficiencies in expressing VP1 protein. Our results showed that the modified vector replicated to higher titers and expressed higher levels of VP1 protein in DF1 cells and in allantoic fluid of embryonated chicken eggs than did the conventional vector. We further demonstrated that the VP1 protein produced by rNDVs was able to self-assemble into virus-like particles (VLPs) that are morphologically similar to baculovirus-expressed VLPs. Evaluation of their immunogenicity in mice showed that the modified rNDV vector induced a higher level of IgG response than those induced by the conventional vector and by the baculovirus-expressed VLPs. The rNDV vectors predominantly induced IgG2a subclass antibody for the Th1 response, and specifically, high levels of gamma interferon (IFN-?), tumor necrosis factor alpha (TNF-?), and interleukin-2 (IL-2) were detected in splenocytes. In addition, the modified rNDV vector induced a higher level of fecal IgA response in mice than did baculovirus-expressed VLPs. Our findings suggest that the rNDV vector is an efficient system to produce cost-effective VLPs in embryonated chicken eggs and has the potential to be used as a live-attenuated vaccine in humans. IMPORTANCE Noroviruses are the major cause of viral gastroenteritis worldwide. Currently, effective vaccines against norovirus infection are not available. In this study, we have evaluated Newcastle disease virus (NDV) as a vaccine vector for norovirus. Our results suggest that NDV can be used not only as a cost-effective method for large-scale production of norovirus-like particle vaccines but also as a live-attenuated vectored vaccine. PMID:24920815

  8. Recombinant rabbit hemorrhagic disease virus capsid protein expressed in baculovirus self-assembles into viruslike particles and induces protection.

    PubMed Central

    Laurent, S; Vautherot, J F; Madelaine, M F; Le Gall, G; Rasschaert, D

    1994-01-01

    VP60, the unique component of rabbit hemorrhagic disease virus capsid, was expressed in the baculovirus system. The recombinant VP60, released in the supernatant of infected insect cells, assembled without the need of any other viral component to form viruslike particles (VLPs), structurally and immunologically indistinguishable from the rabbit hemorrhagic disease virion. Intramuscular vaccination of rabbits with the VLPs conferred complete protection in 15 days; this protection was found to be effective from the fifth day after VLP injection and was accompanied by a strong humoral response. Images PMID:8084017

  9. Particle therapy for noncancer diseases

    SciTech Connect

    Bert, Christoph; Engenhart-Cabillic, Rita; Durante, Marco

    2012-04-15

    Radiation therapy using high-energy charged particles is generally acknowledged as a powerful new technique in cancer treatment. However, particle therapy in oncology is still controversial, specifically because it is unclear whether the putative clinical advantages justify the high additional costs. However, particle therapy can find important applications in the management of noncancer diseases, especially in radiosurgery. Extension to other diseases and targets (both cranial and extracranial) may widen the applications of the technique and decrease the cost/benefit ratio of the accelerator facilities. Future challenges in this field include the use of different particles and energies, motion management in particle body radiotherapy and extension to new targets currently treated by catheter ablation (atrial fibrillation and renal denervation) or stereotactic radiation therapy (trigeminal neuralgia, epilepsy, and macular degeneration). Particle body radiosurgery could be a future key application of accelerator-based particle therapy facilities in 10 years from today.

  10. Metal-sulfide mineral ores, Fenton chemistry and disease--particle induced inflammatory stress response in lung cells.

    PubMed

    Harrington, Andrea D; Smirnov, Alexander; Tsirka, Stella E; Schoonen, Martin A A

    2015-01-01

    The inhalation of mineral particulates and other earth materials, such as coal, can initiate or enhance disease in humans. Workers in occupations with high particulate exposure, such as mining, are particularly at risk. The ability of a material to generate an inflammatory stress response (ISR), a measure of particle toxicity, is a useful tool in evaluating said exposure risk. ISR is defined as the upregulation of cellular reactive oxygen species (ROS) normalized to cell viability. This study compares the ISR of A549 human lung epithelial cells after exposure to well-characterized common metal-sulfide ore mineral separates. The evaluation of the deleterious nature of ore minerals is based on a range of particle loadings (serial dilutions of 0.002m(2)/mL stock) and exposure periods (beginning at 30min and measured systematically for up to 24h). There is a wide range in ISR values generated by the ore minerals. The ISR values produced by the sphalerite samples are within the range of inert materials. Arsenopyrite generated a small ISR that was largely driven by cell death. Galena showed a similar, but more pronounced response. Copper-bearing ore minerals generated the greatest ISR, both by upregulating cellular ROS and generating substantial and sustained cell death. Chalcopyrite and bornite, both containing ferrous iron, generated the greatest ISR overall. Particles containing Fenton metals as major constituents produce the highest ISR, while other heavy metals mainly generate cell death. This study highlights the importance of evaluating the chemistry, oxidation states and structure of a material when assessing risk management. PMID:25107347

  11. Drug-induced pulmonary disease

    MedlinePLUS

    ... induced lung disease improves. Anti-inflammatory medicines called steroids are sometimes used to quickly reverse the lung ... you have known drug reactions. Stay away from illegal drugs to prevent many drug-induced lung diseases.

  12. Foot-and-mouth disease vaccination induces cross-reactive IFN-? responses in cattle that are dependent on the integrity of the 140S particles.

    PubMed

    Bucafusco, Danilo; Di Giacomo, Sebastián; Pega, Juan; Schammas, Juan Manuel; Cardoso, Nancy; Capozzo, Alejandra Victoria; Perez-Filgueira, Mariano

    2015-02-01

    Interferon-? (IFN-?) recall responses against foot-and-mouth disease virus (FMDV) in FMD vaccinated cattle are utilized to study T-lymphocyte immunity against this virus. Here, a recall IFN-? assay based on a commercial ELISA was set up using 308 samples from naïve and vaccinated cattle. The assay was used to study cross-reactive responses between different FMDV vaccine strains. Blood samples from cattle immunized with monovalent vaccines containing A24/Cruzeiro/Brazil/55, A/Argentina/2001 or O1/Campos/Brazil/58 strains were tested using purified-inactivated FMDV from homologous and heterologous strains. A24/Cruzeiro was the most efficient IFN-? inducer in all vaccinated animals, both when included in the vaccine or as stimulating antigen. We demonstrate that this was mainly due to the structural stability of the whole viral particle. These results show that IFN-? production relies on the presence of 140S particles that can maintain their integrity along the incubation process in vitro, and throughout the vaccine's shelf-life, when used in vivo. PMID:25496826

  13. Venezuelan Equine Encephalitis Virus replicon particles can induce rapid protection against Foot-and-Mouth Disease Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have previously shown that swine pretreated with a replication-defective human adenovirus vector (Ad5) containing the porcine type I interferon gene (poIFN-alpha/Beta) are sterilely protected when challenged one day later with Foot-and-Mouth Disease Virus (FMDV), but the dose required is relativ...

  14. Drug Induced Interstitial Lung Disease

    PubMed Central

    Schwaiblmair, Martin; Behr, Werner; Haeckel, Thomas; Märkl, Bruno; Foerg, Wolfgang; Berghaus, Thomas

    2012-01-01

    With an increasing number of therapeutic drugs, the list of drugs that is responsible for severe pulmonary disease also grows. Many drugs have been associated with pulmonary complications of various types, including interstitial inflammation and fibrosis, bronchospasm, pulmonary edema, and pleural effusions. Drug-induced interstitial lung disease (DILD) can be caused by chemotherapeutic agents, antibiotics, antiarrhythmic drugs, and immunosuppressive agents. There are no distinct physiologic, radiographic or pathologic patterns of DILD, and the diagnosis is usually made when a patient with interstitial lung disease (ILD) is exposed to a medication known to result in lung disease. Other causes of ILD must be excluded. Treatment is avoidance of further exposure and systemic corticosteroids in patients with progressive or disabling disease. PMID:22896776

  15. Chromium-induced kidney disease

    SciTech Connect

    Wedeen, R.P. ); Qian, Lifen )

    1991-05-01

    Kidney disease is often cited as one of the adverse effects of chromium, yet chronic renal disease due to occupational or environmental exposure to chromium has not been reported. Occasional cases of acute tubular necrosis (ATN) following massive absorption of chromate have been described. Chromate-induced ATN has been extensively studied in experimental animals following parenteral administration of large doses of potassium chromate (hexavalent). The chromate is selectively accumulated in the convoluted proximal tubule where necrosis occurs. An adverse long-term effect of low-dose chromium exposure on the kidneys is suggested by reports of low molecular weight (LMW) proteinuria in chromium workers. Excessive urinary excretion of {beta}{sub 2}-microglobulin, a specific proximal tubule brush border protein, and retinol-binding protein has been reported among chrome palters and welders. However, LMW proteinuria occurs after a variety of physiologic stresses, is usually reversible, and cannot by itself be considered evidence of chromic renal disease. Chromate-induced ATN and LMW proteinuria in chromium workers, nevertheless, raise the possibility that low-level, long-term exposure may produce persistent renal injury. The absence of evidence of chromate-induced chromic renal disease cannot be interpreted as evidence of the absence of such injury.

  16. Apoptosis induced by parasitic diseases

    PubMed Central

    2010-01-01

    Fatalities caused by parasitic infections often occur as a result of tissue injury that results from a form of host-cell death known as apoptosis. However, instead of being pathogenic, parasite-induced apoptosis may facilitate host survival. Consequently, it is of utmost importance to decipher and understand the process and the role of apoptosis induced or controlled by parasites in humans. Despite this, few studies provide definitive knowledge of parasite-induced host-cell apoptosis. Here, the focus is on a consideration of host-cell apoptosis as either a pathogenic feature or as a factor enabling parasite survival and development. Cell death by apoptotic-like mechanisms could be described as a ride to death with a return ticket, as initiation of the pathway may be reversed, with the potential that it could be manipulated for therapeutic purposes. The management of host-cell apoptosis could thus be an adjunctive factor for parasitic disease treatment. Evidence that the apoptotic process could be reversed by anti-apoptotic drugs has recently been obtained, leading to the possibility of host-cell rescue after injury. An important issue will be to predict the beneficial or deleterious effects of controlling human cell death by apoptotic-like mechanisms during parasitic diseases. PMID:21083888

  17. Radioadaptive Response Induced by Alpha-Particle-Induced Stress

    E-print Network

    Yu, Peter K.N.

    of radioadaptive response (RAR) by com- munication of radiation-induced bystander signals. RAR is a kind of lowRadioadaptive Response Induced by Alpha-Particle-Induced Stress Communicated in Vivo between and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong, and Department

  18. Propylthiouracil-induced autoimmune disease

    PubMed Central

    Paiaulla, Santosh; Venkategowda, Pradeep Marur; Rao, S. Manimala; Balaraju, Banda

    2015-01-01

    Hyperthyroidism is a condition characterized by excessive production of thyroid hormones. Propylthiouracil (PTU) is commonly used as first line drug in the management of hyperthyroidism. This is a case report of 24-year-old female, a known case of hyperthyroidism since 4 years, who came with a history of fever and myalgia since 3 days and dyspnea with coughing out of blood since 1 day. Patient was taking PTU (100 mg per day) since 4 years for hyperthyroidism. Patient was immediately intubated for type-II respiratory failure. Diagnosed to be having PTU-induced autoimmune disease. PTU was stopped and treated with methylprednisolone and cyclophosphamide. Clinical features improved over a period of 8 days and discharged home successfully. Having a high suspicion for the onset of autoimmune disease in hyperthyroidism patients who are on PTU therapy and timely treatment with immunosuppressants and supportive care along with the withdrawal of the drug can make a difference in morbidity and mortality. PMID:26321810

  19. Particle Motion Induced by Bubble Cavitation

    NASA Astrophysics Data System (ADS)

    Poulain, Stéphane; Guenoun, Gabriel; Gart, Sean; Crowe, William; Jung, Sunghwan

    2015-05-01

    Cavitation bubbles induce impulsive forces on surrounding substrates, particles, or surfaces. Even though cavitation is a traditional topic in fluid mechanics, current understanding and studies do not capture the effect of cavitation on suspended objects in fluids. In the present work, the dynamics of a spherical particle due to a cavitation bubble is experimentally characterized and compared with an analytical model. Three phases are observed: the growth of the bubble where the particle is pushed away, its collapse where the particle approaches the bubble, and a longer time scale postcollapse where the particle continues to move toward the collapsed bubble. The particle motion in the longer time scale presumably results from the asymmetric cavitation evolution at an earlier time. Our theory considering the asymmetric bubble dynamics shows that the particle velocity strongly depends on the distance from the bubble as an inverse-fourth-power law, which is in good agreement with our experimentation. This study sheds light on how small free particles respond to cavitation bubbles in fluids.

  20. INDUCED DISEASE RESISTANCE IN PLANTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plants employ multiple types of defenses against microbial invasion. One type of defense is dependent upon the activation of certain defense mechanisms by the invading microbes or abiotic treatment and is termed induced resistance. The objective of this chapter is to review our current understanding...

  1. Diabetic Cardiovascular Disease Induced by Oxidative Stress

    PubMed Central

    Kayama, Yosuke; Raaz, Uwe; Jagger, Ann; Adam, Matti; Schellinger, Isabel N.; Sakamoto, Masaya; Suzuki, Hirofumi; Toyama, Kensuke; Spin, Joshua M.; Tsao, Philip S.

    2015-01-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM). DM can lead to multiple cardiovascular complications, including coronary artery disease (CAD), cardiac hypertrophy, and heart failure (HF). HF represents one of the most common causes of death in patients with DM and results from DM-induced CAD and diabetic cardiomyopathy. Oxidative stress is closely associated with the pathogenesis of DM and results from overproduction of reactive oxygen species (ROS). ROS overproduction is associated with hyperglycemia and metabolic disorders, such as impaired antioxidant function in conjunction with impaired antioxidant activity. Long-term exposure to oxidative stress in DM induces chronic inflammation and fibrosis in a range of tissues, leading to formation and progression of disease states in these tissues. Indeed, markers for oxidative stress are overexpressed in patients with DM, suggesting that increased ROS may be primarily responsible for the development of diabetic complications. Therefore, an understanding of the pathophysiological mechanisms mediated by oxidative stress is crucial to the prevention and treatment of diabetes-induced CVD. The current review focuses on the relationship between diabetes-induced CVD and oxidative stress, while highlighting the latest insights into this relationship from findings on diabetic heart and vascular disease. PMID:26512646

  2. Autophagy in Load-Induced Heart Disease

    PubMed Central

    Rothermel, Beverly A.; Hill, Joseph A.

    2008-01-01

    The heart is a highly plastic organ capable of remodeling in response to changes in physiological or pathological demand. For example, when workload increases, compensatory hypertrophic growth of individual cardiomyocytes occurs to increase cardiac output. Sustained stress, however, such as that occurring with hypertension or following myocardial infarction, triggers changes in energy metabolism and sarcomeric protein composition, loss of cardiomyocytes, ventricular dilation, reduced pump function, and ultimately heart failure. It has been known for some time that autophagy is active in cardiomyocytes, occurring at increased levels in disease. Now, with recent advances in our understanding of molecular mechanisms governing autophagy, the potential contributions of cardiomyocyte autophagy to ventricular remodeling and disease pathogenesis are being explored. As part of this work, several recent studies have focused on autophagy in heart disease elicited by changes in hemodynamic load. Pressure overload stress elicits a robust autophagic response in cardiomyocytes that is maladaptive, contributing to disease progression. In this context, load-induced aggregation of intracellular proteins is a proximal event triggering autophagic clearance mechanisms. These findings in the setting of pressure overload contrast with protein aggregation occurring in a model of protein chaperone malfunction, where activation of autophagy is beneficial, antagonizing disease progression. Here, we review recent studies of cardiomyocyte autophagy in load-induced disease and address molecular mechanisms and unanswered questions. PMID:19059838

  3. Rasagiline induced hypersexuality in Parkinson's disease.

    PubMed

    Reyes, Dennys; Kurako, Kateryna; Galvez-Jimenez, Nestor

    2014-03-01

    Impulse control disorders (ICD) are increasingly recognized in patients with Parkinson's disease (PD), particularly when treated with commonly used dopamine agonists such as pramipexole and ropinirole. Less evident is the possible association between monoamine oxidase inhibitors type B (MAO-B) and the development of ICD. Rasagiline is a second generation MAO-B I inducing moderate symptomatic and possibly disease modifying benefits with apparently good tolerability and safety profile in PD patients. Rasagiline is effective and well tolerated in PD as a monotherapy or in combination with levodopa. Here, we report a patient with PD who developed ICD when treated de novo with MAO-B inhibitors. PMID:24055209

  4. Geraniin suppresses RANKL-induced osteoclastogenesis in vitro and ameliorates wear particle-induced osteolysis in mouse model

    SciTech Connect

    Xiao, Fei; Zhai, Zanjing; Jiang, Chuan; Liu, Xuqiang; Li, Haowei; Qu, Xinhua; Ouyang, Zhengxiao; Fan, Qiming; Tang, Tingting; Qin, An; Gu, Dongyun

    2015-01-01

    Wear particle-induced osteolysis and subsequent aseptic loosening remains the most common complication that limits the longevity of prostheses. Wear particle-induced osteoclastogenesis is known to be responsible for extensive bone erosion that leads to prosthesis failure. Thus, inhibition of osteoclastic bone resorption may serve as a therapeutic strategy for the treatment of wear particle induced osteolysis. In this study, we demonstrated for the first time that geraniin, an active natural compound derived from Geranium thunbergii, ameliorated particle-induced osteolysis in a Ti particle-induced mouse calvaria model in vivo. We also investigated the mechanism by which geraniin exerts inhibitory effects on osteoclasts. Geraniin inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, evidenced by reduced osteoclast formation and suppressed osteoclast specific gene expression. Specially, geraniin inhibited actin ring formation and bone resorption in vitro. Further molecular investigation demonstrated geraniin impaired osteoclast differentiation via the inhibition of the RANKL-induced NF-?B and ERK signaling pathways, as well as suppressed the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Collectively, our data suggested that geraniin exerts inhibitory effects on osteoclast differentiation in vitro and suppresses Ti particle-induced osteolysis in vivo. Geraniin is therefore a potential natural compound for the treatment of wear particle induced osteolysis in prostheses failure. - Highlights: • Geraniin suppresses osteoclasts formation and function in vitro. • Geraniin impairs RANKL-induced nuclear factor-?B and ERK signaling pathway. • Geraniin suppresses osteolysis in vivo. • Geraniin may be used for treating osteoclast related diseases.

  5. Lycorine suppresses RANKL-induced osteoclastogenesis in vitro and prevents ovariectomy-induced osteoporosis and titanium particle-induced osteolysis in vivo

    PubMed Central

    Chen, Shuai; Jin, Gu; Huang, Kang-Mao; Ma, Jian-Jun; Wang, Qiang; Ma, Yan; Tang, Xiao-Zhen; Zhou, Zhi-Jie; Hu, Zhi-Jun; Wang, Ji-Ying; Qin, An; Fan, Shun-Wu

    2015-01-01

    Osteoclasts play an important role in diseases involving bone loss. In this study, we assessed the effect of a plant-derived natural alkaloid (lycorine, or LY) on osteoclastogenesis in vitro and in vivo. Our in vitro study showed that receptor activator of nuclear factor-?B ligand (RANKL)-induced osteoclastogenesis could be inhibited by LY; this effect was due to inhibition of mitogen-activated protein kinase (MAPK) signalling via MAP kinase kinases (MKKs). The MAPK agonist anisomycin could partially rescue the inhibitory effect of LY. Furthermore, LY also played a protective role in both a murine ovariectomy (OVX)-induced osteoporosis model and a titanium particle-induced osteolysis model. These results confirmed that LY was effective in preventing osteoclast-related diseases in vivo. In conclusion, our results show that LY is effective in suppressing osteoclastogenesis and therefore could be used to treat OVX-induced osteoporosis and wear particle-induced osteolysis. PMID:26238331

  6. HDL particle number and size as predictors of cardiovascular disease

    PubMed Central

    Kontush, Anatol

    2015-01-01

    Previous studies indicate that reduced concentrations of circulating high-density lipoprotein (HDL) particles can be superior to HDL-cholesterol (HDL-C) levels as a predictor of cardiovascular disease. Measurements of HDL particle numbers, therefore, bear a potential for the improved assessment of cardiovascular risk. Furthermore, such measurement can be relevant for the evaluation of novel therapeutic approaches targeting HDL. Modern in-depth analyses of HDL particle profile may further improve evaluation of cardiovascular risk. Although clinical relevance of circulating concentrations of HDL subpopulations to cardiovascular disease remains controversial, the negative relationship between the number of large HDL particles and cardiovascular disease suggests that assessment of HDL particle profile can be clinically useful. Reduced mean HDL size is equally associated with cardiovascular disease in large-scale clinical studies. Since HDL-C is primarily carried in the circulation by large, lipid-rich HDL particles, the inverse relationship between HDL size and cardiovascular risk can be secondary to those established for plasma levels of HDL particles, HDL-C, and large HDL. The epidemiological data thereby suggest that HDL particle number may represent a more relevant therapeutic target as compared to HDL-C. PMID:26500551

  7. Particle-induced cytokine responses in cardiac cell cultures--the effect of particles versus soluble mediators released by particle-exposed lung cells.

    PubMed

    Totlandsdal, Annike I; Refsnes, Magne; Skomedal, Tor; Osnes, Jan-Bjørn; Schwarze, Per E; Låg, Marit

    2008-11-01

    Increased levels of particulate matter have been associated with adverse effects in the respiratory as well as the cardiovascular system. The biological mechanisms behind these associations are still unresolved. Among potential mechanisms, particulate matter-associated cardiac effects may be initiated by inhaled small-sized particles, particle components and/or mediators related to inflammation that translocate into the pulmonary circulation. In the present study cytokine responses (interleukin [IL]-6, IL-1beta, and tumor necrosis factor [TNF]-alpha) of primary rat cardiomyocytes and cardiofibroblasts in mono- and cocultures induced by direct exposure to particles, were compared with cytokine responses induced by mediators released by particle-exposed primary rat epithelial lung cells (conditioned media). Cells were exposed to a model ultrafine particle (ultrafine carbon black, Printex 90) and in selected experiments to an urban air particle sample (SRM 1648, St Louis, MO). In lung cell cultures both particle types induced release of IL-6 and IL-1beta, whereas TNF-alpha was only detected upon exposure to St Louis particles. The release of IL-6 by cardiac cells was strongly enhanced upon exposure to conditioned media, and markedly exceeded the response to direct particle exposure. IL-1, but not TNF-alpha, seemed necessary, but not sufficient, for this enhanced IL-6 release. The role of IL-1 was demonstrated by use of an IL-1 receptor antagonist that partially reduced the effect of the conditioned media, and by a stimulating effect on the cardiac cell release of IL-6 by exogenous addition of IL-1alpha and IL-1beta. These in vitro findings lend support to the hypothesis that particle-induced cardiac inflammation and disease may involve lung-derived mediators. PMID:18700232

  8. AUTOPHAGY IN LOAD-INDUCED HEART DISEASE

    PubMed Central

    Zhu, Hongxin; Rothermel, Beverly A.; Hill, Joseph A.

    2009-01-01

    The heart is a highly plastic organ capable of remodeling in response to changes in physiological or pathological demand. When workload increases, the heart compensates through hypertrophic growth of individual cardiomyocytes to increase cardiac output. However, sustained stress, such as occurs with hypertension or following myocardial infarction, triggers changes in sarcomeric protein composition and energy metabolism, loss of cardiomyocytes, ventricular dilation, reduced pump function, and ultimately heart failure. It has been known for some time that autophagy is active in cardiomyocytes, occurring at increased levels in disease. Yet the potential contribution of cardiomyocyte autophagy to ventricular remodeling and disease pathogenesis has only recently been explored. This latter fact stems largely from the recent emergence of tools to probe molecular mechanisms governing cardiac plasticity and to define the role of autophagic flux in the context of heart disease. In this chapter, we briefly review prominent mouse models useful in the study of load-induced heart disease and standard techniques used to assess whether a molecular or cellular event is adaptive or maladaptive. We then outline methods available for monitoring autophagic activity in the heart, providing detailed protocols for several techniques unique to working with heart and other striated muscles. PMID:19216915

  9. Ionizing Radiation-induced Diseases in Korea

    PubMed Central

    Jeong, Meeseon; Moon, Kieun; Jo, Min-Heui; Kang, Seong-Kyu

    2010-01-01

    Radiation risk has become well known through epidemiological studies of clinically or occupationally exposed populations, animal experiments, and in vitro studies; however, the study of radiation related or induced disease has been limited in Korea. This study is to find the level of occupational radiation exposure for various kinds of accidents, compensated occupational diseases, related studies, and estimations on future occupational disease risks. Research data of related institutions were additionally investigated. About 67% of 62,553 radiation workers had no exposure or less than 1.2 mSv per year. The 5 reported cases on radiation accident patients in Korea occurred during nondestructive testing. According to the recent rapid increase in the number of workers exposed to radiation, a higher social recognition of cancer, and an increasing cancer mortality rate, it is expected that occupational disease compensation will rapidly increase as well. Therefore, it is important to develop scientific and objective decision methods, such as probability of causation and screening dose in the establishment of an exposure and health surveillance system. PMID:21258594

  10. Particle transport induced by electrostatic wave fluctuations

    NASA Astrophysics Data System (ADS)

    Rosalem, K. C.; Roberto, M.; Caldas, I. L.

    2015-10-01

    Particle transport driven by electrostatic waves at the plasma edge is numerically investigated, for large aspect ratio tokamaks, by considering a kinetic model derived from guiding-center equations of motion. Initially, the transport is estimated for trajectories obtained from differential equations for a wave spectrum generated by a dominant spatial mode and three time modes. Then, in case of infinite time modes, the differential equations of motion are used to introduce a symplectic map that allows to analyze the particle transport. The particle transport barriers are observed for spatial localized dominant perturbation and infinite modes. In presence of infinite spatial modes, periodic islands arise in between chaotic trajectories at the plasma edge.

  11. Optics of spin-1 particles from gravity-induced phases

    E-print Network

    G. Papini; G. Scarpetta; A. Feoli; G. Lambiase

    2007-11-19

    The Maxwell and Maxwell-de Rham equations can be solved exactly to first order in an external gravitational field. The gravitational background induces phases in the wave functions of spin-1 particles. These phases yield the optics of the particles without requiring any thin lens approximation.

  12. Morphological instability of spherical soft particles induced by surface charges

    NASA Astrophysics Data System (ADS)

    Li, Bo; Feng, Xi-Qiao; Li, Yue; Wang, Gang-Feng

    2009-07-01

    We here demonstrate that surface charges on a spherical soft particle may induce its morphology instability. It is found that various patterns can be obtained by varying the surface charge density. The critical condition for the occurrence of surface instability and the wavelength of the induced surface patterns are derived analytically and, thereby, the morphological phase diagram of soft particles can be provided easily. Besides the electric stress, surface tension also plays a significant role in the surface evolution process. In addition, the morphological evolution behavior of a soft particle is demonstrated to exhibit distinct dependence on its size.

  13. Method for ion implantation induced embedded particle formation via reduction

    DOEpatents

    Hampikian, Janet M (Decatur, GA); Hunt, Eden M (Atlanta, GA)

    2001-01-01

    A method for ion implantation induced embedded particle formation via reduction with the steps of ion implantation with an ion/element that will chemically reduce the chosen substrate material, implantation of the ion/element to a sufficient concentration and at a sufficient energy for particle formation, and control of the temperature of the substrate during implantation. A preferred embodiment includes the formation of particles which are nano-dimensional (<100 m-n in size). The phase of the particles may be affected by control of the substrate temperature during and/or after the ion implantation process.

  14. Ripple induced trapped particle loss in tokamaks

    SciTech Connect

    White, R.B.

    1996-05-01

    The threshold for stochastic transport of high energy trapped particles in a tokamak due to toroidal field ripple is calculated by explicit construction of primary resonances, and a numerical examination of the route to chaos. Critical field ripple amplitude is determined for loss. The expression is given in magnetic coordinates and makes no assumptions regarding shape or up-down symmetry. An algorithm is developed including the effects of prompt axisymmetric orbit loss, ripple trapping, convective banana flow, and stochastic ripple loss, which gives accurate ripple loss predictions for representative Tokamak Fusion Test Reactor and International Thermonuclear Experimental Reactor equilibria. The algorithm is extended to include the effects of collisions and drag, allowing rapid estimation of alpha particle loss in tokamaks.

  15. Aeolian Induced Erosion and Particle Entrainment

    NASA Technical Reports Server (NTRS)

    Saint, Brandon

    2007-01-01

    The Granular Physics Department at The Kennedy Space Center is addressing the problem of erosion on the lunar surface. The early stages of research required an instrument that would produce erosion at a specific rate with a specific sample variation. This paper focuses on the development and experimental procedures to measure and record erosion rates. This was done with the construction of an open air wind tunnel, and examining the relationship between airflow and particle motion.

  16. Light emission from particle beam induced plasma - An overview

    E-print Network

    Ulrich, A

    2015-01-01

    Experiments to study the light emission from plasma produced by particle beams are presented. Fundamental aspects in comparison with discharge plasma formation are discussed. It is shown that the formation of excimer molecules is an important process. This paper summarizes various studies of particle beam induced light emission and presents first results of a direct comparison of light emission induced by electron- and ion beam excitation. Both high energy heavy ion beam and low energy electron beam experiments are described and an overview over applications in the form of light sources, lasers, and ionization devices is given.

  17. Infectious particles, stress, and induced prion amyloids

    PubMed Central

    2013-01-01

    Transmissible encephalopathies (TSEs) are believed by many to arise by spontaneous conversion of host prion protein (PrP) into an infectious amyloid (PrP-res, PrPSc) without nucleic acid. Many TSE agents reside in the environment, with infection controlled by public health measures. These include the disappearance of kuru with the cessation of ritual cannibalism, the dramatic reduction of epidemic bovine encephalopathy (BSE) by removal of contaminated feed, and the lack of endemic scrapie in geographically isolated Australian sheep with susceptible PrP genotypes. While prion protein modeling has engendered an intense focus on common types of protein misfolding and amyloid formation in diverse organisms and diseases, the biological characteristics of infectious TSE agents, and their recognition by the host as foreign entities, raises several fundamental new directions for fruitful investigation such as: (1) unrecognized microbial agents in the environmental metagenome that may cause latent neurodegenerative disease, (2) the evolutionary social and protective functions of different amyloid proteins in diverse organisms from bacteria to mammals, and (3) amyloid formation as a beneficial innate immune response to stress (infectious and non-infectious). This innate process however, once initiated, can become unstoppable in accelerated neuronal aging. PMID:23633671

  18. Myricetin prevents titanium particle-induced osteolysis in vivo and inhibits RANKL-induced osteoclastogenesis in vitro.

    PubMed

    Wu, Chuanlong; Wang, Wengang; Tian, Bo; Liu, Xuqiang; Qu, Xinhua; Zhai, Zanjing; Li, Haowei; Liu, Fengxiang; Fan, Qiming; Tang, Tingting; Qin, An; Zhu, Zhenan

    2015-01-01

    Titanium (Ti) particle-induced periprosthetic osteolysis and subsequent aseptic loosening are a primary reason for total hip arthroplasty failure. The aim of this study was to assess the effect of myricetin on Ti particle-induced osteolysis and osteoclastogenesis. We demonstrated that myricetin, a natural plant extract, exerts potent inhibitory effects on Ti particle-induced osteolysis in a mouse calvarial model. Further histological analysis indicated that the inhibition of osteoclast formation and function, and the secretion of inflammatory factors, are key targets for therapeutic agents in the treatment of wear particle-induced osteolysis. In vitro, we found that myricetin suppressed receptor activator of nuclear factor-?B ligand (RANKL)-mediated osteoclast differentiation, bone resorption, and F-actin ring formation in a dose-dependent manner. Moreover, myricetin significantly reduced the expression of osteoclast-specific markers in mouse bone marrow-derived macrophages, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, the calcitonin receptor, V-ATPase d2, c-fos, and nuclear factor of activated T cells (NFAT) c1. Further investigation revealed that myricetin inhibited osteoclastogenesis through the suppression of the nuclear factor-?B (NF-?B) signaling pathway and mitogen-activated protein kinase (MAPK) pathways involving extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase 1/2 (JNK1/2). While, the inhibition of TNF-? and IL-1? secretion was another reason for the suppressive effect of myricetin on Ti particle-induced osteolysis. Collectively, these findings suggest that myricetin is a potential natural agent for the treatment of periprosthetic osteolysis and other osteoclast-related osteolytic diseases. PMID:25449599

  19. Radiation induces turbulence in particle-laden fluids

    SciTech Connect

    Zamansky, Rémi; Coletti, Filippo; Massot, Marc; Mani, Ali

    2014-07-15

    When a transparent fluid laden with solid particles is subject to radiative heating, non-uniformities in particle distribution result in local fluid temperature fluctuations. Under the influence of gravity, buoyancy induces vortical fluid motion which can lead to strong preferential concentration, enhancing the local heating and more non-uniformities in particle distribution. By employing direct numerical simulations this study shows that the described feedback loop can create and sustain turbulence. The velocity and length scale of the resulting turbulence is not known a priori, and is set by balance between viscous forces and buoyancy effects. When the particle response time is comparable to a viscous time scale, introduced in our analysis, the system exhibits intense fluctuations of turbulent kinetic energy and strong preferential concentration of particles.

  20. Particle-induced amorphization complex ceramic

    SciTech Connect

    Ewing, R.C.; Wang, Lu-Min

    1996-02-16

    The presently funded three-year research program, supported by the Division of Materials Sciences of the Office of Basic Energy Sciences, was initiated on August 1, 1993; during the period in which the grant will have been active, $249,561 of support have been provided to date with an additional $79,723 to be spent during the third, final year (ending July 30, 1996). The primary purpose of the program is to develop an understanding of heavy-particle radiation effects -- {alpha}-recoil nuclei, fission fragments, ion-irradiations -- on ceramic materials and the thermal annealing mechanisms by which crystallinity might be restored. During the past two years, we have completed major studies on zircon (ZrSiO{sub 4}), olivine (Mg{sub 2}SiO{sub 4} and ten other compositions), spinel (MgAl{sub 2}O{sub 4} and four other compositions), and silica polymorphs (quartz, coesite and stishovite), as well as berlinite (AlPO{sub 4}) which is isomorphous with quartz. In addition, based on the above research, we propose the use of zircon as a host phase for the immobilization of plutonium resulting from weapons dismantlement.

  1. Induced-Charge Electrophoresis of Metallodielectric Particles Sumit Gangwal,1

    E-print Network

    Bazant, Martin Z.

    dielectric and one metal-coated hemisphere induced by uniform fields of frequency 100 Hz­10 kHz in Na expanding research field [13­17]. Anisotropic particles with two hemispheres of different polarizabily or conductance have been produced by thermal evaporation [18] or gold sputtering [19]. The mobility

  2. CARDIAC MOLECULAR EFFECTS INDUCED BY AIR POLLUTION PARTICLES

    EPA Science Inventory

    Abstract Submitted to the American Thoracic Society 98th International Conference, May 17 - 22, 2002, Atlanta, GA

    CARDIAC MOLECULAR EFFECTS INDUCED BY AIR POLLUTION PARTICLES
    K. Dreher1, R. Jaskot1, J. Richards1, and T. Knuckles2. 1U. S. Environmental Protection Agency,...

  3. External front instabilities induced by a shocked particle ring.

    PubMed

    Rodriguez, V; Saurel, R; Jourdan, G; Houas, L

    2014-10-01

    The dispersion of a cylindrical particle ring by a blast or shock wave induces the formation of coherent structures which take the form of particle jets. A blast wave, issuing from the discharge of a planar shock wave at the exit of a conventional shock tube, is generated in the center of a granular medium ring initially confined inside a Hele-Shaw cell. With the present experimental setup, under impulsive acceleration, a solid particle-jet formation is observed in a quasi-two-dimensional configuration. The aim of the present investigation is to observe in detail the formation of very thin perturbations created around the external surface of the dispersed particle layer. By means of fast flow visualization with an appropriate recording window, we focus solely on the first instants during which the external particle ring becomes unstable. We find that the critical area of the destabilization of the external ring surface is constant regardless of the acceleration of the initial layer. Moreover, we observe in detail the external front perturbation wavelength, rendered dimensionless by the initial ring perimeter, and follow its evolution with the initial particle layer acceleration. We report this quantity to be constant regardless of the evolution of the initial particle layer acceleration. Finally, we can reasonably assert that external front perturbations depend solely on the material of the particles. PMID:25375599

  4. Alpha particles induce apoptosis through the sphingomyelin pathway.

    PubMed

    Seideman, Jonathan H; Stancevic, Branka; Rotolo, Jimmy A; McDevitt, Michael R; Howell, Roger W; Kolesnick, Richard N; Scheinberg, David A

    2011-10-01

    The sphingomyelin pathway involves the enzymatic cleavage of sphingomyelin to produce ceramide, a second messenger that serves as a key mediator in the rapid apoptotic response to various cell stressors. Low-linear energy transfer (LET) ? radiation can initiate this pathway, independent of DNA damage, via the cell membrane. Whether short-ranged, high-LET ? particles, which are of interest as potent environmental carcinogens, radiotherapies and potential components of dirty bombs, can act through this mechanism to signal apoptosis is unknown. Here we show that irradiation of Jurkat cells with ? particles emitted by the ²²?Ac-DOTA-anti-CD3 IgG antibody construct results in dose-dependent apoptosis. This apoptosis was significantly reduced by pretreating cells with cholesterol-depleting nystatin, a reagent known to inhibit ceramide signaling by interfering with membrane raft coalescence and ceramide-rich platform generation. The effects of nystatin on ?-particle-induced apoptosis were related to disruption of the ceramide pathway and not to microdosimetry alterations, because similar results were obtained after external irradiation of the cells with a broad beam of collimated ? particles using a planar ²?¹Am source. External irradiation allowed for more precise control of the dosimetry and geometry of the irradiation, independent of antibody binding or cell internalization kinetics. Mechanistically consistent with these findings, Jurkat cells rapidly increased membrane concentrations of ceramide after external irradiation with an average of five ?-particle traversals per cell. These data indicate that ? particles can activate the sphingomyelin pathway to induce apoptosis. PMID:21631289

  5. Gravitationally Induced Particle Production: Thermodynamics and Kinetic Theory

    E-print Network

    J. A. S. Lima; I. P. Baranov

    2014-11-24

    A relativistic kinetic description for the irreversible thermodynamic process of gravitationally induced particle production is proposed in the context of an expanding Friedmann-Robertson-Walker (FRW) geometry. We show that the covariant thermodynamic treatment referred to as "adiabatic" particle production provoked by the cosmic time-varying gravitational field has a consistent kinetic counterpart. The variation of the distribution function is associated to a non-collisional kinetic term of quantum-gravitational origin which is proportional to the ratio $\\Gamma/H$, where $\\Gamma$ is the gravitational particle production rate and H is the Hubble parameter. For $\\Gamma kinetically derived for massive and massless particles. The present approach points to the possibility of an exact (semi-classical) quantum-gravitational kinetic treatment by incorporating back-reaction effects in the cosmic background.

  6. Macrophage polarization and activation in response to implant debris: influence by "particle disease" and "ion disease".

    PubMed

    Konttinen, Yrjo T; Pajarinen, Jukka; Takakubo, Yuya; Gallo, Jiri; Nich, Christophe; Takagi, Michiaki; Goodman, Stuart B

    2014-01-01

    Macrophages derive from human embryonic and fetal stem cells and from human bone marrow-derived blood monocytes. They play a major homeostatic role in tissue remodeling and maintenance facilitated by apoptotic "eat me" opsonins like CRP, serum amyloid P, C1q, C3b, IgM, ficolin, and surfactant proteins. Three subsets of monocytes, classic, intermediate, and nonclassic, are mobilized and transmigrate to tissues. Implant-derived wear particles opsonized by danger signals regulate macrophage priming, polarization (M1, M2, M17, and Mreg), and activation. CD14(+) monocytes in healthy controls and CD16(+) monocytes in inflammation differentiate/polarize to foreign body giant cells/osteoclasts or inflammatory dendritic cells (infDC). These danger signal opsonins can be pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs), but in aseptic loosening, usually are damage-associated molecular patterns (DAMPs). Danger signal-opsonized particles elicit "particle disease" and aseptic loosening. They provide soluble and cell membrane-bound co-stimulatory signals that can lead to cell-mediated immune reactions to metal ions. Metal-on-metal implant failure has disclosed that quite like Ni(2+), its neighbor in the periodic table Co(2+) can directly activate toll-like receptor 4 (TLR4) as a lipopolysaccharide-mimic. "Ion disease" concept needs to be incorporated into the "particle disease" concept, due to the toxic, immune, and inflammatory potential of metal ions. PMID:25747030

  7. Proteomic analysis of host brain components that bind to infectious particles in Creutzfeldt-Jakob disease.

    PubMed

    Kipkorir, Terry; Colangelo, Christopher M; Manuelidis, Laura

    2015-09-01

    Transmissible encephalopathies (TSEs), such as Creutzfeldt-Jakob disease (CJD) and scrapie, are caused by infectious agents that provoke strain-specific patterns of disease. Misfolded host prion protein (PrP-res amyloid) is believed to be the causal infectious agent. However, particles that are stripped of PrP retain both high infectivity and viral proteins not detectable in uninfected mouse controls. We here detail host proteins bound with FU-CJD agent infectious brain particles by proteomic analysis. More than 98 proteins were differentially regulated, and 56 FU-CJD exclusive proteins were revealed after PrP, GFAP, C1q, ApoE, and other late pathologic response proteins were removed. Stripped FU-CJD particles revealed HSC70 (144× the uninfected control), cyclophilin B, an FU-CJD exclusive protein required by many viruses, and early endosome-membrane pathways known to facilitate viral processing, replication, and spread. Synaptosomal elements including synapsin-2 (at 33×) and AP180 (a major FU-CJD exclusive protein) paralleled the known ultrastructural location of 25 nm virus-like TSE particles and infectivity in synapses. Proteins without apparent viral or neurodegenerative links (copine-3), and others involved in viral-induced protein misfolding and aggregation, were also identified. Human sCJD brain particles contained 146 exclusive proteins, and heat shock, synaptic, and viral pathways were again prominent, in addition to Alzheimer, Parkinson, and Huntington aggregation proteins. Host proteins that bind TSE infectious particles can prevent host immune recognition and contribute to prolonged cross-species transmissions (the species barrier). Our infectious particle strategy, which reduces background sequences by >99%, emphasizes host targets for new therapeutic initiatives. Such therapies can simultaneously subvert common pathways of neurodegeneration. PMID:25930988

  8. Drift-induced Deceleration of Solar Energetic Particles

    NASA Astrophysics Data System (ADS)

    Dalla, S.; Marsh, M. S.; Laitinen, T.

    2015-07-01

    We investigate the deceleration of solar energetic particles (SEPs) during their propagation from the Sun through interplanetary space, in the presence of weak to strong scattering in a Parker spiral configuration, using relativistic full orbit test particle simulations. The calculations retain all three spatial variables describing particles’ trajectories, allowing us to model any transport across the magnetic field. Large energy change is shown to occur for protons, due to the combined effect of standard adiabatic deceleration and a significant contribution from particle drift in the direction opposite to that of the solar wind electric field. The latter drift-induced deceleration is found to have a stronger effect for SEP energies than for galactic cosmic rays. The kinetic energy of protons injected at 1 MeV is found to be reduced by between 35% and 90% after four days, and for protons injected at 100 MeV by between 20% and 55%. The overall degree of deceleration is a weak function of the scattering mean free path, showing that, although adiabatic deceleration plays a role, a large contribution is due to particle drift. Current SEP transport models are found to account for drift-induced deceleration in an approximate way and their accuracy will need to be assessed in future work.

  9. Neurobiology of Disease Nerve Injury-Induced Neuropathic Pain Causes

    E-print Network

    Senn, Walter

    Neurobiology of Disease Nerve Injury-Induced Neuropathic Pain Causes Disinhibition of the Anterior Neuropathicpaincausedbyperipheralnerveinjuryisadebilitatingneurologicalconditionofhighclinicalrelevance.Onthecellularlevel, the elevated pain sensitivity is induced by plasticity of neuronal function along the pain pathway. Changes in cortical areas involved in pain processing contribute

  10. Prion Disease Induces Alzheimer Disease-Like Neuropathologic Changes.

    PubMed

    Tousseyn, Thomas; Bajsarowicz, Krystyna; Sánchez, Henry; Gheyara, Ania; Oehler, Abby; Geschwind, Michael; DeArmond, Bernadette; DeArmond, Stephen J

    2015-09-01

    We examined the brains of 266 patients with prion disease (PrionD) and found that 46 patients (17%) had Alzheimer disease (AD)-like changes. To explore potential mechanistic links between PrionD and AD, we exposed human brain aggregates (BrnAggs) to a brain homogenate from a patient with sporadic Creutzfeldt-Jakob disease and found that neurons in human BrnAggs produced many ?-amyloid (A?; A?42) inclusions, whereas uninfected control-exposed human BrnAggs did not. Western blot analysis of 20 pooled Creutzfeldt-Jakob disease-infected BrnAggs verified A?42 levels higher than those in controls. We next examined the CA1 region of the hippocampus from 14 patients with PrionD and found that 5 patients had low levels of scrapie-associated prion protein (PrP), many A?42 intraneuronal inclusions, low apolipoprotein E-4 (APOE-4), and no significant nerve cell loss. Seven patients had high levels of PrP, low A?42, high APOE-4, and 40% nerve cell loss, suggesting that APOE-4 and PrP together cause neuron loss in PrionD. There were also increased levels of hyperphosphorylated tau protein (H?) and H?-positive neuropil threads and neuron bodies in both PrionD and AD groups. The brains of 6 age-matched control patients without dementia did not contain A?42 deposits; however, there were rare H?-positive threads in 5 controls, and 2 controls had few H?-positive nerve cell bodies. We conclude that PrionD may trigger biochemical changes similar to those triggered by AD and suggest that PrionD is a disease involving PrP, A?42, APOE-4, and abnormal tau. PMID:26226132

  11. Nuclear reactions induced by high-energy alpha particles

    NASA Technical Reports Server (NTRS)

    Shen, B. S. P.

    1974-01-01

    Experimental and theoretical studies of nuclear reactions induced by high energy protons and heavier ions are included. Fundamental data needed in the shielding, dosimetry, and radiobiology of high energy particles produced by accelerators were generated, along with data on cosmic ray interaction with matter. The mechanism of high energy nucleon-nucleus reactions is also examined, especially for light target nuclei of mass number comparable to that of biological tissue.

  12. Phase transition of vortexlike self-propelled particles induced by a hostile particle.

    PubMed

    Duan, Haibin; Zhang, Xiangyin

    2015-07-01

    When encountering a hostile particle, the avoidance behaviors of the vortex state of self-propelled particles exhibit phase transition phenomena such that the vortex state can change into a crystal state. Based on the self-propelled particle model and a molecular dynamics simulation, the dynamic response of the vortex swarm induced by a hostile particle (predator or obstacle) is studied. Three parameters are defined to characterize the collective escaping behaviors, including the order parameter, the flock size, and the roundness parameter. If a predator moves slower with a larger risk radius, the vortex swarm cannot return to its original vortex state, but rather transforms into a crystal state. The critical phase transition radius, the maximum risk radius of a predator with which the transition from a vortex to crystal state cannot take place, is also examined by considering the influence of the model parameters. To some degree, the critical radius reflects the stability and robustness of the vortex swarm. PMID:26274197

  13. Induced pluripotent stem cells for cardiovascular disease: from product-focused disease modeling to process-focused disease discovery.

    PubMed

    Campbell, Katherine A; Terzic, Andre; Nelson, Timothy J

    2015-09-01

    Induced pluripotent stem (iPS) cell technology offers an unprecedented opportunity to study patient-specific disease. This biotechnology platform enables recapitulation of individualized disease signatures in a dish through differentiation of patient-derived iPS cells. Beyond disease modeling, the in vitro process of differentiation toward genuine patient tissue offers a blueprint to inform disease etiology and molecular pathogenesis. Here, we highlight recent advances in patient-specific cardiac disease modeling and outline the future promise of iPS cell-based disease discovery applications. PMID:26439809

  14. Alpha Particles Induce Apoptosis through the Sphingomyelin Pathway

    PubMed Central

    Seideman, Jonathan H.; Stancevic, Branka; Rotolo, Jimmy A.; McDevitt, Michael R.; Howell, Roger W.; Kolesnick, Richard N.; Scheinberg, David A.

    2011-01-01

    The sphingomyelin pathway involves the enzymatic cleavage of sphingomyelin to produce ceramide, a second messenger that serves as a key mediator in the rapid apoptotic response to various cell stressors. Low-linear energy transfer (LET) ? radiation can initiate this pathway, independent of DNA damage, via the cell membrane. Whether short-ranged, high-LET a particles, which are of interest as potent environmental carcinogens, radiotherapies and potential components of dirty bombs, can act through this mechanism to signal apoptosis is unknown. Here we show that irradiation of Jurkat cells with a particles emitted by the 225Ac-DOTA-anti-CD3 IgG antibody construct results in dose-dependent apoptosis. This apoptosis was significantly reduced by pretreating cells with cholesterol-depleting nystatin, a reagent known to inhibit ceramide signaling by interfering with membrane raft coalescence and ceramide-rich platform generation. The effects of nystatin on ?-particle-induced apoptosis were related to disruption of the ceramide pathway and not to microdosimetry alterations, because similar results were obtained after external irradiation of the cells with a broad beam of collimated a particles using a planar 241Am source. External irradiation allowed for more precise control of the dosimetry and geometry of the irradiation, independent of antibody binding or cell internalization kinetics. Mechanistically consistent with these findings, Jurkat cells rapidly increased membrane concentrations of ceramide after external irradiation with an average of five ?-particle traversals per cell. These data indicate that a particles can activate the sphingomyelin pathway to induce apoptosis. PMID:21631289

  15. APOPTOTIC AND INFLAMMATORY EFFECTS INDUCED BY DIFFERENT PARTICLES IN HUMAN ALVEOLAR MACROPHAGES

    EPA Science Inventory

    Pollutant particles induce apoptosis and inflammation, but the relationship between these two biological processes is not entirely clear. In this study, we compared the proapoptotic and proinflammatory effects of four particles: residual oil fly ash (ROFA), St. Louis particles SR...

  16. Theory of trapped-particle-induced resistive fluid turbulence

    SciTech Connect

    Biglari, H.; Diamond, P.H.

    1987-12-01

    A theory of anomalous electron heat transport, evolving from trapped-particle-induced resistive interchange modes, is proposed. The latter are a new branch of the resistive interchange-ballooning family of instabilities, destabilized when the pressure carried by the unfavorably drifting trapped particles is sufficiently large to overcome stabilizing contributions coming from favorable average curvature. Expressions for the turbulent heat diffusivity and anomalous electron thermal conductivity at saturation are derived for two regimes of trapped-particle energy: (I) a moderately energetic regime, which is ''fluidlike'' in the sense that the unstable mode grows faster than the time that it takes for particles in this energy range to precess once around the torus, and (II) a highly energetic regime, where the trapped species has sufficiently high energy as to be able to interact resonantly with the mode. Unlike previous theories of anomalous transport, the estimates of diffusion and transport obtained here are self-consistent since the trapped particles do not ''see'' the magnetic flutter due to their rapid bounce motion. The theory is valid for moderate electron-temperature, high ion-temperature (auxiliary heated) plasmas and as such, is relevant for present- and future-generation experimental fusion devices.

  17. Theory of trapped-particle-induced resistive fluid turbulence

    SciTech Connect

    Biglari, H.; Diamond, P.H.

    1987-05-01

    A theory of anomalous electron heat transport, evolving from trapped-particle-induced resistive interchange modes, is proposed. These latter are a new branch of the resistive interchange-ballooning family of instabilities, destabilized when the pressure carried by the unfavorably-drifting trapped particles is sufficiently large to overcome stabilizing contributions coming from favorable average curvature. Expressions for the turbulent heat diffusivity and anomalous electron thermal conductivity at saturation are derived for two regimes of trapped particle energy: (1) a moderately-energetic regime, which is ''fluid-like'' in the sense that the unstable mode grows faster than the time that it takes for particles in this energy range to precess once around the torus; and (2) a highly-energetic regime, where the trapped species has sufficiently high energy as to be able to resonantly interact with the mode. Unlike previous theories of anomalous transport, the estimates of diffusion and transport obtained here are self-consistent, since the trapped particles do not ''see'' the magnetic flutter due to their rapid bounce motion. The theory is valid for moderate electron-temperature, high ion-temperature (auxiliary-heated) plasmas, and as such, is relevant for present and future-generation experimental fusion devices.

  18. Use of Recombinant Virus Replicon Particles for Vaccination against Mycobacterium ulcerans Disease

    PubMed Central

    Bolz, Miriam; Kerber, Sarah; Zimmer, Gert; Pluschke, Gerd

    2015-01-01

    Buruli ulcer, caused by infection with Mycobacterium ulcerans, is a necrotizing disease of the skin and subcutaneous tissue, which is most prevalent in rural regions of West African countries. The majority of clinical presentations seen in patients are ulcers on limbs that can be treated by eight weeks of antibiotic therapy. Nevertheless, scarring and permanent disabilities occur frequently and Buruli ulcer still causes high morbidity. A vaccine against the disease is so far not available but would be of great benefit if used for prophylaxis as well as therapy. In the present study, vesicular stomatitis virus-based RNA replicon particles encoding the M. ulcerans proteins MUL2232 and MUL3720 were generated and the expression of the recombinant antigens characterized in vitro. Immunisation of mice with the recombinant replicon particles elicited antibodies that reacted with the endogenous antigens of M. ulcerans cells. A prime-boost immunization regimen with MUL2232-recombinant replicon particles and recombinant MUL2232 protein induced a strong immune response but only slightly reduced bacterial multiplication in a mouse model of M. ulcerans infection. We conclude that a monovalent vaccine based on the MUL2232 antigen will probably not sufficiently control M. ulcerans infection in humans. PMID:26275222

  19. Schisantherin A suppresses osteoclast formation and wear particle-induced osteolysis via modulating RANKL signaling pathways

    SciTech Connect

    He, Yi; Zhang, Qing; Shen, Yi; Chen, Xia; Zhou, Feng; Peng, Dan

    2014-07-04

    Highlights: • Schisantherin A suppresses osteoclasts formation and function in vitro. • Schisantherin A impairs RANKL signaling pathway. • Schisantherin A suppresses osteolysis in vivo. • Schisantherin A may be used for treating osteoclast related diseases. - Abstract: Receptor activator of NF-?B ligand (RANKL) plays critical role in osteoclastogenesis. Targeting RANKL signaling pathways has been a promising strategy for treating osteoclast related bone diseases such as osteoporosis and aseptic prosthetic loosening. Schisantherin A (SA), a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been used as an antitussive, tonic, and sedative agent, but its effect on osteoclasts has been hitherto unknown. In the present study, SA was found to inhibit RANKL-induced osteoclast formation and bone resorption. The osteoclastic specific marker genes induced by RANKL including c-Src, SA inhibited OSCAR, cathepsin K and TRAP in a dose dependent manner. Further signal transduction studies revealed that SA down-regulate RANKL-induced nuclear factor-kappaB (NF-?B) signaling activation by suppressing the phosphorylation and degradation of I?B?, and subsequently preventing the NF-?B transcriptional activity. Moreover, SA also decreased the RANKL-induced MAPKs signaling pathway, including JNK and ERK1/2 posphorylation while had no obvious effects on p38 activation. Finally, SA suppressed the NF-?B and MAPKs subsequent gene expression of NFATc1 and c-Fos. In vivo studies, SA inhibited osteoclast function and exhibited bone protection effect in wear-particle-induced bone erosion model. Taken together, SA could attenuate osteoclast formation and wear particle-induced osteolysis by mediating RANKL signaling pathways. These data indicated that SA is a promising therapeutic natural compound for the treatment of osteoclast-related prosthesis loosening.

  20. Dextropropoxyphene induced hepatotoxicity mimicking biliary tract disease.

    PubMed Central

    Bassendine, M F; Woodhouse, K W; Bennett, M; James, O F

    1986-01-01

    Three patients are described with recurrent jaundice, upper abdominal pain and rigors attributable to dextropropoxyphene hepatotoxicity. The diagnosis was established in each patient by rechallenge; post challenge hepatic histology is reported in two. Twelve previous patients with probable dextropropoxyphene hepatic toxicity have been described and are reviewed. In 10 of the 15 patients, a clinical diagnosis of gall stone disease was made. Liver function tests are usually hepatitic shortly after challenge, but more cholestatic after a few days. No fatalities have been described, but as dextropropoxyphene is widely available in many different analgesic preparations possible toxicity should be considered in patients with relapsing jaundice mimicking biliary disease, in whom gall stones have been excluded. Images Fig. 2 Fig. 3 Fig. 4 PMID:3957112

  1. Neurobiology of Disease Alzheimer's Disease-Like Pathology Induced by Amyloid-

    E-print Network

    Munoz, Douglas Perry

    Neurobiology of Disease Alzheimer's Disease-Like Pathology Induced by Amyloid- Oligomers and cognitive functions. Cardinal features of AD pathology, including synapse loss, tau hyper- phosphorylation of AD that links A oligomers to tau and synaptic pathology has the potential to greatly advance our

  2. SENSITIZATION AND EXACERBATION OF ALLERGIC DISEASES BY DIESEL ENGINE PARTICLES

    SciTech Connect

    Diaz-Sanchez, David

    2000-08-20

    Most studies of the health effects of diesel exhaust have focused on the controversial issue of its role in cancer. However, recently the role of combustion products such as diesel exhaust particles (DEP) in modulating the immune response has garnered much attention. In particular the effect of DEP on allergic and asthmatic diseases has been the focus of many studies. A link between industrialization and allergic disease has long been presumed. Indeed, only 50 years after the first recorded reported case of allergy in 1819, Charles Blackely wrote that the ''hay-fever epidemic'' was associated with the movement of people from the country into the cities. Ishizaki et al. (1987) found that people in Japan living on busy roads lined with cedar trees have more allergies to cedar than residents living on similar streets with much less traffic. Since that time other epidemiological studies have reported similar findings. Kramer, et al., showed that hay fever is greater in residential areas with heavy truck traffic, while Weiland, et al., reported that allergic symptoms correlate with the distance of residences to roads with heavy traffic.

  3. The EPIC-MOS Particle-Induced Background Spectrum

    NASA Technical Reports Server (NTRS)

    Kuntz, K. D.; Snowden, S. L.

    2006-01-01

    We have developed a method for constructing a spectrum of the particle-induced instrumental background of the XMM-Newton EPIC MOS detectors that can be used for observations of the diffuse background and extended sources that fill a significant fraction of the instrument field of view. The strength and spectrum of the particle-induced background, that is, the background due to the interaction of particles with the detector and the detector surroundings, is temporally variable as well as spatially variable over individual chips. Our method uses a combination of the filter-wheel-closed data and a database of unexposed-region data to construct a spectrum of the "quiescent" background. We show that, using this method of background subtraction, the differences between independent observations of the same region of "blank sky" are consistent with the statistical uncertainties except when there is clear evidence of solar wind charge exchange emission. We use the blank sky observations to show that contamination by SWCX emission is a strong function of the solar wind proton flux, and that observations through the flanks of the magnetosheath appear to be contaminated only at much higher solar wind fluxes. We have also developed a spectral model of the residual soft proton flares, which allows their effects to be removed to a substantial degree during spectral fitting.

  4. Drift-induced deceleration of Solar Energetic Particles

    E-print Network

    Dalla, S; Laitinen, T

    2015-01-01

    We investigate the deceleration of Solar Energetic Particles (SEPs) during their propagation from the Sun through interplanetary space, in the presence of weak to strong scattering in a Parker spiral configuration, using relativistic full orbit test particle simulations. The calculations retain all three spatial variables describing particles' trajectories, allowing to model any transport across the magnetic field. Large energy change is shown to occur for protons, due to the combined effect of standard adiabatic deceleration and a significant contribution from particle drift in the direction opposite to that of the solar wind electric field. The latter drift-induced deceleration is found to have a stronger effect for SEP energies than for galactic cosmic rays. The kinetic energy of protons injected at 1 MeV is found to be reduced by between 35 and 90% after four days, and for protons injected at 100 MeV by between 20 and 55%. The overall degree of deceleration is a weak function of the scattering mean free p...

  5. Asian Dust Particles Induce Macrophage Inflammatory Responses via Mitogen-Activated Protein Kinase Activation and Reactive Oxygen Species Production

    PubMed Central

    Higashisaka, Kazuma; Fujimura, Maho; Taira, Mayu; Yoshida, Tokuyuki; Tsunoda, Shin-ichi; Baba, Takashi; Yamaguchi, Nobuyasu; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Nasu, Masao; Tsutsumi, Yasuo

    2014-01-01

    Asian dust is a springtime meteorological phenomenon that originates in the deserts of China and Mongolia. The dust is carried by prevailing winds across East Asia where it causes serious health problems. Most of the information available on the impact of Asian dust on human health is based on epidemiological investigations, so from a biological standpoint little is known of its effects. To clarify the effects of Asian dust on human health, it is essential to assess inflammatory responses to the dust and to evaluate the involvement of these responses in the pathogenesis or aggravation of disease. Here, we investigated the induction of inflammatory responses by Asian dust particles in macrophages. Treatment with Asian dust particles induced greater production of inflammatory cytokines interleukin-6 and tumor necrosis factor-? (TNF-?) compared with treatment with soil dust. Furthermore, a soil dust sample containing only particles ?10??m in diameter provoked a greater inflammatory response than soil dust samples containing particles >10??m. In addition, Asian dust particles-induced TNF-? production was dependent on endocytosis, the production of reactive oxygen species, and the activation of nuclear factor-?B and mitogen-activated protein kinases. Together, these results suggest that Asian dust particles induce inflammatory disease through the activation of macrophages. PMID:24987712

  6. Concise Review: Cardiac Disease Modeling Using Induced Pluripotent Stem Cells.

    PubMed

    Yang, Chunbo; Al-Aama, Jumana; Stojkovic, Miodrag; Keavney, Bernard; Trafford, Andrew; Lako, Majlinda; Armstrong, Lyle

    2015-09-01

    Genetic cardiac diseases are major causes of morbidity and mortality. Although animal models have been created to provide some useful insights into the pathogenesis of genetic cardiac diseases, the significant species differences and the lack of genetic information for complex genetic diseases markedly attenuate the application values of such data. Generation of induced pluripotent stem cells (iPSCs) from patient-specific specimens and subsequent derivation of cardiomyocytes offer novel avenues to study the mechanisms underlying cardiac diseases, to identify new causative genes, and to provide insights into the disease aetiology. In recent years, the list of human iPSC-based models for genetic cardiac diseases has been expanding rapidly, although there are still remaining concerns on the level of functionality of iPSC-derived cardiomyocytes and their ability to be used for modeling complex cardiac diseases in adults. This review focuses on the development of cardiomyocyte induction from pluripotent stem cells, the recent progress in heart disease modeling using iPSC-derived cardiomyocytes, and the challenges associated with understanding complex genetic diseases. To address these issues, we examine the similarity between iPSC-derived cardiomyocytes and their ex vivo counterparts and how this relates to the method used to differentiate the pluripotent stem cells into a cardiomyocyte phenotype. We progress to examine categories of congenital cardiac abnormalities that are suitable for iPSC-based disease modeling. PMID:26033645

  7. Inhaled particles in human disease and animal models: use of electron beam instrumentation.

    PubMed Central

    Brody, A R

    1984-01-01

    The mineral pneumoconioses (lung disease caused by inhalation of inorganic dust) have been an important disease entity for centuries. In the last several decades, the electron microscope has been used to elucidate the distribution and identification of inhaled minerals, to aid in establishing etiologic factors, and less commonly, to determine the basic biologic mechanisms through which inhaled minerals cause lung disease. In this section, I review the instrumentation and tissue preparation currently used to address some modern problems in particle-induced lung disease. For example, human pneumoconioses of undetermined etiology can be clarified by electron microscopy and X-ray energy spectrometry. In addition, the initial deposition patterns of asbestos and silica are demonstrated in animal models, and the contributions of electron microscopy in establishing the initial lesions of asbestosis are described. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. FIGURE 5. FIGURE 6. FIGURE 7. FIGURE 8. FIGURE 9. FIGURE 9. FIGURE 10. FIGURE 11. FIGURE 12. FIGURE 13. FIGURE 14. PMID:6090114

  8. Diesel exhaust particles induce the over expression of tumor necrosis factor-alpha (TNF-alpha) gene in alvelor machrophage and failed to induce apoptosis through activation of nuclear factor-kappaB (NF-kappaB)

    EPA Science Inventory

    Exposure to particulate matter (PM2.5-10), including diesel exhaust particles (DEP) has been reported to induce lung injury and exacerbation of asthma and chronic obstructive pulmonary disease. Alveolar macrophages play a major role in the lung's response to inhaled particles and...

  9. Radiation-Induced Heart Disease: Pathologic Abnormalities and Putative Mechanisms

    PubMed Central

    Taunk, Neil K.; Haffty, Bruce G.; Kostis, John B.; Goyal, Sharad

    2015-01-01

    Breast cancer is a common diagnosis in women. Breast radiation has become critical in managing patients who receive breast conserving surgery, or have certain high-risk features after mastectomy. Most patients have an excellent prognosis, therefore understanding the late effects of radiation to the chest is important. Radiation-induced heart disease (RIHD) comprises a spectrum of cardiac pathology including myocardial fibrosis and cardiomyopathy, coronary artery disease, valvular disease, pericardial disease, and arrhythmias. Tissue fibrosis is a common mediator in RIHD. Multiple pathways converge with both acute and chronic cellular, molecular, and genetic changes to result in fibrosis. In this article, we review the pathophysiology of cardiac disease related to radiation therapy to the chest. Our understanding of these mechanisms has improved substantially, but much work remains to further refine radiation delivery techniques and develop therapeutics to battle late effects of radiation. PMID:25741474

  10. Induced Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Neurodegenerative Diseases.

    PubMed

    Cao, Lei; Tan, Lan; Jiang, Teng; Zhu, Xi-Chen; Yu, Jin-Tai

    2015-08-01

    Although most neurodegenerative diseases have been closely related to aberrant accumulation of aggregation-prone proteins in neurons, understanding their pathogenesis remains incomplete, and there is no treatment to delay the onset or slow the progression of many neurodegenerative diseases. The availability of induced pluripotent stem cells (iPSCs) in recapitulating the phenotypes of several late-onset neurodegenerative diseases marks the new era in in vitro modeling. The iPSC collection represents a unique and well-characterized resource to elucidate disease mechanisms in these diseases and provides a novel human stem cell platform for screening new candidate therapeutics. Modeling human diseases using iPSCs has created novel opportunities for both mechanistic studies as well as for the discovery of new disease therapies. In this review, we introduce iPSC-based disease modeling in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. In addition, we discuss the implementation of iPSCs in drug discovery associated with some new techniques. PMID:25146848

  11. Heavy charged-particle induced lesions in rabbit cerebral cortex

    SciTech Connect

    Woodruff, K.H.; Lyman, J.T.; Fabrikant, J.I.

    1988-02-01

    Fourteen male rabbits received single doses of 20, 40, and 80 Gy of neon irradiation with an extended Bragg peak. They were sacrificed at 1 day, 1 week, and 6 months post-irradiation. The tissue changes which showed a significant time-dose relationship were leakage of carbon particles from blood vessels, focal arachnoiditis, hemorrhage, cystic necrosis, and a total histopathologic score using a point system of grading. The focal nature of the lesions was clearly demonstrated with 2 mm thick macrotome sections. The transition zone between damaged brain and microscopically normal appearing brain was less than 1 mm and the tissue damage induced was morphologically similar to that of other radiation modalities. These findings may have important therapeutic implications for patients. The sharply demarcated boundaries of heavy charged-particle induced lesions suggest these beams will be useful for obliterating tissue in areas where it is critical that a transition from undamaged to severely damaged tissue must occur over a short distance, such as in the central nervous system.

  12. Investigation of the ?-particle induced nuclear reactions on natural molybdenum

    NASA Astrophysics Data System (ADS)

    Ditrói, F.; Hermanne, A.; Tárkányi, F.; Takács, S.; Ignatyuk, A. V.

    2012-08-01

    Cross-sections of alpha particle induced nuclear reactions on natural molybdenum have been studied in the frame of a systematic investigation of charged particle induced nuclear reactions on metals for different applications. The excitation functions of 93mTc, 93gTc(m+), 94mTc, 94gTc, 95mTc, 95gTc, 96gTc(m+), 99mTc, 93mMo, 99Mo(cum), 90Nb(m+), 94Ru, 95Ru,97Ru, 103Ru and 88Zr were measured up to 40 MeV alpha energy by using a stacked foil technique and activation method. The main goals of this work were to get experimental data for accelerator technology, for monitoring of alpha beam, for thin layer activation technique and for testing nuclear reaction theories. The experimental data were compared with critically analyzed published data and with the results of model calculations, obtained by using the ALICE-IPPE, EMPIRE and TALYS codes (TENDL-2011).

  13. VISUALIZING THE FLOW INDUCED BY AN AIR CURTAIN OVER A MANNEQUIN USING STEREO PARTICLE IMAGE VELOCIMETRY

    E-print Network

    Texas at Arlington, University of

    INDUCED BY AN AIR CURTAIN OVER A MANNEQUIN USING STEREO PARTICLE IMAGE VELOCIMETRY John Edward Fernandes, an initial exploratory study was performed using a static mannequin. A stereo particle image velocimetryVISUALIZING THE FLOW INDUCED BY AN AIR CURTAIN OVER A MANNEQUIN USING STEREO PARTICLE IMAGE

  14. Sintered Indium-Tin Oxide Particles Induce Pro-Inflammatory Responses In Vitro, in Part through Inflammasome Activation

    PubMed Central

    Badding, Melissa A.; Schwegler-Berry, Diane; Park, Ju-Hyeong; Fix, Natalie R.; Cummings, Kristin J.; Leonard, Stephen S.

    2015-01-01

    Indium-tin oxide (ITO) is used to make transparent conductive coatings for touch-screen and liquid crystal display electronics. As the demand for consumer electronics continues to increase, so does the concern for occupational exposures to particles containing these potentially toxic metal oxides. Indium-containing particles have been shown to be cytotoxic in cultured cells and pro-inflammatory in pulmonary animal models. In humans, pulmonary alveolar proteinosis and fibrotic interstitial lung disease have been observed in ITO facility workers. However, which ITO production materials may be the most toxic to workers and how they initiate pulmonary inflammation remain poorly understood. Here we examined four different particle samples collected from an ITO production facility for their ability to induce pro-inflammatory responses in vitro. Tin oxide, sintered ITO (SITO), and ventilation dust particles activated nuclear factor kappa B (NF?B) within 3 h of treatment. However, only SITO induced robust cytokine production (IL-1?, IL-6, TNF?, and IL-8) within 24 h in both RAW 264.7 mouse macrophages and BEAS-2B human bronchial epithelial cells. Our lab and others have previously demonstrated SITO-induced cytotoxicity as well. These findings suggest that SITO particles activate the NLRP3 inflammasome, which has been implicated in several immune-mediated diseases via its ability to induce IL-1? release and cause subsequent cell death. Inflammasome activation by SITO was confirmed, but it required the presence of endotoxin. Further, a phagocytosis assay revealed that pre-uptake of SITO or ventilation dust impaired proper macrophage phagocytosis of E. coli. Our results suggest that adverse inflammatory responses to SITO particles by both macrophage and epithelial cells may initiate and propagate indium lung disease. These findings will provide a better understanding of the molecular mechanisms behind an emerging occupational health issue. PMID:25874458

  15. Diesel exhaust particles induce endothelial dysfunction in apoE{sup -/-} mice

    SciTech Connect

    Hansen, Christian S.; Sheykhzade, Majid; Moller, Peter; Folkmann, Janne Kjaergaard; Amtorp, Ole; Jonassen, Thomas; Loft, Steffen . E-mail: s.loft@pubhealth.ku.dk

    2007-02-15

    Background: Particulate air pollution can aggravate cardiovascular disease by mechanisms suggested to involve translocation of particles to the bloodstream and impairment of endothelial function, possibly dependent on present atherosclerosis. Aim: We investigated the effects of exposure to diesel exhaust particles (DEP) in vivo and ex vivo on vasomotor functions in aorta from apoE{sup -/-} mice with slight atherosclerosis and from normal apoE{sup +/+} mice. Methods: DEP 0, 0.5 or 5 mg/kg bodyweight in saline was administered i.p. The mice were sacrificed 1 h later and aorta ring segments were mounted on wire myographs. Segments from unexposed mice were also incubated ex vivo with 0, 10 and 100 {mu}g DEP/ml before measurement of vasomotor functions. Results: Exposure to 0.5 mg/kg DEP in vivo caused a decrease in the endothelium-dependent acetylcholine elicited vasorelaxation in apoE{sup -/-} mice, whereas the response was enhanced in apoE{sup +/+} mice. No significant change was observed after administration of 5 mg/kg DEP. In vivo DEP exposure did not affect constriction induced by K{sup +} or phenylephrine. In vitro exposure to 100 {mu}g DEP/ml enhanced acetylcholine-induced relaxation and attenuated phenylephrine-induced constriction. Vasodilation induced by sodium nitroprusside was not affected by any DEP exposure. Conclusion: Exposure to DEP has acute effect on vascular functions. Endothelial dysfunction possibly due to decreased NO production as suggested by decreased acetylcholine-induced vasorelaxation and unchanged sodium nitroprusside response can be induced by DEP in vivo only in vessels of mice with some atherosclerosis.

  16. Human-induced pluripotent stem cells: potential for neurodegenerative diseases

    PubMed Central

    Ross, Christopher A.; Akimov, Sergey S.

    2014-01-01

    The cell biology of human neurodegenerative diseases has been difficult to study till recently. The development of human induced pluripotent stem cell (iPSC) models has greatly enhanced our ability to model disease in human cells. Methods have recently been improved, including increasing reprogramming efficiency, introducing non-viral and non-integrating methods of cell reprogramming, and using novel gene editing techniques for generating genetically corrected lines from patient-derived iPSCs, or for generating mutations in control cell lines. In this review, we highlight accomplishments made using iPSC models to study neurodegenerative disorders such as Huntington's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, Fronto-Temporal Dementia, Alzheimer's disease, Spinomuscular Atrophy and other polyglutamine diseases. We review disease-related phenotypes shown in patient-derived iPSCs differentiated to relevant neural subtypes, often with stressors or cell “aging”, to enhance disease-specific phenotypes. We also discuss prospects for the future of using of iPSC models of neurodegenerative disorders, including screening and testing of therapeutic compounds, and possibly of cell transplantation in regenerative medicine. The new iPSC models have the potential to greatly enhance our understanding of pathogenesis and to facilitate the development of novel therapeutics. PMID:24824217

  17. Human-induced pluripotent stem cells: potential for neurodegenerative diseases.

    PubMed

    Ross, Christopher A; Akimov, Sergey S

    2014-09-15

    The cell biology of human neurodegenerative diseases has been difficult to study till recently. The development of human induced pluripotent stem cell (iPSC) models has greatly enhanced our ability to model disease in human cells. Methods have recently been improved, including increasing reprogramming efficiency, introducing non-viral and non-integrating methods of cell reprogramming, and using novel gene editing techniques for generating genetically corrected lines from patient-derived iPSCs, or for generating mutations in control cell lines. In this review, we highlight accomplishments made using iPSC models to study neurodegenerative disorders such as Huntington's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, Fronto-Temporal Dementia, Alzheimer's disease, Spinomuscular Atrophy and other polyglutamine diseases. We review disease-related phenotypes shown in patient-derived iPSCs differentiated to relevant neural subtypes, often with stressors or cell "aging", to enhance disease-specific phenotypes. We also discuss prospects for the future of using of iPSC models of neurodegenerative disorders, including screening and testing of therapeutic compounds, and possibly of cell transplantation in regenerative medicine. The new iPSC models have the potential to greatly enhance our understanding of pathogenesis and to facilitate the development of novel therapeutics. PMID:24824217

  18. The inhibition of RANKL-induced osteoclastogenesis through the suppression of p38 signaling pathway by naringenin and attenuation of titanium-particle-induced osteolysis.

    PubMed

    Wang, Wengang; Wu, Chuanlong; Tian, Bo; Liu, Xuqiang; Zhai, Zanjing; Qu, Xinhua; Jiang, Chuan; Ouyang, Zhengxiao; Mao, Yuanqing; Tang, Tingting; Qin, An; Zhu, Zhenan

    2014-01-01

    The aim of this study was to assess the effect of naringenin on osteoclastogenesis and titanium particle-induced osteolysis. Osteolysis from wear-induced particles and aseptic loosening are the most frequent late complications of total joint arthroplasty leading to revision of the prosthesis. Osteolysis during aseptic loosening is most likely due to increased bone resorption by osteoclasts. Through in vitro studies, we demonstrated that naringenin, a naturally occurring flavanone in grapefruit and tomatoes, exerts potent inhibitory effects on the ligand of the receptor activator of nuclear factor-?B (RANKL)-induced osteoclastogenesis and revealed that the mechanism of action of naringenin, which inhibited osteoclastogenesis by suppression of the p38 signaling pathway. Through in vivo studies, we proved that naringenin attenuated titanium particle-induced osteolysis in a mouse calvarial model. In general, we demonstrated that naringenin inhibited osteoclastogenesis via suppression of p38 signaling in vitro and attenuated titanium particle-induced osteolysis in vivo. This study also suggested that naringenin has significant potential for the treatment of osteolysis-related diseases caused by excessive osteoclast formation and activity. PMID:25464380

  19. Development of disease-resistant rice using regulatory components of induced disease resistance

    PubMed Central

    Takatsuji, Hiroshi

    2014-01-01

    Infectious diseases cause huge crop losses annually. In response to pathogen attacks, plants activate defense systems that are mediated through various signaling pathways. The salicylic acid (SA) signaling pathway is the most powerful of these pathways. Several regulatory components of the SA signaling pathway have been identified, and are potential targets for genetic manipulation of plants’ disease resistance. However, the resistance associated with these regulatory components is often accompanied by fitness costs; that is, negative effects on plant growth and crop yield. Chemical defense inducers, such as benzothiadiazole and probenazole, act on the SA pathway and induce strong resistance to various pathogens without major fitness costs, owing to their ‘priming effect.’ Studies on how benzothiadiazole induces disease resistance in rice have identified WRKY45, a key transcription factor in the branched SA pathway, and OsNPR1/NH1. Rice plants overexpressing WRKY45 were extremely resistant to rice blast disease caused by the fungus Magnaporthe oryzae and bacterial leaf blight disease caused by Xanthomonas oryzae pv. oryzae (Xoo), the two major rice diseases. Disease resistance is often accompanied by fitness costs; however, WRKY45 overexpression imposed relatively small fitness costs on rice because of its priming effect. This priming effect was similar to that of chemical defense inducers, although the fitness costs were amplified by some environmental factors. WRKY45 is degraded by the ubiquitin–proteasome system, and the dual role of this degradation partly explains the priming effect. The synergistic interaction between SA and cytokinin signaling that activates WRKY45 also likely contributes to the priming effect. With a main focus on these studies, I review the current knowledge of SA-pathway-dependent defense in rice by comparing it with that in Arabidopsis, and discuss potential strategies to develop disease-resistant rice using signaling components. PMID:25431577

  20. Geraniin suppresses RANKL-induced osteoclastogenesis in vitro and ameliorates wear particle-induced osteolysis in mouse model.

    PubMed

    Xiao, Fei; Zhai, Zanjing; Jiang, Chuan; Liu, Xuqiang; Li, Haowei; Qu, Xinhua; Ouyang, Zhengxiao; Fan, Qiming; Tang, Tingting; Qin, An; Gu, Dongyun

    2015-01-01

    Wear particle-induced osteolysis and subsequent aseptic loosening remains the most common complication that limits the longevity of prostheses. Wear particle-induced osteoclastogenesis is known to be responsible for extensive bone erosion that leads to prosthesis failure. Thus, inhibition of osteoclastic bone resorption may serve as a therapeutic strategy for the treatment of wear particle induced osteolysis. In this study, we demonstrated for the first time that geraniin, an active natural compound derived from Geranium thunbergii, ameliorated particle-induced osteolysis in a Ti particle-induced mouse calvaria model in vivo. We also investigated the mechanism by which geraniin exerts inhibitory effects on osteoclasts. Geraniin inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, evidenced by reduced osteoclast formation and suppressed osteoclast specific gene expression. Specially, geraniin inhibited actin ring formation and bone resorption in vitro. Further molecular investigation demonstrated geraniin impaired osteoclast differentiation via the inhibition of the RANKL-induced NF-?B and ERK signaling pathways, as well as suppressed the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Collectively, our data suggested that geraniin exerts inhibitory effects on osteoclast differentiation in vitro and suppresses Ti particle-induced osteolysis in vivo. Geraniin is therefore a potential natural compound for the treatment of wear particle induced osteolysis in prostheses failure. PMID:25016282

  1. Lithium-Induced Minimal Change Disease and Acute Kidney Injury

    PubMed Central

    Tandon, Parul; Wong, Natalie; Zaltzman, Jeffrey S

    2015-01-01

    Context: Lithium carbonate is a psychiatric medication commonly used in the treatment of bipolar disorder. It has been implicated in inducing nephrogenic diabetes inspidus, chronic tubulointerstitial nephropathy, and acute tubular necrosis. We describe a case of lithium-induced minimal change disease (MCD) and acute kidney injury (AKI). Case Report: A 32-year-old female with a medical history of bipolar disorder treated with chronic lithium therapy presented with anasarca, fatigue, and tremors. Work-up revealed supra-therapeutic lithium levels, hypoalbuminemia, and significant proteinuria. The patient was treated conservatively with fluids and discontinuation of lithium therapy. Subsequently, she developed significant AKI and persistent proteinuria. She underwent a renal biopsy that demonstrated effacement of podocyte foot processes consistent with lithium-induced MCD. This was treated with corticosteroids, which decreased the proteinuria and resolved all the patient's symptoms. Conclusion: Lithium-induced MCD is a rare disease that affects patients of all ages. It is often associated with therapeutic lithium and is typically resolved with discontinuation of lithium. In some cases, concurrent AKI may result due to vascular obstruction from hyperalbuminuria and associated renal interstitial edema. Corticosteroids may be needed to reduce the proteinuria and prevent progression to chronic kidney disease. As such, patients on lithium therapy may benefit from monitoring of glomerular function via urinalysis to prevent the onset of nephrotic syndrome. PMID:26258081

  2. Ultra Fine Particles from Diesel Engines Induce Vascular Oxidative Stress via JNK Activation

    PubMed Central

    Li, Rongsong; Ning, Zhi; Cui, Jeffery; Khalsa, Bhavraj; Ai, Lisong; Takabe, Wakako; Beebe, Tyler; Majumdar, Rohit; Sioutas, Constantinos; Hsiai, Tzung

    2011-01-01

    Exposure of particulate air pollution is linked to increased incidences of cardiovascular diseases. Ambient ultra fine particles (UFP) from diesel vehicle engines have been shown to be pro-atherogenic in apoE knockout mice and may constitute a major cardiovascular risk in humans. We posited that circulating nano-sized particles from traffic pollution sources induced vascular oxidative stress via JNK activation in endothelial cells. Diesel UFP were collected from a 1998 Kenworth truck. Intra-cellular superoxide assay revealed that these UFP dose-dependently induced superoxide (O2·-) production in human aortic endothelial cells (HAEC). Flow cytometry (FACS) showed that UFP increased MitoSOX Red intensity specific for mitochondrial superoxide. Protein carbonyl content is increased by UFP as an indication of vascular oxidative stress. UFP also up-regulated hemeoxygenase-1 (HO-1) and tissue factor (TF) mRNA expression, and pre-treatment with antioxidant, N-acetyl cysteine (NAC), significantly decreased their expression. Furthermore, UFP transiently activated JNK in HAEC. Treatment with JNK inhibitor SP600125 and silencing of both JNK1 and JNK2 with siRNA inhibited UFP stimulated O2·- production and mRNA expression of HO-1 and TF. Our findings suggest that JNK activation play an important role in UFP-induced oxidative stress and stress response gene expression. PMID:19154785

  3. Using Human Induced Pluripotent Stem Cells to Model Skeletal Diseases.

    PubMed

    Barruet, Emilie; Hsiao, Edward C

    2016-01-01

    Musculoskeletal disorders affecting the bones and joints are major health problems among children and adults. Major challenges such as the genetic origins or poor diagnostics of severe skeletal disease hinder our understanding of human skeletal diseases. The recent advent of human induced pluripotent stem cells (human iPS cells) provides an unparalleled opportunity to create human-specific models of human skeletal diseases. iPS cells have the ability to self-renew, allowing us to obtain large amounts of starting material, and have the potential to differentiate into any cell types in the body. In addition, they can carry one or more mutations responsible for the disease of interest or be genetically corrected to create isogenic controls. Our work has focused on modeling rare musculoskeletal disorders including fibrodysplasia ossificans progressive (FOP), a congenital disease of increased heterotopic ossification. In this review, we will discuss our experiences and protocols differentiating human iPS cells toward the osteogenic lineage and their application to model skeletal diseases. A number of critical challenges and exciting new approaches are also discussed, which will allow the skeletal biology field to harness the potential of human iPS cells as a critical model system for understanding diseases of abnormal skeletal formation and bone regeneration. PMID:25549831

  4. Key Node Selection for Containing Infectious Disease Spread Using Particle Swarm Optimization

    E-print Network

    Wong, Limsoon

    Key Node Selection for Containing Infectious Disease Spread Using Particle Swarm Optimization Xiuju infectious diseases have grown into global health threats due to high human mobility. It is important to have intervention plans for containing the spread of such infectious diseases. Among various intervention strategies

  5. Energetic particle induced desorption of water vapor cryo-condensate

    SciTech Connect

    Menon, M.M.; Owen, L.W.; Simpkins, J.E.; Uckan, T.; Mioduszewski, P.K.

    1990-01-01

    An in-vessel cryo-condensation pump is being designed for the Advanced Divertor configuration of the DIII-D tokamak. To assess the importance of possible desorption of water vapor from the cryogenic surfaces of the pump due to impingement of energetic particles from the plasma, a 77 K surface on which a thin layer of water vapor was condensed was exposed to a tenuous plasma (density = 2 {times} 10{sup 10} cm{sup {minus}3}, electron temperature = 3 eV). Significant desorption of the condensate occurred, suggesting that impingement of energeticparticles (10 eV) at flux levels of {approximately}10{sup 16} cm{sup 2}s{sup {minus}1} on cryogenic surfaces could potentially induce impurity problems in the tokamak plasma. A pumping configuration is presented in which this problem is minimized without sacrificing the pumping speed.

  6. Visual phenomena induced by cosmic rays and accelerated particles

    NASA Technical Reports Server (NTRS)

    Tobias, C. A.; Budinger, T. F.; Leith, J. T.; Mamoon, A.; Chapman, P. K.

    1972-01-01

    Experiments, conducted at cyclotrons together with observations by Apollo astronauts, suggest with little doubt that cosmic nuclei interacting with the visual apparatus cause the phenomenon of light flashes seen on translunar and transearth coast over the past four Apollo missions. Other experiments with high and low energy neutrons and a helium ion beam suggest that slow protons and helium ions with a stopping power greater than 10 to the 8th power eV/gram sq cm can cause the phenomenon in the dark adapted eye. It was demonstrated that charged particles induced by neutrons and helium ions can stimulate the visual apparatus. Some approaches to understanding the long term mission effects of galactic cosmic nuclei interacting with man and his nervous system are outlined.

  7. Antifungal-Associated Drug-Induced Cardiac Disease.

    PubMed

    Cleary, John D; Stover, Kayla R

    2015-12-01

    The etiology of cardiomyopathies are classified into 4 main groupings (dilated, hypertrophic, restrictive, and idiopathic) and can be mechanistically caused by myocarditis, conduction abnormalities, focal direct injury, or nutritional deficiency. Based on our review of this topic, evidence suggests that echinocandin-related cardiac dysfunction is a mitochondrial drug-induced disease caused by focal direct myocyte injury. With caspofungin or anidulafungin administration into the heart via central line, exposure is likely extreme enough to induce the acute toxicity. Chronic or low-dose exposure may lead to hypertrophic cardiomyopathy; however, only acute exposures have been explored to date. PMID:26567285

  8. Dielectric response of particles in flowing media: the effect of shear-induced rotation on the variation in particle polarizability.

    PubMed

    Nikolic-Jaric, Marija; Ferrier, Graham A; Thomson, Douglas J; Bridges, Greg E; Freeman, Mark R

    2011-07-01

    When particles in liquid suspensions flow through channels and pipes in a laminar fashion, the resulting parabolic velocity profile gives rise to shear, which induces the particles to rotate. If flowing suspensions containing dielectric particles are immersed in an external electric field, the anisotropic polarization induced in rotating nonspherical particles will vary with the orientation of the particle with respect to the external field; what results is an uncertainty in experimental measurements that involve particle polarization. The present study establishes the limits of this uncertainty and shows that departure from spherical symmetry in individual particles can lead to a significant overlap in measurements attempting to discriminate between particle subpopulations in suspensions. For example, the uncertainty in signal amplitude for a population of activated T-lymphocytes can be as high as 20%. Such concerns arise in applications like field-flow fractionation, dielectrophoretic sorting of particles, flow impedance measurements and cytometry, and, most recently, isodielectric separation, all of which are used to separate particles in a flow based on their dielectric response. This paper considers axisymmetric particles as the first departure from the approximation of spherical symmetry, shows how to calculate an estimate of the size of the population overlap, and suggests possible strategies to minimize it. PMID:21867228

  9. Nitric oxide mediates glial-induced neurodegeneration in Alexander disease

    PubMed Central

    Wang, Liqun; Hagemann, Tracy L.; Kalwa, Hermann; Michel, Thomas; Messing, Albee; Feany, Mel B.

    2015-01-01

    Glia play critical roles in maintaining the structure and function of the nervous system; however, the specific contribution that astroglia make to neurodegeneration in human disease states remains largely undefined. Here we use Alexander disease, a serious degenerative neurological disorder caused by astrocyte dysfunction, to identify glial-derived NO as a signalling molecule triggering astrocyte-mediated neuronal degeneration. We further find that NO acts through cGMP signalling in neurons to promote cell death. Glial cells themselves also degenerate, via the DNA damage response and p53. Our findings thus define a specific mechanism for glial-induced non-cell autonomous neuronal cell death, and identify a potential therapeutic target for reducing cellular toxicity in Alexander disease, and possibly other neurodegenerative disorders with glial dysfunction. PMID:26608817

  10. Contact nucleation of ice induced by biological aerosol particles

    NASA Astrophysics Data System (ADS)

    Kiselev, Alexei; Hoffmann, Nadine; Schaefer, Manfred; Duft, Denis; Leisner, Thomas

    2014-05-01

    The contact freezing of supercooled water droplets is one of the potentially important and the least understood heterogeneous mechanism of ice formation in tropospheric clouds. On the time scales of cloud lifetime the freezing of supercooled water droplets via contact mechanism may occur at higher temperature compared to the same IN immersed in the droplet. Recently we have developed an experimental method allowing for quantification of the freezing probability on a single droplet-particle collision event [1]. In the previous experimental studies with mineral dust (kaolinite, illite, feldspar, and hematite) we have been able to show that the rate of freezing at a given temperature is governed by the rate of droplet - particle collisions, and by the properties of the contact ice nuclei: its size, morphology and composition [1, 2]. In this contribution, we focus on the contact freezing efficiency of biological ice nuclei. We demonstrate that the contact freezing efficiency of Snomax (freeze-dried fragments of Pseudomonas syringae bacteria) follows very similar pattern observed in immersion freezing experiments, indicating that the INA-protein identified as the ice nucleation agent in the immersion freezing mode is also responsible for initiation of contact freezing. The same similarity is observed for contact freezing induced by semi-dry residual particles of birch pollen washing water, providing an evidence for the importance of organic macromolecules of biological origin for nucleation of atmospheric ice. Finally, our experiments show that mixing the birch pollen washing water with mineral dust (illite) significantly increases the IN efficiency of mineral dust and extends the temperature range of its IN activity. These findings suggest a possible route of multiplication of the effect of biological IN beyond observed atmospheric concentrations of pollen grains. [1] - Hoffmann, N., Kiselev, A., Rzesanke, D., Duft, D., and Leisner, T.: Experimental quantification of contact freezing in an electrodynamic balance Atmos. Meas. Tech., 6, 2373-2382, 2013. [2] - Hoffmann, N., Duft, D., Kiselev, A., and Leisner, T.: Contact freezing efficiency of mineral dust aerosols studied in an electrodynamic balance: quantitative size and temperature dependence for illite particles, Faraday Discuss., 2013.

  11. Seamless Correction of the Sickle Cell Disease Mutation of the HBB Gene in Human Induced

    E-print Network

    Zhao, Huimin

    Seamless Correction of the Sickle Cell Disease Mutation of the HBB Gene in Human Induced ABSTRACT: Sickle cell disease (SCD) is the most common human genetic disease which is caused by a single effector nucleases; induced pluripotent stem cells; piggyBac transposon; sickle cell disease; gene therapy

  12. Ambient air pollution particles and the acute exacerbation of chronic obstructive pulmonary disease

    EPA Science Inventory

    Investigation has repeatedly demonstrated an association between exposure to ambient air pollution particles and numerous indices of human morbidity and mortality. Individuals with chronic obstructive pulmonary disease (COPD) are among those with an increased sensitivity to air p...

  13. Particle image velocimetry and planar laser-induced fluorescence measurements on lobed jet mixing flows

    E-print Network

    Hu, Hui

    Particle image velocimetry and planar laser-induced fluorescence measurements on lobed jet mixing-induced ¯uores- cence (PLIF) and particle image velocimetry (PIV) were used to accomplish ¯ow visualisation character- istics downstream of a lobed nozzle/mixer systematically by using laser Doppler velocimetry (LDV

  14. Possible mechanisms for arsenic-induced proliferative diseases

    SciTech Connect

    Wetterhahn, K.E.; Dudek, E.J.; Shumilla, J.A.

    1996-12-31

    Possible mechanisms for cardiovascular diseases and cancers which have been observed on chronic exposure to arsenic have been investigated. We tested the hypothesis that nonlethal levels of arsenic are mitogenic, cause oxidative stress, increase nuclear translocation of trans-acting factors, and increase expression of genes involved in proliferation. Cultured porcine vascular (from aorta) endothelial cells were used as a model cell system to study the effects of arsenic on the target cells for cardiovascular diseases. Treatment of postconfluent cell cultures with nonovertly toxic concentrations of arsenite increased DNA synthesis, similar to the mitogenic response observed with hydrogen peroxide. Within 1 hour of adding noncytotoxic concentrations of arsenite, cellular levels of oxidants increased relative to control levels, indicating that arsenite promotes cellular oxidations. Arsenite treatment increased nuclear translocation of NF-{kappa}B, an oxidative stress-responsive transcription factor, in a manner similar to that observed with hydrogen peroxide. Pretreatment of intact cells with the antioxidants N-acetylcysteine and dimethylfumarate prevented the arsenite-induced increases in cellular oxidant formation and NF-KB translocation. Arsenite had little or no effect on binding of NF-KB to its DNA recognition sequence in vitro, indicating that it is unlikely that arsenite directly affects NF-KB. The steady-state mRNA levels of intracellular adhesion molecule and urokinase-like plasminogen activator, genes associated with the active endothelial phenotype in arteriosclerosis and cancer metastasis, were increased by nontoxic concentrations of arsenite. These data suggest that arsenite promotes proliferative diseases like heart disease and cancer by activating oxidant-sensitive endothelial cell signaling and gene expression. It is possible that antioxidant therapy would be useful in preventing arsenic-induced cardiovascular disease and cancer.

  15. Effect of the induced-dipole force on charging rates of aerosol particles

    SciTech Connect

    Robertson, Scott; Sternovsky, Zoltan

    2008-04-15

    Natanson's model (Zh. Tekh. Fiz., 30, 573 (1960) [English translation: Sov. Phys. Tech. Phys. 5, 538 (1960)]) for the collection of ions by aerosol particles is modified so that both the Coulomb force and the induced-dipole force are included for the case of attractive aerosol particles. Natanson included the induced-dipole force and the Coulomb force together only for the Coulomb force being repelling. The induced-dipole force increases ion collection rates by about a factor of 2 for the smallest aerosol particles. The results are applicable to the collection of both ions and electrons by noctilucent cloud particles and meteoritic dust in the mesosphere.

  16. The Role of Hedgehog Signaling in Tumor Induced Bone Disease

    PubMed Central

    Cannonier, Shellese A.; Sterling, Julie A.

    2015-01-01

    Despite significant progress in cancer treatments, tumor induced bone disease continues to cause significant morbidities. While tumors show distinct mutations and clinical characteristics, they behave similarly once they establish in bone. Tumors can metastasize to bone from distant sites (breast, prostate, lung), directly invade into bone (head and neck) or originate from the bone (melanoma, chondrosarcoma) where they cause pain, fractures, hypercalcemia, and ultimately, poor prognoses and outcomes. Tumors in bone secrete factors (interleukins and parathyroid hormone-related protein) that induce RANKL expression from osteoblasts, causing an increase in osteoclast mediated bone resorption. While the mechanisms involved varies slightly between tumor types, many tumors display an increase in Hedgehog signaling components that lead to increased tumor growth, therapy failure, and metastasis. The work of multiple laboratories has detailed Hh signaling in several tumor types and revealed that tumor establishment in bone can be controlled by both canonical and non-canonical Hh signaling in a cell type specific manner. This review will explore the role of Hh signaling in the modulation of tumor induced bone disease, and will shed insight into possible therapeutic interventions for blocking Hh signaling in these tumors. PMID:26343726

  17. Drug Induced Steatohepatitis: An Uncommon Culprit of a Common Disease

    PubMed Central

    Rabinowich, Liane; Shibolet, Oren

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease in developed countries. Its frequency is increasing in the general population mostly due to the widespread occurrence of obesity and the metabolic syndrome. Although drugs and dietary supplements are viewed as a major cause of acute liver injury, drug induced steatosis and steatohepatitis are considered a rare form of drug induced liver injury (DILI). The complex mechanism leading to hepatic steatosis caused by commonly used drugs such as amiodarone, methotrexate, tamoxifen, valproic acid, glucocorticoids, and others is not fully understood. It relates not only to induction of the metabolic syndrome by some drugs but also to their impact on important molecular pathways including increased hepatocytes lipogenesis, decreased secretion of fatty acids, and interruption of mitochondrial ?-oxidation as well as altered expression of genes responsible for drug metabolism. Better familiarity with this type of liver injury is important for early recognition of drug hepatotoxicity and crucial for preventing severe forms of liver injury and cirrhosis. Moreover, understanding the mechanisms leading to drug induced hepatic steatosis may provide much needed clues to the mechanism and potential prevention of the more common form of metabolic steatohepatitis. PMID:26273591

  18. The Role of Hedgehog Signaling in Tumor Induced Bone Disease.

    PubMed

    Cannonier, Shellese A; Sterling, Julie A

    2015-01-01

    Despite significant progress in cancer treatments, tumor induced bone disease continues to cause significant morbidities. While tumors show distinct mutations and clinical characteristics, they behave similarly once they establish in bone. Tumors can metastasize to bone from distant sites (breast, prostate, lung), directly invade into bone (head and neck) or originate from the bone (melanoma, chondrosarcoma) where they cause pain, fractures, hypercalcemia, and ultimately, poor prognoses and outcomes. Tumors in bone secrete factors (interleukins and parathyroid hormone-related protein) that induce RANKL expression from osteoblasts, causing an increase in osteoclast mediated bone resorption. While the mechanisms involved varies slightly between tumor types, many tumors display an increase in Hedgehog signaling components that lead to increased tumor growth, therapy failure, and metastasis. The work of multiple laboratories has detailed Hh signaling in several tumor types and revealed that tumor establishment in bone can be controlled by both canonical and non-canonical Hh signaling in a cell type specific manner. This review will explore the role of Hh signaling in the modulation of tumor induced bone disease, and will shed insight into possible therapeutic interventions for blocking Hh signaling in these tumors. PMID:26343726

  19. Single Particle Fluorescence Burst Analysis of Epsin Induced Membrane Fission

    PubMed Central

    Kustigian, Lauren; Puchalla, Jason; Carr, Chavela M.; Rye, Hays S.

    2015-01-01

    Vital cellular processes, from cell growth to synaptic transmission, rely on membrane-bounded carriers and vesicles to transport molecular cargo to and from specific intracellular compartments throughout the cell. Compartment-specific proteins are required for the final step, membrane fission, which releases the transport carrier from the intracellular compartment. The role of fission proteins, especially at intracellular locations and in non-neuronal cells, while informed by the dynamin-1 paradigm, remains to be resolved. In this study, we introduce a highly sensitive approach for the identification and analysis of membrane fission machinery, called burst analysis spectroscopy (BAS). BAS is a single particle, free-solution approach, well suited for quantitative measurements of membrane dynamics. Here, we use BAS to analyze membrane fission induced by the potent, fission-active ENTH domain of epsin. Using this method, we obtained temperature-dependent, time-resolved measurements of liposome size and concentration changes, even at sub-micromolar concentration of the epsin ENTH domain. We also uncovered, at 37°C, fission activity for the full-length epsin protein, supporting the argument that the membrane-fission activity observed with the ENTH domain represents a native function of the full-length epsin protein. PMID:25799353

  20. Excitation of high-n toroidicity-induced shear Alfven eigenmodes by energetic particles and fusion alpha particles in tokamaks

    SciTech Connect

    Fu, G.Y.; Cheng, C.Z.

    1992-07-01

    The stability of high-n toroidicity-induced shear Alfven eigenmodes (TAE) in the presence of fusion alpha particles or energetic ions in tokamaks is investigated. The TAE modes are discrete in nature and thus can easily tap the free energy associated with energetic particle pressure gradient through wave particle resonant interaction. A quadratic form is derived for the high-n TAE modes using gyro-kinetic equation. The kinetic effects of energetic particles are calculated perturbatively using the ideal MHD solution as the lowest order eigenfunction. The finite Larmor radius (FLR) effects and the finite drift orbit width (FDW) effects are included for both circulating and trapped energetic particles. It is shown that, for circulating particles, FLR and FDW effects have two opposite influences on the stability of the high-n TAE modes. First, they have the usual stabilizing effects by reducing the wave particle interaction strength. Second, they also have destabilizing effects by allowing more particles to resonate with the TAE modes. It is found that the growth rate induced by the circulating alpha particles increase linearly with toroidal mode number n for small {kappa}{sub {theta}}{rho}{sub {alpha}}, and decreases as 1/n for {kappa}{sub {theta}}{rho}{sub {alpha}} {much_gt} 1. The maximum growth rate is obtained at {kappa}{sub {theta}}{rho}{sub {alpha}} on the order of unity and is nearly constant for the range of 0.7 < {upsilon}{sub {alpha}}/{upsilon}{sub A} < 2.5. On the other hand, the trapped particle response is dominated by the precessional drift resonance. The bounce resonant contribution is negligible. The growth rate peaks sharply at the value of {kappa}{sub {theta}}{rho}{sub {alpha}} such that the precessional drift resonance occurs for the most energetic trapped particles. The maximum growth rate due to the energetic trapped particles is comparable to that of circulating particles.

  1. Excitation of high-n toroidicity-induced shear Alfven eigenmodes by energetic particles and fusion alpha particles in tokamaks

    SciTech Connect

    Fu, G.Y.; Cheng, C.Z.

    1992-07-01

    The stability of high-n toroidicity-induced shear Alfven eigenmodes (TAE) in the presence of fusion alpha particles or energetic ions in tokamaks is investigated. The TAE modes are discrete in nature and thus can easily tap the free energy associated with energetic particle pressure gradient through wave particle resonant interaction. A quadratic form is derived for the high-n TAE modes using gyro-kinetic equation. The kinetic effects of energetic particles are calculated perturbatively using the ideal MHD solution as the lowest order eigenfunction. The finite Larmor radius (FLR) effects and the finite drift orbit width (FDW) effects are included for both circulating and trapped energetic particles. It is shown that, for circulating particles, FLR and FDW effects have two opposite influences on the stability of the high-n TAE modes. First, they have the usual stabilizing effects by reducing the wave particle interaction strength. Second, they also have destabilizing effects by allowing more particles to resonate with the TAE modes. It is found that the growth rate induced by the circulating alpha particles increase linearly with toroidal mode number n for small {kappa}{sub {theta}}{rho}{sub {alpha}}, and decreases as 1/n for {kappa}{sub {theta}}{rho}{sub {alpha}} {much gt} 1. The maximum growth rate is obtained at {kappa}{sub {theta}}{rho}{sub {alpha}} on the order of unity and is nearly constant for the range of 0.7 < {upsilon}{sub {alpha}}/{upsilon}{sub A} < 2.5. On the other hand, the trapped particle response is dominated by the precessional drift resonance. The bounce resonant contribution is negligible. The growth rate peaks sharply at the value of {kappa}{sub {theta}}{rho}{sub {alpha}} such that the precessional drift resonance occurs for the most energetic trapped particles. The maximum growth rate due to the energetic trapped particles is comparable to that of circulating particles.

  2. Recombinant Adeno-Vaccine Expressing Enterovirus 71-Like Particles against Hand, Foot, and Mouth Disease

    PubMed Central

    Tsou, Yueh-Liang; Lin, Yi-Wen; Shao, Hsiao-Yun; Yu, Shu-Ling; Wu, Shang-Rung; Lin, Hsiao-Yu; Liu, Chia-Chyi; Huang, Chieh; Chong, Pele; Chow, Yen-Hung

    2015-01-01

    Enterovirus 71 (EV71) and coxsackieviruses (CV) are the major causative agents of hand, foot and mouth disease (HFMD). There is not currently a vaccine available against HFMD, even though a newly developed formalin-inactivated EV71 (FI-EV71) vaccine has been tested in clinical trial and has shown efficacy against EV71. We have designed and genetically engineered a recombinant adenovirus Ad-EVVLP with the EV71 P1 and 3CD genes inserted into the E1/E3-deleted adenoviral genome. Ad-EVVLP were produced in HEK-293A cells. In addition to Ad-EVVLP particles, virus-like particles (VLPs) formed from the physical association of EV71 capsid proteins, VP0, VP1, and VP3 expressed from P1 gene products. They were digested by 3CD protease and confirmed to be produced by Ad-EVVLP-producing cells, as determined using transmission electron microscopy and western blotting. Mouse immunogenicity studies showed that Ad-EVVLP-immunized antisera neutralized the EV71 B4 and C2 genotypes. Activation of VLP-specific CD4+ and CD8+/IFN-? T cells associated with Th1/Th2-balanced IFN-?, IL-17, IL-4, and IL-13 was induced; in contrast, FI-EV71 induced only Th2-mediated neutralizing antibody against EV71 and low VLP-specific CD4+ and CD8+ T cell responses. The antiviral immunity against EV71 was clearly demonstrated in mice vaccinated with Ad-EVVLP in a hSCARB2 transgenic (hSCARB2-Tg) mouse challenge model. Ad-EVVLP-vaccinated mice were 100% protected and demonstrated reduced viral load in both the CNS and muscle tissues. Ad-EVVLP successfully induced anti-CVA16 immunities. Although antisera had no neutralizing activity against CVA16, the 3C-specific CD4+ and CD8+/IFN-? T cells were identified, which could mediate protection against CVA16 challenge. FI-EV71 did not induce 3C-mediated immunity and had no efficacy against the CVA16 challenge. These results suggest that Ad-EVVLP can enhance neutralizing antibody and protective cellular immune responses to prevent EV71 infection and cellular immune responses against CV infection. PMID:25855976

  3. Thermally relativistic flows induced by gravitational-force-free particle motion in curved spacetime

    SciTech Connect

    Yano, Ryosuke; Suzuki, Kojiro; Kuroda, Hisayasu

    2009-12-15

    Thermally relativistic flows in the early Universe can be characterized by the emergence of flows induced by gravitational-force-free particle motion in curved spacetime as well as induced by the gravitational force. In this paper, thermally relativistic flows induced by gravitational-force-free particle motion in curved spacetime are discussed on the basis of the general relativistic Boltzmann equation. As an object of analysis, we consider the flow from the static state inside the Schwarzschild radius of a thermally relativistic stuffed black hole induced by such motion. Analytical results obtained using the collisionless, nongravitational general relativistic Boltzmann equation reveal that the initial cluster is induced by gravitational-force-free particle motion. Numerical results obtained using the nongravitational general relativistic Anderson-Witting model confirm the presence of an initial cluster inside the thermally relativistic stuffed black hole, which is induced by gravitational-force-free particle motion.

  4. Influence of Magnolol on the bystander effect induced by alpha-particle irradiation

    E-print Network

    Yu, Peter K.N.

    Influence of Magnolol on the bystander effect induced by alpha-particle irradiation T.P.W. Wong, Hong Kong a r t i c l e i n f o Keywords: Bystander effect Alpha-particle CHO cells Magnolol a b s t r a c t In this work, the influence of Magnolol on the bystander effect in alpha-particle irradiated

  5. Energetic-Particle-Induced Geodesic Acoustic Mode Princeton Plasma Physics Laboratory, Princeton, New Jersey 08543, USA

    E-print Network

    , Princeton, New Jersey 08543, USA (Received 24 June 2008; published 30 October 2008) A new energetic particle that energetic particles can indeed excite a new GAM-like mode via free energy associated with velocity space, the new mode, to be called EGAM (for energetic- particle-induced GAM), is intrinsically an energetic parti

  6. Applying Particle Image Velocimetry to Map Fire Ant Alate Wing Beat Induced Flows Lichuan Gui1

    E-print Network

    Gui, Lichuan

    Applying Particle Image Velocimetry to Map Fire Ant Alate Wing Beat Induced Flows Lichuan Gui1, Mississippi A particle image velocimetry (PIV) system was built at the University of Mississippi's National that the air flow can be visualized with fog particles and captured with a digital imaging system. A Nd

  7. Mineralogical and geochemical aspects of mineral-induced disease

    SciTech Connect

    Guthrie, G.; Raymond, R.; Saffiotti, U.; Aust, A.; Mossman, B.

    1996-04-01

    Many minerals are known to cause disease following inhalation, including asbestos, silica, zeolites, and clays. The mineralogical properties that determine toxicity are not known, hindering effective risk assessment. Consequently, many minerals that do not pose risks are controlled excessively and many minerals that do pose risk remain uncontrolled. The authors are integrating mineralogy and biology in an interdisciplinary scientific investigation of the mechanisms of mineral-induced disease. The biological endpoints include the formation of ferruginous bodies and chemical signaling (e.g., production of cytokines or active oxygen species) by cells; the mineralogical variables include structure, composition, and surface properties. The authors are also determining what information about the biological reaction is preserved in the mineral surface.

  8. Hypoxia inducible factor-1 as a target for neurodegenerative diseases.

    PubMed

    Zhang, Z; Yan, J; Chang, Y; ShiDu Yan, S; Shi, H

    2011-01-01

    Hypoxia inducible factor-1 (HIF-1) is a transcriptional factor responsible for cellular and tissue adaption to low oxygen tension. HIF-1, a heterodimer consisting of a constitutively expressed ? subunit and an oxygen-regulated ? subunit, regulates a series of genes that participate in angiogenesis, iron metabolism, glucose metabolism, and cell proliferation/survival. The activity of HIF-1 is controlled by post-translational modifications on different amino acid residues of its subunits, mainly the alpha subunit. Besides in ischemic stroke (see review [1]), emerging evidence has revealed that HIF-1 activity and expression of its down-stream genes, such as vascular endothelial growth factor and erythropoietin, are altered in a range of neurodegenerative diseases. At the same time, experimental and clinical evidence has demonstrated that regulating HIF-1 might ameliorate the cellular and tissue damage in the neurodegenerative diseases. These new findings suggest HIF-1 as a potential medicinal target for the neurodegenerative diseases. This review focuses on HIF-1? protein modifications and HIF-1's potential neuroprotective roles in Alzheimer's (AD), Parkinson's (PD), Huntington's diseases (HD), and amyotrophic lateral sclerosis (ALS). PMID:21861815

  9. Memantine-induced Myoclonus in a Patient with Alzheimer Disease

    PubMed Central

    Murgai, Aditya A.; LeDoux, Mark S.

    2015-01-01

    Background Myoclonus can be a clinical manifestation of numerous neurodegenerative disorders and an adverse drug reaction to medications used in their treatment. Case Report Herein, we report memantine-induced myoclonus in a patient with Alzheimer disease. The myoclonus seen in our patient was generalized (proximal limbs and trunk), present at rest and with action, and stimulus sensitive. A structured evaluation with the Unified Myoclonus Rating Scale showed that the myoclonus had no significant effect on functional capacity. After discontinuation of memantine, myoclonus slowly resolved over the course of several weeks. Discussion Memantine may cause myoclonus in susceptible individuals. PMID:26317045

  10. Hypoxia-Inducible Factor 1 and Cardiovascular Disease

    PubMed Central

    Semenza, Gregg L.

    2015-01-01

    Cardiac function is required for blood circulation and systemic oxygen delivery. However, the heart has intrinsic oxygen demands that must be met to maintain effective contractility. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis in all metazoan species. HIF-1 controls oxygen delivery, by regulating angiogenesis and vascular remodeling, and oxygen utilization, by regulating glucose metabolism and redox homeostasis. Analysis of animal models suggests that by activation of these homeostatic mechanisms, HIF-1 plays a critical protective role in the pathophysiology of ischemic heart disease and pressure-overload heart failure. PMID:23988176

  11. Animal models of beryllium-induced lung disease

    SciTech Connect

    Finch, G.L.; Hoover, M.D.; Hahn, F.F.

    1996-10-01

    The Inhalation Toxicology Research Institute (ITRI) is conducting research to improve the understanding of chronic beryllium disease (CBD) and beryllium-induced lung cancer. Initial animal studies examined beagle dogs that inhaled BeO calcined at either 500 or 1000{degrees}C. At similar lung burdens, the 500{degrees}C BeO induced more severe and extensive granulomatous pneumonia, lymphocytic infiltration into the lung, and positive Be-specific lymphocyte proliferative responses in vitro than the 1000{degrees}C BeO. However, the progressive nature of human CBD was not duplicated. More recently, Strains A/J and C3H/HeJ mice were exposed to Be metal by inhalation. This produced a marked granulomatous pneumonia, diffuse infiltrates, and multifocal aggregates of interstitial lymphocytes with a pronounced T helper component and pulmonary in situ lymphocyte proliferation. With respect to lung cancer, at a mean lung burden as low as 17 pg Be/g lung, inhaled Be metal induced benign and/or malignant lung tumors in over 50% of male and female F344 rats surviving {ge}1 year on study. Substantial tumor multiplicity was found, but K-ras and p53 gene mutations were virtually absent. In mice, however, a lung burden of approximately 60 {mu}g ({approximately}300 {mu}g Be/g lung) caused only a slight increase in crude lung tumor incidence and multiplicity over controls in strain A/J mice and no elevated incidence in strain C3H mice. Taken together, this research program constitutes a coordinated effort to understand beryllium-induced lung disease in experimental animal models. 47 refs., 1 fig., 3 tabs.

  12. Different particle determinants induce apoptosis and cytokine release in primary alveolar macrophage cultures

    PubMed Central

    Refsnes, Magne; Hetland, Ragna B; Øvrevik, Johan; Sundfør, Idunn; Schwarze, Per E; Låg, Marit

    2006-01-01

    Background Particles are known to induce both cytokine release (MIP-2, TNF-?), a reduction in cell viability and an increased apoptosis in alveolar macrophages. To examine whether these responses are triggered by the same particle determinants, alveolar macrophages were exposed in vitro to mineral particles of different physical-chemical properties. Results The crystalline particles of the different stone types mylonite, gabbro, basalt, feldspar, quartz, hornfels and fine grain syenite porphyr (porphyr), with a relatively equal size distribution (? 10 ?m), but different chemical/mineral composition, all induced low and relatively similar levels of apoptosis. In contrast, mylonite and gabbro induced a marked MIP-2 response compared to the other particles. For particles of smaller size, quartz (? 2 ?m) seemed to induce a somewhat stronger apoptotic response than even smaller quartz (? 0.5 ?m) and larger quartz (? 10 ?m) in relation to surface area, and was more potent than hornfels and porphyr (? 2 ?m). The reduction in cell viability induced by quartz of the different sizes was roughly similar when adjusted to surface area. With respect to cytokines, the release was more marked after exposure to quartz ? 0.5 ?m than to quartz ? 2 ?m and ? 10 ?m. Furthermore, hornfels (? 2 ?m) was more potent than the corresponding hornfels (? 10 ?m) and quartz (? 2 ?m) to induce cytokine responses. Pre-treatment of hornfels and quartz particles ? 2 ?m with aluminium lactate, to diminish the surface reactivity, did significantly reduce the MIP-2 response to hornfels. In contrast, the apoptotic responses to the particles were not affected. Conclusion These results indicate that different determinants of mineral/stone particles are critical for inducing cytokine responses, reduction in cell viability and apoptosis in alveolar macrophages. The data suggest that the particle surface reactivity was critical for cytokine responses, but contributed less to cell death for the types of particles tested. The size-dependent variations, specially in cytokine release, seem not to be explained only by particle surface area. PMID:16774673

  13. Microembolic Renal Disease in Rats Induced with Sephadex

    PubMed Central

    Solez, K.; Richter, G. W.

    1972-01-01

    Sephadex particles (20-80 ? in size) were injected into the abdominal aorta of 134 male Sprague-Dawley rats near the renal arteries. In 31 rats, the right kidney was then removed. The Sephadex particles lodged in glomerular capillaries, afferent glomerular arterioles and interlobular arteries, creating renal infarcts, some of which were grossly visible. Shortly after injection, arterial blood pressure rose significantly in most animals. The hypertension in uninephrectomized rats was not demonstrably different from that in rats with two Kidneys. Severity and duration of hypertension (up to 8 months) were positively correlated with the number of Sephadex particles in renal vessels, and there was also a positive correlation between the degree of hypertension and serum urea nitrogen levels, and between degree of hypertension and degree of cardiac hypertrophy. The vascular permeability in acutely hypertensive rats was abnormal, as judged from penetration of iron-dextran into vessel walls. This experimental model resembles atheromatous microembolic renovascular disease, which may play a significant role in the pathogenesis of unexplained hypertension in patients with advanced aortic atherosclerosis. ImagesFig 12Fig 13Fig 5Fig 6Fig 7Fig 14Fig 8Fig 9Fig 1Fig 10Fig 11Fig 2Fig 3Fig 4 PMID:4257858

  14. High-density lipoprotein particles, coronary heart disease, and niacin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In clinical trials, the use of statins in patients with high risk for cardiovascular disease (CVD) has resulted in a 25% to 40% decrease in major clinical events. However, despite a marked reduction (up to 60%) in LDL-C, approximately 50% (or more) of patients continue to have CVD events. This high ...

  15. Optically induced rotation of Rayleigh particles by vortex beams with different states of polarization

    NASA Astrophysics Data System (ADS)

    Li, Manman; Yan, Shaohui; Yao, Baoli; Liang, Yansheng; Lei, Ming; Yang, Yanlong

    2016-01-01

    Optical vortex beams carry optical orbital angular momentum (OAM) and can induce an orbital motion of trapped particles in optical trapping. We show that the state of polarization (SOP) of vortex beams will affect the details of this optically induced orbital motion to some extent. Numerical results demonstrate that focusing the vortex beams with circular, radial or azimuthal polarizations can induce a uniform orbital motion on a trapped Rayleigh particle, while in the focal field of the vortex beam with linear polarization the particle experiences a non-uniform orbital motion. Among the formers, the vortex beam with circular polarization induces a maximum optical torque on the particle. Furthermore, by varying the topological charge of the vortex beams, the vortex beam with circular polarization gives rise to an optimum torque superior to those given by the other three vortex beams. These facts suggest that the circularly polarized vortex beam is more suitable for rotating particles.

  16. Placental Induced Growth Factor (PIGf) in Coronary Artery Disease

    NASA Technical Reports Server (NTRS)

    Sundaresan, Alamelu; Carabello, Blaise; Mehta, Satish; Schlegel, Todd; Pellis, Neal; Ott, Mark; Pierson, Duane

    2010-01-01

    Our previous studies on normal human lymphocytes have shown a five-fold increase (p less than 0.001) in angiogenic inducers such as Placental Induced Growth Factor (PIGf) in physiologically stressful environments such as modeled microgravity, a space analog. This suggests de-regulation of cardiovascular signalling pathways indicated by upregulation of PIGf. In the current study, we measured PIGf in the plasma of 33 patients with and without coronary artery disease (CAD) to investigate whether such disease is associated with increased levels of PIGf. A control consisting of 31 sex matched apparently healthy subjects was also included in the study. We observed that the levels of PIGf in CAD patients were significantly increased compared to those in healthy control subjects (p less than 0.001) and usually increased beyond the clinical threshold level (greater than 27ng/L). The mechanisms leading to up-regulation of angiogenic factors and the adaptation of organisms to stressful environments such as isolation, high altitude, hypoxia, ischemia, microgravity, increased radiation, etc are presently unknown and require further investigation in spaceflight and these other physiologically stressed environments.

  17. Shear induced alignment and dynamics of elongated granular particles

    E-print Network

    Tamas Borzsonyi; Balazs Szabo; Sandra Wegner; Kirsten Harth; Janos Torok; Ellak Somfai; Tomasz Bien; Ralf Stannarius

    2012-11-13

    The alignment, ordering and rotation of elongated granular particles was studied in shear flow. The time evolution of the orientation of a large number of particles was monitored in laboratory experiments by particle tracking using optical imaging and x-ray computed tomography. The experiments were complemented by discrete element simulations. The particles develop an orientational order. In the steady state the time and ensemble averaged direction of the main axis of the particles encloses a small angle with the streamlines. This shear alignment angle is independent of the applied shear rate, and it decreases with increasing grain aspect ratio. At the grain level the steady state is characterized by a net rotation of the particles, as dictated by the shear flow. The distribution of particle rotational velocities was measured both in the steady state and also during the initial transients. The average rotation speed of particles with their long axis perpendicular to the shear alignment angle is larger, while shear aligned particles rotate slower. The ratio of this fast/slow rotation increases with particle aspect ratio. During the initial transient starting from an unaligned initial condition, particles having an orientation just beyond the shear alignment angle rotate opposite to the direction dictated by the shear flow.

  18. Shear-induced particle migration in binary colloidal suspensions

    NASA Astrophysics Data System (ADS)

    Semwogerere, Denis; Weeks, Eric R.

    2008-04-01

    We present experimental investigations of the spatial and temporal evolution of particle migration in pressure driven flows of Brownian particle suspensions. Binary suspensions of 1.4 and 3.0?m diameter colloidal particles are pumped through a 50×500?m2 rectangular-cross-section capillary tube. Shear rate gradients caused by the resulting parabolic velocity profile drive the particles away from the walls toward the center of the channel, where the shear rate is lowest. The flows are directly imaged using high-speed laser scanning confocal microscopy. Size segregation of the particles is observed. Depending on the conditions, either the large or the small particles enrich the center. We measure the development of the size segregation by tracking the evolution of the cross-stream concentrations of the particles.

  19. In vivo Expression of Inducible Nitric Oxide Synthase in Experimentally Induced Neurologic Diseases

    NASA Astrophysics Data System (ADS)

    Koprowski, Hilary; Zheng, Yong Mu; Heber-Katz, Ellen; Fraser, Nigel; Rorke, Lucy; Fu, Zhen Fang; Hanlon, Cathleen; Dietzschold, Bernhard

    1993-04-01

    The purpose of this study was to investigate the induction of inducible nitric oxide synthase (iNOS) mRNA in the brain tissue of rats and mice under the following experimental conditions: in rats infected with borna disease virus and rabies virus, in mice infected with herpes simplex virus, and in rats after the induction of experimental allergic encephalitis. The results showed that iNOS mRNA, normally nondetectable in the brain, was present in animals after viral infection or after induction of experimental allergic encephalitis. The induction of iNOS mRNA coincided with the severity of clinical signs and in some cases with the presence of inflammatory cells in the brain. The results indicate that nitric oxide produced by cells induced by iNOS may be the toxic factor accounting for cell damage and this may open the door to approaches to the study of the pathogenesis of neurological diseases.

  20. Increased response to visual feedback of drug-induced dyskinetic movements in advanced Parkinson's disease

    E-print Network

    Miall, Chris

    Increased response to visual feedback of drug-induced dyskinetic movements in advanced Parkinson, we have tested six advanced Parkinson's disease (PD) patients with drug-induced dyskinetic movements reserved. Keywords: Visual feedback; Tracking; Drug-induced dyskinesia; Parkinson's disease We have been

  1. Hepatic Differentiation of Murine Disease-Specific Induced Pluripotent Stem Cells Allows Disease Modelling In Vitro

    PubMed Central

    Eggenschwiler, Reto; Loya, Komal; Sgodda, Malte; André, Francoise; Cantz, Tobias

    2011-01-01

    Direct reprogramming of somatic cells into pluripotent cells by retrovirus-mediated expression of OCT4, SOX2, KLF4, and C-MYC is a promising approach to derive disease-specific induced pluripotent stem cells (iPSCs). In this study, we focused on three murine models for metabolic liver disorders: the copper storage disorder Wilson's disease (toxic-milk mice), tyrosinemia type 1 (fumarylacetoacetate-hydrolase deficiency, FAH?/? mice), and alpha1-antitrypsin deficiency (PiZ mice). Colonies of iPSCs emerged 2-3 weeks after transduction of fibroblasts, prepared from each mouse strain, and were maintained as individual iPSC lines. RT-PCR and immunofluorescence analyses demonstrated the expression of endogenous pluripotency markers. Hepatic precursor cells could be derived from these disease-specific iPSCs applying an in vitro differentiation protocol and could be visualized after transduction of a lentiviral albumin-GFP reporter construct. Functional characterization of these cells allowed the recapitulation of the disease phenotype for further studies of underlying molecular mechanisms of the respective disease. PMID:21977043

  2. Shear-induced segregation of particles by material density

    NASA Astrophysics Data System (ADS)

    Fan, Yi; Hill, K. M.

    2015-08-01

    Recently, shear rate gradients and associated gradients in velocity fluctuations (e.g., granular temperatures or kinetic stresses) have been shown to drive segregation of different-sized particles in a manner that reverses at relatively high solids fractions (>0.50 ). Here we investigate these effects in mixtures of particles differing in material density through computational and theoretical studies of particles sheared in a vertical chute where we vary the solids fraction from =0.2 to 0.6. We find that in sparse flows, =0.2 to 0.4, the heavier (denser) particles segregate to lower shear rates similarly to the heavier (larger) particles in mixtures of particles differing only in size. However, there is no segregation reversal at high f in mixtures of particles differing in density. At all solids fractions, heavier (denser) particles segregate to regions of lower shear rates and lower granular temperatures, in contrast with segregation of different-sized particles at high f , where the heavier (larger) particles segregate to the region of higher shear rates. Kinetic theory predicts well the segregation for both types of systems at low f but breaks down at higher f 's. Our recently proposed mixture theory for high f granular mixtures captures the segregation trends well via the independent partitioning of kinetic and contact stresses between the two species. In light of these results, we discuss possible directions forward for a model framework that encompasses segregation effects more broadly in these systems.

  3. Disease-induced resource constraints can trigger explosive epidemics.

    PubMed

    Böttcher, L; Woolley-Meza, O; Araújo, N A M; Herrmann, H J; Helbing, D

    2015-01-01

    Advances in mathematical epidemiology have led to a better understanding of the risks posed by epidemic spreading and informed strategies to contain disease spread. However, a challenge that has been overlooked is that, as a disease becomes more prevalent, it can limit the availability of the capital needed to effectively treat those who have fallen ill. Here we use a simple mathematical model to gain insight into the dynamics of an epidemic when the recovery of sick individuals depends on the availability of healing resources that are generated by the healthy population. We find that epidemics spiral out of control into "explosive" spread if the cost of recovery is above a critical cost. This can occur even when the disease would die out without the resource constraint. The onset of explosive epidemics is very sudden, exhibiting a discontinuous transition under very general assumptions. We find analytical expressions for the critical cost and the size of the explosive jump in infection levels in terms of the parameters that characterize the spreading process. Our model and results apply beyond epidemics to contagion dynamics that self-induce constraints on recovery, thereby amplifying the spreading process. PMID:26568377

  4. Modeling Huntington's disease with induced pluripotent stem cells.

    PubMed

    Kaye, Julia A; Finkbeiner, Steven

    2013-09-01

    Huntington's disease (HD) causes severe motor dysfunction, behavioral abnormalities, cognitive impairment and death. Investigations into its molecular pathology have primarily relied on murine tissues; however, the recent discovery of induced pluripotent stem cells (iPSCs) has opened new possibilities to model neurodegenerative disease using cells derived directly from patients, and therefore may provide a human-cell-based platform for unique insights into the pathogenesis of HD. Here, we will examine the practical implementation of iPSCs to study HD, such as approaches to differentiate embryonic stem cells (ESCs) or iPSCs into medium spiny neurons, the cell type most susceptible in HD. We will explore the HD-related phenotypes identified in iPSCs and ESCs and review how brain development and neurogenesis may actually be altered early, before the onset of HD symptoms, which could inform the search for drugs that delay disease onset. Finally, we will speculate on the exciting possibility that ESCs or iPSCs might be used as therapeutics to restore or replace dying neurons in HD brains. PMID:23459227

  5. Disease-induced resource constraints can trigger explosive epidemics

    NASA Astrophysics Data System (ADS)

    Böttcher, L.; Woolley-Meza, O.; Araújo, N. A. M.; Herrmann, H. J.; Helbing, D.

    2015-11-01

    Advances in mathematical epidemiology have led to a better understanding of the risks posed by epidemic spreading and informed strategies to contain disease spread. However, a challenge that has been overlooked is that, as a disease becomes more prevalent, it can limit the availability of the capital needed to effectively treat those who have fallen ill. Here we use a simple mathematical model to gain insight into the dynamics of an epidemic when the recovery of sick individuals depends on the availability of healing resources that are generated by the healthy population. We find that epidemics spiral out of control into “explosive” spread if the cost of recovery is above a critical cost. This can occur even when the disease would die out without the resource constraint. The onset of explosive epidemics is very sudden, exhibiting a discontinuous transition under very general assumptions. We find analytical expressions for the critical cost and the size of the explosive jump in infection levels in terms of the parameters that characterize the spreading process. Our model and results apply beyond epidemics to contagion dynamics that self-induce constraints on recovery, thereby amplifying the spreading process.

  6. Disease-induced resource constraints can trigger explosive epidemics

    PubMed Central

    Böttcher, L.; Woolley-Meza, O.; Araújo, N. A. M.; Herrmann, H. J.; Helbing, D.

    2015-01-01

    Advances in mathematical epidemiology have led to a better understanding of the risks posed by epidemic spreading and informed strategies to contain disease spread. However, a challenge that has been overlooked is that, as a disease becomes more prevalent, it can limit the availability of the capital needed to effectively treat those who have fallen ill. Here we use a simple mathematical model to gain insight into the dynamics of an epidemic when the recovery of sick individuals depends on the availability of healing resources that are generated by the healthy population. We find that epidemics spiral out of control into “explosive” spread if the cost of recovery is above a critical cost. This can occur even when the disease would die out without the resource constraint. The onset of explosive epidemics is very sudden, exhibiting a discontinuous transition under very general assumptions. We find analytical expressions for the critical cost and the size of the explosive jump in infection levels in terms of the parameters that characterize the spreading process. Our model and results apply beyond epidemics to contagion dynamics that self-induce constraints on recovery, thereby amplifying the spreading process. PMID:26568377

  7. Toxicogenomic analysis of the particle dose- and size-response relationship of silica particles-induced toxicity in mice

    NASA Astrophysics Data System (ADS)

    Lu, Xiaoyan; Jin, Tingting; Jin, Yachao; Wu, Leihong; Hu, Bin; Tian, Yu; Fan, Xiaohui

    2013-01-01

    This study investigated the relationship between particle size and toxicity of silica particles (SP) with diameters of 30, 70, and 300 nm, which is essential to the safe design and application of SP. Data obtained from histopathological examinations suggested that SP of these sizes can all induce acute inflammation in the liver. In vivo imaging showed that intravenously administrated SP are mainly present in the liver, spleen and intestinal tract. Interestingly, in gene expression analysis, the cellular response pathways activated in the liver are predominantly conserved independently of particle dose when the same size SP are administered or are conserved independently of particle size, surface area and particle number when nano- or submicro-sized SP are administered at their toxic doses. Meanwhile, integrated analysis of transcriptomics, previous metabonomics and conventional toxicological results support the view that SP can result in inflammatory and oxidative stress, generate mitochondrial dysfunction, and eventually cause hepatocyte necrosis by neutrophil-mediated liver injury.

  8. Shaking-induced motility in suspensions of soft active particles

    NASA Astrophysics Data System (ADS)

    Bartolo, Denis; Lauga, Eric

    2010-02-01

    We investigate theoretically the collective dynamics of soft active particles living in a viscous fluid. We focus on a minimal model for active but nonmotile particles consisting of N>1 elastic dimers deformed by active stresses and interacting hydrodynamically. We first derive a set of effective equations of motion for the positions of the particles. We then exploit these equations in two experimentally relevant cases: uncorrelated random internal stresses, and uniform monochromatic external shaking. In both cases, we show that small groups of intrinsically nonmotile particles can display nontrivial modes of locomotion resulting from the hydrodynamic correlations between the particle-conformation fluctuations. In addition, we demonstrate that a coherent shaking yields spatial ordering in suspension of soft particles interacting solely through the fluid.

  9. Microscopic observations of shear-induced migration of Brownian particles

    NASA Astrophysics Data System (ADS)

    Weeks, Eric; Anderson, Douglas

    2001-11-01

    We use confocal microscopy to visualize the flow of concentrated suspensions of 2 micron diameter colloidal particles through small rectangular pipes. Confocal microscopy allows us to observe the flow deep within the channel, far from the top and bottom walls, yet encompassing the narrow dimension of the channel (20 particle diameters across). At low flow rates, Brownian motion homogenizes the distribution of particles throughout the cross section of the pipe. At higher flow rates, particles migrate away from the walls of the tubes towards the center of the pipe. We investigate this behavior as a function of particle concentration (volume fractions from 0.05 to 0.4) and flow rate (Peclet number from 0.01 to 100), and compare our observed concentration profiles to theoretical predictions. Additionally, we study the onset of particle migration as the flow rate is increased.

  10. Passing particle toroidal precession induced by electric field in a tokamak

    SciTech Connect

    Andreev, V. V.; Ilgisonis, V. I.; Sorokina, E. A.; NRC “Kurchatov Institute”, Kurchatov Sq. 1, Moscow 123182

    2013-12-15

    Characteristics of a rotation of passing particles in a tokamak with radial electric field are calculated. The expression for time-averaged toroidal velocity of the passing particle induced by the electric field is derived. The electric-field-induced additive to the toroidal velocity of the passing particle appears to be much smaller than the velocity of the electric drift calculated for the poloidal magnetic field typical for the trapped particle. This quantity can even have the different sign depending on the azimuthal position of the particle starting point. The unified approach for the calculation of the bounce period and of the time-averaged toroidal velocity of both trapped and passing particles in the whole volume of plasma column is presented. The results are obtained analytically and are confirmed by 3D numerical calculations of the trajectories of charged particles.

  11. Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease

    PubMed Central

    Castiella, Agustin; Zapata, Eva; Lucena, M Isabel; Andrade, Raúl J

    2014-01-01

    The aetiology of autoimmune hepatitis (AIH) is uncertain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs. AIH usually develops in individuals with a genetic background mainly consisting of some risk alleles of the major histocompatibility complex (HLA). Many drugs have been linked to AIH phenotypes, which sometimes persist after drug discontinuation, suggesting that they awaken latent autoimmunity. At least three clinical scenarios have been proposed that refers to drug- induced autoimmune liver disease (DIAILD): AIH with drug-induced liver injury (DILI); drug induced-AIH (DI-AIH); and immune mediated DILI (IM-DILI). In addition, there are instances showing mixed features of DI-AIH and IM-DILI, as well as DILI cases with positive autoantibodies. Histologically distinguishing DILI from AIH remains a challenge. Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however, a detailed standardised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diagnosis between both entities. Growing information on the relationship of drugs and AIH is being available, being drugs like statins and biologic agents more frequently involved in cases of DIAILD. In addition, there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepatotoxicity. Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of disease PMID:24799984

  12. Gross Cystic Disease Fluid Protein-15/Prolactin-Inducible Protein as a Biomarker for Keratoconus Disease

    PubMed Central

    Priyadarsini, Shrestha; Hjortdal, Jesper; Sarker-Nag, Akhee; Sejersen, Henrik; Asara, John M.; Karamichos, Dimitrios

    2014-01-01

    Keratoconus (KC) is a bilateral degenerative disease of the cornea characterized by corneal bulging, stromal thinning, and scarring. The etiology of the disease is unknown. In this study, we identified a new biomarker for KC that is present in vivo and in vitro. In vivo, tear samples were collected from age-matched controls with no eye disease (n?=?36) and KC diagnosed subjects (n?=?17). Samples were processed for proteomics using LC-MS/MS. In vitro, cells were isolated from controls (Human Corneal Fibroblasts-HCF) and KC subjects (Human Keratoconus Cells-HKC) and stimulated with a Vitamin C (VitC) derivative for 4 weeks, and with one of the three transforming growth factor-beta (TGF-?) isoforms. Samples were analyzed using real-time PCR and Western Blots. By using proteomics analysis, the Gross cystic disease fluid protein-15 (GCDFP-15) or prolactin-inducible protein (PIP) was found to be the best independent biomarker able to discriminate between KC and controls. The intensity of GCDFP-15/PIP was significantly higher in healthy subjects compared to KC-diagnosed. Similar findings were seen in vitro, using a 3D culture model. All three TGF-? isoforms significantly down-regulated the expression of GCDFP-15/PIP. Zinc-alpha-2-glycoprotein (AZGP1), a protein that binds to PIP, was identified by proteomics and cell culture to be highly regulated. In this study by different complementary techniques we confirmed the potential role of GCDFP-15/PIP as a novel biomarker for KC disease. It is likely that exploring the GCDFP-15/PIP-AZGP1 interactions will help better understand the mechanism of KC disease. PMID:25405607

  13. DIESEL EXHAUST PARTICLES INDUCE ABERRANT ALVEOLAR EPITHELIAL DIRECTED CELL MOVEMENT BY DISRUPTION OF POLARITY MECHANISMS

    EPA Science Inventory

    Disruption of the respiratory epithelium contributes to the progression of a variety of respiratory diseases that are aggravated by exposure to air pollutants, specifically traffic-based pollutants such as diesel exhaust particles (DEP). Recognizing that lung repair following inj...

  14. Radiation induced heart disease: Pathogenesis, management and review literature.

    PubMed

    Madan, R; Benson, R; Sharma, D N; Julka, P K; Rath, G K

    2015-12-01

    Radiation therapy (RT) is a very important part of multimodality cancer therapy. Addition of RT improves survival in many cancers, but there are some accompaniments of radiation. One of them is radiation induced heart disease (RIHD). RT for mediastinal lymphoma, breast, lung and oesophageal cancer is associated with the development of RIHD. The problem can be intensified with the addition of chemotherapy. Therapeutic modalities for RIHD are the same as in the non-irradiated population. However, surgery may be difficult in the irradiated patients. The long latent period is the reason why RIHD is not extensively studied. Survival of cancer patients has improved over past few decades, so RIHD is a growing concern especially in younger patients. In this review article, we have discussed the pathogenesis, clinical manifestation and management of RIHD along with impact of chemotherapeutic agents. PMID:26296945

  15. Crystallization of Brownian Particles from Walls Induced by a Uniform External Force

    NASA Astrophysics Data System (ADS)

    Sato, Masahide; Katsuno, Hiroyasu; Suzuki, Yoshihisa

    2013-08-01

    Keeping the formation of colloidal crystal under a centrifugal force in mind, we study the ordering of Brownian particles induced by a uniform external force. When the uniform external force is added, the particles move in the direction of the external force and the density of particles near walls becomes high. The ordering of particles starts on the walls, and successive ordering in bulk occurs near the walls. In bulk, both domains of the face-centered cubic structure and hexagonal close-packed structure appear. By controlling the direction and the strength of the external force, the number of ordered particles and distribution of cluster size are changed.

  16. Modeling three-dimensional constituent particle microstructure and particle-induced pitting corrosion in rolled aluminum alloys

    NASA Astrophysics Data System (ADS)

    Cullin, Matthew Joseph

    In the last two decades there has been a surge in research surrounding the corrosion and fatigue properties of high strength aluminum alloys aimed at extending the service life of commercial and military aircraft. It is recognized that corrosion damage in aluminum alloys is the direct result of local galvanic coupling between constituent particles and the metal matrix. As the corrosion pit associated with an individual particle grows it often coalesces with adjacent pits and can expose subsurface constituent particles, perpetuating the evolution of corrosion damage. As a result, heavily clustered groups of constituent particles tend to foster the most severe corrosion pits, and the morphology of these multi-particle pits has been found to exhibit a strong correlation with that of the instigating particle cluster. Severe pits are particularly detrimental to the fatigue life of aluminum components, nucleating fatigue cracks and circumventing the low growth rates of the short crack regime. The goal of this work is to provide a tool for predicting the evolution of particle-induced corrosion damage in rolled aluminum alloys by way of numerical simulation techniques. A three-dimensional constituent particle microstructure model is proposed. This model is used to generate statistically representative three-dimensional constituent particle microstructure from two-dimensional, orthogonal sections. The temporal evolution of severe corrosion damage for a particular constituent particle microstructure can then be simulated via a particle-based corrosion model. This corrosion simulation algorithm makes it possible to perform material-specific, numerical corrosion analyses and represents a significant advancement in the quest to develop reliable and cost efficient life-cycle prediction methods for aging airframes.

  17. Inhibition of RANKL-induced osteoclastogenesis through the suppression of the ERK signaling pathway by astragaloside IV and attenuation of titanium-particle-induced osteolysis.

    PubMed

    Li, Mingjun; Wang, Wengang; Geng, Li; Qin, Yanru; Dong, Wenjie; Zhang, Xudong; Qin, An; Zhang, Mingzhi

    2015-11-01

    Astragaloside IV (AS-IV) is a natural plant extract that enhances osteoblast activity, and therefore, has the potential to treat osteoclast?related diseases. Such diseases include osteoporosis, periodontal disease, rheumatoid arthritis and aseptic prosthesis loosening. However, data associating the effects of AS?IV on osteoclasts are limited. The aim of the present study was to assess the effect of AS?IV on osteoclasts in vitro and in vivo. The in vitro studies demonstrated that AS?IV exerts potent inhibitory effects on the ligand of the receptor activator of nuclear factor??B?induced osteoclastogenesis and revealed the mechanism of action of AS?IV, which inhibited osteoclastogenesis by suppression of the extracellular signal?regulated kinase signaling pathway. The in vivo studies proved that AS?IV attenuated titanium particle?induced osteolysis in a mouse calvarial model. Collectively, the findings of the study suggest that AS?IV is a potential natural agent for the treatment of osteoclast-related diseases. PMID:26324422

  18. The prevention of titanium-particle-induced osteolysis by OA-14 through the suppression of the p38 signaling pathway and inhibition of osteoclastogenesis.

    PubMed

    Tian, Bo; Jiang, Tao; Shao, Zhanying; Zhai, Zanjing; Li, Haowei; Fan, Qiming; Liu, Xuqiang; Ouyang, Zhengxiao; Tang, Tingting; Jiang, Qing; Zheng, Minghao; Dai, Kerong; Qin, An; Yu, Yongping; Zhu, Zhenan

    2014-10-01

    Wear-particle-induced osteolysis leads to prosthesis loosening, which is one of the most common causes of joint-implant failure, a problem that must be fixed using revision surgery. Thus, a potential treatment for prosthetic loosening is focused on inhibiting osteoclastic bone resorption, which prevents wear-particle-induced osteolysis. In this study, we synthesized a compound named OA-14 (N-(3- (dodecylcarbamoyl)phenyl)-1H-indole-2-carboxamide) and examined how OA-14 affects titanium (Ti)-particle-induced osteolysis and osteoclastogenesis. We report that OA-14 treatment protected against Ti-particle-induced osteolysis in a mouse calvarial model. Interestingly, the number of tartrate-resistant acid phosphatase-positive osteoclasts decreased after treatment with OA-14 in vivo, which suggested that OA-14 inhibits osteoclast formation. To test this hypothesis, we conducted in vitro studies, and our results revealed that OA-14 markedly diminished osteoclast differentiation and osteoclast-specific gene expression in a dose- and time-dependent manner. Moreover, OA-14 suppressed osteoclastic bone resorption and F-actin ring formation. Furthermore, we determined that OA-14 inhibited osteoclastogenesis by specifically blocking the p38-Mitf-c-fos-NFATc1 signaling cascade induced by RANKL (ligand of receptor activator of nuclear factor ?B). Collectively, our results suggest that the compound OA-14 can be safely used for treating particle-induced peri-implant osteolysis and other diseases caused by excessive osteoclast formation and function. PMID:25086794

  19. Interstitial lung disease induced by alectinib (CH5424802/RO5424802).

    PubMed

    Ikeda, Satoshi; Yoshioka, Hiroshige; Arita, Machiko; Sakai, Takahiro; Sone, Naoyuki; Nishiyama, Akihiro; Niwa, Takashi; Hotta, Machiko; Tanaka, Tomohiro; Ishida, Tadashi

    2015-02-01

    A 75-year-old woman with anaplastic lymphoma kinase (ALK)-rearranged Stage IV lung adenocarcinoma was administered the selective anaplastic lymphoma kinase inhibitor, alectinib, as a third-line treatment in a Phase 1-2 study. On the 102nd day, chest computed tomography showed diffuse ground glass opacities. Laboratory data revealed high serum levels of KL-6, SP-D and lactate dehydrogenase without any clinical symptoms. There was no evidence of infection. Marked lymphocytosis was seen in bronchoalveolar lavage fluid analysis, and transbronchial lung biopsy showed mild thickening of alveolar septa and lymphocyte infiltration. Interstitial lung disease was judged to be related to alectinib based on improvements in imaging findings and serum biomarkers after discontinuation of alectinib. To our knowledge, this is the first reported case of alectinib-induced interstitial lung disease. Alectinib is a promising drug for ALK-rearranged non-small cell lung cancer. Clinical trials of this selective anaplastic lymphoma kinase inhibitor will facilitate the meticulous elucidation of its long-term safety profile. PMID:25398579

  20. Numerical Simulation of Intercalation-Induced Stress in Li-Ion Battery Electrode Particles

    E-print Network

    Sastry, Ann Marie

    , to fully three-dimensional 3D simulations of ellipsoidal particles, to systematically studyNumerical Simulation of Intercalation-Induced Stress in Li-Ion Battery Electrode Particles and manufacturing methods for these cells. Both global and localized loads must be estimated, in order to select

  1. Aging induced changes on NEXAFS fingerprints in individual combustion particles

    NASA Astrophysics Data System (ADS)

    Zelenay, V.; Mooser, R.; Tritscher, T.; K?epelová, A.; Heringa, M. F.; Chirico, R.; Prévôt, A. S. H.; Weingartner, E.; Baltensperger, U.; Dommen, J.; Watts, B.; Raabe, J.; Huthwelker, T.; Ammann, M.

    2011-11-01

    Soot particles can significantly influence the Earth's climate by absorbing and scattering solar radiation as well as by acting as cloud condensation nuclei. However, despite their environmental (as well as economic and political) importance, the way these properties are affected by atmospheric processing of the combustion exhaust gases is still a subject of discussion. In this work, individual soot particles emitted from two different vehicles, a EURO 2 transporter, a EURO 3 passenger car, and a wood stove were investigated on a single-particle basis. The emitted exhaust, including the particulate and the gas phase, was processed in a smog chamber with artificial solar radiation. Single particle specimens of both unprocessed and aged soot were characterized using near edge X-ray absorption fine structure spectroscopy (NEXAFS) and scanning electron microscopy. Comparison of NEXAFS spectra from the unprocessed particles and those resulting from exhaust photooxidation in the chamber revealed changes in the carbon functional group content. For the wood stove emissions, these changes were minor, related to the relatively mild oxidation conditions. For the EURO 2 transporter emissions, the most apparent change was that of carboxylic carbon from oxidized organic compounds condensing on the primary soot particles. For the EURO 3 car emissions oxidation of primary soot particles upon photochemical aging has likely contributed as well. Overall, the changes in the NEXAFS fingerprints were in qualitative agreement with data from an aerosol mass spectrometer. Furthermore, by taking full advantage of our in situ microreactor concept, we show that the soot particles from all three combustion sources changed their ability to take up water under humid conditions upon photochemical aging of the exhaust. Due to the selectivity and sensitivity of the NEXAFS technique for the water mass, also small amounts of water taken up into the internal voids of agglomerated particles could be detected. Because such small amounts of water uptake do not lead to measurable changes in particle diameter, it may remain beyond the limits of volume growth measurements, especially for larger agglomerated particles.

  2. Mechanism of bubble coalescence induced by surfactant covered antifoam particles.

    PubMed

    Joshi, K S; Baumann, A; Jeelani, S A K; Blickenstorfer, C; Naegeli, I; Windhab, E J

    2009-11-15

    Mechanism of inter-bubble coalescence by an aqueous fatty alcohol particle suspension antifoam containing a nonionic surfactant has been investigated. By observing visually two colliding air bubbles in a liquid pool in the presence of the antifoam, a four-step mechanism is identified. The role of the surfactant in the antifoam is, for the first time, proposed. A surface tension gradient due to the local surfactant concentration difference enables a surfactant laden hydrophobic particle located on bubble surface to move from the periphery of a liquid film between two colliding air bubbles to their region of contact. Drop volume tensiometry and macroscopic foam column experiments are used to further prove this observation. Subsequently, the particle bridges and dewets the bubbles resulting in film rupture. The rate of drainage of the liquid film depends on the particle hydrophobicity, which necessitates complete surfactant desorption from particle surface. This is corroborated experimentally by Wilhelmy plate tensiometry. In addition, cryo-scanning electron and atomic force microscopy are used to determine the particle shape and the force for its entry into the bubble. PMID:19726048

  3. Additives Induced Structural Transformation of ABC Triblock Copolymer Particles.

    PubMed

    Xu, Jiangping; Yang, Yi; Wang, Ke; Li, Jingyi; Zhou, Huamin; Xie, Xiaolin; Zhu, Jintao

    2015-10-13

    Here we report the structural control of polystyrene-b-polyisoprene-b-poly(2-vinylpyridine) (PS-b-PI-b-P2VP) asymmetric ABC triblock copolymer particles under 3D confinement by tuning the interactions among blocks. The additives, including 3-n-pentadecylphenol, homopolystyrene, and solvents, which can modulate the interactions among polymer blocks, play significant roles in the particle morphology. Moreover, the structured particles can be disassembled into isolated micellar aggregates with novel morphologies or mesoporous particles with tunable pore shape. Interestingly, the formed pupa-like PS-b-PI-b-P2VP particles display interesting dynamic stretch-retraction behavior when the solvent property is changed after partial cross-linking of the P2VP block. We further prove that such dynamic behavior is closely related to the density of cross-linking. The strategies presented here are believed to be promising routes to rationally design and fabricate block copolymer particles with desirable shape and internal structure. PMID:26388457

  4. Turbulence-induced Relative Velocity of Dust Particles. I. Identical Particles

    NASA Astrophysics Data System (ADS)

    Pan, Liubin; Padoan, Paolo

    2013-10-01

    We study the relative velocity of inertial particles suspended in turbulent flows and discuss implications for dust particle collisions in protoplanetary disks. We simulate a weakly compressible turbulent flow, evolving 14 particle species with friction timescale, ?p, covering the entire range of scales in the flow. The particle Stokes numbers, St, measuring the ratio of ?p to the Kolmogorov timescale, are in the range 0.1 <~ St <~ 800. Using simulation results, we show that the model by Pan & Padoan gives satisfactory predictions for the rms relative velocity between identical particles. The probability distribution function (PDF) of the relative velocity is found to be highly non-Gaussian. The PDF tails are well described by a 4/3 stretched exponential function for particles with ?p ~= 1-2 T L, where T L is the Lagrangian correlation timescale, consistent with a prediction based on PP10. The PDF approaches Gaussian only for very large particles with ?p >~ 54 T L. We split particle pairs at given distances into two types with low and high relative speeds, referred to as continuous and caustic types, respectively, and compute their contributions to the collision kernel. Although amplified by the effect of clustering, the continuous contribution vanishes in the limit of infinitesimal particle distance, where the caustic contribution dominates. The caustic kernel per unit cross section rises rapidly as St increases toward ~= 1, reaches a maximum at ?p ~= 2 T L, and decreases as \\tau _p^{-1/2} for ?p Gt T L.

  5. The use of Nanotrap particles for biodefense and emerging infectious disease diagnostics.

    PubMed

    Shafagati, Nazly; Patanarut, Alexis; Luchini, Alessandra; Lundberg, Lindsay; Bailey, Charles; Petricoin, Emanuel; Liotta, Lance; Narayanan, Aarthi; Lepene, Benjamin; Kehn-Hall, Kylene

    2014-07-01

    Detection of early infectious disease may be challenging due to the low copy number of organisms present. To overcome this limitation and rapidly measure low concentrations of the pathogen, we developed a novel technology: Nanotrap particles, which are designed to capture, concentrate, and protect biomarkers from complex biofluids. Nanotrap particles are thermoresponsive hydrogels that are capable of antigen capture through the coupling of affinity baits to the particles. Here, we describe recent findings demonstrating that Nanotrap particles are able to capture live infectious virus, viral RNA, and viral proteins. Capture is possible even in complex mixtures such as serum and allows the concentration and protection of these analytes, providing increased performance of downstream assays. The Nanotrap particles are a versatile sample preparation technology that has far reaching implications for biomarker discovery and diagnostic assays. PMID:24449537

  6. Shear-induced particle migration in one-, two-, and three-dimensional flows.

    PubMed

    Gao, C; Gilchrist, J F

    2008-02-01

    We investigate the segregation resulting from the competition between advection and shear-induced migration of suspensions in steady open flows. Herringbone channels form a concentration profile deviating from the particle focusing found in straight channels. Transients can result from a buckling instability during the onset of migration when particle-depleted fluid is injected into particle-rich fluid. In chaotic flows, the better mixing found at low bulk volume fraction is not seen at higher bulk volume fraction. Thus, the ability of static mixers to reduce the effects of shear-induced migration is significantly limited. PMID:18352080

  7. Role of direct estrogen receptor signaling in wear particle-induced osteolysis

    PubMed Central

    Nich, Christophe; Rao, Allison J.; Valladares, Roberto D.; Li, Chenguang; Christman, Jane E.; Antonios, Joseph K.; Yao, Zhenyu; Zwingenberger, Stefan; Petite, Hervé; Hamadouche, Moussa; Goodman, Stuart B.

    2014-01-01

    Estrogen withdrawal following surgical ovariectomy was recently shown to mitigate particle-induced osteolysis in the murine calvarial model. Currently, we hypothesize that estrogen receptors (ERs) were involved in this paradoxical phenomenon. To test this hypothesis, we first evaluated polyethylene (PE) particle-induced osteolysis in the murine calvarial model, using wild type (WT) C57BL6J female mice, ER? deficient (ER?KO) mice, and WT mice either treated with 17?-estradiol (E2) or with the ER pan-antagonist ICI 182,780. According to micro-CT and histomorphometry, we showed that bone resorption was consistently altered in both ER?KO and ICI 182,780 treated mice as compared to WT and E2 groups. Then, we demonstrated that ER disruption consistently decreased both PE and polymethylmethacrylate (PMMA) particle-induced production of TNF-? by murine macrophages in vitro. Similar results were obtained following ER blockade using ICI 182,780 in RAW 264.7 and WT macrophages. ER disruption and pre treatment with ICI 182,780 resulted in a consistent down-regulation of particle-induced TNF-? mRNA expression relative to WT macrophages or untreated RAW cells. These results indicate that the response to wear particles involves estrogen receptors in female mice, as part of macrophage activation. Estrogen receptors may be considered as a future therapeutic target for particle-induced osteolysis. PMID:23113918

  8. Adjuvant effects of chitosan and calcium phosphate particles in an inactivated Newcastle disease vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The adjuvant activity of chitosan and calcium phosphate-particles (CAP) was studied following intranasal coadministration of commercial chickens with inactivated Newcastle disease virus (NDV) vaccine. After three vaccinations with inactivated NDV in combination with chitosan or CAP an increase in an...

  9. FACTORS THAT INFLUENCE THE RELATIVE POTENCY OF DIESEL EXHAUST PARTICLES AS ADJUVANTS IN ALLERGIC AIRWAY DISEASE

    EPA Science Inventory

    Description: Studies have shown that diesel exhaust particles (DEP) worsen respiratory diseases including allergic asthma. The adjuvant effects of DEP in the airways have been widely reported; however, the precise determinants and mechanisms of these effects are ill-defined. S...

  10. Disease and the Extended Phenotype: Parasites Control Host Performance and Survival through Induced

    E-print Network

    Johnson, Pieter

    Disease and the Extended Phenotype: Parasites Control Host Performance and Survival through Induced fitness. Citation: Goodman BA, Johnson PTJ (2011) Disease and the Extended Phenotype: Parasites Control, parasites harm their hosts. However, some forms of parasite-induced alterations increase parasite

  11. Apoptotic and inflammatory effects induced by different particles in human alveolar macrophages.

    PubMed

    Huang, Yuh-Chin T; Li, Zhuowei; Harder, Shirley D; Soukup, Joleen M

    2004-12-15

    Pollutant particles induce apoptosis and inflammation, but the relationship between these two biological processes is not entirely clear. In this study, we compared the proapoptotic and proinflammatory effects of four particles: residual oil fly ash (ROFA), St. Louis particles SRM 1648 (SL), Chapel Hill PM10 (CHP), and Mount St. Helens dust (MSH). Human alveolar macrophages (AM) were incubated with these particles at 100 microg/ml. Cell death was assessed by annexin V (AV) expression, histone release, nuclear morphology, caspase 3-like activity and release of caspase 1 for apoptosis, and propidium iodide (PI) for necrosis, and inflammation was measured by interleukin (IL)-1beta and IL-6. We found that particle effects on these cell death measurements varied, and ROFA affected most (four out of five) endpoints, including nuclear morphological changes. CHP and SL also caused necrosis. For cytokine release, the potency was CHP > SL > ROFA > MSH. The proapoptotic and proinflammatory effects induced by the whole particles were unaltered after the particles were washed with water. The water-soluble fraction was relatively inactive, as were individual soluble metals (V, Ni, Fe). ROFA-induced nuclear fragmentation was associated with upregulation and mitochondrial release of apoptosis-inducing factor (AIF), a caspase-independent chromatin condensation factor, and upregulation of DNase II, a lysosomal acid endonuclease. These results indicate that the potential for particles to induce apoptosis does not correlate with their proinflammatory properties, although active components for both processes reside in the water-insoluble core. Both apoptosis and inflammatory endpoints should be included when the toxicity of different pollutant particles is assessed. PMID:15764474

  12. TURBULENCE-INDUCED RELATIVE VELOCITY OF DUST PARTICLES. I. IDENTICAL PARTICLES

    SciTech Connect

    Pan, Liubin; Padoan, Paolo E-mail: ppadoan@icc.ub.edu

    2013-10-10

    We study the relative velocity of inertial particles suspended in turbulent flows and discuss implications for dust particle collisions in protoplanetary disks. We simulate a weakly compressible turbulent flow, evolving 14 particle species with friction timescale, ?{sub p}, covering the entire range of scales in the flow. The particle Stokes numbers, St, measuring the ratio of ?{sub p} to the Kolmogorov timescale, are in the range 0.1 ?< St ?< 800. Using simulation results, we show that the model by Pan and Padoan gives satisfactory predictions for the rms relative velocity between identical particles. The probability distribution function (PDF) of the relative velocity is found to be highly non-Gaussian. The PDF tails are well described by a 4/3 stretched exponential function for particles with ?{sub p} ? 1-2 T{sub L}, where T{sub L} is the Lagrangian correlation timescale, consistent with a prediction based on PP10. The PDF approaches Gaussian only for very large particles with ?{sub p} ?> 54 T{sub L}. We split particle pairs at given distances into two types with low and high relative speeds, referred to as continuous and caustic types, respectively, and compute their contributions to the collision kernel. Although amplified by the effect of clustering, the continuous contribution vanishes in the limit of infinitesimal particle distance, where the caustic contribution dominates. The caustic kernel per unit cross section rises rapidly as St increases toward ? 1, reaches a maximum at ?{sub p} ? 2 T{sub L}, and decreases as ?{sub p}{sup -1/2} for ?{sub p} >> T{sub L}.

  13. The preferential targeting of the diseased microvasculature by disk-like particles.

    PubMed

    Adriani, Giulia; de Tullio, Marco Donato; Ferrari, Mauro; Hussain, Fazle; Pascazio, Giuseppe; Liu, Xuewu; Decuzzi, Paolo

    2012-08-01

    Different classes of nanoparticles (NPs) have been developed for controlling and improving the systemic administration of therapeutic and contrast agents. Particle shape has been shown to be crucial in the vascular transport and adhesion of NPs. Here, we use mesoporous silicon non-spherical particles, of disk and rod shapes, ranging in size from 200nm to 1800nm. The fabrication process of the mesoporous particles is described in detail, and their transport and adhesion properties under flow are studied using a parallel plate flow chamber. Numerical simulations predict the hydrodynamic forces on the particles and help in interpreting their distinctive behaviors. Under microvascular flow conditions, for disk-like shape, 1000×400nm particles show maximum adhesion, whereas smaller (600×200nm) and larger (1800×600nm) particles adhere less by a factor of about two. Larger rods (1800×400nm) are observed to adhere at least 3 times more than smaller ones (1500×200nm). For particles of equal volumes, disks adhere about 2 times more than rods. Maximum adhesion for intermediate sized disks reflects the balance between adhesive interfacial interactions and hydrodynamic dislodging forces. In view of the growing evidence on vascular molecular heterogeneity, the present data suggests that thin disk-like particles could more effectively target the diseased microvasculature as compared to spheres and slender rods. PMID:22579236

  14. Toxicity of aged gasoline exhaust particles to normal and diseased airway epithelia

    PubMed Central

    Künzi, Lisa; Krapf, Manuel; Daher, Nancy; Dommen, Josef; Jeannet, Natalie; Schneider, Sarah; Platt, Stephen; Slowik, Jay G.; Baumlin, Nathalie; Salathe, Matthias; Prévôt, André S. H.; Kalberer, Markus; Strähl, Christof; Dümbgen, Lutz; Sioutas, Constantinos; Baltensperger, Urs; Geiser, Marianne

    2015-01-01

    Particulate matter (PM) pollution is a leading cause of premature death, particularly in those with pre-existing lung disease. A causative link between particle properties and adverse health effects remains unestablished mainly due to complex and variable physico-chemical PM parameters. Controlled laboratory experiments are required. Generating atmospherically realistic aerosols and performing cell-exposure studies at relevant particle-doses are challenging. Here we examine gasoline-exhaust particle toxicity from a Euro-5 passenger car in a uniquely realistic exposure scenario, combining a smog chamber simulating atmospheric ageing, an aerosol enrichment system varying particle number concentration independent of particle chemistry, and an aerosol deposition chamber physiologically delivering particles on air-liquid interface (ALI) cultures reproducing normal and susceptible health status. Gasoline-exhaust is an important PM source with largely unknown health effects. We investigated acute responses of fully-differentiated normal, distressed (antibiotics-treated) normal, and cystic fibrosis human bronchial epithelia (HBE), and a proliferating, single-cell type bronchial epithelial cell-line (BEAS-2B). We show that a single, short-term exposure to realistic doses of atmospherically-aged gasoline-exhaust particles impairs epithelial key-defence mechanisms, rendering it more vulnerable to subsequent hazards. We establish dose-response curves at realistic particle-concentration levels. Significant differences between cell models suggest the use of fully-differentiated HBE is most appropriate in future toxicity studies. PMID:26119831

  15. Toxicity of aged gasoline exhaust particles to normal and diseased airway epithelia

    NASA Astrophysics Data System (ADS)

    Künzi, Lisa; Krapf, Manuel; Daher, Nancy; Dommen, Josef; Jeannet, Natalie; Schneider, Sarah; Platt, Stephen; Slowik, Jay G.; Baumlin, Nathalie; Salathe, Matthias; Prévôt, André S. H.; Kalberer, Markus; Strähl, Christof; Dümbgen, Lutz; Sioutas, Constantinos; Baltensperger, Urs; Geiser, Marianne

    2015-06-01

    Particulate matter (PM) pollution is a leading cause of premature death, particularly in those with pre-existing lung disease. A causative link between particle properties and adverse health effects remains unestablished mainly due to complex and variable physico-chemical PM parameters. Controlled laboratory experiments are required. Generating atmospherically realistic aerosols and performing cell-exposure studies at relevant particle-doses are challenging. Here we examine gasoline-exhaust particle toxicity from a Euro-5 passenger car in a uniquely realistic exposure scenario, combining a smog chamber simulating atmospheric ageing, an aerosol enrichment system varying particle number concentration independent of particle chemistry, and an aerosol deposition chamber physiologically delivering particles on air-liquid interface (ALI) cultures reproducing normal and susceptible health status. Gasoline-exhaust is an important PM source with largely unknown health effects. We investigated acute responses of fully-differentiated normal, distressed (antibiotics-treated) normal, and cystic fibrosis human bronchial epithelia (HBE), and a proliferating, single-cell type bronchial epithelial cell-line (BEAS-2B). We show that a single, short-term exposure to realistic doses of atmospherically-aged gasoline-exhaust particles impairs epithelial key-defence mechanisms, rendering it more vulnerable to subsequent hazards. We establish dose-response curves at realistic particle-concentration levels. Significant differences between cell models suggest the use of fully-differentiated HBE is most appropriate in future toxicity studies.

  16. Toxicity of aged gasoline exhaust particles to normal and diseased airway epithelia.

    PubMed

    Künzi, Lisa; Krapf, Manuel; Daher, Nancy; Dommen, Josef; Jeannet, Natalie; Schneider, Sarah; Platt, Stephen; Slowik, Jay G; Baumlin, Nathalie; Salathe, Matthias; Prévôt, André S H; Kalberer, Markus; Strähl, Christof; Dümbgen, Lutz; Sioutas, Constantinos; Baltensperger, Urs; Geiser, Marianne

    2015-01-01

    Particulate matter (PM) pollution is a leading cause of premature death, particularly in those with pre-existing lung disease. A causative link between particle properties and adverse health effects remains unestablished mainly due to complex and variable physico-chemical PM parameters. Controlled laboratory experiments are required. Generating atmospherically realistic aerosols and performing cell-exposure studies at relevant particle-doses are challenging. Here we examine gasoline-exhaust particle toxicity from a Euro-5 passenger car in a uniquely realistic exposure scenario, combining a smog chamber simulating atmospheric ageing, an aerosol enrichment system varying particle number concentration independent of particle chemistry, and an aerosol deposition chamber physiologically delivering particles on air-liquid interface (ALI) cultures reproducing normal and susceptible health status. Gasoline-exhaust is an important PM source with largely unknown health effects. We investigated acute responses of fully-differentiated normal, distressed (antibiotics-treated) normal, and cystic fibrosis human bronchial epithelia (HBE), and a proliferating, single-cell type bronchial epithelial cell-line (BEAS-2B). We show that a single, short-term exposure to realistic doses of atmospherically-aged gasoline-exhaust particles impairs epithelial key-defence mechanisms, rendering it more vulnerable to subsequent hazards. We establish dose-response curves at realistic particle-concentration levels. Significant differences between cell models suggest the use of fully-differentiated HBE is most appropriate in future toxicity studies. PMID:26119831

  17. Experimental background due to particle induced gas desorption in RHIC

    SciTech Connect

    Zhang,S.Y.; Trbojevic, D.

    2008-08-10

    Beam-gas collision created experimental background, i.e., singles, has affected heavy ion and polarized proton operations in Relativistic Heavy Ion Collider at Brookhaven National Laboratory. The gas molecules in interaction region are mainly caused by the electron induced gas desorption. and the electrons are produced from the beam induced electron multipacting, or called electron cloud. The background has a dependence on the usual electron cloud related parameters, such as the bunch intensity, bunch spacing, and the solenoid field. With the RHIC upgrade plan, the experimental background may become a luminosity limiting factor. Mitigations are discussed.

  18. Alpha-particle-induced bystander effects between zebrafish embryos in vivo E.H.W. Yum a

    E-print Network

    Yu, Peter K.N.

    Alpha-particle-induced bystander effects between zebrafish embryos in vivo E.H.W. Yum a , V Keywords: Bystander effect Alpha particles Zebrafish embryos PADC a b s t r a c t Dechorionaed embryos-particle-induced bystander effects between zebrafish embryos in vivo, and a general positive correlation between the cell

  19. Marek's disease virus induced transient paralysis--a closer look

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s Disease (MD) is a lymphoproliferative disease of domestic chickens caused by a highly cell-associated alpha herpesvirus, Marek’s disease virus (MDV). Clinical signs of MD include depression, crippling, weight loss, and transient paralysis (TP). TP is a disease of the central nervous system...

  20. Pollutant particles induce arginase II in human bronchial epithelial cells

    EPA Science Inventory

    Exposure to particulate matter (PM) is associated with adverse pulmonary effects, including induction and exacerbation of asthma. Recently arginase was shown to play an important role in the pathogenesis of asthma. In this study, we hypothesized that PM exposure would induce ar...

  1. Energetic particle-induced enhancements of stratospheric nitric acid

    NASA Technical Reports Server (NTRS)

    Aikin, Arthur C.

    1994-01-01

    Inclusion of complete ion chemistry in the calculation of minor species production during energetic particle deposition events leads to significant enhancement in the calculated nitric acid concentration during precipitation. An ionization rate of 1.2 x 10(exp 3)/cu cm/s imposed for 1 day increases HNO3 from 3 x 10(exp 5) to 6 x 10(exp 7)/cu cm at 50 km. With an ionization rate of 600 cu cm/s, the maximum HNO3 is 3 x 10(exp 7)/cu cm. Calculations which neglect negative ions predict the nitric acid will fall during precipitation events. The decay time for converting HNO3 into odd nitrogen and hydrogen is more than 1 day for equinoctial periods at 70 deg latitude. Examination of nitric acid data should yield important information on the magnitude and frequency of charged particle events.

  2. Marek's Disease Virus-Induced Immunosuppression: Array Analysis of Chicken Immune Response Gene Expression Profiling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of chickens induced by a highly cell-associated oncogenic alpha-herpesvirus, Marek’s disease virus (MDV). MDV replicates in chicken lymphocytes and establishes a latency infection within CD4+ T cells. Host-virus interaction, immune responses to...

  3. An Inducible Mouse Model of Late Onset TaySachs Disease

    E-print Network

    An Inducible Mouse Model of Late Onset Tay­Sachs Disease Mylvaganam Jeyakumar, David Smith, Elena gangliosidoses, Tay­Sachs and Sandhoff disease, are null for the hex- osaminidase and subunits respectively the blocked catabolic pathway and escape disease. We have investigated whether a subset of Tay­Sachs mice

  4. DISEASE-SPECIFIC SUSCEPTIBILITY TO ACUTE OZONE-INDUCED INJURY AND INFLAMMATION IN EIGHT RAT STRAINS

    EPA Science Inventory

    Susceptibility to environmental pollutant-induced injuries may be influenced by presence of disease and genetic make-up. To identify disease-specific susceptibility phenotype, we used eight rat strains with or without genetic cardiovascular disease. Male 12-15 wk old Sprague Dawl...

  5. Vasoactive alteration and inflammation induced by polycyclic aromatic hydrocarbons and trace metals of vehicle exhaust particles.

    PubMed

    Chuang, Hsiao-Chi; Fan, Ching-Wen; Chen, Kuan-Yu; Chang-Chien, Guo-Ping; Chan, Chang-Chuan

    2012-10-17

    Exposure to particulate matter (PM) increases the incidence of cardiovascular disease, but the underlying mechanisms remain unclear. To characterise ambient PM collected from a coach station in an urban area, particulate polycyclic aromatic hydrocarbons (PAHs) and trace metals were evaluated, and diagnostic ratios were then used to determine the sources based on the PAHs identified in PM. To elucidate the mechanism of PM-induced vascular toxicology, human coronary artery endothelial cells (HCAECs) were exposed to PM, PM-free supernatant and residual PM, and the associations between PAHs and trace metals, nitric oxide (NO), endothelin-1 (ET-1) and interleukin-6 (IL-6) were investigated. Petrogenic-related particulate emissions, such as vehicle exhaust, accounted for 68.75% and 75.00% of mass in the 0.1-1-?m PM (PM(0.1-1)) and <0.1-?m PM (PM(0.1)) size fractions, respectively. Vehicle exhaust particles (VEPs) caused significant NO suppression and increase in ET-1 and IL-6, whereas residual PM caused an increase in NO, ET-1 and IL-6 compared with the effects of the corresponding supernatants. PAHs in PM, particularly those with 4-6 rings, were associated with NO suppression, and ET-1 and IL-6 were positively correlated with the amount of trace metal compounds. These findings suggest that chemical components affect the regulation of vasoactive function and inflammation. PMID:22940192

  6. Experimental Investigation of Fluid and Particle Motion in Shear-Induced Scour

    NASA Astrophysics Data System (ADS)

    An, Zhongfeng; Krueger, Paul

    2012-11-01

    A submerged particle bed subjected to fluid shear exhibits particle motion (scour) induced by drag and lift forces from the fluid at sufficiently high shear rates. To investigate this behavior, a particle bed was subjected to fluid shear in a narrow rectangular channel. The flow was driven by a pump for channel Reynolds numbers in the range 3500 - 6000. The particle bed consisted of monodisperse borosilicate glass spheres at several initial particle bed heights. The velocity field of the continuous phase was measured using digital particle image velocimetry (DPIV), while the velocities of the particles were obtained by image segmentation and processing of the dispersed phase from the DPIV images. To aide in visualizing the flow, the working fluid was an aqueous solution of sodium iodide with a refractive index matched to the particles. Comparing the velocity of the two phases, a particle velocity lag was observed at higher elevations, suggesting drag was the dominant fluid force on the particles, while observations of the particle motion indicated that collisions were important near the bed surface. Effects of different flow and initial conditions will be discussed. This material is based upon work supported by the National Science Foundation under Grant No. 1000908.

  7. Wave induced transport and mixing of buoyant particles

    NASA Astrophysics Data System (ADS)

    Drivdal, Magnus; Broström, Göran; Christensen, Kai H.

    2014-05-01

    The modeling of wave-current and wave-turbulence interactions have received much attention during recent years. Both the breaking of surface waves and the inclusion of the Stokes shear production have been shown to increase the upper ocean turbulence. Furthermore the Coriolis force acting on the Stokes drift redistributes the momentum in the upper ocean, leading to a deflection of the currents. An important application affected by these processes that still needs to be studied is the mixing and drift of particles. Using an ocean column model, modified to take surface wave effects into account, we investigate how the increased mixing by wave breaking and Stokes shear production as well as the stronger veering by the Coriolis-Stokes force effects the drift of suspended particles. Here the suspended particles are buoyant tracers that can represent oil droplets or plankton, for example fish eggs and larvae. The energy and momentum fluxes as well as the Stokes drift depend on the directional wave spectrum that can be obtained from a wave model or from observations. Comparing with classical Ekman theory some physical effects on the system are studied, and as a realistic test case we use the model to study the oil drift after an offshore oil spill that took place outside the western coast of Norway in 2007. During this accident the average net drift of oil was observed to be approximately 0.1% of the wind speed at an angle of about 90-120 degrees to the right, far slower and more deflected away from the wind direction than predicted by both numerical and empirical models. With wind and wave forcing from ECMWF reanalysis data, it is shown that the wave effects are important for the resultant drift in this case, and has the potential to improve drift forecasting.

  8. Collective two-particle resonances induced by photon entanglement

    SciTech Connect

    Richter, Marten; Mukamel, Shaul

    2011-06-15

    An assembly of noninteracting atoms may become correlated upon interaction with entangled photons, and certain elements of their joint density matrix can then show collective resonances. We explore experimental signatures of these resonances in the nonlinear response of a pair of two-level atoms. We find that these resonances are canceled out in stimulated signals such as pump-probe and two-photon absorption due to the destructive interference of two-photon-absorption and emission pathways in the joint two-particle space. However, they may be observed in photon statistics (Hanbury-Brown-Twiss) measurements through the attenuation of two-time intensity correlations.

  9. The Role of MAC1 in Diesel Exhaust Particle-induced Microglial Activation and Loss of Dopaminergic Neuron Function

    PubMed Central

    Levesque, Shannon; Taetzsch, Thomas; Lull, Melinda E.; Johnson, Jo Anne; McGraw, Constance; Block, Michelle L.

    2013-01-01

    Increasing reports support that air pollution causes neuroinflammation and is linked to central nervous system (CNS) disease/damage. Diesel exhaust particles (DEP) are a major component of urban air pollution, which has been linked to microglial activation and Parkinson’s disease-like pathology. To begin to address how DEP may exert CNS effects, microglia and neuron-glia cultures were treated with either nanometer-sized DEP (<0.22 µM; 50µg/mL), ultrafine carbon black (ufCB, 50µg/ml), or DEP extracts (eDEP; from 50 µg/ml DEP) and the effect of microglial activation and dopaminergic (DA) neuron function was assessed. All three treatments showed enhanced amoeboid microglia morphology, increased H2O2 production, and decreased DA uptake. Mechanistic inquiry revealed that the scavenger receptor inhibitor fucoidan blocked DEP internalization in microglia, but failed to alter DEP-induced H2O2 production in microglia. However, pretreatment with the MAC1/CD11b inhibitor antibody blocked microglial H2O2 production in response to DEP. MAC1?/? mesencephalic neuron-glia cultures were protected from DEP-induced loss of DA neuron function, as measured by DA uptake. These findings support that DEP may activate microglia through multiple mechanisms, where scavenger receptors regulate internalization of DEP and the MAC1 receptor is mandatory for both DEP-induced microglial H2O2 production and loss of DA neuron function. PMID:23470120

  10. Flow-induced segregation in confined multicomponent suspensions: Effects of particle size and rigidity

    NASA Astrophysics Data System (ADS)

    Graham, Michael; Kumar, Amit

    2013-11-01

    The effects of particle size and rigidity on segregation in confined flow of binary suspensions of fluid-filled capsules are investigated in a model system resembling whole blood. We study this problem using a boundary integral method as well as with a master equation model that incorporates wall-induced migration and hydrodynamic pair collisions. Boundary integral results indicate that, in a mixture of large and small particles, the small particles marginate, while the large particles antimarginate. Here margination refers to localization of particles near walls, while antimargination refers to the opposite. In a mixture of particles with equal size and unequal stiffness, the stiffer particles marginate while the flexible ones antimarginate. The master equation model traces the origins of these behaviors to the size and rigidity dependence of the wall-induced migration velocity and of the cross-stream particle displacements in various types of collisions. Finally, a set of coupled non-local drift-diffusion equations is derived, providing further insights in terms of the drift and diffusion of various species.

  11. Self-Induced Polar Order of Active Brownian Particles in a Harmonic Trap

    NASA Astrophysics Data System (ADS)

    Hennes, Marc; Wolff, Katrin; Stark, Holger

    2014-06-01

    Hydrodynamically interacting active particles in an external harmonic potential form a self-assembled fluid pump at large enough Péclet numbers. Here, we give a quantitative criterion for the formation of the pump and show that particle orientations align in the self-induced flow field in surprising analogy to ferromagnetic order where the active Péclet number plays the role of inverse temperature. The particle orientations follow a Boltzmann distribution ?(p)˜exp(Apz) where the ordering mean field A scales with the active Péclet number and polar order parameter. The mean flow field in which the particles' swimming directions align corresponds to a regularized Stokeslet with strength proportional to swimming speed. Analytic mean-field results are compared with results from Brownian dynamics simulations with hydrodynamic interactions included and are found to capture the self-induced alignment very well.

  12. Measurement of Fluorescence Spectra from Ambient Aerosol Particles Using Laser-induced Fluorescence Technique

    NASA Astrophysics Data System (ADS)

    Taketani, F.; Kanaya, Y.; Nakamura, T.; Moteki, N.; Takegawa, N.

    2011-12-01

    To obtain the information of composition of organic aerosol particles in atmosphere, we developed an instrument using laser-induced fluorescence (LIF) technique. To measure the fluorescence from a particle, we employed two lasers. Scattering light signal derived from a single particle upon crossing the 635nm-CW laser triggers the 266nm-pulsed laser to excite the particle. Fluorescence from the particle in the wavelength range 300-600nm is spectrally dispersed by a grating spectrometer and then detected by a 32-Ch photo-multiplier tube(PMT). The aerosol stream is surrounded by a coaxial sheath air flow and delivered to the optical chamber at atmospheric pressure. Using PSL particles with known sizes, we made a calibration curve to estimate particle size from scattering light intensity. With the current setup of the instrument we are able to detect both scattering and fluorescence from particles whose diameters are larger than 0.5um. Our system was able to differentiate particles composed of mono-aromatic species (e.g. Tryptophan) from those of Riboflavin, by their different fluorescence wavelengths. Also, measurements of fluorescence spectra of ambient particles were demonstrated in our campus in Yokosuka city, facing Tokyo bay in Japan. We obtained several types of florescence spectra in the 8 hours. Classification of the measured fluorescence spectra will be discussed in the presentation.

  13. Gravitationally induced adiabatic particle productions: From Big Bang to de Sitter

    E-print Network

    Jaume de Haro; Supriya Pan

    2015-12-07

    In the background of a flat homogeneous and isotropic space-time, we consider a scenario of the universe driven by the gravitationally induced constant `adiabatic' particle productions. We have shown that this universe attains a big bang singularity in the past and at late-time, it asymptotically becomes de Sitter. To clarify this model universe, we perform a dynamical analysis. Further, we discussed the possible effects of this particle creations in the context of loop quantum cosmology.

  14. Gravitationally induced adiabatic particle productions: From Big Bang to de Sitter

    E-print Network

    de Haro, Jaume

    2015-01-01

    In the background of a flat homogeneous and isotropic space-time, we consider a scenario of the universe driven by the gravitationally induced constant `adiabatic' particle productions. We have shown that this universe attains a big bang singularity in the past and at late-time, it asymptotically becomes de Sitter. To clarify this model universe, we perform a dynamical analysis. Further, we discussed the possible effects of this particle creations in the context of loop quantum cosmology.

  15. PINK1-induced mitophagy promotes neuroprotection in Huntington's disease

    PubMed Central

    Khalil, B; El Fissi, N; Aouane, A; Cabirol-Pol, M-J; Rival, T; Liévens, J-C

    2015-01-01

    Huntington's disease (HD) is a fatal neurodegenerative disorder caused by aberrant expansion of CAG repeat in the huntingtin gene. Mutant Huntingtin (mHtt) alters multiple cellular processes, leading to neuronal dysfunction and death. Among those alterations, impaired mitochondrial metabolism seems to have a major role in HD pathogenesis. In this study, we used the Drosophila model system to further investigate the role of mitochondrial damages in HD. We first analyzed the impact of mHtt on mitochondrial morphology, and surprisingly, we revealed the formation of abnormal ring-shaped mitochondria in photoreceptor neurons. Because such mitochondrial spheroids were previously detected in cells where mitophagy is blocked, we analyzed the effect of PTEN-induced putative kinase 1 (PINK1), which controls Parkin-mediated mitophagy. Consistently, we found that PINK1 overexpression alleviated mitochondrial spheroid formation in HD flies. More importantly, PINK1 ameliorated ATP levels, neuronal integrity and adult fly survival, demonstrating that PINK1 counteracts the neurotoxicity of mHtt. This neuroprotection was Parkin-dependent and required mitochondrial outer membrane proteins, mitofusin and the voltage-dependent anion channel. Consistent with our observations in flies, we demonstrated that the removal of defective mitochondria was impaired in HD striatal cells derived from HdhQ111 knock-in mice, and that overexpressing PINK1 in these cells partially restored mitophagy. The presence of mHtt did not affect Parkin-mediated mitochondrial ubiquitination but decreased the targeting of mitochondria to autophagosomes. Altogether, our findings suggest that mitophagy is altered in the presence of mHtt and that increasing PINK1/Parkin mitochondrial quality control pathway may improve mitochondrial integrity and neuroprotection in HD. PMID:25611391

  16. Marek's disease virus induces Th-2 activity during cytolytic infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of chickens that is caused by a highly cell-associated oncogenic alpha-herpesvirus, Marek’s disease virus (MDV). The role of cytokines and other related proteins in MD pathogenesis and immunity is poorly understood. The aim of this study was to...

  17. NF-?B decoy oligodeoxynucleotide inhibits wear particle-induced inflammation in a murine calvarial model.

    PubMed

    Sato, Taishi; Pajarinen, Jukka; Lin, Tzu-Hua; Tamaki, Yasunobu; Loi, Florence; Egashira, Kensuke; Yao, Zhenyu; Goodman, Stuart B

    2015-12-01

    Wear particles induce periprosthetic inflammation and osteolysis through activation of nuclear factor kappa B (NF-?B), which up-regulates the downstream target gene expression for proinflammatory cytokines in macrophages. It was hypothesized that direct suppression of NF-?B activity in the early phases of this disorder could be a therapeutic strategy for preventing the inflammatory response to wear particles, potentially mitigating osteolysis. NF-?B activity can be suppressed via competitive binding with double stranded NF-?B decoy oligodeoxynucleotides (ODNs) that blocks this transcription factor from binding to the promoter regions of targeted genes. In this murine calvarial study, clinically relevant polyethylene particles (PEs) with/without ODN were subcutaneously injected over the calvarial bone. In the presence of PE particles, macrophages migrated to the inflammatory site and induced tumor necrosis factor alpha (TNF-?) and receptor activator of nuclear factor kappa B ligand (RANKL) expression, resulting in an increase in the number of osteoclasts. Local injections of ODN mitigated the expression of TNF-?, RANKL, and induced the expression of two anti-inflammatory, antiresorptive cytokines: interleukin-1 receptor antagonist and osteoprotegerin. Local intervention with NF-?B decoy ODN in early cases of particle-induced inflammation in which the prosthesis is still salvageable may potentially preserve periprosthetic bone stock. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3872-3878, 2015. PMID:26123702

  18. The effect of induced charges on low-energy particle trajectories near conducting and semiconducting plates

    NASA Technical Reports Server (NTRS)

    Coffey, Victoria N.; Moore, Thomas E.

    1992-01-01

    The effect of the induced charge was found on particles less than 1 eV as they passed through simulated parallel, grounded channels that are comparable in dimension to those that are presently in space plasma instruments which measure the flux of low-energy ions. Applications were made to both conducting and semiconducting channels that ranged in length from 0.1 to 50 mm and in aspect ratio from 1 to 100. The effect of the induced charge on particle trajectories from simple straight lines. Several configurations of channel aspect ratio and detector locations are considered. The effect is important only at very low energies with small dimensions.

  19. Non-targeted effects induced by high LET charged particles

    NASA Astrophysics Data System (ADS)

    Hei, Tom K.; Chai, Yunfei; Hamada, Nobuyuki; Kakinuma, Shizuko; Uchihori, Yukio

    Radiation-induced non-targeted response represents a paradigm shift in our understanding of the radiobiological effects of ionizing radiation in that extranuclear and extracellular effects may also contribute to the final biological consequences of exposure to low doses of radiation. Using the gpt delta transgenic mouse model, there is evidence that irradiation of a small area (1 cm by 1 cm) of the lower abdominal area of animals with a 5 Gy dose of X-rays induced cyclooxygenase-2 as well as deletion mutations in the out-of-field lung tissues of the animals. The mutation correlated with an increase in prostaglandin levels in the bystander lung tissues and with an increase in the level of 8-hydroxydeoxyguanosine (8-OHdG), an oxidative DNA damage marker. An increase in COX-2 level was also detected in the out-of-field lung tissues of animals similarly exposed to high LET argon and carbon ions accelerated at the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Sciences in Japan. These results provide the first evidence that the COX-2 -related pathway, which is essential in mediating cellular inflammatory response, is the critical signaling link for the non-targeted, bystander phenomenon. A better understanding of the cellular and molecular mechanisms of the non-targeted, out of field phenomenon together with evidence of their occurrence in vivo will allow us to formulate a more accurate assessment of radiation risk.

  20. ULTRAFINE CARBON PARTICLES INDUCE INTERLEUKIN-8 GENE TRANSCRIPTION AND P38 MAPK ACTIVATION IN NORMAL BRONCHIAL EPITHELIAL CELLS

    EPA Science Inventory

    Epidemiological studies suggest that ultrafine particles contribute to particulate matter-induced adverse health effects. Interleukin (IL)-8 is an important proinflammatory cytokine in the human lung that is induced in respiratory cells exposed to a variety of environmental insul...

  1. Description of particle induced damage on protected silver coatings.

    PubMed

    Schwinde, Stefan; Schürmann, Mark; Jobst, Paul Johannes; Kaiser, Norbert; Tünnermann, Andreas

    2015-06-01

    In the visible to infrared spectral range, highly-reflective silver mirrors are applied in the manufacture of optical instruments such as telescopes. However, it is still difficult to combine high reflectivity and long-term stability of the protected silver coating. We show that the deposition of impervious protective layers is necessary but often not sufficient for long-term environmental stability. Hygroscopic air borne particles absorbed by the protections surface attract water molecules and form a solution. This solution first damages the protection, subsequently permeates the protection and finally damages the silver whereby the reflectivity is reduced. We demonstrate this particular damage mechanism with different experiments and describe this mechanism in detail. PMID:26192652

  2. Dynamic ultramicroscopy of laser-induced flows in colloidal solutions of plasmon-resonance particles

    SciTech Connect

    Fedosov, I V; Tuchin, V V; Nefedov, I S; Khlebtsov, B N

    2008-06-30

    A method is proposed for visualisation of the velocity fields of colloidal plasmon-resonance nanoparticles moving in a laser beam. The method uses the particle image velocimetry for processing ultramicroscopic images. Particles in a thick layer of colloidal solution are illuminated by a slit laser ultramicroscopic source with a large numerical aperture providing a high contrast of particle images and visualisation of the transverse velocity distribution in laser-induced flows with a high spatial resolution. (special issue devoted to application of laser technologies in biophotonics and biomedical studies)

  3. Is atherosclerotic disease associated with organic components of ambient fine particles?

    PubMed

    Keebaugh, Andrew J; Sioutas, Constantinos; Pakbin, Payam; Schauer, James J; Mendez, Loyda B; Kleinman, Michael T

    2015-11-15

    Heart disease is a major killer in western societies; coronary artery disease and atherosclerosis are important contributors to this mortality. Atherosclerosis in mice with a deleted apoE gene (apoE-/-) is accelerated by exposure to ambient ultrafine particles (UFP) which are particles smaller than 180 nm in diameter. UFP contain organic components that are pro-oxidant and may cause or aggravate heart disease. Could removal of these organic constituents mitigate adverse cardiovascular effects? ApoE-/- mice were exposed to concentrated UFP (CAP), CAP from which organic constituents were removed by thermal denuding (deCAP) or purified air (controls) for 5 hr/day, 4 days/week for 8 weeks. Heart rate (HR), heart rate variability (HRV), biomarkers of oxidative stress and the sizes of arterial plaques were measured. Adverse effects were seen in CAP-exposed mice (increased size of arterial plaque, increased oxidative stress and decreased HRV, compared to controls). Adverse effects were not observed in deCAP-exposed mice. Removal of organic constituents from ambient particles resulted in significant reduction of toxic cardiovascular effects of air pollution exposure. PMID:26151650

  4. The mechanism of particles transport induced by electrostatic perturbation in tokamak

    SciTech Connect

    Feng, Zhichen; Qiu, Zhiyong; Sheng, Zhengmao

    2013-12-15

    Particle transport in tokamak devices due to wave-particle resonance induced diffusion is studied. The diffusion coefficient is derived both analytically using quasilinear theory, and numerically using a test particle code, and the obtained diffusion coefficient agrees with each other in its validity regime. Dependence of the diffusion coefficient on turbulence intensity, turbulence radial mode structures, and particle energy is investigated. It is found that the diffusion coefficient is proportional to the turbulence intensity, and the diffusion is maximized for E{sub t}?T{sub i}, and k{sub r}?{sub 0}?1. Here, E{sub t} is the test particle energy, T{sub i} is the thermal ion temperature, ?{sub 0} is the distance between neighboring mode rational surfaces, and 1/k{sub r} is the half width of the fine radial mode structure on each rational surface.

  5. On the tidally induced gravitational collapse of a particle cluster

    E-print Network

    Kashif Alvi; Yuk Tung Liu

    2001-10-22

    An important issue in the dynamics of neutron star binaries is whether tidal interaction can cause the individual stars to collapse into black holes during inspiral. To understand this issue better, we study the dynamics of a cluster of collisionless particles orbiting a non-rotating black hole, which is part of a widely separated circular binary. The companion body's electric- and magnetic-type tidal fields distort the black hole and perturb the cluster, eventually causing the cluster to collapse into the hole as the companion spirals in under the influence of gravitational radiation reaction. We find that magnetic-type tidal forces do not significantly influence the evolution of the cluster as a whole. However, individual orbits can be strongly affected by these forces. For example, some orbits are destabilized due to the addition of magnetic-type tidal forces. We find that the most stable orbits are close to the companion's orbital plane and retrograde with respect to the companion's orbit.

  6. Local effect of IL-4 delivery on polyethylene particle induced osteolysis in the murine calvarium.

    PubMed

    Rao, Allison J; Nich, Christophe; Dhulipala, Lakshmi S; Gibon, Emmanuel; Valladares, Roberto; Zwingenberger, Stefan; Smith, R Lane; Goodman, Stuart B

    2013-07-01

    Wear particles generated with use of total joint replacements incite a chronic macrophage-mediated inflammatory reaction, which leads to implant failure. Macrophage activation may be polarized into two states, with an M1 proinflammatory state dominating an alternatively activated M2 anti-inflammatory state. We hypothesized that IL-4, an activator of M2 macrophages, could modulate polyethylene (PE) particle-induced osteolysis in an experimental murine model. Four animal groups included (a) calvarial saline injection with harvest at 14 days (b) single calvarial injection of PE particles subcutaneously (SC) without IL-4 (c) PE particles placed as in (b), then IL-4 given SC for 14 consecutive days and (d) PE particles as in (b) then IL-4 beginning 7 days after particle injection for 7 days. The calvarial bone volume to total tissue volume was measured using microCT and histomorphometry. Calvaria were cultured for 24 h to assess release of RANKL, OPG, TNF-?, and IL-1ra and isolation and identification of M1 and M2 specific proteins. MicroCT and histomorphometric analysis showed that bone loss was significantly decreased following IL-4 administration to PE treated calvaria for both 7 and 14 days. Western blot analysis showed an increased M1/M2 ratio in the PE treated calvaria, which decreased with addition of IL-4. Cytokine analysis showed that the RANKL/OPG ratio and TNF-?/IL-1ra ratio decreased in PE-treated calvaria following IL-4 addition for 14 days. IL-4 delivery mitigated PE particle-induced osteolysis through macrophage polarization. Modulation of macrophage polarization is a potential treatment strategy for wear particle induced periprosthetic osteolysis. PMID:23225668

  7. Baculovirus-Induced Climbing Behavior Favors Intraspecific Necrophagy and Efficient Disease Transmission in Spodoptera exigua

    PubMed Central

    Rebolledo, Dulce; Guevara, Roger; Murillo, Rosa

    2015-01-01

    Shortly prior to death, many species of Lepidoptera infected with nucleopolyhedrovirus climb upwards on the host plant. This results in improved dissemination of viral occlusion bodies over plant foliage and an increased probability of transmission to healthy conspecific larvae. Following applications of Spodoptera exigua multiple nucleopolyhedrovirus for control of Spodoptera exigua on greenhouse-grown sweet pepper crops, necrophagy was observed by healthy S. exigua larvae that fed on virus-killed conspecifics. We examined whether this risky behavior was induced by olfactory or phagostimulant compounds associated with infected cadavers. Laboratory choice tests and olfactometer studies, involving infected and non-infected cadavers placed on spinach leaf discs, revealed no evidence for greater attraction of healthy larvae to virus-killed over non-infected cadavers. Physical contact or feeding on infected cadavers resulted in a very high incidence of transmission (82–93% lethal disease). Observations on the behavior of S. exigua larvae on pepper plants revealed that infected insects died on the uppermost 10% of foliage and closer to the plant stem than healthy conspecifics of the same stage, which we considered clear evidence of baculovirus-induced climbing behavior. Healthy larvae that subsequently foraged on the plant were more frequently observed closer to the infected than the non-infected cadaver. Healthy larvae also encountered and fed on infected cadavers significantly more frequently and more rapidly than larvae that fed on non-infected cadavers. Intraspecific necrophagy on infected cadavers invariably resulted in virus transmission and death of the necrophagous insect. We conclude that, in addition to improving the dissemination of virus particles over plant foliage, baculovirus-induced climbing behavior increases the incidence of intraspecific necrophagy in S. exigua, which is the most efficient mechanism of transmission of this lethal pathogen. PMID:26402061

  8. Light flash phenomena induced by HzE particles

    NASA Technical Reports Server (NTRS)

    Mcnulty, P. J.; Pease, V. P.

    1980-01-01

    Astronauts and Apollo and Skylab missions have reported observing a variety of visual phenomena when their eyes are closed and adapted to darkness. These phenomena have been collectively labelled as light flashes. Visual phenomena which are similar in appearance to those observed in space have been demonstrated at the number of accelerator facilities by expressing the eyes of human subjects to beams of various types of radiation. In some laboratory experiments Cerenkov radiation was found to be the basis for the flashes observed while in other experiments Cerenkov radiation could apparently be ruled out. Experiments that differentiate between Cerenkov radiation and other possible mechanisms for inducing visual phenomena was then compared. The phenomena obtained in the presence and absence of Cerenkov radiation were designed and conducted. A new mechanism proposed to explain the visual phenomena observed by Skylab astronauts as they passed through the South Atlantic Anomaly, namely nuclear interactions in and near the sensitive layer of the retina, is covered. Also some studies to search for similar transient effects of space radiation on sensors and microcomputer memories are described.

  9. DIESEL EXHAUST PARTICLE INDUCED GENE EXPRESSION CHANGES IN A MURINE MUCOSAL SENSITIZATION MODEL

    EPA Science Inventory

    Studies in humans and animals have shown diesel exhaust particles (DEP) can act as an immunological adjuvant to enhance the development of allergic lung disease and this effect is influenced by the chemical composition of the DEP. The adjuvancy of NIST SRM 2975 (NDEP) generated...

  10. Contrast induced neurotoxicity following coronary angiogram with Iohexol in an end stage renal disease patient.

    PubMed

    Gollol Raju, Narasimha Swamy; Joshi, Deepak; Daggubati, Ramesh; Movahed, Assad

    2015-11-16

    Neurotoxicity is an infrequent adverse reaction to iodinated contrast agents. Contrast induced neurotoxicity following coronary angiogram is very rare. Renal disease is a risk factor for contrast induced neurotoxicity. We report a case of contrast induced neurotoxicity following coronary angiogram and intervention using Iohexol (Omnipaque 350) in an end stage renal disease patient on peritoneal dialysis who had prior exposure to iodinated contrast without any adverse reaction. Hemodialysis had to be initiated for rapid removal of the contrast agent with subsequent complete resolution of neurological deficits. This case highlights the need for interventionalists to be aware of an important adverse reaction to iodinated contrast agents, especially in individuals with renal dysfunction, and that neurotoxicity is a possibility even with prior uneventful exposures. The role and timing of hemodialysis in contrast induced neurotoxicity in patients with chronic kidney disease and in those without chronic kidney disease needs further deliberation. PMID:26601097

  11. Contrast induced neurotoxicity following coronary angiogram with Iohexol in an end stage renal disease patient

    PubMed Central

    Gollol Raju, Narasimha Swamy; Joshi, Deepak; Daggubati, Ramesh; Movahed, Assad

    2015-01-01

    Neurotoxicity is an infrequent adverse reaction to iodinated contrast agents. Contrast induced neurotoxicity following coronary angiogram is very rare. Renal disease is a risk factor for contrast induced neurotoxicity. We report a case of contrast induced neurotoxicity following coronary angiogram and intervention using Iohexol (Omnipaque 350) in an end stage renal disease patient on peritoneal dialysis who had prior exposure to iodinated contrast without any adverse reaction. Hemodialysis had to be initiated for rapid removal of the contrast agent with subsequent complete resolution of neurological deficits. This case highlights the need for interventionalists to be aware of an important adverse reaction to iodinated contrast agents, especially in individuals with renal dysfunction, and that neurotoxicity is a possibility even with prior uneventful exposures. The role and timing of hemodialysis in contrast induced neurotoxicity in patients with chronic kidney disease and in those without chronic kidney disease needs further deliberation. PMID:26601097

  12. Dewetting-induced collapse of hydrophobic particles X. Huang, C. J. Margulis, and B. J. Berne*

    E-print Network

    Berne, Bruce J.

    -organization of amphiphiles into micelles and membranes (1), capillary evaporation (2­5), protein folding (6­11), and gas), it is now appreciated that large, strongly hydrophobic particles should induce a liquid­ vapor been able to observe thus far this phenom- enon (i.e., the proximal water density less than the bulk

  13. Observations of shear-induced particle migration for oscillatory flow of a suspension within a tube

    E-print Network

    Observations of shear-induced particle migration for oscillatory flow of a suspension within a tube of Texas at Austin, Austin, Texas 78712-1062 Received 1 February 1999; accepted 22 June 1999 Suspensions Reynolds number along the axis of a circular tube. Using nuclear magnetic resonance imaging NMRI

  14. URBAN PARTICLE-INDUCED PULMONARY ARTERY CONSTRUCTION IS MEDIATED BY SUPEROXIDE PRODUCTION

    EPA Science Inventory

    URBAN PARTICLE-INDUCED PULMONARY ARTERY CONSTRICTION IS MEDIATED BY SUPEROXIDE PRODUCTION.Jacqueline D. Carter, Zhuowei Li, Lisa A. Dailey, Yuh-Chin T. Huang. CEMALB, University of North Carolina, and ORD, US EPA, Chapel Hill, North Carolina.

    Exposure to particulate matter...

  15. CARDIOVASCULAR FUNCTIONAL, CELLULAR, AND MOLECULAR EFFECTS INDUCED BY EMISSION SOURCE PARTICLE CONSTITUENTS

    EPA Science Inventory

    Epidemiological, clinical and toxicological studies have demonstrated the ability of ambient PM and certain emission source particles to altered autonomic control of the heart and induce arrhythmia. A number of hypotheses have been proposed to explain these effects such as direct...

  16. DIESEL AND CARBON PARTICLES ENHANCE HOUSE DUST MITE-INDUCED PULMONARY HYPERSENSITIVITY IN BROWN NORWAY RATS

    EPA Science Inventory

    Diesel and Carbon Particles Enhance House Dust Mite-Induced Pulmonary Hypersensitivity in Brown Norway Rats. P. Singh1, M.J. Daniels2, D. Winsett2, J. Richards2, K. Crissman2, M. Madden2 and M.I. Gilmour2. 1NCSU, Raleigh, NC and 2 USEPA, Research Triangle Park, NC.

    Ep...

  17. Sheath-induced distortions in particle distributions near enhanced polar outflow probe particle sensors

    SciTech Connect

    Hussain, S.; Marchand, R.

    2014-07-15

    We discuss sheath and kinetic effects on ion and electron distribution functions at the aperture of enhanced Polar Outflow Probe particle sensors. For this purpose, the interaction between the CASSIOPE spacecraft and space environment is simulated fully kinetically using the electrostatic Particle In Cell code PTetra. The simulations account for the geometry of the main features of the spacecraft body, the booms, and the sensors. In addition to the background plasma, the model also accounts for Earth magnetic field. The plasma parameters assumed in the simulations are obtained from the latest version of the International Reference Ionosphere (IRI) model and the value of magnetic field is obtained from the International Geophysical Reference Field model. Our analysis shows significant distortions in the ion distribution function in the plane of the sensor aperture, as well as in the direction along the boom holding the sensor. We argue that significant distortions and asymmetries should also occur at the aperture of the suprathermal electron imager when suprathermal electrons are detected, with energies of 5?eV or more.

  18. Particle irradiation induces FGF2 expression in normal human lens cells

    NASA Technical Reports Server (NTRS)

    Chang, P. Y.; Bjornstad K, A.; Chang, E.; McNamara, M.; Barcellos-Hoff, M. H.; Lin, S. P.; Aragon, G.; Polansky, J. R.; Lui, G. M.; Blakely, E. A.

    2000-01-01

    Particle Irradiation Induces FGF2 Expression in Normal Human Lens Cells. Particle radiations, including both proton and helium-ion beams, have been used to successfully treat choroidal melanoma, but with the complication of radiation-induced cataract. We have investigated a role for radiation-induced changes in the expression of basic fibroblast growth factor (FGF2) gene expression as part of the mechanism(s) underlying lens cell injury associated with cataract. Normal human lens epithelial (HLE) cells were cultured in vitro on extracellular matrix (ECM) originated from bovine corneal endothelial cells. This study reports evidence for rapid but transient induction of FGF2 transcripts, an increase of between 5- and 8-fold, within 0.5 h after exposure to particle radiation, followed by another wave of increased transcription at 2-3 h postirradiation. Immunofluorescence results confirm the enhanced levels of FGF2 protein rapidly after exposure to protons or helium ions, followed by another wave of increased activity unique to helium at 6 h postirradiation. This second wave of increased immunoreactivity was not observed in the proton-irradiated samples. Total FGF2 protein analysis after helium-ion exposures shows induced expression of three FGF2 isoforms, with an increase of up to 2-fold in the 18-kDa low-molecular-weight species. Studies of the effects of protons on individual FGF2 protein isoforms are in progress. Several mechanisms involving a role for FGF2 in radiation-induced cataract are discussed.

  19. A Study of Interfacial-Instability-Induced Mixing in Explosive Dispersal of Particles

    NASA Astrophysics Data System (ADS)

    Rollin, Bertrand; Annamalai, Subramanian; Ouellet, Frederick

    2015-06-01

    Recent experiments have shown that when a bed of particles is explosively dispersed, a multiphase instability front may occur, and lead to the formation of aerodynamically stable jet-particle structures. It is believed that these coherent structures originates from the early phase of explosive dispersal, in particular, in the manner in which the initial layer of particles undergoes instability, as it rapidly expands in the radial direction. In this work we want to isolate and study the effect of gas-particle two-way interaction on the nature of Rayleigh-Taylor (RT) and Richtmyer-Meshkov (RM) instabilities of an explosively driven particle layer. As a result we perform numerical experiments, where we limit the initial volume fraction of the particle layer. The focus of this investigation is on the RT and RM growth mechanisms in the linear and non-linear stages under the complexity of the cylindrical geometry, very high pressures and densities associated with the detonation process. Thus, in addition to the initial disturbance created by the random distribution of particles, we explicitly vary the initial density of the particle and gas distribution. Detailed analyses of single mode and two-mode RT/RM-induced mixing are presented. This work was supported (in part) by the U.S. DoE, NNSA, ASC Program, as a Cooperative Agreement under the Predictive Science Academic Alliance Program, under Contract No. DE-NA0002378.

  20. Fluid-induced propulsion of rigid particles in wormlike micellar solutions

    NASA Astrophysics Data System (ADS)

    Gagnon, David A.; Keim, Nathan C.; Shen, Xiaoning; Arratia, Paulo E.

    2014-10-01

    In the absence of inertia, a reciprocal swimmer achieves no net motion in a viscous Newtonian fluid. Here, using tracking methods and birefringence imaging, we investigate the ability of a reciprocally actuated particle to translate through a complex fluid that possesses a network. A geometrically polar particle, a rod with a bead on one end, is reciprocally rotated using magnetic fields. The particle is immersed in a wormlike micellar (WLM) solution that is known to be susceptible to the formation of shear bands and other localized structures due to shear-induced remodeling of its microstructure. Results show that the nonlinearities present in this WLM solution break time-reversal symmetry under certain conditions, and enable propulsion of an artificial "swimmer." We find three regimes dependent on the Deborah number (De): net motion towards the bead-end of the particle at low De, net motion towards the rod-end of the particle at intermediate De, and no appreciable propulsion at high De. At low De, where the particle time scale is longer than the fluid relaxation time, we believe that propulsion is caused by an imbalance in the fluid first normal stress differences between the two ends of the particle (bead and rod). At De ˜ 1, however, we observe the emergence of a region of network anisotropy near the rod using birefringence imaging. This anisotropy suggests alignment of the micellar network, which is "locked in" due to the shorter time scale of the particle relative to the fluid.

  1. Icariin protects against titanium particle-induced osteolysis and inflammatory response in a mouse calvarial model.

    PubMed

    Shao, Hongguo; Shen, Ji; Wang, Mingjun; Cui, Jingfu; Wang, Yijun; Zhu, Shijun; Zhang, Wen; Yang, Huilin; Xu, Yaozeng; Geng, Dechun

    2015-08-01

    Periprosthetic osteolysis and subsequent aseptic loosening are common in implant failure, a complication with revision surgery being the only established treatment. Wear particle-induced inflammation and extensive osteoclastogenesis play critical roles in periprosthetic osteolysis. A recent approach in limiting osteolysis is therefore focused on inhibiting osteoclastic bone resorption. This study aimed to investigate the potential impact of icariin, the major ingredient of Epimedium, on titanium particle-induced osteolysis in a mouse calvarial model. Eighty-four male C57BL/J6 mice were divided randomly into four groups. Mice in the sham group underwent sham surgery only, whereas animals in the vehicle, low- and high-concentration icariin groups received titanium particles. Mice in the low- and high-concentration icariin groups were gavage-fed with icariin at 0.1 or 0.3 mg/g/day, respectively, until sacrifice. Mice in the sham and vehicle groups received phosphate-buffered saline daily. After 2 weeks, mouse calvariae were collected for micro-computed tomography, histomorphometry and molecular analysis. Icariin significantly reduced particle-induced bone resorption compared with the vehicle group. Icariin also prevented an increase in receptor activator of nuclear factor kappa B ligand/osteoprotegerin ratio and subsequently suppressed osteoclast formation in titanium particle-charged calvariae. In addition, immunohistochemical analysis and enzyme-linked immunosorbent assay showed icariin significantly reduced expression and secretion of tumor necrosis factor-?, interleukin-1? and interleukin-6 in the calvariae of titanium-stimulated mice. Collectively, these results suggest that icariin represents a potential treatment for titanium particle-induced osteolysis and could be developed as a new therapeutic candidate for the prevention and treatment of aseptic loosening. PMID:25985156

  2. Alpha particle induced gamma yields in uranium hexafluoride

    NASA Astrophysics Data System (ADS)

    Croft, Stephen; Swinhoe, Martyn T.; Miller, Karen A.

    2013-01-01

    Fluorine has a relatively large (?,n) production cross-section in the MeV range, the energy range of interest for special nuclear materials. In the uranium fuel cycle enriched UF6 in particular is a reasonably prolific source of (?,n) neutrons because along with 235U, 234U becomes enriched and it has a relatively short half-life. This enables the mass content of storage cylinders containing UF6 to be verified by neutron counting methods. In association with such measurements high resolution gamma-ray spectrometry (HRGS) measurements using a high-purity Ge detector are often undertaken to determine the 235U enrichment based off the intensity of the direct 186 keV line. The specific (?,n) neutron production, neutrons per second per gram of U, is sensitive to the relative isotopic composition, particularly the 234U concentration, and the traditional gross neutron counting approach is needed to quantitatively interpret the data. In addition to F(?,n) neutrons, ?-induced reaction ?-rays are generated, notably at 110, 197, 582, 891, 1236 and 1275 keV. If one could observe 19F(?,x?) gamma-lines in the HRGS spectra the thought was that perhaps the ?-activity could be estimated directly, and in turn the 234U abundance obtained. For example, by utilizing the ratio of the detected 197-186 keV full energy peaks. However, until now there has been no readily available estimate of the expected strength of the reaction gamma-rays nor any serious consideration as to whether they might be diagnostic or not. In this work we compute the thick target yields of the chief reaction gamma-rays in UF6 using published thin target data. Comparisons are made to the neutron production rates to obtain ?/n estimates, and also to the 235U decay line at 186 keV which we take as a fiducial line. It is shown that the reaction gamma-rays are produced but are far too weak for practical safeguards purposes. Now that the underlying numerical data is readily available however, it can be used to support neutron and gamma production calculations in other fluorine compounds, for example impure plutonium reference materials where fluorine may be present only at the parts per million by weight level yet still present a serious nuisance addition to the neutron production rate.

  3. Studying effects of Magnolol on alpha-particle induced bystander effects using PADC-film based dishes

    E-print Network

    Yu, Peter K.N.

    Studying effects of Magnolol on alpha-particle induced bystander effects using PADC-film based May 2009 Accepted 17 October 2009 Keywords: Bystander effect Alpha-particle CHO cells Magnolol PADC a b s t r a c t Radiation-induced bystander effect refers to the biological response found in cells

  4. Examination of Susceptibility to Libby Amphibole Asbestos-Induced Injury in Rat Models of Cardiovascular Disease

    EPA Science Inventory

    Although cardiovascular disease (CVD) is considered a risk factor for the exacerbation of air pollution health effects, no studies have been done assessing the influence of the disease on the development of lung injury induced by asbestos exposure. In this study we examined lung ...

  5. Environmentally induced epigenetic transgenerational inheritance of phenotype and disease.

    PubMed

    Guerrero-Bosagna, Carlos; Skinner, Michael K

    2012-05-01

    Environmental epigenetics has an important role in regulating phenotype formation or disease etiology. The ability of environmental factors and exposures early in life to alter somatic cell epigenomes and subsequent development is a critical factor in how environment affects biology. Environmental epigenetics provides a molecular mechanism to explain long term effects of environment on the development of altered phenotypes and "emergent" properties, which the "genetic determinism" paradigm cannot. When environmental factors permanently alter the germ line epigenome, then epigenetic transgenerational inheritance of these environmentally altered phenotypes and diseases can occur. This environmental epigenetic transgenerational inheritance of phenotype and disease is reviewed with a systems biology perspective. PMID:22020198

  6. Induced pluripotent stem cells (iPSCs) and neurological disease modeling: progress and promises

    PubMed Central

    Marchetto, Maria C.; Brennand, Kristen J.; Boyer, Leah F.; Gage, Fred H.

    2011-01-01

    The systematic generation of neurons from patients with neurological disorders can provide important insights into disease pathology, progression and mechanism. This review will discuss recent progress in modeling neurodegenerative and neurodevelopmental diseases using induced pluripotent stem cells (iPSCs) and highlight some of the current challenges in the field. Combined with other technologies previously used to study brain disease, iPSC modeling has the promise to influence modern medicine on several fronts: early diagnosis, drug development and effective treatment. PMID:21828073

  7. Mechanism of production of light complex particles in nucleon-induced reactions

    E-print Network

    Dexian Wei; Ning Wang; Li Ou

    2014-02-10

    The Improved Quantum Molecular Dynamics (ImQMD) model incorporated with the statistical decay model is successful in describing emission of nucleons in the intermediate energy spallation reactions, but not good enough in describing productions of light complex particles, i.e. $d$, $t$, $^3$He and $^4$He. To improve the description on emission of light complex particles, a phenomenological mechanism called surface coalescence and emission is introduced into ImQMD model: nucleon ready to escape from the compound nuclei can coalesce with the other nucleon(s) to form light complex particle and be emitted. With updated ImQMD model, the description on the experimental data of light complex particles produced in nucleon-induced reactions are great improved.

  8. Human alkaloid biosynthesis : chemical inducers of Parkinson's disease?

    E-print Network

    Hatzios, Stavroula K. (Stavroula-Artemis K.)

    2005-01-01

    The occurrence of certain alkaloids in the human brain appears to be associated with the onset of Parkinson's disease (PD). Recently, a human protein bearing homology to an alkaloid synthase in plants was identified. This ...

  9. Finite-difference lattice Boltzmann simulation on acoustics-induced particle deposition

    NASA Astrophysics Data System (ADS)

    Fu, Sau-Chung; Yuen, Wai-Tung; Wu, Chili; Chao, Christopher Yu-Hang

    2015-10-01

    Particle manipulation by acoustics has been investigated for many years. By a proper design, particle deposition can be induced by the same principle. The use of acoustics can potentially be developed into an energy-efficient technique for particle removal or filtration system as the pressure drop due to acoustic effects is low and the flow velocity is not necessary to be high. Two nonlinear acoustic effects, acoustic streaming and acoustic radiation pressure, are important. Acoustic streaming introduces vortices and stagnation points on the surface of an air duct and removes the particles by deposition. Acoustic radiation pressure causes particles to form agglomerates and enhances inertial impaction and/or gravitational sedimentation. The objective of this paper is to develop a numerical model to investigate the particle deposition induced by acoustic effects. A three-step approach is adopted and lattice Boltzamnn technique is employed as the numerical method. This is because the lattice Boltzmann equation is hyperbolic and can be solved locally, explicitly, and efficiently on parallel computers. In the first step, the acoustic field and its mean square fluctuation values are calculated. Due to the advantage of the lattice Boltzmann technique, a simple, stable and fast lattice Boltzmann method is proposed and verified. The result of the first step is input into the second step to solve for acoustic streaming. Another finite difference lattice Boltzmann method, which has been validated by a number of flows and benchmark cases in the literature, is used. The third step consists in tracking the particle's motion by a Lagrangian approach where the acoustic radiation pressure is considered. The influence of the acoustics effects on particle deposition is explained. The numerical result matches with an experiment. The model is a useful tool for optimizing the design and helps to further develop the technique.

  10. Lateral aggregation induced by magnetic perturbations in a magnetorheological fluid based on non-Brownian particles.

    PubMed

    Moctezuma, R E; Donado, F; Arauz-Lara, J L

    2013-09-01

    A study of lateral aggregation, induced by an oscillatory field, in a magnetorheological fluid based on non-Brownian magnetic particles is presented. We investigate the behavior of chains formed by the particles, due to the simultaneous application of a static magnetic field and a sinusoidal magnetic field transverse to each other. We show that the effective oscillating field enhances the aggregation process. We discuss this result in terms of an effective particle concentration induced by the oscillating field when chains oscillate angularly and sweep the area around them. The oscillating field produces a lateral aggregation similar to that observed in systems composed of Brownian particles which is induced by thermal fluctuations. We study the effect of the oscillating field on the angular amplitude described by single chains. It is observed that the angular amplitude decreases as the frequency of the oscillating field increases; we discuss this behavior numerically in terms of a simple model for this system. Lateral aggregation is studied in detail in isolated pairs of chains of equal length at several conditions of separation and displacement. From the results, a phase diagram is obtained showing the conditions under which aggregation is possible. PMID:24125266

  11. Influence of soot particle aggregation on time-resolved laser-induced incandescence signals

    NASA Astrophysics Data System (ADS)

    Bladh, H.; Johnsson, J.; Rissler, J.; Abdulhamid, H.; Olofsson, N.-E.; Sanati, M.; Pagels, J.; Bengtsson, P.-E.

    2011-08-01

    Laser-induced incandescence (LII) is a versatile technique for quantitative soot measurements in flames and exhausts. When used for particle sizing, the time-resolved signals are analysed as these will show a decay rate dependent on the soot particle size. Such an analysis has traditionally been based on the assumption of isolated primary particles. However, soot particles in flames and exhausts are usually aggregated, which implies loss of surface area, less heat conduction and hence errors in estimated particle sizes. In this work we present an experimental investigation aiming to quantify this effect. A soot generator, based on a propane diffusion flame, was used to produce a stable soot stream and the soot was characterised by transmission electron microscopy (TEM), a scanning mobility particle sizer (SMPS) and an aerosol particle mass analyzer coupled in series after a differential mobility analyzer (DMA-APM). Despite nearly identical primary particle size distributions for three selected operating conditions, LII measurements resulted in signal decays with significant differences in decay rate. However, the three cases were found to have quite different levels of aggregation as shown both in TEM images and mobility size distributions, and the results agree qualitatively with the expected effect of diminished heat conduction from aggregated particles resulting in longer LII signal decays. In an attempt to explain the differences quantitatively, the LII signal dependence on aggregation was modelled using a heat and mass transfer model for LII given the primary particle and aggregate size distribution data as input. Quantitative agreement was not reached and reasons for this discrepancy are discussed.

  12. Hydrodynamic interactions in metal rod-like particle suspensions due to induced charge electroosmosis

    SciTech Connect

    Rose, K A; Hoffman, B; Saintillan, D; Shaqfeh, E G; Santiago, J G

    2008-05-05

    We present a theoretical and experimental study of the role of hydrodynamic interactions on the motion and dispersion of metal rod-like particles in the presence of an externally applied electric field. In these systems, the electric field polarizes the particles and induces an electroosmosis flow relative to the surface of each particle. The simulations include the effect of the gravitational body force, buoyancy, far-field hydrodynamic interactions, near-field lubrication forces, and electric field interactions. The particles in the simulations and experiments were observed to experience repeated pairing interactions in which they come together axially with their ends approaching each other, slide past one another until their centers approach, and then push apart. These interactions were confirmed in measurements of particle orientations and velocities, pair distribution functions, and net dispersion of the suspension. For large electric fields, the pair distribution functions show accumulation and depletion regions consistent with many pairing events. For particle concentrations of 1e8 particles/mL and higher, dispersion within the suspension dramatically increases with increased field strength.

  13. Particles deposition induced by the magnetic field in the coronary bypass graft model

    NASA Astrophysics Data System (ADS)

    Bernad, Sandor I.; Totorean, Alin F.; Vekas, Ladislau

    2016-03-01

    Bypass graft failures is a complex process starting with intimal hyperplasia development which involve many hemodynamic and biological factors. This work presents experimental results regarding the possibility to use magnetic drug delivery to prevent the development of the intimal hyperplasia using a simplified but intuitive model. The primary goal is to understand the magnetic particle deposition in the anastomosis region of the bypass graft taking into account the complex flow field created in this area which involves recirculation region, flow mixing and presence of particles with high residence time. The three-dimensional geometry model was used to simulate the motion and accumulation of the particles under the magnetic field influence in anastomotic region of the coronary bypass graft. The flow patterns are evaluated both numerically and experimentally and show a good correlation in term of flow parameters like vortex length and flow stagnation point positions. Particle depositions are strongly dependent on the magnet position and consequently of the magnetic field intensity and field gradient. Increased magnetic field controlled by the magnet position induces increased particle depositions in the bypass graft anastomosis. The result shows that particle depositions depend on the bypass graft angle, and the deposition shape and particle accumulation respectively, depend by the flow pattern in the anastomosis region.

  14. Nimesulide Improves the Symptomatic and Disease Modifying Effects of Leflunomide in Collagen Induced Arthritis

    PubMed Central

    Al-Abd, Ahmed M.; Al-Abbasi, Fahad A.; Nofal, Salwa M.; Khalifa, Amani E.; Williams, Richard O.; El-Eraky, Wafaa I.; Nagy, Ayman A.; Abdel-Naim, Ashraf B.

    2014-01-01

    Nimesulide is a COX-2 inhibitor used for symptomatic relief of rheumatoid arthritis. Leflunomide is an anti-pyrimidine used to manage the progression of rheumatoid arthritis. Herein we studied the influence of nimesulide and leflunomide combination in terms of disease symptoms and progression using collagen-induced arthritis model in mice, as a model for rheumatoid arthritis. Collagen induced arthritis was induced by immunization with type II collagen. Assessment of joint stiffness and articular hyperalgesia were evaluated using a locomotor activity cage and the Hargreaves method, respectively. Disease progression was assessed via arthritic index scoring, X-ray imaging, myeloperoxidase enzyme activity and histopathologic examination. Nimesulide induced only transient symptomatic alleviation on the top of decreased leucocytic infiltration compared to arthritis group. However, nimesulide alone failed to induce any significant improvement in the radiological or pathological disease progression. Leflunomide alone moderately alleviates the symptoms of arthritis and moderately retarded the radiological and pathological disease progression. Combination of nimesulide and leflunomide significantly improved symptomatic (analgesia and joint stiffness) and arthritic disease progression (radiological, pathological and Myeloperoxidase enzyme activity) in collagen induced arthritis animal model. PMID:25375820

  15. Prediction of Lung Cells Oncogenic Transformation for Induced Radon Progeny Alpha Particles Using Sugarscape Cellular Automata

    PubMed Central

    Baradaran, Samaneh; Maleknasr, Niaz; Setayeshi, Saeed; Akbari, Mohammad Esmaeil

    2014-01-01

    Background Alpha particle irradiation from radon progeny is one of the major natural sources of effective dose in the public population. Oncogenic transformation is a biological effectiveness of radon progeny alpha particle hits. The biological effects which has caused by exposure to radon, were the main result of a complex series of physical, chemical, biological and physiological interactions. The cellular and molecular mechanisms for radon-induced carcinogenesis have not been clear yet. Methods Various biological models, including cultured cells and animals, have been found useful for studying the carcinogenesis effects of radon progeny alpha particles. In this paper, sugars cape cellular automata have been presented for computational study of complex biological effect of radon progeny alpha particles in lung bronchial airways. The model has included mechanism of DNA damage, which has been induced alpha particles hits, and then formation of transformation in the lung cells. Biomarkers were an objective measure or evaluation of normal or abnormal biological processes. In the model, the metabolism rate of infected cell has been induced alpha particles traversals, as a biomarker, has been followed to reach oncogenic transformation. Results The model results have successfully validated in comparison with “in vitro oncogenic transformation data” for C3H 10T1/2 cells. This model has provided an opportunity to study the cellular and molecular changes, at the various stages in radiation carcinogenesis, involving human cells. Conclusion It has become well known that simulation could be used to investigate complex biomedical systems, in situations where traditional methodologies were difficult or too costly to employ. PMID:25250147

  16. The suppression of charged-particle-induced noise in infrared detectors

    NASA Technical Reports Server (NTRS)

    Houck, J. R.; Briotta, D. A., Jr.

    1982-01-01

    A d.c.-coupled transimpedance amplifier/pulse suppression circuit designed to remove charged-particle-induced noise from infrared detectors is described. Noise spikes produced by single particle events are large and have short rise times, and can degrade the performance of an infrared detector in moderate radiation environments. The use of the suppression circuit improves the signal-to-noise ratio by a factor of 1.6:1, which corresponds to a reduction in required observing time by a factor of about 2.6.

  17. Gravitationally Induced Particle Production and its Impact on the WIMP Abundance

    E-print Network

    I. Baranov; J. A. S. Lima

    2015-10-21

    A large set of independent astronomical observations have provided a strong evidence for nonbaryonic dark matter in the Universe. One of the most investigated candidates is an unknown long-lived Weakly Interacting Massive Particle (WIMP) which was in thermal equilibrium with the primeval plasma. Here we investigate the WIMP abundance based on the relativistic kinetic treatment for gravitationally induced particle production recently proposed in the literature (Lima \\& Baranov, Phys. Rev. D {\\bf 90}, 043515, 2014). The new evolution equation is deduced and solved both numerically and also through a semi-analytical approach. The predictions of the WIMP observables are discussed and compared with the ones obtained in the standard approach.

  18. Gravitationally induced particle production and its impact on the WIMP abundance

    NASA Astrophysics Data System (ADS)

    Baranov, I.; Lima, J. A. S.

    2015-12-01

    A large set of independent astronomical observations have provided a strong evidence for nonbaryonic dark matter in the Universe. One of the most investigated candidates is an unknown long-lived Weakly Interacting Massive Particle (WIMP) which was in thermal equilibrium with the primeval plasma. Here we investigate the WIMP abundance based on the relativistic kinetic treatment for gravitationally induced particle production recently proposed in the literature (Lima and Baranov, 2014) [16]. The new evolution equation is deduced and solved both numerically and through a semi-analytical approach. The predictions of the WIMP observables are discussed and compared with the ones obtained in the standard approach.

  19. Quantification of particle-induced inflammatory stress response: a novel approach for toxicity testing of earth materials

    PubMed Central

    2012-01-01

    Background Reactive oxygen species (ROS) are vital regulators of many cellular functions in the body. The intracellular ROS concentration is highly regulated by a balance between pro-oxidants and anti-oxidants. A chronic excess of pro-oxidants leads to elevated ROS concentrations and inflammation, possibly initiating or enhancing disease onset. Mineral-induced generation of ROS, the role of minerals in upregulating cellular ROS, and their role in the development of several occupational diseases are now widely recognized. However, there is no standard protocol to determine changes in ROS production in cells after exposure to mineral dust or earth materials in general. In this study, a new method for determining the degree of cellular toxicity (i.e., cytotoxicity) of particles is described that will help bridge the gap in knowledge. Results By measuring the production of ROS and the viability of cells, an inflammatory stress response (ISR) indicator is defined. This approach normalizes the ROS upregulation with respect to the number of viable cells at the time of measurement. We conducted experiments on a series of minerals and soils that represent materials that are inert (i.e., glass beads, anatase, and a soil with low trace element content), moderately reactive (i.e., soil with high trace element content), and highly reactive (i.e., pyrite). Inert materials generated the lowest ISR, averaging 350% compared to the control. Acid washed pyrite produced the highest ISR (1,100 fold higher than the control). The measurements conducted as a function of time showed a complex response. Most materials showed an increase in ISR with particle loading. Conclusions The amount of cellularly generated ROS and cell viability combined provide a better understanding of particle-induced oxidative stress. The results indicate that some earth materials may solicit an initial burst of ROS, followed by a second phase in which cell viability decreases and ROS production increases, leading to a high ISR value. Hence, measurements conducted over a range of particle loading combined with multiple data measurements up to 24 hours can provide new insights in the possible effect of exposure to earth materials on human health. PMID:22513118

  20. Epigenetic Transgenerational Inheritance of Vinclozolin Induced Mouse Adult Onset Disease and Associated Sperm Epigenome Biomarkers

    PubMed Central

    Guerrero-Bosagna, Carlos; Covert, Trevor R.; Haque, Md. M.; Settles, Matthew; Nilsson, Eric E.; Anway, Matthew D.; Skinner, Michael K.

    2012-01-01

    The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease. PMID:23041264

  1. Carbimazole-induced cholestatic hepatitis in Graves’ disease

    PubMed Central

    Kota, Sunil K.; Meher, Lalit K.; Kota, Siva K.; Jammula, Sruti; Modi, Kirtikumar D.

    2013-01-01

    Antithyroid medications are one of the treatment options for Graves’ disease. Carbimazole is widely used as the drug of choice, except in pregnancy, where propythiouracil is preferred by many. It is generally well-tolerated. Its side-effects include allergy, upper gastrointestinal upset, a rare occurrence of granulocytosis, and others. Hepatitis is another rare, but serious side-effect. We report a healthy 30-year-old male patient with Graves’ disease, who developed cholestatic jaundice after Carbimazole therapy for four months. He made a full recovery after the drug was discontinued. An idiosyncratic mechanism seemed likely. PMID:23776913

  2. Hormetic Effect Induced by Alpha-Particle-Induced Stress Communicated In Vivo between Zebrafish Embryos

    E-print Network

    Yu, Peter K.N.

    Embryos V. W. Y. Choi, A. L. Y. Cheung, S. H. Cheng,,§ and K. N. Yu*,,§ Department of Physics data showing that embryos of the zebrafish, Danio rerio, at 1.5 h post fertilization (hpf) subjected be communicated to unirradiated bystander zebrafish embryos sharing the same water medium to induce a hormetic

  3. Emerging Mechanistic Targets in Lung Injury Induced by Combustion-Generated Particles

    PubMed Central

    Fariss, Marc W.; Gilmour, M. Ian; Reilly, Christopher A.; Liedtke, Wolfgang; Ghio, Andrew J.

    2013-01-01

    The mechanism for biological effect following exposure to combustion-generated particles is incompletely defined. The identification of pathways regulating the acute toxicological effects of these particles provides specific targets for therapeutic manipulation in an attempt to impact disease following exposures. Transient receptor potential (TRP) cation channels were identified as “particle sensors” in that their activation was coupled with the initiation of protective responses limiting airway deposition and inflammatory responses, which promote degradation and clearance of the particles. TRPA1, V1, V4, and M8 have a capacity to mediate adverse effects after exposure to combustion-generated particulate matter (PM); relative contributions of each depend upon particle composition, dose, and deposition. Exposure of human bronchial epithelial cells to an organic extract of diesel exhaust particle was followed by TRPV4 mediating Ca++ influx, increased RAS expression, mitogen-activated protein kinase signaling, and matrix metalloproteinase-1 activation. These novel pathways of biological effect can be targeted by compounds that specifically inhibit critical signaling reactions. In addition to TRPs and calcium biochemistry, humic-like substances (HLS) and cell/tissue iron equilibrium were identified as potential mechanistic targets in lung injury after particle exposure. In respiratory epithelial cells, iron sequestration by HLS in wood smoke particle (WSP) was associated with oxidant generation, cell signaling, transcription factor activation, and release of inflammatory mediators. Similar to WSP, cytotoxic insoluble nanosized spherical particles composed of HLS were isolated from cigarette smoke condensate. Therapies that promote bioelimination of HLS and prevent the disruption of iron homeostasis could function to reduce the harmful effects of combustion-generated PM exposure. PMID:23322347

  4. INK: A computer program for accurate analysis of particle-induced X-ray emission spectra

    NASA Astrophysics Data System (ADS)

    Jabr, I. J.; Saleh, N. S.; Hallak, A. B.

    A computer program, INK, for the analysis of spectra obtained in proton induced X-ray emission (PIXE) is described. It fits Gaussian-shaped lines to the characteristic peaks. The continuum is fitted by an exponential function representing bremsstrahlung of the incident particles, secondary electron induced bremsstrahlung and different Compton scattering processes. The program is largely automatic. It is capable of providing fits for up to 20 elements in one to four minutes on a small microcomputer. It locates all peaks in a read-in spectrum and determines their energies, areas and elemental abundances. Applications to biological and geological samples are discussed.

  5. Quantitative elemental detection of size-segregated particles using laser-induced breakdown spectroscopy

    NASA Astrophysics Data System (ADS)

    Wang, Zhen Zhen; Deguchi, Yoshihiro; Kuwahara, Masakazu; Taira, Takuya; Zhang, Xiao Bo; Yan, Jun Jie; Liu, Ji Ping; Watanabe, Hiroaki; Kurose, Ryoichi

    2013-09-01

    In order to simulate coal combustion and develop optimal and stable boiler control systems in real power plants, it is imperative to obtain the detailed information in coal combustion processes as well as to measure species contents in fly ash, which should be controlled and analyzed for enhancing boiler efficiency and reducing environmental pollution. The fly ash consists of oxides (SiO2, Al2O3, Fe2O3, CaO, and so on), unburned carbon, and other minor elements. Recently laser-induced breakdown spectroscopy (LIBS) technique has been applied to coal combustion and other industrial fields because of the fast response, high sensitivity, real-time and non-contact features. In these applications it is important to measure controlling factors without any sample preparation to maintain the real-time measurement feature. The relation between particle content and particle diameter is also one of the vital researches, because compositions of particles are dependent on their diameter. In this study, we have detected the contents of size-segregated particles using LIBS. Particles were classified by an Anderson cascade impactor and their contents were measured using the output of 1064 nm YAG laser, a spectrograph and an ICCD camera. The plasma conditions such as plasma temperature are dependent on the size of particles and these effects must be corrected to obtain quantitative information. The plasma temperature was corrected by the emission intensity ratio from the same atom. Using this correction method, the contents of particles can be measured quantitatively in fixed experimental parameters. This method was applied to coal and fly ash from a coal-fired burner to measure unburned carbon and other contents according to the particle diameter. The acquired results demonstrate that the LIBS technique is applicable to measure size-segregated particle contents in real time and this method is useful for the analysis of coal combustion and its control because of its sensitive and fast analysis features.

  6. Lupine Induced "Crooked Calf Disease": The Last 20 Years

    Technology Transfer Automated Retrieval System (TEKTRAN)

    “Crooked calf disease” is used to describe a number of skeletal malformations in newborn calves, including a twisted spine, neck, and one or both forelimbs. These malformations develop when the pregnant cow eats toxic lupines containing the alkaloids anagyrine, ammodendrine, and N-methyl ammodendri...

  7. Dopamine-Induced Nonmotor Symptoms of Parkinson's Disease

    PubMed Central

    Park, Ariane; Stacy, Mark

    2011-01-01

    Nonmotor symptoms of Parkinson's disease (PD) may emerge secondary to the underlying pathogenesis of the disease, while others are recognized side effects of treatment. Inevitably, there is an overlap as the disease advances and patients require higher dosages and more complex medical regimens. The non-motor symptoms that emerge secondary to dopaminergic therapy encompass several domains, including neuropsychiatric, autonomic, and sleep. These are detailed in the paper. Neuropsychiatric complications include hallucinations and psychosis. In addition, compulsive behaviors, such as pathological gambling, hypersexuality, shopping, binge eating, and punding, have been shown to have a clear association with dopaminergic medications. Dopamine dysregulation syndrome (DDS) is a compulsive behavior that is typically viewed through the lens of addiction, with patients needing escalating dosages of dopamine replacement therapy. Treatment side effects on the autonomic system include nausea, orthostatic hypotension, and constipation. Sleep disturbances include fragmented sleep, nighttime sleep problems, daytime sleepiness, and sleep attacks. Recognizing the non-motor symptoms that can arise specifically from dopamine therapy is useful to help optimize treatment regimens for this complex disease. PMID:21603184

  8. Kinetic Arrest in Polyion-Induced Inhomogeneously-Charged Colloidal Particle Aggregation

    E-print Network

    D. Truzzolillo; F. Bordi; F. Sciortino; C. Cametti

    2008-05-26

    Polymer chains adsorbed onto oppositely charged spherical colloidal particles can significantly modify the particle-particle interactions. For sufficient amounts of added polymers, the original electrostatic repulsion can even turn into an effective attraction and relatively large kinetically stable aggregates can form which display several unexpected and interesting peculiarities and some intriguing biotechnological implications. The attractive interaction contribution between two oppositely particles arises from the correlated adsorption of polyions at the oppositely charged particle surfaces, resulting in a non-homogeneous surface charge distribution. Here, we investigate the aggregation kinetics of polyion-induced colloidal complexes through Monte Carlo simulation, in which the effect of charge anisotropy is taken into account by a DLVO-like intra-particle potential, as recentely proposed by Velegol and Thwar [D. Velegol and P.K. Thwar, Langmuir, 17, 2001]. The results reveal that in the presence of a charge heterogeneity the aggregation process slows down due to the progressive increase of the potential barrier height upon clustering. Within this framework, the experimentally observed cluster phases in polyelectrolyte-liposomes solutions should be considered as a kinetic arrested state.

  9. On inducing finite dimensional physical field representations for massless particles in even dimensions

    NASA Technical Reports Server (NTRS)

    Bhansali, Vineer

    1993-01-01

    Assuming trivial action of Euclidean translations, the method of induced representations is used to derive a correspondence between massless field representations transforming under the full generalized even dimensional Lorentz group, and highest weight states of the relevant little group. This gives a connection between 'helicity' and 'chirality' in all dimensions. Restrictions on 'gauge independent' representations for physical particles that this induction imposes are also stated.

  10. Stress-induced Start Codon Fidelity Regulates Arsenite-inducible Regulatory Particle-associated Protein (AIRAP) Translation*

    PubMed Central

    Zach, Lolita; Braunstein, Ilana; Stanhill, Ariel

    2014-01-01

    Initial steps in protein synthesis are highly regulated processes as they define the reading frame of the translation machinery. Eukaryotic translation initiation is a process facilitated by numerous factors (eIFs), aimed to form a “scanning” mechanism toward the initiation codon. Translation initiation of the main open reading frame (ORF) in an mRNA transcript has been reported to be regulated by upstream open reading frames (uORFs) in a manner of re-initiation. This mode of regulation is governed by the phosphorylation status of eIF2? and controlled by cellular stresses. Another mode of translational initiation regulation is leaky scanning, and this regulatory process has not been extensively studied. We have identified arsenite-inducible regulatory particle-associated protein (AIRAP) transcript to be translationally induced during arsenite stress conditions. AIRAP transcript contains a single uORF in a poor-kozak context. AIRAP translation induction is governed by means of leaky scanning and not re-initiation. This induction of AIRAP is solely dependent on eIF1 and the uORF kozak context. We show that eIF1 is phosphorylated under specific conditions that induce protein misfolding and have biochemically characterized this site of phosphorylation. Our data indicate that leaky scanning like re-initiation is responsive to stress conditions and that leaky scanning can induce ORF translation by bypassing poor kozak context of a single uORF transcript. PMID:24898249

  11. A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

    SciTech Connect

    Yannam, Govardhana Rao; Han, Bing; Setoyama, Kentaro; Yamamoto, Toshiyuki; Ito, Ryotaro; Brooks, Jenna M.; Guzman-Lepe, Jorge; Galambos, Csaba; Fong, Jason V.; Deutsch, Melvin; Quader, Mubina A.; Yamanouchi, Kosho; Kabarriti, Rafi; Mehta, Keyur; Soto-Gutierrez, Alejandro; and others

    2014-02-01

    Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ?40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury.

  12. Role of mutagenicity in asbestos fiber-induced carcinogenicity and other diseases.

    PubMed

    Huang, Sarah X L; Jaurand, Marie-Claude; Kamp, David W; Whysner, John; Hei, Tom K

    2011-01-01

    The cellular and molecular mechanisms of how asbestos fibers induce cancers and other diseases are not well understood. Both serpentine and amphibole asbestos fibers have been shown to induce oxidative stress, inflammatory responses, cellular toxicity and tissue injuries, genetic changes, and epigenetic alterations in target cells in vitro and tissues in vivo. Most of these mechanisms are believe to be shared by both fiber-induced cancers and noncancerous diseases. This article summarizes the findings from existing literature with a focus on genetic changes, specifically, mutagenicity of asbestos fibers. Thus far, experimental evidence suggesting the involvement of mutagenesis in asbestos carcinogenicity is more convincing than asbestos-induced fibrotic diseases. The potential contributions of mutagenicity to asbestos-induced diseases, with an emphasis on carcinogenicity, are reviewed from five aspects: (1) whether there is a mutagenic mode of action (MOA) in fiber-induced carcinogenesis; (2) mutagenicity/carcinogenicity at low dose; (3) biological activities that contribute to mutagenicity and impact of target tissue/cell type; (4) health endpoints with or without mutagenicity as a key event; and finally, (5) determinant factors of toxicity in mutagenicity. At the end of this review, a consensus statement of what is known, what is believed to be factual but requires confirmation, and existing data gaps, as well as future research needs and directions, is provided. PMID:21534089

  13. Role of Mutagenicity in Asbestos Fiber-Induced Carcinogenicity and Other Diseases

    PubMed Central

    Huang, Sarah X. L.; Jaurand, Marie-Claude; Kamp, David W.; Whysner, John; Hei, Tom K.

    2011-01-01

    The cellular and molecular mechanisms of how asbestos fibers induce cancers and other diseases are not well understood. Both serpentine and amphibole asbestos fibers have been shown to induce oxidative stress, inflammatory responses, cellular toxicity and tissue injuries, genetic changes, and epigenetic alterations in target cells in vitro and tissues in vivo. Most of these mechanisms are believe to be shared by both fiber-induced cancers and noncancerous diseases. This article summarizes the findings from existing literature with a focus on genetic changes, specifically, mutagenicity of asbestos fibers. Thus far, experimental evidence suggesting the involvement of mutagenesis in asbestos carcinogenicity is more convincing than asbestos-induced fibrotic diseases. The potential contributions of mutagenicity to asbestos-induced diseases, with an emphasis on carcinogenicity, are reviewed from five aspects: (1) whether there is a mutagenic mode of action (MOA) in fiber-induced carcinogenesis; (2) mutagenicity/carcinogenicity at low dose; (3) biological activities that contribute to mutagenicity and impact of target tissue/cell type; (4) health endpoints with or without mutagenicity as a key event; and finally, (5) determinant factors of toxicity in mutagenicity. At the end of this review, a consensus statement of what is known, what is believed to be factual but requires confirmation, and existing data gaps, as well as future research needs and directions, is provided. PMID:21534089

  14. A Lipidomic Readout of Disease Progression in A Diet-Induced Mouse Model of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Sanyal, Arun J.; Pacana, Tommy

    2015-01-01

    Multiple changes in lipid metabolism occur in nonalcoholic fatty liver disease. However, it is not known which of these contribute to disease progression. The objective of this study was to define changes in hepatic lipid composition over time in a diet-induced model of nonalcoholic fatty liver disease to identify changes associated with disease progression. A lipidomic approach was used to quantify individual lipid species with lipid classes of interest including diacylglycerols (DAG), cholesterol, phospholipids, plasmalogens, sphingolipids, and eicosanoids. C57b/S129J mice fed a high-fat, high-cholesterol diet developed fatty liver, inflammation, and ballooning by 16 weeks and extensive fibrosis by week 52. There was a marked increase in monounsaturated fatty acid containing DAGs and cholesterol esters by week 16 which decreased by week 52. The changes in DAG were associated with a 500- to 600-fold increase in phosphatidic acid (< 0.001) and its downstream product phosphatidylglycerol (P <0.01) whereas phosphatidylethanolamine, phosphatidylcholine, and phsophatidylserine all decreased. Disease progression was associated with a significant further decrease in phosphatidylcholine and phosphatidylethanolamine while several lysolecithin species increased. Disease progression was associated with a significant increase in the plasmalogen PC-P 16:0/16:1. Saturated fatty acid (16:0 and 18:0) containing ceramides, sphingosine, sphingosine-1-phosphate, dihydrosphingosine, and dihydrophingosine-1-phosphate increased by week 16 after high-fat high-cholesterol diet. Globotrioseacylceramide (GB3) also increased significantly by week 16 and increased further with disease progression. 12-hydroxyeicosatetranoic acid decreased at week 16 but increased with disease progression. In conclusion, multiple lipids were associated with disease progression and provide clues regarding lipid drivers of nonalcoholic steatohepatitis. PMID:26330688

  15. Further study on mechanism of production of light complex particles in nucleon-induced reactions

    E-print Network

    Dexian Wei; Lihua Mao; Ning Wang; Min Liu; Li Ou

    2015-09-11

    The Improved Quantum Molecular Dynamics (ImQMD) model incorporated with the statistical decay model is used to investigate the intermediate energy nucleon-induced reactions. In our last work, the description on light complex particle emission has been great improved with a phenomenological mechanism called surface coalescence and emission introduced into ImQMD model. In this work, taking account of different specific binding energies and separation energies for various light complex particles, the phase space parameters in surface coalescence model are readjusted. By using the new phase space parameters set with better physical fundament, the double differential cross sections of emitted light complex particles are found to be in better agreement with experimental data.

  16. Mitogenic activity for fibroblasts induced by silica and titanium dioxide particles in vitro and in vivo.

    PubMed Central

    Kumar, R. K.; O'Grady, R.; Li, W.; Velan, G. M.

    1992-01-01

    Experimental studies on particle-induced pulmonary fibrosis have not provided consistent evidence for the specific induction of fibroblast-regulating cytokines by pulmonary macrophages in response to fibrogenic as compared to non-fibrogenic particles. Using an optimized, wholly serum-free bioassay, we assessed mitogenic activity for pulmonary fibroblasts in supernatants of short-term cultures of alveolar macrophages exposed to either fibrogenic silica or non-fibrogenic titanium dioxide ducts. The responses to these supernatants were influenced by the replicative status of the target cells, in that samples which stimulated non-cycling fibroblasts caused inhibition of DNA synthesis by cycling cells when tested at the same concentration. However, both silica and titanium dioxide elicited comparable secretion of growth factor activity by macrophages, following either in-vitro or in-vivo administration of particles. In contrast, bronchoalveolar lavage fluids from animals that received intratracheal injections of silica, but not from those that received titanium dioxide, exhibited a sustained reduction in fibroblast-stimulating activity. We conclude that secretion of growth factor activity by alveolar macrophages in culture is induced by particles in a non-specific manner. However, alterations in mitogenic activity in bronchoalveolar lavage fluid may constitute a biological marker of the pattern of pulmonary injury which progresses to fibrosis. PMID:1329913

  17. Particles from wood smoke and traffic induce differential pro-inflammatory response patterns in co-cultures

    SciTech Connect

    Kocbach, Anette Herseth, Jan Inge; Lag, Marit; Refsnes, Magne; Schwarze, Per E.

    2008-10-15

    The inflammatory potential of particles from wood smoke and traffic has not been well elucidated. In this study, a contact co-culture of monocytes and pneumocytes was exposed to 10-40 {mu}g/cm{sup 2} of particles from wood smoke and traffic for 12, 40 and 64 h to determine their influence on pro-inflammatory cytokine release (TNF-{alpha}, IL-1, IL-6, IL-8) and viability. To investigate the role of organic constituents in cytokine release the response to particles, their organic extracts and the washed particles were compared. Antagonists were used to investigate source-dependent differences in intercellular signalling (TNF-{alpha}, IL-1). The cytotoxicity was low after exposure to particles from both sources. However, wood smoke, and to a lesser degree traffic-derived particles, induced a reduction in cell number, which was associated with the organic fraction. The release of pro-inflammatory cytokines was similar for both sources after 12 h, but traffic induced a greater release than wood smoke particles with increasing exposure time. The organic fraction accounted for the majority of the cytokine release induced by wood smoke, whereas the washed traffic particles induced a stronger response than the corresponding organic extract. TNF-{alpha} and IL-1 antagonists reduced the release of IL-8 induced by particles from both sources. In contrast, the IL-6 release was only reduced by the IL-1 antagonist during exposure to traffic-derived particles. In summary, particles from wood smoke and traffic induced differential pro-inflammatory response patterns with respect to cytokine release and cell number. Moreover, the influence of the organic particle fraction and intercellular signalling on the pro-inflammatory response seemed to be source-dependent.

  18. Shear-induced particle migration and margination in a cellular suspension

    NASA Astrophysics Data System (ADS)

    Zhao, Hong; Shaqfeh, Eric S. G.; Narsimhan, Vivek

    2012-01-01

    We simulate the cross-flow migration of rigid particles such as platelets in a red blood cell (RBC) suspension using the Stokes flow boundary integral equation method. Two types of flow environments are investigated: a suspension undergoing a bulk shear motion and a suspension flowing in a microchannel or duct. In a cellular suspension undergoing bulk shear deformation, the cross-flow migration of particles is diffusional. The velocity fluctuations in the suspension, which are the root cause of particle migration, are analyzed in detail, including their magnitude, the autocorrelation of Lagrangian tracer points and particles, and the associated integral time scales. The orientation and morphology of red blood cells vary with the shear rate, and these in turn cause the dimensionless particle diffusivity to vary non-monotonically with the flow capillary number. By simulating RBCs and platelets flowing in a microchannel of 34 ?m height, we demonstrate that the velocity fluctuations in the core cellular flow region cause the platelets to migrate diffusively in the wall normal direction. A mean lateral velocity of particles, which is most significant near the edge of the cell-free layer, further expels them toward the wall, leading to their excess concentration in the cell-free layer. The calculated shear-induced particle diffusivity in the cell-laden region is in qualitative agreement with the experimental measurements of micron-sized beads in a cylindrical tube of a comparable diameter. In a smaller duct of 10 × 15 ?m cross section, the volume exclusion becomes the dominant mechanism for particle margination, which occurs at a much shorter time scale than the migration in the bigger channel.

  19. Disease-induced resource constraints can trigger explosive epidemics

    E-print Network

    Böttcher, Lucas; Araújo, Nuno A M; Herrmann, Hans J; Helbing, Dirk

    2015-01-01

    Advances in mathematical epidemiology have led to a better understanding of the risks posed by epidemic spreading and informed strategies to contain disease spread. However, a challenge that has been overlooked is that, as a disease becomes more prevalent, it can limit the availability of the capital needed to effectively treat those who have fallen ill. Here we use a simple mathematical model to gain insight into the dynamics of an epidemic when the recovery of sick individuals depends on the availability of healing resources that are generated by the healthy population. We find that epidemics spiral out of control into "explosive" spread if the cost of recovery is above a critical cost. This can occur even when the disease would die out without the resource constraint. The onset of explosive epidemics is very sudden, exhibiting a discontinuous transition under very general assumptions. We find analytical expressions for the critical cost and the size of the explosive jump in infection levels in terms of the...

  20. Brain signaling and behavioral responses induced by exposure to (56)Fe-particle radiation

    NASA Technical Reports Server (NTRS)

    Denisova, N. A.; Shukitt-Hale, B.; Rabin, B. M.; Joseph, J. A.

    2002-01-01

    Previous experiments have demonstrated that exposure to 56Fe-particle irradiation (1.5 Gy, 1 GeV) produced aging-like accelerations in neuronal and behavioral deficits. Astronauts on long-term space flights will be exposed to similar heavy-particle radiations that might have similar deleterious effects on neuronal signaling and cognitive behavior. Therefore, the present study evaluated whether radiation-induced spatial learning and memory behavioral deficits are associated with region-specific brain signaling deficits by measuring signaling molecules previously found to be essential for behavior [pre-synaptic vesicle proteins, synaptobrevin and synaptophysin, and protein kinases, calcium-dependent PRKCs (also known as PKCs) and PRKA (PRKA RIIbeta)]. The results demonstrated a significant radiation-induced increase in reference memory errors. The increases in reference memory errors were significantly negatively correlated with striatal synaptobrevin and frontal cortical synaptophysin expression. Both synaptophysin and synaptobrevin are synaptic vesicle proteins that are important in cognition. Striatal PRKA, a memory signaling molecule, was also significantly negatively correlated with reference memory errors. Overall, our findings suggest that radiation-induced pre-synaptic facilitation may contribute to some previously reported radiation-induced decrease in striatal dopamine release and for the disruption of the central dopaminergic system integrity and dopamine-mediated behavior.

  1. Cellular and molecular analysis of mutagenesis induced by charged particles of defined linear energy transfer

    NASA Technical Reports Server (NTRS)

    Zhu, L. X.; Waldren, C. A.; Vannias, D.; Hei, T. K.; Chatterjee, A. (Principal Investigator)

    1996-01-01

    Mutation induction by charged particles of defined linear energy transfer (LET) and gamma rays was scored using human-hamster hybrid AL cells. The LET values for charged particles accelerated at the Radiological Research Accelerator Facility ranged from 10 keV/microm protons to 150 keV/microm 4He ions. The induced mutant fractions at both the S1 and HGPRT loci were dependent on the dose and LET. In addition, for each dose examined, the mutant yield at the S1 locus was 30-60 fold higher than at the corresponding HGPRT locus. To determine whether the mutation spectrum was comparably dependent on dose and LET, independent S1- and HGPRT- mutants induced by 150 keV/microm 4He ions and gamma rays were isolated, and their DNA was analyzed by both Southern blotting and multiplex PCR methods. While the majority of radiation-induced mutants showed deletions of varying sizes, the relative percentage of large deletions was found to be related to both the dose and LET of the radiation examined. Using a mutation system that can detect multilocus changes, results of the present study show that radiation-induced chromosomal loss can be in the millions of base pairs.

  2. Human Metapneumovirus Virus-Like Particles Induce Protective B and T Cell Responses in a Mouse Model

    PubMed Central

    Cox, Reagan G.; Erickson, John J.; Hastings, Andrew K.; Becker, Jennifer C.; Johnson, Monika; Craven, Ryan E.; Tollefson, Sharon J.; Boyd, Kelli L.

    2014-01-01

    ABSTRACT Human metapneumovirus (HMPV) is a leading cause of respiratory disease in infants, children, and the elderly worldwide, yet no licensed vaccines exist. Live-attenuated vaccines present safety challenges, and protein subunit vaccines induce primarily antibody responses. Virus-like particles (VLPs) are an attractive alternative vaccine approach because of reduced safety concerns compared with live vaccines. We generated HMPV VLPs by expressing viral proteins in suspension-adapted human embryonic kidney epithelial (293-F) cells and found that the viral matrix (M) and fusion (F) proteins were sufficient to form VLPs. We previously reported that the VLPs resemble virus morphology and incorporate fusion-competent F protein (R. G. Cox, S. B. Livesay, M. Johnson, M. D. Ohi, and J. V. Williams, J. Virol. 86:12148–12160, 2012), which we hypothesized would elicit F-specific antibody and T cell responses. In this study, we tested whether VLP immunization could induce protective immunity to HMPV by using a mouse model. C57BL/6 mice were injected twice intraperitoneally with VLPs alone or with adjuvant and subsequently challenged with HMPV. Mice were euthanized 5 days postinfection, and virus titers, levels of neutralizing antibodies, and numbers of CD3+ T cells were quantified. Mice immunized with VLPs mounted an F-specific antibody response and generated CD8+ T cells recognizing an F protein-derived epitope. VLP immunization induced a neutralizing-antibody response that was enhanced by the addition of either TiterMax Gold or ?-galactosylceramide adjuvant, though adjuvant reduced cellular immune responses. Two doses of VLPs conferred complete protection from HMPV replication in the lungs of mice and were not associated with a Th2-skewed cytokine response. These results suggest that nonreplicating VLPs are a promising vaccine candidate for HMPV. IMPORTANCE Human metapneumovirus (HMPV) is a leading cause of acute respiratory infection in infants, children, and the elderly worldwide, yet no licensed vaccines exist. Live-attenuated vaccines present safety challenges, and protein subunit vaccines induce primarily antibody responses. Virus-like particles (VLPs) are an attractive alternative vaccine approach. We generated HMPV VLPs by expressing the viral matrix (M) and fusion (F) proteins in mammalian cells. We found that mice immunized with VLPs mounted an F-specific antibody response and generated CD8+ T cells recognizing an F protein-derived epitope. VLP immunization induced a neutralizing-antibody response that was enhanced by the addition of either TiterMax Gold or ?-galactosylceramide adjuvant. Two doses of VLPs conferred complete protection against HMPV replication in the lungs of mice and were not associated with a Th2-skewed cytokine response. These results suggest that nonreplicating VLPs are a promising vaccine candidate for HMPV. PMID:24672031

  3. Human induced pluripotent stem cells in Parkinson's disease: A novel cell source of cell therapy and disease modeling.

    PubMed

    Li, Wen; Chen, Shengdi; Li, Jia-Yi

    2015-11-01

    Human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) are two novel cell sources for studying neurodegenerative diseases. Dopaminergic neurons derived from hiPSCs/hESCs have been implicated to be very useful in Parkinson's disease (PD) research, including cell replacement therapy, disease modeling and drug screening. Recently, great efforts have been made to improve the application of hiPSCs/hESCs in PD research. Considerable advances have been made in recent years, including advanced reprogramming strategies without the use of viruses or using fewer transcriptional factors, optimized methods for generating highly homogeneous neural progenitors with a larger proportion of mature dopaminergic neurons and better survival and integration after transplantation. Here we outline the progress that has been made in these aspects in recent years, particularly during the last year, and also discuss existing issues that need to be addressed. PMID:26408505

  4. Efficient particle-mesh Ewald based approach to fixed and induced dipolar interactions

    NASA Astrophysics Data System (ADS)

    Toukmaji, Abdulnour; Sagui, Celeste; Board, John; Darden, Tom

    2000-12-01

    We have implemented classical Ewald and particle-mesh Ewald (PME) based treatments of fixed and induced point dipoles into the sander molecular dynamics (MD) module of AMBER 6. During MD the induced dipoles can be propagated along with the atomic positions either by iteration to self-consistency at each time step, or by a Car-Parrinello (CP) technique using an extended Lagrangian formalism. In this paper we present the derivation of the new algorithms and compare the various options with respect to accuracy, efficiency, and effect on calculated properties of a polarizable water model. The use of PME for electrostatics of fixed charges and induced dipoles together with a CP treatment of dipole propagation in MD simulations leads to a cost overhead of only 33% above that of MD simulations using standard PME with fixed charges, allowing the study of polarizability in large macromolecular systems.

  5. Soybean (Glycine max L. Merr.) Sprouts Germinated under Red Light Irradiation Induce Disease Resistance against Bacterial Rotting Disease

    PubMed Central

    Dhakal, Radhika; Park, Euiho; Lee, Se-Weon; Baek, Kwang-Hyun

    2015-01-01

    Specific wavelengths of light can exert various physiological changes in plants, including effects on responses to disease incidence. To determine whether specific light wavelength had effects on rotting disease caused by Pseudomonas putida 229, soybean sprouts were germinated under a narrow range of wavelengths from light emitting diodes (LEDs), including red (650–660), far red (720–730) and blue (440–450 nm) or broad range of wavelength from daylight fluorescence bulbs. The controls were composed of soybean sprouts germinated in darkness. After germination under different conditions for 5 days, the soybean sprouts were inoculated with P. putida 229 and the disease incidence was observed for 5 days. The sprouts exposed to red light showed increased resistance against P. putida 229 relative to those grown under other conditions. Soybean sprouts germinated under red light accumulated high levels of salicylic acid (SA) accompanied with up-regulation of the biosynthetic gene ICS and the pathogenesis- related (PR) gene PR-1, indicating that the resistance was induced by the action of SA via de novo synthesis of SA in the soybean sprouts by red light irradiation. Taken together, these data suggest that only the narrow range of red light can induce disease resistance in soybean sprouts, regulated by the SA-dependent pathway via the de novo synthesis of SA and up-regulation of PR genes. PMID:25679808

  6. Excitation of high-[ital n] toroidicity-induced shear Alfven eigenmodes by energetic particles and fusion alpha particles in tokamaks

    SciTech Connect

    Fu, G.Y.; Cheng, C.Z. )

    1992-11-01

    The stability of high-[ital n] toroidicity-induced shear Alfven eigenmodes (TAE) in the presence of fusion alpha particles or energetic ions in tokamaks is investigated. The TAE modes are discrete in nature, and thus can easily tap the free energy associated with energetic particle pressure gradient through wave particle resonant interaction. A quadratic form is derived for the high-[ital n] TAE modes using gyrokinetic equation. The kinetic effects of energetic particles are calculated perturbatively using the ideal magnetohydrodynamic (MHD) solution as the lowest-order eigenfunction. The finite Larmor radius (FLR) effects and the finite drift orbit width (FDW) effects are included for both circulating and trapped energetic particles. It is shown that, for circulating particles, FLR and FDW effects have two opposite influences on the stability of the high-[ital n] TAE modes. First, they have the usual stabilizing effects by reducing the wave particle interaction strength. Second, they also have destabilizing effects by allowing more particles to resonate with the TAE modes. It is found that the growth rate induced by the circulating alpha particles increases linearly with the toroidal mode number [ital n] for small [ital k][sub [theta

  7. Fine ambient particles induce oxidative stress and metal binding genes in human alveolar macrophages.

    PubMed

    Huang, Yuh-Chin T; Li, Zhuowei; Carter, Jacqueline D; Soukup, Joleen M; Schwartz, David A; Yang, Ivana V

    2009-11-01

    Exposure to pollutant particles increased respiratory morbidity and mortality. The alveolar macrophages (AMs) are one cell type in the lung directly exposed to particles. Upon contact with particles, AMs are activated and produce reactive oxygen species, but the scope of this oxidative stress response remains poorly defined. In this study, we determined the gene expression profile in human AMs exposed to particles, and sought to characterize the global response of pro- and antioxidant genes. We exposed AMs obtained by bronchoscopy from normal individuals to Chapel Hill particulate matter of 2.5-microm diameter or smaller (PM(2.5); 1 microg/ml) or vehicle for 4 hours (n = 6 independent samples). mRNAs were extracted, amplified, and hybridized to Agilent human 1A microarray. Significant genes were identified by significance analysis of microarrays (false discovery rate, 10%; P < or = 0.05) and mapped with Gene Ontology in the Database for Annotation, Visualization, and Integrated Discovery. We found 34 and 41 up- and down-regulated genes, respectively; 22 genes (approximately 30%) were involved in metal binding, and 11 were linked to oxidative stress, including up-regulation of five metallothionein (MT)-1 isoforms. Exogenous MT1 attenuated PM(2.5)-induced H2O2 release. PM(2.5) premixed with MT1 stimulated less H2O2 release. Knockdown of MT1F gene increased PM(2.5)-induced H2O2 release. PM(2.5) at 1 microg/ml did not increase H2O2 release. Mount St. Helens PM(2.5) and acid-extracted Chapel Hill PM(2.5), both poor in metals, did not induce MT1F or H2O2 release. Our results show that PM(2.5) induced a gene expression profile prevalent with genes related to metal binding and oxidative stress in human AMs, independent of oxidative stress. Metals associated with PM may play an important role in particle-induced gene changes. PMID:19251948

  8. The Effects of Disease-Induced Juvenile Mortality on the Transient and Asymptotic Population Dynamics of Chinook Salmon (Oncorhynchus tshawytscha) 

    E-print Network

    Fujiwara, Masami; Mohr, Michael S.; Greenberg, Aaron

    2014-01-10

    The effects of an increased disease mortality rate on the transient and asymptotic dynamics of Chinook salmon (Oncorhynchus tshawytscha) were investigated. Disease-induced mortality of juvenile salmon has become a serious concern in recent years...

  9. Therapeutic application of metallic nanoparticles combined with particle-induced x-ray emission effect

    NASA Astrophysics Data System (ADS)

    Kim, Jong-Ki; Seo, Seung-Jun; Kim, Ki-Hong; Kim, Tae-Jeong; Chung, Myung-Hwan; Kim, Kye-Ryung; Yang, Tae-Keun

    2010-10-01

    Metallic nanoparticles (MNP) are able to release localized x-rays when activated with a high energy proton beam by the particle-induced x-ray emission (PIXE) effect. The exploitation of this phenomenon in the therapeutic irradiation of tumors has been investigated. PIXE-based x-ray emission directed at CT26 tumor cells in vitro, when administered with either gold (average diameter 2 and 13 nm) or iron (average diameter 14 nm) nanoparticles (GNP or SNP), increased with MNP solution concentration over the range of 0.1-2 mg ml - 1. With irradiation by a 45 MeV proton therapy (PT) beam, higher concentrations had a decreased cell survival fraction. An in vivo study in CT26 mouse tumor models with tumor regression assay demonstrated significant tumor dose enhancement, thought to be a result of the PIXE effect when compared to conventional PT without MNP (radiation-only group) using a 45 MeV proton beam (p < 0.02). Those receiving GNP or SNP injection doses of 300 mg kg - 1 body weight before proton beam therapy demonstrated 90% or 75% tumor volume reduction (TVR) in 20 days post-PT while the radiation-only group showed only 18% TVR and re-growth of tumor volume after 20 days. Higher complete tumor regression (CTR) was observed in 14-24 days after a single treatment of PT with an average rate of 33-65% for those receiving MNP compared with 25% for the radiation-only group. A lower bound of therapeutic effective MNP concentration range, in vivo, was estimated as 30-79 µg g - 1 tissue for both gold and iron nanoparticles. The tumor dose enhancement may compensate for an increase in entrance dose associated with conventional PT when treating large, solid tumors with a spread-out Bragg peak (SOBP) technique. The use of a combined high energy Bragg peak PT with PIXE generated by MNP, or PIXE alone, may result in new treatment options for infiltrative metastatic tumors and other diffuse inflammatory diseases.

  10. Transmission dynamics of Tasmanian devil facial tumor disease may lead to disease-induced extinction.

    PubMed

    McCallum, Hamish; Jones, Menna; Hawkins, Clare; Hamede, Rodrigo; Lachish, Shelly; Sinn, David L; Beeton, Nick; Lazenby, Billie

    2009-12-01

    Most pathogens threatening to cause extinction of a host species are maintained on one or more reservoir hosts, in addition to the species that is threatened by disease. Further, most conventional host-pathogen theory assumes that transmission is related to host density, and therefore a pathogen should become extinct before its sole host. Tasmanian devil facial tumor disease is a recently emerged infectious cancer that has led to massive population declines and grave concerns for the future persistence of this largest surviving marsupial carnivore. Here we report the results of mark-recapture studies at six sites and use these data to estimate epidemiological parameters critical to both accurately assessing the risk of extinction from this disease and effectively managing this disease threat. Three sites were monitored from before or close to the time of disease arrival, and at three others disease was well established when trapping began, in one site for at least 10 years. We found no evidence for sex-specific differences in disease prevalence and little evidence of consistent seasonal variation in the force of infection. At all sites, the disease was maintained at high levels of prevalence (>50% in 2-3-year-old animals), despite causing major population declines. We also provide the first estimates of the basic reproductive rate R0 for this disease. Using a simple age-structured deterministic model, we show that our results are not consistent with transmission being proportional to the density of infected hosts but are consistent with frequency-dependent transmission. This conclusion is further supported by the observation that local disease prevalence in 2-3-year-olds still exceeds 50% at a site where population density has been reduced by up to 90% in the past 12 years. These findings lend considerable weight to concerns that this host-specific pathogen will cause the extinction of the Tasmanian devil. Our study highlights the importance of rapidly implementing monitoring programs to determine how transmission depends on host density and emphasizes the need for ongoing management strategies involving a disease-free "insurance population," along with ongoing field monitoring programs to confirm whether local population extinction occurs. PMID:20120807

  11. Triptolide inhibits osteoclast formation, bone resorption, RANKL-mediated NF-?B activation and titanium particle-induced osteolysis in a mouse model.

    PubMed

    Huang, Jianbin; Zhou, Lin; Wu, Huafei; Pavlos, Nathan; Chim, Shek Man; Liu, Qian; Zhao, Jinmin; Xue, Wei; Tan, Ren Xiang; Ye, Jiming; Xu, Jun; Ang, Estabelle S; Feng, Haotian; Tickner, Jennifer; Xu, Jiake; Ding, Yue

    2015-01-01

    The RANKL-induced NF-?B signaling pathway is required for osteoclast formation and function. By screening for compounds that inhibit RANKL-induced NF-?B activation using a luciferase reporter gene assay in RAW264.7 cells, we identified triptolide (PG490), as a candidate compound targeting osteoclast differentiation and osteoclast-mediated osteolysis. Triptolide (PG490) is an active compound of the medicinal herb Tripterygium wilfordii Hook F (TWHF) or Lei Gong Teng with known anti-inflammatory properties. We found that triptolide inhibited osteoclastogenesis and bone resorption, as well as RANKL-induced NF-?B activities as monitored by luciferase reporter gene assays and the nuclear translocation of p65. In vivo studies showed that triptolide attenuates titanium-induced osteolysis and osteoclast formation in a mouse calvarial model. Considering that drugs which protect against localized bone loss are critically needed for the effective treatment of particle-induced osteolysis, our data suggest that triptolide might have therapeutic potential for the treatment of bone lytic diseases caused by prosthetic wear particles. PMID:25448849

  12. Manipulation of particles by laser tweezers-induced gradient of order in the nematic liquid crystal

    NASA Astrophysics Data System (ADS)

    Škarabot, Miha; Osterman, Natan; Lokar, Žiga; Muševi?, Igor

    2014-09-01

    Manipulation and transport of microparticles and even fluorescent molecules by thermally induced gradient of the order parameter is demonstrated in the nematic liquid crystal. IR light absorption of a focused beam of the laser tweezers is used to heat locally a thin layer of the nematic liquid crystal by several degrees, thus creating a spatial gradient of temperature of the nematic liquid crystal over tens of micrometers. It is observed that a colloidal particle with dipolar symmetry of the director configuration is attracted into the hot spot of the tweezers. The strength of trapping potential increases linearly with particle radius, which indicates that the trapping is due to elastic energy of the distorted nematic liquid crystal around the particle. By using fluorescent molecules instead of colloidal particles, we observed that this thermal trapping of colloidal particles is efficient down to the nanoscale, as fluorescent molecules are also attracted to the hotter regions of the liquid crystal. This effect is absent in the isotropic phase.

  13. The Effect of Surface Induced Flows on Bubble and Particle Aggregation

    NASA Technical Reports Server (NTRS)

    Guelcher, Scott A.; Solomentsev, Yuri E.; Anderson, John L.; Boehmer, Marcel; Sides, Paul J.

    1999-01-01

    Almost 20 years have elapsed since a phenomenon called "radial specific coalescence" was identified. During studies of electrolytic oxygen evolution from the back side of a vertically oriented, transparent tin oxide electrode in alkaline electrolyte, one of the authors (Sides) observed that large "collector" bubbles appeared to attract smaller bubbles. The bubbles moved parallel to the surface of the electrode, while the electric field was normal to the electrode surface. The phenomenon was reported but not explained. More recently self ordering of latex particles was observed during electrophoretic deposition at low DC voltages likewise on a transparent tin oxide electrode. As in the bubble work, the field was normal to the electrode while the particles moved parallel to it. Fluid convection caused by surface induced flows (SIF) can explain these two apparently different experimental observations: the aggregation of particles on an electrode during electrophoretic deposition, and a radial bubble coalescence pattern on an electrode during electrolytic gas evolution. An externally imposed driving force (the gradient of electrical potential or temperature), interacting with the surface of particles or bubbles very near a planar conducting surface, drives the convection of fluid that causes particles and bubbles to approach each other on the electrode.

  14. Detection of tire tread particles using laser-induced breakdown spectroscopy

    NASA Astrophysics Data System (ADS)

    Prochazka, David; Bilík, Martin; Prochazková, Petra; Klus, Jakub; Po?ízka, Pavel; Novotný, Jan; Novotný, Karel; Ticová, Barbora; Bradá?, Albert; Semela, Marek; Kaiser, Jozef

    2015-06-01

    The objective of this paper is a study of the potential of laser induced breakdown spectroscopy (LIBS) for detection of tire tread particles. Tire tread particles may represent pollutants; simultaneously, it is potentially possible to exploit detection of tire tread particles for identification of optically imperceptible braking tracks at locations of road accidents. The paper describes the general composition of tire treads and selection of an element suitable for detection using the LIBS method. Subsequently, the applicable spectral line is selected considering interferences with lines of elements that might be present together with the detected particles, and optimization of measurement parameters such as incident laser energy, gate delay and gate width is performed. In order to eliminate the matrix effect, measurements were performed using 4 types of tires manufactured by 3 different producers. An adhesive tape was used as a sample carrier. The most suitable adhesive tape was selected from 5 commonly available tapes, on the basis of their respective LIBS spectra. Calibration standards, i.e. an adhesive tape with different area content of tire tread particles, were prepared for the selected tire. A calibration line was created on the basis of the aforementioned calibration standards. The linear section of this line was used for determination of the detection limit value applicable to the selected tire. Considering the insignificant influence of matrix of various types of tires, it is possible to make a simple recalculation of the detection limit value on the basis of zinc content in a specific tire.

  15. Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn's disease

    PubMed Central

    ten Hove, T; van Montfrans, C; Peppelenbosch, M P; van Deventer, S J H

    2002-01-01

    Background and aims: Treatment with infliximab induces remission in about 70% of patients with steroid refractory Crohn's disease. Because Crohn's disease is considered to be mediated by uncontrolled activation of mucosal T lymphocytes, we hypothesised that infliximab could induce apoptosis of T lymphocytes. Methods: Induction of apoptosis in vivo was studied in 10 patients with therapy refractory Crohn's disease. In vitro, resting or stimulated Jurkat T cells were incubated with infliximab. Results: Infusion of infliximab (5 mg/kg) in steroid refractory patients with Crohn's disease induced a clinical response in 9/10 patients but did not influence expression of activation markers, homing receptors, memory cells, Fas expression, or Bax/Bcl-2 expression on peripheral blood T lymphocytes. In contrast, a significant increase in CD3 and TUNEL positive cells within colonic biopsies was detected 24 hours after infusion of infliximab, suggesting that infliximab stimulates apoptosis of activated T lymphocytes but not of resting T cells. To test this hypothesis, the effects of infliximab on Jurkat T cells were investigated. We observed that infliximab induced apoptosis and an increase in the Bax/Bcl-2 ratio of CD3/CD28 stimulated Jurkat T cells but not of unstimulated Jurkat cells. Conclusions: Our data indicate that infliximab treatment causes a rapid and specific increase in apoptosis of T lymphocytes in the gut mucosa. These findings may explain the rapid and sustained therapeutic effects of infliximab in Crohn's disease. PMID:11788561

  16. Glia Maturation Factor Induces Interleukin-33 Release from Astrocytes: Implications for Neurodegenerative Diseases

    PubMed Central

    Kempuraj, Duraisamy; Khan, Mohammad Moshahid; Thangavel, Ramasamy; Xiong, Zhi; Yang, Evert; Zaheer, Asgar

    2013-01-01

    Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and Multiple sclerosis (MS) involve activation of glial cells and release of inflammatory mediators leading to death of neurons. Glia maturation factor (GMF) is up-regulated in the central nervous system (CNS) in these neurodegenerative diseases. Interleukin-33 (IL-33) is highly expressed constitutively in the CNS. We have treated mouse astrocytes, mixed culture with glial cells and neurons, and only neurons with GMF and/or IL-33 in vitro. Both GMF and IL-33-induced chemokine (C-C motif) ligand 2 (CCL2) release in a dose and time-dependent manner. We report that GMF induced IL-33 release, and that IL-33 augments GMF-induced TNF-? release from mouse astrocytes. IL-33 induces CCL2, TNF-? and nitric oxide release through phosphorylation of ERK in mouse astrocytes. Incubation of mixed culture containing glial cells and neurons or only neuronal culture with IL-33 reduced the number of neurons positive for microtubule-associated protein 2. In conclusion, IL-33 augments GMF-mediated neuroinflammation and may provide a new drug target for neurodegenerative and autoimmune diseases. PMID:23397250

  17. Glia maturation factor induces interleukin-33 release from astrocytes: implications for neurodegenerative diseases.

    PubMed

    Kempuraj, Duraisamy; Khan, Mohammad Moshahid; Thangavel, Ramasamy; Xiong, Zhi; Yang, Evert; Zaheer, Asgar

    2013-06-01

    Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and Multiple sclerosis (MS) involve activation of glial cells and release of inflammatory mediators leading to death of neurons. Glia maturation factor (GMF) is up-regulated in the central nervous system (CNS) in these neurodegenerative diseases. Interleukin-33 (IL-33) is highly expressed constitutively in the CNS. We have treated mouse astrocytes, mixed culture with glial cells and neurons, and only neurons with GMF and/or IL-33 in vitro. Both GMF and IL-33-induced chemokine (C-C motif) ligand 2 (CCL2) release in a dose and time-dependent manner. We report that GMF induced IL-33 release, and that IL-33 augments GMF-induced tumor necrosis factor-alpha (TNF-?) release from mouse astrocytes. IL-33 induces CCL2, TNF-? and nitric oxide release through phosphorylation of ERK in mouse astrocytes. Incubation of mixed culture containing glial cells and neurons or only neuronal culture with IL-33 reduced the number of neurons positive for microtubule-associated protein 2. In conclusion, IL-33 augments GMF-mediated neuroinflammation and may provide a new drug target for neurodegenerative and autoimmune diseases. PMID:23397250

  18. Strontium ranelate inhibits titanium-particle-induced osteolysis by restraining inflammatory osteoclastogenesis in vivo.

    PubMed

    Liu, Xing; Zhu, Shijun; Cui, Jingfu; Shao, Hongguo; Zhang, Wen; Yang, Huilin; Xu, Yaozeng; Geng, Dechun; Yu, Long

    2014-11-01

    Wear-particle-induced osteolysis is considered to be the main reason for revision after arthroplasty. Although the exact mechanism remains unclear, inflammatory osteoclastogenesis plays an important role in this process. Strontium ranelate (SR) was found to have a therapeutic effect on osteoporosis in postmenopausal women. Based on prior studies, the present authors hypothesized that SR prevents wear-particle-induced osteolysis through restraining inflammatory osteoclastogenesis. The present study used 80 male C57BL/J6 mice to test this hypothesis in a murine osteolysis model. All experimental animals were randomly divided into four groups: a control group; a SR group; a titanium group; and a titanium+SR group. Once titanium particles had been implanted in mice, the mice were administered SR (900 mg kg(-1) day(-1)) by gavage for 14 days. After 14 days, the calvaria were collected for micro-computed tomography (?CT), histological and molecular analysis. The results of ?CT and histomorphometric analysis demonstrated that SR markedly inhibited bone resorption and the generation of tartrate-resistant acid-phosphatase-positive cells in vivo, compared with titanium-stimulated calvaria. Reverse transcription polymerase chain reaction and ELISAs showed that SR stimulated the mRNA and protein expression of osteoprotegerin, and inhibited gene and protein expression of receptor activators of nuclear factor-kappa B ligand in titanium-particle-charged calvaria. In addition, SR obviously reduced the secretion of tumor necrosis factor-? and interleukin-1? in the calvaria of the titanium group. It was concluded that SR inhibits titanium-induced osteolysis by restraining inflammatory osteoclastogenesis, and that it could be developed as a new drug to prevent and treat aseptic loosening. PMID:25078426

  19. Protein Kinase C–? Mediates Lung Injury Induced by Diesel Exhaust Particles

    PubMed Central

    Caraballo, Juan C.; Borcherding, Jennifer; Thorne, Peter S.

    2013-01-01

    Recently, we reported that diesel exhaust particles (DEPs) disrupt tight junctions (TJs) in alveolar epithelial cells (AECs) via an increase in reactive oxygen species (ROS). In this study, we investigated the role of protein kinase C (PKC)–? activation in DEP-induced lung injury. C57/bl6 mice were instilled intratracheally with 50 ?l of saline containing 100 ?g of DEPs or titanium dioxide (TiO2). Twenty-four hours later, bronchoalveolar lavage was performed to assess neutrophil counts and protein concentrations. In addition, in vitro experiments were performed in primary rat and human AECs exposed to DEPs (50 ?g/cm2) for 3 hours. Transepithelial electrical conductance was measured, and TJ protein association was analyzed by immunoprecipitation. To determine whether the overexpression of antioxidants prevented DEP-induced lung injury, AECs and mice were infected with adenoviruses containing catalase and manganese superoxide dismutase (MnSOD) plasmids. In vivo, the overexpression of catalase and MnSOD prevented DEP-induced neutrophil recruitment. The inhibition of PKC-? activation also prevented DEP-induced neutrophil recruitment in vivo. In vitro, DEPs activated PKC-? in AECs, but not in alveolar macrophages. Using a specific myristolated PKC-? pseudosubstrate pepetide (PKC-? ps), we showed that PKC-? mediated the DEP-induced dissociation of occludin and zonula occludin–1 (ZO1) in rat and human AECs. In addition, the overexpression of constitutively active PKC-? induced the dissociation of occludin and ZO1 in AECs. DEP-induced TJ disruption occurs via PKC-?. TJ disruption seems to be in part responsible for DEP-induced lung injury. PMID:23221045

  20. Toll-like Receptors-2 and 4 are overexpressed in an experimental model of particle-induced osteolysis

    PubMed Central

    Valladares, Roberto D.; Nich, Christophe; Zwingenberger, Stefan; Li, Chenguang; Swank, Katherine R.; Gibon, Emmanuel; Rao, Allison J.; Yao, Zhenyu; Goodman, Stuart B.

    2014-01-01

    Aseptic loosening secondary to particle-associated periprosthetic osteolysis remains a major cause of failure of total joint replacements (TJR) in the mid- and long-term. As sentinels of the innate immune system, macrophages are central to the recognition and initiation of the inflammatory cascade which results in the activation of bone resorbing osteoclasts. Toll-like receptors (TLRs) are involved in the recognition of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPS). Experimentally, polymethylmethacrylate (PMMA) and polyethylene (PE) particles have been shown to activate macrophages via the TLR pathway. The specific TLRs involved in PE particle-induced osteolysis remain largely unknown. We hypothesized that TLR-2, -4 and -9 mediated responses play a critical role in the development of PE wear particle-induced osteolysis in the murine calvarium model. To test this hypothesis, we first demonstrated that PE particles caused observable osteolysis, visible by microCT and bone histomorphometry when the particles were applied to the calvarium of C57BL/6 mice. The number of TRAP positive osteoclasts was significantly greater in the PE-treated group when compared to the control group without particles. Finally, using immunohistochemistry, TLR-2 and TLR-4 were highly expressed in PE particle-induced osteolytic lesions, whereas TLR-9 was downregulated. TLR-2 and -4 may represent novel therapeutic targets for prevention of wear particle-induced osteolysis and accompanying TJR failure. PMID:24115330

  1. Turbulence-induced Relative Velocity of Dust Particles. IV. The Collision Kernel

    NASA Astrophysics Data System (ADS)

    Pan, Liubin; Padoan, Paolo

    2014-12-01

    Motivated by its importance for modeling dust particle growth in protoplanetary disks, we study turbulence-induced collision statistics of inertial particles as a function of the particle friction time, ?p. We show that turbulent clustering significantly enhances the collision rate for particles of similar sizes with ?p corresponding to the inertial range of the flow. If the friction time, ?p, h, of the larger particle is in the inertial range, the collision kernel per unit cross section increases with increasing friction time, ?p, l, of the smaller particle and reaches the maximum at ?p, l = ?p, h, where the clustering effect peaks. This feature is not captured by the commonly used kernel formula, which neglects the effect of clustering. We argue that turbulent clustering helps alleviate the bouncing barrier problem for planetesimal formation. We also investigate the collision velocity statistics using a collision-rate weighting factor to account for higher collision frequency for particle pairs with larger relative velocity. For ?p, h in the inertial range, the rms relative velocity with collision-rate weighting is found to be invariant with ?p, l and scales with ?p, h roughly as {\\propto?} _p,h1/2. The weighting factor favors collisions with larger relative velocity, and including it leads to more destructive and less sticking collisions. We compare two collision kernel formulations based on spherical and cylindrical geometries. The two formulations give consistent results for the collision rate and the collision-rate weighted statistics, except that the spherical formulation predicts more head-on collisions than the cylindrical formulation.

  2. TURBULENCE-INDUCED RELATIVE VELOCITY OF DUST PARTICLES. IV. THE COLLISION KERNEL

    SciTech Connect

    Pan, Liubin; Padoan, Paolo E-mail: ppadoan@icc.ub.edu

    2014-12-20

    Motivated by its importance for modeling dust particle growth in protoplanetary disks, we study turbulence-induced collision statistics of inertial particles as a function of the particle friction time, ?{sub p}. We show that turbulent clustering significantly enhances the collision rate for particles of similar sizes with ?{sub p} corresponding to the inertial range of the flow. If the friction time, ?{sub p,} {sub h}, of the larger particle is in the inertial range, the collision kernel per unit cross section increases with increasing friction time, ?{sub p,} {sub l}, of the smaller particle and reaches the maximum at ?{sub p,} {sub l} = ?{sub p,} {sub h}, where the clustering effect peaks. This feature is not captured by the commonly used kernel formula, which neglects the effect of clustering. We argue that turbulent clustering helps alleviate the bouncing barrier problem for planetesimal formation. We also investigate the collision velocity statistics using a collision-rate weighting factor to account for higher collision frequency for particle pairs with larger relative velocity. For ?{sub p,} {sub h} in the inertial range, the rms relative velocity with collision-rate weighting is found to be invariant with ?{sub p,} {sub l} and scales with ?{sub p,} {sub h} roughly as ? ?{sub p,h}{sup 1/2}. The weighting factor favors collisions with larger relative velocity, and including it leads to more destructive and less sticking collisions. We compare two collision kernel formulations based on spherical and cylindrical geometries. The two formulations give consistent results for the collision rate and the collision-rate weighted statistics, except that the spherical formulation predicts more head-on collisions than the cylindrical formulation.

  3. Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil Particles

    PubMed Central

    Johnson, Christopher J; Pedersen, Joel A; Chappell, Rick J; McKenzie, Debbie; Aiken, Judd M

    2007-01-01

    Soil may serve as an environmental reservoir for prion infectivity and contribute to the horizontal transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) of sheep, deer, and elk. TSE infectivity can persist in soil for years, and we previously demonstrated that the disease-associated form of the prion protein binds to soil particles and prions adsorbed to the common soil mineral montmorillonite (Mte) retain infectivity following intracerebral inoculation. Here, we assess the oral infectivity of Mte- and soil-bound prions. We establish that prions bound to Mte are orally bioavailable, and that, unexpectedly, binding to Mte significantly enhances disease penetrance and reduces the incubation period relative to unbound agent. Cox proportional hazards modeling revealed that across the doses of TSE agent tested, Mte increased the effective infectious titer by a factor of 680 relative to unbound agent. Oral exposure to Mte-associated prions led to TSE development in experimental animals even at doses too low to produce clinical symptoms in the absence of the mineral. We tested the oral infectivity of prions bound to three whole soils differing in texture, mineralogy, and organic carbon content and found soil-bound prions to be orally infectious. Two of the three soils increased oral transmission of disease, and the infectivity of agent bound to the third organic carbon-rich soil was equivalent to that of unbound agent. Enhanced transmissibility of soil-bound prions may explain the environmental spread of some TSEs despite the presumably low levels shed into the environment. Association of prions with inorganic microparticles represents a novel means by which their oral transmission is enhanced relative to unbound agent. PMID:17616973

  4. Role of NK cells in vaccine-induced immunity against Marek’s disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The antiviral activity of vaccine-induced immunity that markedly reduces the level of early cytolytic infection, production of cell-free infectious virus particles in the FFE, and lymphoma formation by interrupting the normal cascade of pathogenic events is a significant factor in protective efficac...

  5. Fluid fragmentation shapes rain-induced foliar disease transmission.

    PubMed

    Gilet, T; Bourouiba, L

    2015-03-01

    Plant diseases represent a growing threat to the global food supply. The factors contributing to pathogen transmission from plant to plant remain poorly understood. Statistical correlations between rainfalls and plant disease outbreaks were reported; however, the detailed mechanisms linking the two were relegated to a black box. In this combined experimental and theoretical study, we focus on the impact dynamics of raindrops on infected leaves, one drop at a time. We find that the deposition range of most of the pathogen-bearing droplets is constrained by a hydrodynamical condition and we quantify the effect of leaf size and compliance on such constraint. Moreover, we identify and characterize two dominant fluid fragmentation scenarios as responsible for the dispersal of most pathogen-bearing droplets emitted from infected leaves: (i) the crescent-moon ejection is driven by the direct interaction between the impacting raindrop and the contaminated sessile drop and (ii) the inertial detachment is driven by the motion imparted to the leaf by the raindrop, leading to catapult-like droplet ejections. We find that at first, decreasing leaf size or increasing compliance reduces the range of pathogen-bearing droplets and the subsequent epidemic onset efficiency. However, this conclusion only applies for the crescent moon ejection. Above a certain compliance threshold a more effective mechanism of contaminated fluid ejection, the inertial detachment, emerges. This compliance threshold is determined by the ratio between the leaf velocity and the characteristic velocity of fluid fragmentation. The inertial detachment mechanism enhances the range of deposition of the larger contaminated droplets and suggests a change in epidemic onset pattern and a more efficient potential of infection of neighbouring plants. Dimensionless parameters and scaling laws are provided to rationalize our observations. Our results link for the first time the mechanical properties of foliage with the onset dynamics of foliar epidemics through the lens of fluid fragmentation. We discuss how the reported findings can inform the design of mitigation strategies acting at the early stage of a foliar disease outbreak. PMID:25652459

  6. Turbulence-induced relative velocity of dust particles. II. The bidisperse case

    SciTech Connect

    Pan, Liubin; Padoan, Paolo; Scalo, John E-mail: ppadoan@icc.ub.edu

    2014-08-10

    We extend our earlier work on turbulence-induced relative velocity between equal-size particles (Paper I, in this series) to particles of arbitrarily different sizes. The Pan and Padoan (PP10) model shows that the relative velocity between different particles has two contributions, named the generalized shear and acceleration terms, respectively. The generalized shear term represents the particles' memory of the spatial flow velocity difference across the particle distance in the past, while the acceleration term is associated with the temporal flow velocity difference on individual particle trajectories. Using the simulation of Paper I, we compute the root-mean-square relative velocity, (w {sup 2}){sup 1/2}, as a function of the friction times, ?{sub p1} and ?{sub p2}, of the two particles and show that the PP10 prediction is in satisfactory agreement with the data, confirming its physical picture. For a given ?{sub p1} below the Lagrangian correlation time of the flow, T{sub L}, (w {sup 2}){sup 1/2} as a function of ?{sub p2} shows a dip at ?{sub p2} ? ?{sub p1}, indicating tighter velocity correlation between similar particles. Defining a ratio f ? ?{sub p,{sub l}}/?{sub p,{sub h}}, with ?{sub p,{sub l}} and ?{sub p,{sub h}} the friction times of the smaller and larger particles, we find that (w {sup 2}){sup 1/2} increases with decreasing f due to the generalized acceleration contribution, which dominates at f ? 1/4. At a fixed f, our model predicts that (w {sup 2}){sup 1/2} scales as ?{sub p,h}{sup 1/2} for ?{sub p,{sub h}} in the inertial range of the flow, stays roughly constant for T{sub L} ? ?{sub p,{sub h}} ? T{sub L}/f, and finally decreases as ?{sub p,h}{sup ?1/2} for ?{sub p,{sub h}} >> T{sub L}/f. The acceleration term is independent of the particle distance, r, and reduces the r dependence of (w {sup 2}){sup 1/2} in the bidisperse case.

  7. Epicuticular lipids induce aggregation in Chagas disease vectors

    PubMed Central

    Figueiras, Alicia N Lorenzo; Girotti, Juan R; Mijailovsky, Sergio J; Juárez, M Patricia

    2009-01-01

    Background The triatomine bugs are vectors of the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. Aggregation behavior plays an important role in their survival by facilitating the location of refuges and cohesion of aggregates, helping to keep them safely assembled into shelters during daylight time, when they are vulnerable to predators. There are evidences that aggregation is mediated by thigmotaxis, by volatile cues from their faeces, and by hexane-extractable contact chemoreceptive signals from their cuticle surface. The epicuticular lipids of Triatoma infestans include a complex mixture of hydrocarbons, free and esterified fatty acids, alcohols, and sterols. Results We analyzed the response of T. infestans fifth instar nymphs after exposure to different amounts either of total epicuticular lipid extracts or individual lipid fractions. Assays were performed in a circular arena, employing a binary choice test with filter papers acting as aggregation attractive sites; papers were either impregnated with a hexane-extract of the total lipids, or lipid fraction; or with the solvent. Insects were significantly aggregated around papers impregnated with the epicuticular lipid extracts. Among the lipid fractions separately tested, only the free fatty acid fraction promoted significant bug aggregation. We also investigated the response to different amounts of selected fatty acid components of this fraction; receptiveness varied with the fatty acid chain length. No response was elicited by hexadecanoic acid (C16:0), the major fatty acid component. Octadecanoic acid (C18:0) showed a significant assembling effect in the concentration range tested (0.1 to 2 insect equivalents). The very long chain hexacosanoic acid (C26:0) was significantly attractant at low doses (? 1 equivalent), although a repellent effect was observed at higher doses. Conclusion The detection of contact aggregation pheromones has practical application in Chagas disease vector control. These data may be used to help design new tools against triatomine bugs. PMID:19173716

  8. New Insights Into Tobacco-Induced Vascular Disease: Clinical Ramifications

    PubMed Central

    Cooke, John P.

    2015-01-01

    Tobacco smoke contains more than 4,000 compounds. These include phenols, carbonyls, and nitrosamines that may be irritants and carcinogens; particulate matter such as tars; volatiles and gases such as carbon monoxide; and nicotine. Many of these compounds may contribute to the adverse health effects of tobacco. For example, recent findings have shown that the angiogenic and proliferative effects of nicotine are mediated by activation of nicotinic receptors on the vascular cells. Nicotine-induced activation of vascular cells may contribute to pathological neovascularization in cancer, age-related macular degeneration, and atherosclerosis. This review focuses on how nicotine adversely affects cardiovascular health and highlights intriguing new data about nicotine's potent angiogenic and proliferative properties. PMID:26634022

  9. Is delayed genomic instability specifically induced by high-LET particles?

    NASA Astrophysics Data System (ADS)

    Testard, Isabelle; Sabatier, Laure

    1998-12-01

    Ionizing radiation can induce a large variety of damages in the DNA. The processing or repair of this damage occurs in the first minutes up to several hours after irradiation. Afterwhile the remaining lesions are fixed in an irreparable state. However, in recent years, data have accumulated to suggest that genomic instability can manifest in the progeny of irradiated cells leading to accumulation of damage through cell generations. Different biological endpoints were described: delayed cell death, delayed mutations, de novo chromosomal instability. The question regarding the ability of sparsely ionizing X-or ?-rays to induce such phenomenon is still unclear for normal cells. In most of the reports, high linear energy transfer (LET) particles are able to induce genomic instability but not low-LET particles. The mechanisms underlying this phenomenon are still unknown. In human fibroblasts irradiated by heavy ions in a large range of LETs, we showed that the chromosomal instability is characterized by telomeric associations (TAS) involving specific chromosomes. The same instability is observed during the senescence process and during the first passages after viral transfection. The specific chromosomal instability that we observed after irradiation would not be a direct consequence of irradiation but would be a natural phenomenon occurring after many cell divisions. The effect of the irradiation would lie on the bypass of the senescence process that would permit cells with end to end fusions to survive and be transmitted through cell generations, accumulating chromosome rearrangements and chromosome imbalances. Research on molecular mechanisms of chromosomal instability is focused on the role of telomeres in end to end fusions. Such observations could contribute to understand why chromosomal instability is not a dose dependant phenomenon. Why high-LET particles would be so potent in inducing delayed instability? The answer might lie in the study of primary effects of ionizing radiations (X-rays, ?-rays and heavy ions). Cell survival studies showed that K-shell ionizations could be the primary physical events responsible of cell death. The quality of the DNA damages and gene mutations high-LET induced could be the keyhole leading to the great efficiency of these particles.

  10. Non-random distribution of DNA double-strand breaks induced by particle irradiation

    NASA Technical Reports Server (NTRS)

    Lobrich, M.; Cooper, P. K.; Rydberg, B.; Chatterjee, A. (Principal Investigator)

    1996-01-01

    Induction of DNA double-strand breaks (dsbs) in mammalian cells is dependent on the spatial distribution of energy deposition from the ionizing radiation. For high LET particle radiations the primary ionization sites occur in a correlated manner along the track of the particles, while for X-rays these sites are much more randomly distributed throughout the volume of the cell. It can therefore be expected that the distribution of dsbs linearly along the DNA molecule also varies with the type of radiation and the ionization density. Using pulsed-field gel and conventional gel techniques, we measured the size distribution of DNA molecules from irradiated human fibroblasts in the total range of 0.1 kbp-10 Mbp for X-rays and high LET particles (N ions, 97 keV/microns and Fe ions, 150 keV/microns). On a mega base pair scale we applied conventional pulsed-field gel electrophoresis techniques such as measurement of the fraction of DNA released from the well (FAR) and measurement of breakage within a specific NotI restriction fragment (hybridization assay). The induction rate for widely spaced breaks was found to decrease with LET. However, when the entire distribution of radiation-induced fragments was analysed, we detected an excess of fragments with sizes below about 200 kbp for the particles compared with X-irradiation. X-rays are thus more effective than high LET radiations in producing large DNA fragments but less effective in the production of smaller fragments. We determined the total induction rate of dsbs for the three radiations based on a quantitative analysis of all the measured radiation-induced fragments and found that the high LET particles were more efficient than X-rays at inducing dsbs, indicating an increasing total efficiency with LET. Conventional assays that are based only on the measurement of large fragments are therefore misleading when determining total dsb induction rates of high LET particles. The possible biological significance of this non-randomness for dsb induction is discussed.

  11. Near-infrared-induced heating of confined water in polymeric particles for efficient payload release.

    PubMed

    Viger, Mathieu L; Sheng, Wangzhong; Doré, Kim; Alhasan, Ali H; Carling, Carl-Johan; Lux, Jacques; de Gracia Lux, Caroline; Grossman, Madeleine; Malinow, Roberto; Almutairi, Adah

    2014-05-27

    Near-infrared (NIR) light-triggered release from polymeric capsules could make a major impact on biological research by enabling remote and spatiotemporal control over the release of encapsulated cargo. The few existing mechanisms for NIR-triggered release have not been widely applied because they require custom synthesis of designer polymers, high-powered lasers to drive inefficient two-photon processes, and/or coencapsulation of bulky inorganic particles. In search of a simpler mechanism, we found that exposure to laser light resonant with the vibrational absorption of water (980 nm) in the NIR region can induce release of payloads encapsulated in particles made from inherently non-photo-responsive polymers. We hypothesize that confined water pockets present in hydrated polymer particles absorb electromagnetic energy and transfer it to the polymer matrix, inducing a thermal phase change. In this study, we show that this simple and highly universal strategy enables instantaneous and controlled release of payloads in aqueous environments as well as in living cells using both pulsed and continuous wavelength lasers without significant heating of the surrounding aqueous solution. PMID:24717072

  12. Near-Infrared-Induced Heating of Confined Water in Polymeric Particles for Efficient Payload Release

    PubMed Central

    2015-01-01

    Near-infrared (NIR) light-triggered release from polymeric capsules could make a major impact on biological research by enabling remote and spatiotemporal control over the release of encapsulated cargo. The few existing mechanisms for NIR-triggered release have not been widely applied because they require custom synthesis of designer polymers, high-powered lasers to drive inefficient two-photon processes, and/or coencapsulation of bulky inorganic particles. In search of a simpler mechanism, we found that exposure to laser light resonant with the vibrational absorption of water (980 nm) in the NIR region can induce release of payloads encapsulated in particles made from inherently non-photo-responsive polymers. We hypothesize that confined water pockets present in hydrated polymer particles absorb electromagnetic energy and transfer it to the polymer matrix, inducing a thermal phase change. In this study, we show that this simple and highly universal strategy enables instantaneous and controlled release of payloads in aqueous environments as well as in living cells using both pulsed and continuous wavelength lasers without significant heating of the surrounding aqueous solution. PMID:24717072

  13. Mitochondrial Disease-Specific Induced Pluripotent Stem Cell Models: Generation and Characterization.

    PubMed

    Zhang, Xuan; Li, Shishi; Yang, Wei; Pan, Huaye; Qin, Dajiang; Zhu, Xufen; Yan, Qingfeng

    2016-01-01

    Mitochondrial disease is a group of disorders caused by dysfunctional mitochondria, of which the mutation in the mitochondrial DNA is one of the primary factors. However, the molecular pathogenesis of mitochondrial diseases remains poorly understood due to lack of cell models. Patient-specific induced pluripotent stem cells (iPS cells or iPSCs) are originated from individuals suffering different diseases but carrying unchanged disease causing gene. Therefore, patient-specific iPS cells can be used as excellent cell models to elucidate the mechanisms underlying mitochondrial diseases. Here we present a detailed protocol for generating iPS cells from urine cells and fibroblasts for instance, as well as a series of characterizations. PMID:25646615

  14. Fast Particle Finite Orbit Width and Larmor Radius E ects on Low-n Toroidicity induced Alfv en Eigenmode Excitation

    E-print Network

    radius FLR of fast particles on the stability of low-n toroidicity-induced Alfv en eigenmodes TAE that both FOW and FLR e ects are typically stabilizing: the TAE growth rate can be reduced by as much radius FLR comparable to the TAE mode scale length. A large radial displacement of particle orbit may

  15. A Kinetic Model of Protein Adsorption/Surface-Induced Transition Kinetics Evaluated by the Scaled Particle Theory

    E-print Network

    Brusatori, Michelle A.

    A Kinetic Model of Protein Adsorption/Surface-Induced Transition Kinetics Evaluated by the Scaled Particle Theory Michelle A. Brusatori and Paul R. Van Tassel1 Department of Chemical Engineering of spreading disks. In this work, we employ the scaled particle theory (SPT) to derive approximate analytical

  16. Long-term changes in amphetamine-induced reinforcement and aversion in rats following exposure to 56Fe particle

    NASA Astrophysics Data System (ADS)

    Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

    Exposing rats to heavy particles produces alterations in the functioning of dopaminergic neurons and in the behaviors that depend upon the integrity of the dopaminergic system. Two of these dopamine-dependent behaviors include amphetamine-induced reinforcement, measure using the conditioned place preference procedure, and amphetamine-induced reinforcement, measured using the conditioned place preference procedure, and amphetamine-induced aversion, measured using the conditioned taste aversion. Previous research has shown that exposing rats to 1.0 Gy of 1GeV/n 56Fe particles produced a disruption of an amphetamine-induced taste aversion 3 days following exposure, but produced an apparent enhancement of the aversion 112 days following exposure. The present experiments were designed to provide a further evaluation of these results by examining taste aversion learning 154 days following exposure to 1.0Gy 56Fe particles and to establish the convergent validity of the taste aversion results by looking at the effects of exposure on the establishment of an amphetamine-induced conditioned place preference 3, 7, and 16 weeks following irradiation. The taste aversion results failed to confirm the apparent enhancement of the amphetamine-induced CTA observed in the prior experiment. However, exposure to 56Fe particles prevented the acquisition of amphetamine-induced place preference at all three-time intervals. The results are interpreted as indicating that exposure to heavy particles can produce long-term changes in behavioral functioning.

  17. Long-term changes in amphetamine-induced reinforcement and aversion in rats following exposure to 56Fe particle

    NASA Technical Reports Server (NTRS)

    Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

    2003-01-01

    Exposing rats to heavy particles produces alterations in the functioning of dopaminergic neurons and in the behaviors that depend upon the integrity of the dopaminergic system. Two of these dopamine-dependent behaviors include amphetamine-induced reinforcement, measure using the conditioned place preference procedure, and amphetamine-induced reinforcement, measured using the conditioned place preference procedure, and amphetamine-induced aversion, measured using the conditioned taste aversion. Previous research has shown that exposing rats to 1.0 Gy of 1GeV/n 56Fe particles produced a disruption of an amphetamine-induced taste aversion 3 days following exposure, but produced an apparent enhancement of the aversion 112 days following exposure. The present experiments were designed to provide a further evaluation of these results by examining taste aversion learning 154 days following exposure to 1.0 Gy 56Fe particles and to establish the convergent validity of the taste aversion results by looking at the effects of exposure on the establishment of an amphetamine-induced conditioned place preference 3, 7, and 16 weeks following irradiation. The taste aversion results failed to confirm the apparent enhancement of the amphetamine-induced CTA observed in the prior experiment. However, exposure to 56Fe particles prevented the acquisition of amphetamine-induced place preference at all three-time intervals. The results are interpreted as indicating that exposure to heavy particles can produce long-term changes in behavioral functioning. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

  18. Application of human induced pluripotent stem cells for modeling and treating neurodegenerative diseases.

    PubMed

    Payne, Natalie L; Sylvain, Aude; O'Brien, Carmel; Herszfeld, Daniella; Sun, Guizhi; Bernard, Claude C A

    2015-01-25

    The advent of human induced pluripotent stem cells (hiPSCs), reprogrammed in vitro from both healthy and disease-state human somatic cells, has triggered an enormous global research effort to realize personalized regenerative medicine for numerous degenerative conditions. hiPSCs have been generated from cells of many tissue types and can be differentiated in vitro to most somatic lineages, not only for the establishment of disease models that can be utilized as novel drug screening platforms and to study the molecular and cellular processes leading to degeneration, but also for the in vivo cell-based repair or modulation of a patient's disease profile. hiPSCs derived from patients with the neurodegenerative diseases amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease and multiple sclerosis have been successfully differentiated in vitro into disease-relevant cell types, including motor neurons, dopaminergic neurons and oligodendrocytes. However, the generation of functional iPSC-derived neural cells that are capable of engraftment in humans and the identification of robust disease phenotypes for modeling neurodegeneration still require several key challenges to be addressed. Here, we discuss these challenges and summarize recent progress toward the application of iPSC technology for these four common neurodegenerative diseases. PMID:24815224

  19. Docetaxel-induced polyploidization may underlie chemoresistance and disease relapse.

    PubMed

    Ogden, Angela; Rida, Padmashree C G; Knudsen, Beatrice S; Kucuk, Omer; Aneja, Ritu

    2015-10-28

    Although docetaxel significantly improves survival in a variety of malignancies, its clinical utility is severely restricted by acquired chemoresistance and disease relapse. To uncover the mechanisms underlying these all too common occurrences, an abundance of research has focused on mutations and gene expression patterns; however, these findings are yet to translate into improved outcomes for patients being administered this drug. These analyses have overlooked a promising lead in the quest to discern key mediators of resistance and relapse following docetaxel therapy: polyploidization. This process is manifested following docetaxel-mediated mitotic arrest by the appearance of giant, multinucleated cells, which slipped from mitosis without undergoing cytokinesis. Polyploid cells generally possess supernumerary centrosomes, are chromosomally instable, and resist chemotherapy. We thus suspect that chemoresistance and relapse following treatment with docetaxel might be combatted by co-administration of centrosome declustering drugs, which could selectively destroy polyploid cells given that normal cells do not possess amplified centrosomes, an intriguing paradigm that warrants further investigation. PMID:26185000

  20. Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease.

    PubMed

    Zhang, Liang; Trushin, Sergey; Christensen, Trace A; Bachmeier, Benjamin V; Gateno, Benjamin; Schroeder, Andreas; Yao, Jia; Itoh, Kie; Sesaki, Hiromi; Poon, Wayne W; Gylys, Karen H; Patterson, Emily R; Parisi, Joseph E; Diaz Brinton, Roberta; Salisbury, Jeffrey L; Trushina, Eugenia

    2016-01-01

    Altered brain metabolism is associated with progression of Alzheimer's Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture of the brain tissue and organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction to visualize mitochondrial structure in the brain tissue from patients and mouse models of AD. We identified a previously unknown mitochondrial fission arrest phenotype that results in elongated interconnected organelles, "mitochondria-on-a-string" (MOAS). Our data suggest that MOAS formation may occur at the final stages of fission process and was not associated with altered translocation of activated dynamin related protein 1 (Drp1) to mitochondria but with reduced GTPase activity. Since MOAS formation was also observed in the brain tissue of wild-type mice in response to hypoxia or during chronological aging, fission arrest may represent fundamental compensatory adaptation to bioenergetic stress providing protection against mitophagy that may preserve residual mitochondrial function. The discovery of novel mitochondrial phenotype that occurs in the brain tissue in response to energetic stress accurately detected only using 3D EM reconstruction argues for a major role of mitochondrial dynamics in regulating neuronal survival. PMID:26729583

  1. NEUTROPHILS PLAY A CRITICAL ROLE IN THE DEVELOPMENT OF LPS-INDUCED AIRWAY DISEASE

    EPA Science Inventory

    ETD-02-045 (GAVETT) GPRA # 10108

    Neutrophils Play a Critical Role in the Development of LPS-Induced Airway Disease.
    Jordan D. Savov, Stephen H. Gavett*, David M. Brass, Daniel L. Costa*, and David A. Schwartz

    ABSTRACT
    We investigated the role of neutrophils...

  2. Neurobiology of Disease Cisplatin-Induced Hair Cell Death Requires STAT1 and Is

    E-print Network

    Rubel, Edwin

    primarily affects the hearing of high frequencies and corresponds to loss of mechanosensory hair cellsNeurobiology of Disease Cisplatin-Induced Hair Cell Death Requires STAT1 and Is Attenuated that frequently causes auditory impairment due to the death of mechanosensory hair cells. Cisplatin ototoxicity

  3. SHORT COMMUNICATION Development of diet-induced fatty liver disease in

    E-print Network

    SHORT COMMUNICATION Development of diet-induced fatty liver disease in the aging mouse and age on liver morphology and biochemistry was characterized, while evaluating the potential of 15 min) to suppress lipid accumulation in the liver. Following a 36-week protocol (animals 43 weeks of age

  4. Effect of media-induced social distancing on disease transmission in a two patch setting

    E-print Network

    Arino, Julien

    Effect of media-induced social distancing on disease transmission in a two patch setting Chengjun 2011 Keywords: Media coverage Metapopulation Global dynamics Uniform persistence a b s t r a c t We formulate an SIS epidemic model on two patches. In each patch, media coverage about the cases pres- ent

  5. Avian oncogenesis induced by lymphoproliferative disease virus: a neglected or emerging retroviral pathogen?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lymphoproliferative disease virus (LPDV) is an exogenous oncogenic retrovirus that induces lymphoid tumors in some galliform species of birds. Historically, outbreaks of LPDV have been reported from Europe and Israel. Although the virus has previously never been detected in North America, herein we ...

  6. SPONTANEOUSLY HYPERTENSIVE RATS ARE SUSCEPTIBLE TO AIRWAY DISEASE INDUCED BY SULFUR DIOXIDE

    EPA Science Inventory

    Rodent models of chronic pulmonary diseases induced by sulfur dioxide (SO2), elastase or tobacco smoke have limited utility because of their lack of chronicity of inflammation, and they demonstrate limited sensitivity to a given experimental manipulation. We hypothesized that dis...

  7. EFFECTS OF SYSTEMIC NEUTROPHIL DEPLETION ON LPS-INDUCED AIRWAY DISEASE

    EPA Science Inventory

    Effects of Systemic Neutrophil Depletion on LPS-induced Airway Disease
    Jordan D. Savov, Stephen H. Gavett*, David M. Brass, Daniel L. Costa*, David A. Schwartz
    Pulmonary and Critical Care Division, Dept of Medicine ? Duke University Medical Center
    * National Health and E...

  8. New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases

    PubMed Central

    2014-01-01

    Alcohol-induced liver disease increasingly contributes to human mortality worldwide. Alcohol-induced endoplasmic reticulum (ER) stress and disruption of cellular protein homeostasis have recently been established as a significant mechanism contributing to liver diseases. The alcohol-induced ER stress occurs not only in cultured hepatocytes but also? in vivo??in the livers of several species including mouse, rat, minipigs, zebrafish, and humans. Identified causes for the ER stress include acetaldehyde, oxidative stress, impaired one carbon metabolism, toxic lipid species, insulin resistance, disrupted calcium homeostasis, and aberrant epigenetic modifications. Importance of each of the causes in alcohol-induced liver injury depends on doses, duration and patterns of alcohol exposure, genetic disposition, environmental factors, cross-talks with other pathogenic pathways, and stages of liver disease. The ER stress may occur more or less all the time during alcohol consumption, which interferes with hepatic protein homeostasis, proliferation, and cell cycle progression promoting development of advanced liver diseases. Emerging evidence indicates that long-term alcohol consumption and ER stress may directly be involved in hepatocellular carcinogenesis (HCC). Dissecting ER stress signaling pathways leading to tumorigenesis will uncover potential therapeutic targets for intervention and treatment of human alcoholics with liver cancer. PMID:24868470

  9. Appraisal of experimental and commercial Marek's disease vaccines to induce bursal and thymic atrophy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recently, several experimental Marek’s disease (MD) vaccines were developed that appear to protect equally or better than the best commercial vaccines. However, some of the experimental vaccines were reported to induce transient bursal and thymic atrophies. We will report on two promising experiment...

  10. Fructose Induced Endotoxemia in Pediatric Nonalcoholic Fatty Liver Disease

    PubMed Central

    Patel, Shivani S.; Sun, Xiaoyan; Song, Ming; Mannery, Yanci O.; McClain, Craig J.; Vos, Miriam B.

    2014-01-01

    In preclinical studies of fructose-induced NAFLD, endotoxin appears to play an important role. We retrospectively examined samples from three pediatric cohorts (1) to investigate whether endotoxemia is associated with the presence of hepatic steatosis; (2) to evaluate postprandial endotoxin levels in response to fructose beverage in an acute 24-hour feeding challenge, and (3) to determine the change of fasting endotoxin amounts in a 4-week randomized controlled trial comparing fructose to glucose beverages in NAFLD. We found that adolescents with hepatic steatosis had elevated endotoxin levels compared to obese controls and that the endotoxin level correlated with insulin resistance and several inflammatory cytokines. In a 24-hour feeding study, endotoxin levels in NAFLD adolescents increased after fructose beverages (consumed with meals) as compared to healthy children. Similarly, endotoxin was significantly increased after adolescents consumed fructose beverages for 2 weeks and remained high although not significantly at 4 weeks. In conclusion, these data provide support for the concept of low level endotoxemia contributing to pediatric NAFLD and the possible role of fructose in this process. Further studies are needed to determine if manipulation of the microbiome or other methods of endotoxin reduction would be useful as a therapy for pediatric NAFLD. PMID:25328713

  11. Investigation into process-induced de-aggregation of cohesive micronised API particles.

    PubMed

    Hoffmann, Magnus; Wray, Patrick S; Gamble, John F; Tobyn, Mike

    2015-09-30

    The aim of this study was to assess the impact of unit processes on the de-aggregation of a cohesive micronised API within a pharmaceutical formulation using near-infrared chemical imaging. The impact on the primary API particles was also investigated using an image-based particle characterization system with integrated Raman analysis. The blended material was shown to contain large, API rich domains which were distributed in-homogeneously across the sample, suggesting that the blending process was not aggressive enough to disperse aggregates of micronised drug particles. Cone milling, routinely used to improve the homogeneity of such cohesive formulations, was observed to substantially reduce the number and size of API rich domains; however, several smaller API domains survived the milling process. Conveyance of the cone milled formulation through the Alexanderwerk WP120 powder feed system completely dispersed all remaining aggregates. Importantly, powder feed transmission of the un-milled formulation was observed to produce an equally homogeneous API distribution. The size of the micronised primary drug particles remained unchanged during powder feed transmission. These findings provide further evidence that this powder feed system does induce shear, and is in fact better able to disperse aggregates of a cohesive micronised API within a blend than the blend-mill-blend step. PMID:26235919

  12. Improving diode-laser-induced fluorescence detection of airborne biological particles by exciting multiple biofluorophores

    NASA Astrophysics Data System (ADS)

    Wilson, Geoffrey A.; DeFreez, Richard K.

    2004-08-01

    Laser-induced fluorescence provides a real-time technique for detecting airborne pathogens. Discrimination between biological and non-biological particles can be improved by simultaneously testing for more than one of the several common biofluorophores. Typically, this requires excitation with two or more laser wavelengths, considerably increasing the cost, size and complexity of sensors based on mainframe lasers. Recent advances in UV-emitting AlGaN diode lasers present an opportunity for compact and inexpensive multi-wavelength excitation. In this paper, we will present a model for choosing the best excitation wavelengths and emission bands for discriminating between biological and non-biological particles. We will discuss recent advances in detection, and present fluorescence photon counting experimental results. We will describe techniques for simultaneous excitation and detection at multiple wavelengths to improve selectivity and guard against false positives.

  13. Analytical Applications Of Particle-Induced X-Ray Emission (PIXE)

    SciTech Connect

    Popescu, I. V.; Stihi, C.; Bancuta, A.; Dima, G.; Ene, A.; Badica, T.; Ghisa, V.

    2007-04-23

    In this paper a complex study of the capabilities of Particle-Induced X-ray Emission (PIXE) technique for the determination of major, minor and trace constituents of metallurgical, biological and environmental samples has been done. The elements identified in the metallurgical samples (steels) using PIXE were: K, Ca, V, Cr, Mn, Fe, Co, Cu, Ni, Zn, W, Ga, As, Pb, Mo, Rb, In, Rh, Zr, Pd, Nb, Sn and Sb. In the investigated biological and environmental samples (vegetals leaves, soil and mosses) PIXE analysis allowed determination of: S, Cl, K, Ca, Ti, Mn, Fe, Ni, Cu, Zn, As, Hg and Pb.

  14. CHANG'E-3 Active Particle-induced X-ray Spectrometer: ground verification test

    NASA Astrophysics Data System (ADS)

    Guo, Dongya; Peng, Wenxi; Cui, XingZhu; Wang, Huanyu

    The Active Particle-induced X-ray Spectrometer (APXS) is one of the payloads of Chang’E-3 rover Yutu, with which the major elemental composition of lunar soils and rocks can be measured on site. In order to assess the instrument performance and the accuracy of determination, ground verification test was carried out with two blind samples(basaltic rock, powder). Details of the experiments and data analysis method are discussed. The results show that the accuracy of quantitative analysis for major elements(Mg,Al,Si,K,Ca,Ti,Fe) is better than 15%.

  15. Experimental Study of the Cross Sections of {alpha}-Particle Induced Reactions on 209Bi

    SciTech Connect

    Hermanne, A.; Tarkanyi, F.; Takacs, S.; Szucs, Z.

    2005-05-24

    Alpha particle induced reactions for generation of 211At used in therapeutic nuclear medicine and possible contaminants were investigated with the stacked foil activation technique on natural bismuth targets up to E{alpha}=39 MeV. Excitation functions for the reactions 209Bi({alpha},2n)211At, 209Bi({alpha},3n)210At, 209Bi({alpha},x) 210Po obtained from direct alpha emission measurements and gamma spectra from decay products are compared with earlier literature values. Thick target yields have been deduced from the experimental cross sections.

  16. Anomalous effect of trench-oxide depth on alpha-particle-induced charge collection

    SciTech Connect

    Shin, H.; Kim, N.M.

    1999-06-01

    The effect of trench-oxide depth on the alpha-particle-induced charge collection is analyzed for the first time. From the simulation results, it was found that the depth of trench oxide has a considerable influence on the amount of collected charge. The confining of generated charge by the trench oxide was identified as a cause of this anomalous effect. Therefore, the tradeoff between soft error rate and cell to cell isolation characteristics should be considered in optimizing the depth of trench oxide.

  17. Analysis of radiation-induced small Cu particle cluster formation in aqueous CuCl2

    USGS Publications Warehouse

    Jayanetti, Sumedha; Mayanovic, Robert A.; Anderson, Alan J.; Bassett, William A.; Chou, I.-Ming

    2001-01-01

    Radition-induced small Cu particle cluster formation in aqueous CuCl2 was analyzed. It was noticed that nearest neighbor distance increased with the increase in the time of irradiation. This showed that the clusters approached the lattice dimension of bulk copper. As the average cluster size approached its bulk dimensions, an increase in the nearest neighbor coordination number was found with the decrease in the surface to volume ratio. Radiolysis of water by incident x-ray beam led to the reduction of copper ions in the solution to themetallic state.

  18. [The role of induced pluripotent stem cells in modeling of neurological diseases].

    PubMed

    Balogh, Zoltán; Réthelyi, János; Molnár, Mária

    2015-06-28

    The longitudinal follow-up of the development and course of central nervous system related diseases on a molecular level was unsolved for decades. Direct examination of the pathological state on organ or tissue levels was feasible in the late stage of the disease. Modeling diseases has an important role in studying the pathophysiological mechanism underlying central nervous system disorders but animals used as model organism due to species specific nervous system differences can lead to less valid conclusions in translational research. The model of induced pluripotent stem cells may help to solve partially these types of problems. In recent years this model had a strong effect on understanding the pathogenesis of neurodegenerative and neurodevelopmental disorders. Although induced pluripotent stem cells have a low impact on clinical research studies, they have a prominent role in the field of cell physiology and molecular biology research. PMID:26104665

  19. Automobile diesel exhaust particles induce lipid droplet formation in macrophages in vitro.

    PubMed

    Cao, Yi; Jantzen, Kim; Gouveia, Ana Cecilia Damiao; Skovmand, Astrid; Roursgaard, Martin; Loft, Steffen; Møller, Peter

    2015-07-01

    Exposure to diesel exhaust particles (DEP) has been associated with adverse cardiopulmonary health effects, which may be related to dysregulation of lipid metabolism and formation of macrophage foam cells. In this study, THP-1 derived macrophages were exposed to an automobile generated DEP (A-DEP) for 24h to study lipid droplet formation and possible mechanisms. The results show that A-DEP did not induce cytotoxicity. The production of reactive oxygen species was only significantly increased after exposure for 3h, but not 24h. Intracellular level of reduced glutathione was increased after 24h exposure. These results combined indicate an adaptive response to oxidative stress. Exposure to A-DEP was associated with significantly increased formation of lipid droplets, as well as changes in lysosomal function, assessed as reduced LysoTracker staining. In conclusion, these results indicated that exposure to A-DEP may induce formation of lipid droplets in macrophages in vitro possibly via lysosomal dysfunction. PMID:26122084

  20. Mechanical behaviors of the dispersion nuclear fuel plates induced by fuel particle swelling and thermal effect II: Effects of variations of the fuel particle diameters

    NASA Astrophysics Data System (ADS)

    Ding, Shurong; Wang, Qiming; Huo, Yongzhong

    2010-02-01

    In order to predict the irradiation mechanical behaviors of plate-type dispersion nuclear fuel elements, the total burnup is divided into two stages: the initial stage and the increasing stage. At the initial stage, the thermal effects induced by the high temperature differences between the operation temperatures and the room temperature are mainly considered; and at the increasing stage, the intense mechanical interactions between the fuel particles and the matrix due to the irradiation swelling of fuel particles are focused on. The large-deformation thermo-elasto-plasticity finite element analysis is performed to evaluate the effects of particle diameters on the in-pile mechanical behaviors of fuel elements. The research results indicate that: (1) the maximum Mises stresses and equivalent plastic strains at the matrix increase with the fuel particle diameters; the effects of particle diameters on the maximum first principal stresses vary with burnup, and the considered case with the largest particle diameter holds the maximum values all along; (2) at the cladding near the interface between the fuel meat and the cladding, the Mises stresses and the first principal stresses undergo major changes with increasing burnup, and different variations exist for different particle diameter cases; (3) the maximum Mises stresses at the fuel particles rise with the particle diameters.

  1. Protection of cisplatin-induced spermatotoxicity, DNA damage and chromatin abnormality by selenium nano-particles

    SciTech Connect

    Rezvanfar, Mohammad Amin; Rezvanfar, Mohammad Ali; Shahverdi, Ahmad Reza; Ahmadi, Abbas; Baeeri, Maryam; Mohammadirad, Azadeh; Abdollahi, Mohammad

    2013-02-01

    Cisplatin (CIS), an anticancer alkylating agent, induces DNA adducts and effectively cross links the DNA strands and so affects spermatozoa as a male reproductive toxicant. The present study investigated the cellular/biochemical mechanisms underlying possible protective effect of selenium nano-particles (Nano-Se) as an established strong antioxidant with more bioavailability and less toxicity, on reproductive toxicity of CIS by assessment of sperm characteristics, sperm DNA integrity, chromatin quality and spermatogenic disorders. To determine the role of oxidative stress (OS) in the pathogenesis of CIS gonadotoxicity, the level of lipid peroxidation (LPO), antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) and peroxynitrite (ONOO) as a marker of nitrosative stress (NS) and testosterone (T) concentration as a biomarker of testicular function were measured in the blood and testes. Thirty-two male Wistar rats were equally divided into four groups. A single IP dose of CIS (7 mg/kg) and protective dose of Nano-Se (2 mg/kg/day) were administered alone or in combination. The CIS-exposed rats showed a significant increase in testicular and serum LPO and ONOO level, along with a significant decrease in enzymatic antioxidants levels, diminished serum T concentration and abnormal histologic findings with impaired sperm quality associated with increased DNA damage and decreased chromatin quality. Coadministration of Nano-Se significantly improved the serum T, sperm quality, and spermatogenesis and reduced CIS-induced free radical toxic stress and spermatic DNA damage. In conclusion, the current study demonstrated that Nano-Se may be useful to prevent CIS-induced gonadotoxicity through its antioxidant potential. Highlights: ? Cisplatin (CIS) affects spermatozoa as a male reproductive toxicant. ? Effect of Nano-Se on CIS-induced spermatotoxicity was investigated. ? CIS-exposure induces oxidative sperm DNA damage and impairs steroidogenesis. ? Nano-Se retained sperm quality against CIS-induced free radicals toxic stress.

  2. Interaction of the human cytomegalovirus particle with the host cell induces hypoxia-inducible factor 1 alpha

    SciTech Connect

    McFarlane, Steven; Nicholl, Mary Jane; Sutherland, Jane S.; Preston, Chris M.

    2011-05-25

    The cellular protein hypoxia-inducible factor 1 alpha (HIF-1{alpha}) was induced after infection of human fibroblasts with human cytomegalovirus (HCMV). HCMV irradiated with ultraviolet light (uv-HCMV) also elicited the effect, demonstrating that the response was provoked by interaction of the infecting virion with the cell and that viral gene expression was not required. Although induction of HIF-1{alpha} was initiated by an early event, accumulation of the protein was not detected until 9 hours post infection, with levels increasing thereafter. Infection with uv-HCMV resulted in increased abundance of HIF-1{alpha}-specific RNA, indicating stimulation of transcription. In addition, greater phosphorylation of the protein kinase Akt was observed, and the activity of this enzyme was required for induction of HIF-1{alpha} to occur. HIF-1{alpha} controls the expression of many cellular gene products; therefore the findings reveal new ways in which interaction of the HCMV particle with the host cell may cause significant alterations to cellular physiology.

  3. Applications of Induced Pluripotent Stem Cells in Studying the Neurodegenerative Diseases

    PubMed Central

    Wan, Wenbin; Cao, Lan; Kalionis, Bill; Xia, Shijin; Tai, Xiantao

    2015-01-01

    Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons. Incurable neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) show dramatic rising trends particularly in the advanced age groups. However, the underlying mechanisms are not yet fully elucidated, and to date there are no biomarkers for early detection or effective treatments for the underlying causes of these diseases. Furthermore, due to species variation and differences between animal models (e.g., mouse transgenic and knockout models) of neurodegenerative diseases, substantial debate focuses on whether animal and cell culture disease models can correctly model the condition in human patients. In 2006, Yamanaka of Kyoto University first demonstrated a novel approach for the preparation of induced pluripotent stem cells (iPSCs), which displayed similar pluripotency potential to embryonic stem cells (ESCs). Currently, iPSCs studies are permeating many sectors of disease research. Patient sample-derived iPSCs can be used to construct patient-specific disease models to elucidate the pathogenic mechanisms of disease development and to test new therapeutic strategies. Accordingly, the present review will focus on recent progress in iPSC research in the modeling of neurodegenerative disorders and in the development of novel therapeutic options. PMID:26240571

  4. Chemical characterization of single micro- and nano-particles by optical catapulting-optical trapping-laser-induced breakdown spectroscopy

    NASA Astrophysics Data System (ADS)

    Fortes, Francisco J.; Fernández-Bravo, Angel; Javier Laserna, J.

    2014-10-01

    Spectral identification of individual micro- and nano-sized particles by the sequential intervention of optical catapulting, optical trapping and laser-induced breakdown spectroscopy is presented. The three techniques are used for different purposes. Optical catapulting (OC) serves to put the particulate material under inspection in aerosol form. Optical trapping (OT) permits the isolation and manipulation of individual particles from the aerosol, which are subsequently analyzed by laser-induced breakdown spectroscopy (LIBS). Once catapulted, the dynamics of particle trapping depends both on the laser beam characteristics (power and intensity gradient) and on the particle properties (size, mass and shape). Particles are stably trapped in air at atmospheric pressure and can be conveniently manipulated for a precise positioning for LIBS analysis. The spectra acquired from the individually trapped particles permit a straightforward identification of the material inspected. Variability of LIBS signal for the inspection of Ni microspheres was 30% relative standard deviation. OC-OT-LIBS permits the separation of particles in a heterogeneous mixture and the subsequent analysis of the isolated particle of interest. In order to evaluate the sensitivity of the approach, the number of absolute photons emitted by a single trapped particle was calculated. The limit of detection (LOD) for Al2O3 particles was calculated to be 200 attograms aluminium.

  5. Biological dose estimation of UVA laser microirradiation utilizing charged particle-induced protein foci

    PubMed Central

    Splinter, J.; Jakob, B.; Lang, M.; Yano, K.; Engelhardt, J.; Hell, S. W.; Chen, D. J.; Durante, M.; Taucher-Scholz, G.

    2010-01-01

    The induction of localized DNA damage within a discrete nuclear volume is an important tool in DNA repair studies. Both charged particle irradiation and laser microirradiation (LMI) systems allow for such a localized damage induction, but the results obtained are difficult to compare, as the delivered laser dose cannot be measured directly. Therefore, we revisited the idea of a biological dosimetry based on the microscopic evaluation of irradiation-induced Replication Protein A (RPA) foci numbers. Considering that local dose deposition is characteristic for both LMI and charged particles, we took advantage of the defined dosimetry of particle irradiation to estimate the locally applied laser dose equivalent. Within the irradiated nuclear sub-volumes, the doses were in the range of several hundreds of Gray. However, local dose estimation is limited by the saturation of the RPA foci numbers with increasing particle doses. Even high-resolution 4Pi microscopy did not abrogate saturation as it was not able to resolve single lesions within individual RPA foci. Nevertheless, 4Pi microscopy revealed multiple and distinct 53BP1- and ?H2AX-stained substructures within the lesion flanking chromatin domains. Monitoring the local recruitment of the telomere repeat-binding factors TRF1 and TRF2 showed that both proteins accumulated at damage sites after UVA–LMI but not after densely ionizing charged particle irradiation. Hence, our results indicate that the local dose delivered by UVA–LMI is extremely high and cannot be accurately translated into an equivalent ionizing radiation dose, despite the sophisticated techniques used in this study. PMID:20167590

  6. Alpha particle induced DNA damage and repair in normal cultured thyrocytes of different proliferation status.

    PubMed

    Lyckesvärd, Madeleine Nordén; Delle, Ulla; Kahu, Helena; Lindegren, Sture; Jensen, Holger; Bäck, Tom; Swanpalmer, John; Elmroth, Kecke

    2014-07-01

    Childhood exposure to ionizing radiation increases the risk of developing thyroid cancer later in life and this is suggested to be due to higher proliferation of the young thyroid. The interest of using high-LET alpha particles from Astatine-211 ((211)At), concentrated in the thyroid by the same mechanism as (131)I [1], in cancer treatment has increased during recent years because of its high efficiency in inducing biological damage and beneficial dose distribution when compared to low-LET radiation. Most knowledge of the DNA damage response in thyroid is from studies using low-LET irradiation and much less is known of high-LET irradiation. In this paper we investigated the DNA damage response and biological consequences to photons from Cobolt-60 ((60)Co) and alpha particles from (211)At in normal primary thyrocytes of different cell cycle status. For both radiation qualities the intensity levels of ?H2AX decreased during the first 24h in both cycling and stationary cultures and complete repair was seen in all cultures but cycling cells exposed to (211)At. Compared to stationary cells alpha particles were more harmful for cycling cultures, an effect also seen at the pChk2 levels. Increasing ratios of micronuclei per cell nuclei were seen up to 1Gy (211)At. We found that primary thyrocytes were much more sensitive to alpha particle exposure compared with low-LET photons. Calculations of the relative biological effectiveness yielded higher RBE for cycling cells compared with stationary cultures at a modest level of damage, clearly demonstrating that cell cycle status influences the relative effectiveness of alpha particles. PMID:24769180

  7. Protective effects of PEP-1-Catalase on stress-induced cellular toxicity and MPTP-induced Parkinson’s disease

    PubMed Central

    Eom, Seon Ae; Kim, Dae Won; Shin, Min Jea; Ahn, Eun Hee; Chung, Seok Young; Sohn, Eun Jeong; Jo, Hyo Sang; Jeon, Su-Jeong; Kim, Duk-Soo; Kwon, Hyeok Yil; Cho, Sung-Woo; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2015-01-01

    Parkinson’s disease (PD) is a neurodegenerative disability caused by a decrease of dopaminergic neurons in the substantia nigra (SN). Although the etiology of PD is not clear, oxidative stress is believed to lead to PD. Catalase is antioxidant enzyme which plays an active role in cells as a reactive oxygen species (ROS) scavenger. Thus, we investigated whether PEP-1-Catalase protects against 1-methyl-4-phenylpyridinium (MPP+) induced SH-SY5Y neuronal cell death and in a 1-methyl-4-phenyl-1,2,3,6-trtrahydropyridine (MPTP) induced PD animal model. PEP-1-Catalase transduced into SH-SY5Y cells significantly protecting them against MPP+-induced death by decreasing ROS and regulating cellular survival signals including Akt, Bax, Bcl-2, and p38. Immunohistochemical analysis showed that transduced PEP-1-Catalase markedly protected against neuronal cell death in the SN in the PD animal model. Our results indicate that PEP-1-Catalase may have potential as a therapeutic agent for PD and other oxidative stress related diseases. [BMB Reports 2015; 48(7): 395-400] PMID:25322954

  8. Mineral particles of varying composition induce differential chemokine release from epithelial lung cells: importance of physico-chemical characteristics.

    PubMed

    Ovrevik, J; Myran, T; Refsnes, M; Låg, M; Becher, R; Hetland, R B; Schwarze, P E

    2005-04-01

    Presently, little is known about the potential health effects of mineral particles other than asbestos and quartz. In this study, a human epithelial lung cell line (A549), primary human small airway epithelial cells (SAECs) and primary rat type 2 (T2) cells were exposed to stone quarry particles of two size fractions (<10 and <2.5 microm) from nine different rock samples. The ability to induce the release of chemokines from lung cells was investigated and compared with the particles' mineral and element composition and the amount of soluble elements. The stone particles induced the release of only low levels of interleukin (IL)-8 from A549 cells. In contrast, some of the other particles induced the release of high levels of macrophage inflammatory protein (MIP)-2 from T2 cells, and high levels of IL-8 from SAECs. Differences in particle surface area could account for differences in activity between the <10 and <2.5 microm fractions of six out of the nine rock samples. For two samples the <2.5 microm fraction was most active and for one sample the <10 microm fraction was most active. Content of the mineral plagioclase displayed a strong, negative correlation with the potential to induce MIP-2, whereas the mineral pyroxene was positively correlated with MIP-2 induction. However, neither plagioclase nor pyroxene content was sufficient to explain differences in bioactivity between the particles. No statistically significant correlation was found between the amounts of total or soluble elements and MIP-2 release. In conclusion, the results suggest that mineral particles with a high content of plagioclase have a low potential to induce a pro-inflammatory response. However, a particular mineral or element responsible for eliciting strong increases in chemokine release could not be identified. Thus, at present it appears that analysing mineral and element content is insufficient to predict stone particle bioactivity, and that biological testing is a necessity. PMID:15640311

  9. UHMWPE carrying estradiol to treat the particle-induced osteolysis-Processing and characterizing.

    PubMed

    Liu, Aiqin; Qu, Shuxin; Chao, Mengmeng; Zhu, Minhao; Weng, Jie; Zhou, Zhongrong

    2009-08-01

    The objective of this study was to explore the possibility of UHMWPE implant used as the drug carrier to treat particle-induced osteolysis. 17beta-estradiol (E2), which had the potential application on osteolysis treatment and the high melting point, was added into UHMWPE powder to produce UHMWPE-E2 composites through hot press processing. The hydrophobicity, crystallinity, mechanical properties, and wear performance of the UHMWPE-E2 were characterized compared with the control UHMWPE. The thermal analysis and Fourier Transform Infrared Spectroscopy results demonstrated that the hot press processing would not alter the functional groups of E2 in this study. There were no significant differences in the hydrophobicity and crystallinity between the UHMWPE-E2 and UHMWPE. The UHMWPE-E2 showed satisfying mechanical properties, including ultimate tensile strength (47.2 +/- 3.6 MPa), yield strength (25.0 +/- 0.6 MPa) and elongation at break (320 +/- 25.5 %), which were similar with the control UHMWPE. The friction coefficients and worn scars were similar between the UHMWPE-E2 and the control UHMWPE. The wear mechanism of the UHMWPE-E2 and UHMWPE both were abrasive wear under dry friction. The UHMWPE-E2 possesses the approving mechanical properties and wear performance compared with the control UHMWPE, which might be used as the potential implanted drug carrier to prevent the particle-induced osteolysis in joint replacements. PMID:18563828

  10. Asian Dust Particles Induce TGF-?1 via Reactive Oxygen Species in Bronchial Epithelial Cells

    PubMed Central

    Kyung, Sun Young; Yoon, Jin Young; Kim, Yu Jin; Lee, Sang Pyo; Park, Jeong-Woong

    2012-01-01

    Background Asian dust storms can be transported across eastern Asia. In vitro, Asian dust particle-induced inflammation and enhancement of the allergic reaction have been observed. However, the fibrotic effects of Asian dust particles are not clear. Production of transforming growth factor ?1 (TGF-?1) and fibronectin were investigated in the bronchial epithelial cells after exposure to Asian dust particulate matter (AD-PM10). Methods During Asian dust storm periods, air samples were collected. The bronchial epithelial cells were exposed to AD-PM10 with and without the antioxidant, N-acetyl-L-cysteine (NAC). Then TGF-?1 and fibronectin were detected by Western blotting. The reactive oxygen species (ROS) was detected by the measurement of dicholorodihydrofluorescin (DCF), using a FACScan, and visualized by a confocal microscopy. Results The expression of TGF-?1, fibronectin and ROS was high after being exposed to AD-PM10, compared to the control. NAC attenuated both TGF-?1 and fibronectin expression in the AD-PM10-exposed the bronchial epithelial cells. Conclusion AD-PM10 may have fibrotic potential in the bronchial epithelial cells and the possible mechanism is AD-PM10-induced intracellular ROS. PMID:23166540

  11. Plant virus particles carrying tumour antigen activate TLR7 and Induce high levels of protective antibody.

    PubMed

    Jobsri, Jantipa; Allen, Alex; Rajagopal, Deepa; Shipton, Michael; Kanyuka, Kostya; Lomonossoff, George P; Ottensmeier, Christian; Diebold, Sandra S; Stevenson, Freda K; Savelyeva, Natalia

    2015-01-01

    Induction of potent antibody is the goal of many vaccines targeted against infections or cancer. Modern vaccine designs that use virus-like particles (VLP) have shown efficacy for prophylactic vaccination against virus-associated cancer in the clinic. Here we used plant viral particles (PVP), which are structurally analogous to VLP, coupled to a weak idiotypic (Id) tumour antigen, as a conjugate vaccine to induce antibody against a murine B-cell malignancy. The Id-PVP vaccine incorporates a natural adjuvant, the viral ssRNA, which acts via TLR7. It induced potent protective anti-Id antibody responses in an in vivo mouse model, superior to the "gold standard" Id vaccine, with prevalence of the IgG2a isotype. Combination with alum further increased antibody levels and maintained the IgG2a bias. Engagement of TLR7 in vivo was followed by secretion of IFN-? by plasmacytoid dendritic cells and by activation of splenic CD11chi conventional dendritic cells. The latter was apparent from up-regulation of co-stimulatory molecules and from secretion of a wide range of inflammatory cytokines and chemokines including the Th1-governing cytokine IL-12, in keeping with the IgG2a antibody isotype distribution. PVP conjugates are a novel cancer vaccine design, offering an attractive molecular form, similar to VLP, and providing T-cell help. In contrast to VLP, they also incorporate a safe "in-built" ssRNA adjuvant. PMID:25692288

  12. HZE particle radiation induces tissue-specific and p53-dependent mutagenesis in transgenic animals

    NASA Technical Reports Server (NTRS)

    Chang, P. Y.; Kanazawa, N.; Lutze-Mann, L.; Winegar, R.

    2001-01-01

    Transgenic animals, with the integrated target gene, provide a unique approach for measuring and characterizing mutations in any tissue of the animal. We are using the plasmid-based lacZ transgenic mice with different p53 genetic background to examine radiation-induced genetic damage resulting from exposure to heavy particle radiation. We measured lacZ mutation frequencies (MF) in the brain and spleen tissues at various times after exposing animals to an acute dose of 1 Gy of 1GeV/amu iron particles. MF in the spleen of p53+/+ animals increased up to 2.6-fold above spontaneous levels at 8 weeks post irradiation. In contrast, brain MF from the same animals increased 1.7-fold above controls in the same period. In the p53-/- animals, brain MF increased to 2.2-fold above spontaneous levels at 1 week after treatment, but returned to control levels thereafter. Radiation also induced alterations in the spectrum of mutants in both tissues, accompanied by changes in the frequency of mutants with deletions extending past the transgene into mouse genomic DNA. Our results indicate that the accumulation of transgene MF after radiation exposure is dependant on the tissue examined as well as the p53 genetic background of the animals.

  13. Opportunities and Limitations of Modelling Alzheimer’s Disease with Induced Pluripotent Stem Cells

    PubMed Central

    Ovchinnikov, Dmitry A.; Wolvetang, Ernst J.

    2014-01-01

    Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) has opened the way for patient-specific disease modelling. Following their differentiation into neuronal cell types, iPSC have enabled the investigation of human neurodegenerative diseases, such as Alzheimer’s disease (AD). While human iPSCs certainly provide great opportunities to repeatedly interrogate specific human brain cell types of individuals with familial and sporadic forms of the disease, the complex aetiology and timescale over which AD develops in humans poses particular challenges to iPSC-based AD models. Here, we discuss the current state-of-play in the context of these and other iPSC model-related challenges and elaborate on likely future developments in this field of research. PMID:26237606

  14. Cardiovascular Disease Modeling Using Patient-Specific Induced Pluripotent Stem Cells

    PubMed Central

    Tanaka, Atsushi; Yuasa, Shinsuke; Node, Koichi; Fukuda, Keiichi

    2015-01-01

    The generation of induced pluripotent stem cells (iPSCs) has opened up a new scientific frontier in medicine. This technology has made it possible to obtain pluripotent stem cells from individuals with genetic disorders. Because iPSCs carry the identical genetic anomalies related to those disorders, iPSCs are an ideal platform for medical research. The pathophysiological cellular phenotypes of genetically heritable heart diseases such as arrhythmias and cardiomyopathies, have been modeled on cell culture dishes using disease-specific iPSC-derived cardiomyocytes. These model systems can potentially provide new insights into disease mechanisms and drug discoveries. This review focuses on recent progress in cardiovascular disease modeling using iPSCs, and discusses problems and future perspectives concerning their use. PMID:26274955

  15. Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease.

    PubMed

    Johnson, Reed F; Hammoud, Dima A; Lackemeyer, Matthew G; Yellayi, Srikanth; Solomon, Jeffrey; Bohannon, Jordan K; Janosko, Krisztina B; Jett, Catherine; Cooper, Kurt; Blaney, Joseph E; Jahrling, Peter B

    2015-07-01

    Cowpox virus (CPXV) inoculation of nonhuman primates (NHPs) has been suggested as an alternate model for smallpox (Kramski et al., 2010, PLoS One, 5, e10412). Previously, we have demonstrated that intrabronchial inoculation of CPXV-Brighton Red (CPXV-BR) into cynomolgus monkeys resulted in a disease that shared many similarities to smallpox; however, severe respiratory tract disease was observed (Smith et al., 2011, J. Gen. Virol.). Here we describe the course of disease after small particle aerosol exposure of rhesus monkeys using computed tomography (CT) to monitor respiratory disease progression. Subjects developed a severe respiratory disease that was uniformly lethal at 5.7 log10 PFU of CPXV-BR. CT indicated changes in lung architecture that correlated with changes in peripheral blood monocytes and peripheral oxygen saturation. While the small particle aerosol inoculation route does not accurately mimic human smallpox, the data suggest that CT can be used as a tool to monitor real-time disease progression for evaluation of animal models for human diseases. PMID:25776759

  16. Nanoparticle-Induced Gelation of Bimodal Slurries with Highly Size-Asymmetric Particles: Effect of Surface Chemistry and Concentration.

    PubMed

    Lee, Jooyoung; Lee, Seong Jae; Ahn, Kyung Hyun; Lee, Seung Jong

    2015-12-29

    A systematic study has been performed to investigate the effect of surface potential of nanoparticles on the rheological behavior of bimodal suspensions, using a model system consisting of polystyrene latex (primary size ?530 nm) and alumina-coated silica (primary size ?12 nm) particles. The surface potential of small particles was tuned by varying the solution pH, causing them to be repulsive to each other, attractive to each other, and oppositely charged to the large particles, while the large particles remained electrostatically stabilized. We found that the rheological properties could be dramatically changed from viscous to gel-like depending on the surface potential and concentration of small particles. A colloidal gel was induced by small particles when the small particles had the opposite charge to the large particles and a volume fraction of 10(-4) < ?small < 10(-3), and when the small particles were attractive to each other above a critical threshold, ?small > 10(-4). Cryo-SEM distinguished the gel structures to be either short bridging gels produced by oppositely charged small particles or long bridging gels or dense gels produced by attractive small particles. On the basis of this rheological behavior and microstructure, we prepared a phase diagram of highly size-asymmetric bimodal colloids with respect to the surface chemistry and concentration of small particles. PMID:26634946

  17. RTN1 mediates progression of kidney disease by inducing ER stress

    PubMed Central

    Fan, Ying; Xiao, Wenzhen; Li, Zhengzhe; Li, Xuezhu; Chuang, Peter Y.; Jim, Belinda; Zhang, Weijia; Wei, Chengguo; Wang, Niansong; Jia, Weiping; Xiong, Huabao; Lee, Kyung; He, John C.

    2015-01-01

    Identification of new biomarkers and drug targets for chronic kidney disease (CKD) is required for the development of more effective therapy. Here we report an association between expression of reticulon 1 (RTN1) and severity of CKD. An isoform-specific increase in the expression of RTN1A is detected in the diseased kidneys from mice and humans, and correlates inversely with renal function in patients with diabetic nephropathy. RTN1 overexpression in renal cells induces ER stress and apoptosis, whereas RTN1 knockdown attenuates tunicamycin-induced and hyperglycaemia-induced ER stress and apoptosis. RTN1A interacts with PERK through its N-terminal and C-terminal domains, and mutation of these domains prevents this effect on ER stress. Knockdown of Rtn1a expression in vivo attenuates ER stress and renal fibrosis in mice with unilateral ureteral obstruction, and also attenuates ER stress, proteinuria, glomerular hypertrophy and mesangial expansion in diabetic mice. Together, these data indicate that RTN1A contributes to progression of kidney disease by inducing ER stress. PMID:26227493

  18. Violet diode laser-induced chlorophyll fluorescence: a tool for assessing mosaic disease severity in cassava (Manihot esculenta Crantz) cultivars.

    PubMed

    Anderson, Benjamin; Eghan, Moses J; Asare-Bediako, Elvis; Buah-Bassuah, Paul K

    2012-01-01

    Violet diode laser-induced chlorophyll fluorescence was used in agronomical assessment (disease severity and average yield per plant). Because cassava (Manihot esculenta Crantz) is of economic importance, improved cultivars with various levels of affinity for cassava mosaic disease were investigated. Fluorescence data correlated with cassava mosaic disease severity levels and with the average yield per plant. PMID:22519123

  19. Particle-induced cell migration assay (PICMA): A new in vitro assay for inflammatory particle effects based on permanent cell lines.

    PubMed

    Westphal, Götz A; Schremmer, Isabell; Rostek, Alexander; Loza, Kateryna; Rosenkranz, Nina; Brüning, Thomas; Epple, Matthias; Bünger, Jürgen

    2015-08-01

    Inflammation is a decisive pathophysiologic mechanism of particle toxicity and accumulation of neutrophils in the lung is believed to be a crucial step in this process. This study describes an in vitro model for investigations of the chemotactic attraction of neutrophils in response to particles using permanent cell lines. We challenged NR8383 rat macrophages with particles that were characterized concerning chemical nature, crystallinity, and size distribution in the dry state and in the culture medium. The cell supernatants were used to investigate migration of differentiated human leukemia cells (dHL-60 cells). The dose range for the tests was determined using an impedance-based Real-Time Cell Analyzer. The challenge of NR8383 cells with 32-96 ?g cm(-2) coarse and nanosized particles resulted in cell supernatants which induced strong and dose-dependent migration of dHL-60 cells. Quartz caused the strongest effects - exceeding the positive control "fetal calf serum" (FCS) several-fold, followed by silica, rutile, carbon black, and anatase. BaSO4 served as inert control and induced no cell migration. Particles caused NR8383 cells to secrete chemotactic compounds. The assay clearly distinguished between the particles of different inflammatory potential in a highly reproducible way. Specificity of the test is suggested by negative results with BaSO4. PMID:25896209

  20. A theoretical study of induced-charge dipolophoresis of ideally polarizable asymmetrically slipping Janus particles

    NASA Astrophysics Data System (ADS)

    Boymelgreen, Alicia M.; Miloh, Touvia

    2011-07-01

    We consider the non linear electrophoretic transport of uncharged, ideally polarizable hydrodynamic Janus spheres, the inhomogeneity of which is produced by a variable Navier slip condition at the particle surface. A general, three dimensional formulation enabling calculation of the electrophoretic mobility of any patchy particle, with an arbitrary tensorial slip boundary condition is provided. The solution avoids the common assumption of an infinitely thin electric double layer (?) and Navier slip coefficient (b) and is thereby valid for finite values of these parameters, which is of particular importance at the nanoscale. The specific case of a Janus sphere, consisting of two equal hemispheres, each with a different but constant slip boundary condition is solved semi-analytically and numerically. In the instance where the slip coefficients at each hemisphere are equal, induced charge electro-osmotic flow is evident at an increased rate as compared to a homogeneous sphere with no slip. If the slip coefficients differ from each other, the particle is found to self-align with the electric field and travel with the slip surface facing forward. The increased pumping rates and mobility found in the cases of the homogeneous and Janus spheres respectively, occur as a function of the ratio b/b? ? and are most significant for the combination of a thin electric double layer (EDL) and large slip length. However, it is also illustrated that the size of the EDL independently dominates the effects of slip.

  1. Generating induced pluripotent stem cell derived endothelial cells and induced endothelial cells for cardiovascular disease modelling and therapeutic angiogenesis.

    PubMed

    Clayton, Z E; Sadeghipour, S; Patel, S

    2015-10-15

    Standard therapy for atherosclerotic coronary and peripheral arterial disease is insufficient in a significant number of patients because extensive disease often precludes effective revascularization. Stem cell therapy holds promise as a supplementary treatment for these patients, as pre-clinical and clinical research has shown transplanted cells can promote angiogenesis via direct and paracrine mechanisms. Induced pluripotent stem cells (iPSCs) are a novel cell type obtained by reprogramming somatic cells using exogenous transcription factor cocktails, which have been introduced to somatic cells via viral or plasmid constructs, modified mRNA or small molecules. IPSCs are now being used in disease modelling and drug testing and are undergoing their first clinical trial, but despite recent advances, the inefficiency of the reprogramming process remains a major limitation, as does the lack of consensus regarding the optimum transcription factor combination and delivery method and the uncertainty surrounding the genetic and epigenetic stability of iPSCs. IPSCs have been successfully differentiated into vascular endothelial cells (iPSC-ECs) and, more recently, induced endothelial cells (iECs) have also been generated by direct differentiation, which bypasses the pluripotent intermediate. IPSC-ECs and iECs demonstrate endothelial functionality in vitro and have been shown to promote neovessel growth and enhance blood flow recovery in animal models of myocardial infarction and peripheral arterial disease. Challenges remain in optimising the efficiency, safety and fidelity of the reprogramming and endothelial differentiation processes and establishing protocols for large-scale production of clinical-grade, patient-derived cells. PMID:26123569

  2. Epizootic Hemorrhagic Disease Virus Induces and Benefits from Cell Stress, Autophagy, and Apoptosis

    PubMed Central

    Shai, Ben; Schmukler, Eran; Yaniv, Roy; Ziv, Naomi; Horn, Galit; Bumbarov, Velizar; Yadin, Hagai; Smorodinsky, Nechama I.; Bacharach, Eran; Pinkas-Kramarski, Ronit

    2013-01-01

    The mode and timing of virally induced cell death hold the potential of regulating viral yield, viral transmission, and the severity of virally induced disease. Orbiviruses such as the epizootic hemorrhagic disease virus (EHDV) are nonenveloped and cytolytic. To date, the death of cells infected with EHDV, the signal transduction pathways involved in this process, and the consequence of their inhibition have yet to be characterized. Here, we report that the Ibaraki strain of EHDV2 (EHDV2-IBA) induces apoptosis, autophagy, a decrease in cellular protein synthesis, the activation of c-Jun N-terminal kinase (JNK), and the phosphorylation of the JNK substrate c-Jun. The production of infectious virions decreased upon inhibition of apoptosis with the pan-caspase inhibitor Q-VD-OPH (quinolyl-valyl-O-methylaspartyl-[-2,6-difluorophenoxy]-methyl ketone), upon inhibition of autophagy with 3-methyladenine or via the knockout of the autophagy regulator Atg5, or upon treatment of infected cells with the JNK inhibitor SP600125 or the cyclin-dependent kinase (CDK) inhibitor roscovitine, which also inhibited c-Jun phosphorylation. Moreover, Q-VD-OPH, SP600125, and roscovitine partially reduced EHDV2-IBA-induced cell death, and roscovitine diminished the induction of autophagy by EHDV2-IBA. Taken together, our results imply that EHDV induces and benefits from the activation of signaling pathways involved in cell stress and death. PMID:24089565

  3. Generation and Characterization of Patient-Specific Induced Pluripotent Stem Cell for Disease Modeling.

    PubMed

    Sivapatham, Renuka; Zeng, Xianmin

    2016-01-01

    One major hurdle to the development of effective treatments to many diseases is the lack of suitable human model systems. The ability to reprogram human somatic cells to induced pluripotent stem cells (iPSC) offers an excellent opportunity to generate human disease models with primary cells. Currently, several methods to generate iPSC lines exist, and iPSC can be generated from various tissue sources including skin fibroblasts, blood, hair follicles, dental tissue, and urine. In this chapter we describe the generation and characterization of iPSC from blood or fibroblast on a routine base and focus on the integration-free methodologies. PMID:25520284

  4. Oral immunization with recombinant lactobacillus plantarum induces a protective immune response in mice with Lyme disease.

    PubMed

    del Rio, Beatriz; Dattwyler, Raymond J; Aroso, Miguel; Neves, Vera; Meirelles, Luciana; Seegers, Jos F M L; Gomes-Solecki, Maria

    2008-09-01

    Mucosal immunization is advantageous over other routes of antigen delivery because it can induce both mucosal and systemic immune responses. Our goal was to develop a mucosal delivery vehicle based on bacteria generally regarded as safe, such as Lactobacillus spp. In this study, we used the Lyme disease mouse model as a proof of concept. We demonstrate that an oral vaccine based on live recombinant Lactobacillus plantarum protects mice from tick-transmitted Borrelia burgdorferi infection. Our method of expressing vaccine antigens in L. plantarum induces both systemic and mucosal immunity after oral administration. This platform technology can be applied to design oral vaccine delivery vehicles against several microbial pathogens. PMID:18632920

  5. A new mechanism for DNA alterations induced by alpha particles such as those emitted by radon and radon progeny.

    PubMed Central

    Lehnert, B E; Goodwin, E H

    1997-01-01

    The mechanism(s) by which alpha (alpha) particles like those emitted from inhaled radon and radon progeny cause their carcinogenic effects in the lung remains unclear. Although direct nuclear traversals by alpha-particles may be involved in mediating these outcomes, increasing evidence indicates that a particles can cause alterations in DNA in the absence of direct hits to cell nuclei. Using the occurrence of excessive sister chromatid exchanges (SCE) as an index of DNA damage in human lung fibroblasts, we investigated the hypothesis that alpha-particles may induce DNA damage through the generation of extracellular factors. We have found that a relatively low dose of alpha-particles can result in the generation of extracellular factors, which, upon transfer to unexposed normal human cells, can cause excessive SCE to an extent equivalent to that observed when the cells are directly irradiated with the same irradiation dose. A short-lived, SCE-inducing factor(s) is generated in alpha-irradiated culture medium containing serum in the absence of cells. A more persistent SCE-inducing factor(s), which can survive freeze-thaw and is heat labile is produced by fibroblasts after exposure to the alpha-particles. These results indicate that the initiating target for alpha-particle-induced genetic changes can be larger than a cell's nucleus or even a whole cell. How transmissible factors like those observed here in vitro may extend to the in vivo condition in the context of a-particle-induced carcinogenesis in the respiratory tract remains to be determined. PMID:9400706

  6. Anacardic Acids from Cashew Nuts Ameliorate Lung Damage Induced by Exposure to Diesel Exhaust Particles in Mice

    PubMed Central

    Carvalho, Ana Laura Nicoletti; Annoni, Raquel; Torres, Larissa Helena Lobo; Durão, Ana Carolina Cardoso Santos; Shimada, Ana Lucia Borges; Almeida, Francine Maria; Hebeda, Cristina Bichels; Lopes, Fernanda Degobbi Tenorio Quirino Santos; Dolhnikoff, Marisa; Martins, Milton Arruda; Silva, Luiz Fernando Ferraz; Farsky, Sandra Helena Poliselli; Saldiva, Paulo Hilário Nascimento; Ulrich, Cornelia M.; Owen, Robert W.; Marcourakis, Tania; Trevisan, Maria Teresa Salles; Mauad, Thais

    2013-01-01

    Anacardic acids from cashew nut shell liquid, a Brazilian natural substance, have antimicrobial and antioxidant activities and modulate immune responses and angiogenesis. As inflammatory lung diseases have been correlated to environmental pollutants exposure and no reports addressing the effects of dietary supplementation with anacardic acids on lung inflammation in vivo have been evidenced, we investigated the effects of supplementation with anacardic acids in a model of diesel exhaust particle- (DEP-) induced lung inflammation. BALB/c mice received an intranasal instillation of 50??g of DEP for 20 days. Ten days prior to DEP instillation, animals were pretreated orally with 50, 150, or 250?mg/kg of anacardic acids or vehicle (100??L of cashew nut oil) for 30 days. The biomarkers of inflammatory and antioxidant responses in the alveolar parenchyma, bronchoalveolar lavage fluid (BALF), and pulmonary vessels were investigated. All doses of anacardic acids ameliorated antioxidant enzyme activities and decreased vascular adhesion molecule in vessels. Animals that received 50?mg/kg of anacardic acids showed decreased levels of neutrophils and tumor necrosis factor in the lungs and BALF, respectively. In summary, we demonstrated that AAs supplementation has a potential protective role on oxidative and inflammatory mechanisms in the lungs. PMID:23533495

  7. Anacardic acids from cashew nuts ameliorate lung damage induced by exposure to diesel exhaust particles in mice.

    PubMed

    Carvalho, Ana Laura Nicoletti; Annoni, Raquel; Torres, Larissa Helena Lobo; Durão, Ana Carolina Cardoso Santos; Shimada, Ana Lucia Borges; Almeida, Francine Maria; Hebeda, Cristina Bichels; Lopes, Fernanda Degobbi Tenorio Quirino Santos; Dolhnikoff, Marisa; Martins, Milton Arruda; Silva, Luiz Fernando Ferraz; Farsky, Sandra Helena Poliselli; Saldiva, Paulo Hilário Nascimento; Ulrich, Cornelia M; Owen, Robert W; Marcourakis, Tania; Trevisan, Maria Teresa Salles; Mauad, Thais

    2013-01-01

    Anacardic acids from cashew nut shell liquid, a Brazilian natural substance, have antimicrobial and antioxidant activities and modulate immune responses and angiogenesis. As inflammatory lung diseases have been correlated to environmental pollutants exposure and no reports addressing the effects of dietary supplementation with anacardic acids on lung inflammation in vivo have been evidenced, we investigated the effects of supplementation with anacardic acids in a model of diesel exhaust particle- (DEP-) induced lung inflammation. BALB/c mice received an intranasal instillation of 50? ? g of DEP for 20 days. Ten days prior to DEP instillation, animals were pretreated orally with 50, 150, or 250?mg/kg of anacardic acids or vehicle (100? ? L of cashew nut oil) for 30 days. The biomarkers of inflammatory and antioxidant responses in the alveolar parenchyma, bronchoalveolar lavage fluid (BALF), and pulmonary vessels were investigated. All doses of anacardic acids ameliorated antioxidant enzyme activities and decreased vascular adhesion molecule in vessels. Animals that received 50?mg/kg of anacardic acids showed decreased levels of neutrophils and tumor necrosis factor in the lungs and BALF, respectively. In summary, we demonstrated that AAs supplementation has a potential protective role on oxidative and inflammatory mechanisms in the lungs. PMID:23533495

  8. Diesel Exhaust Particles Induce the Over expression of Tumor Necrosis Factor-? (TNF-?) Gene in Alveolar Macrophages and Failed to Induce Apoptosis through Activation of Nuclear Factor-?B (NF-?B)

    PubMed Central

    Kafoury, Ramzi M.; Madden, Michael C.

    2005-01-01

    Exposure to particulate matter (PM2.5–10), including diesel exhaust particles (DEP) has been reported to induce lung injury and exacerbation of asthma and chronic obstructive pulmonary disease. Alveolar macrophages play a major role in the lung’s response to inhaled particles and therefore, are a primary target for PM2.5–10 effect. The molecular and cellular events underlying DEP-induced toxicity in the lung, however, remain unclear. To determine the effect of DEP on alveolar macrophages, RAW 264.7 cells were grown in RPMI 1640 with supplements until confluency. RAW 264.7 cultures were exposed to Hank’s buffered saline solution (vehicle), vehicle containing an NF-?B inhibitor, BAY11-7082 (25?M with 11/2 hr pre-incubation), or vehicle containing DEP (250?g/ml) in the presence or absence of BAY11-7082 (25?M with 11/2 hr pre-incubation) for 4 hr and TNF-? release was determined by enzyme-linked immunosorbent assay and confirmed by western blots. RAW 264.7 apoptotic response was determined by DNA fragmentation assays. U937 cells treated with campothecin (4 ?g/ml × 3 hr), an apoptosis-inducing agent, were used as positive control. We report that exposure to the carbonaceous core of DEP induces significant release of TNF-? in a concentration-dependent fashion (31 ± 4 pg/ml, n = 4, p = 0.08; 162 ± 23 pg/ml, n = 4, p < 0.05; 313 ± 31 pg/ml, n = 4, p < 0.05 at 25, 100, and 250 ?g/ml, respectively). DEP exposure, however, failed to induce any apoptotic response in RAW 264.7 cells. Moreover, inhibition of NF-?B binding activity has resulted in DEP-induced apoptotic response in alveolar macrophages, as demonstrated by the NF-?B inhibitor, BAY11-7082 studies. The results of the present study indicate that DEP induce the release of TNF-? in alveolar macrophages, a primary target for inhaled particles effect. DEP-induced TNF-? gene expression is regulated at the transcriptional level by NF-?B. Furthermore, DEP-induced increase in NF-?B-DNA binding activity appears to protect against apoptosis. PMID:16705808

  9. Understanding the mechanisms of sickle cell disease by simulations with a discrete particle model

    NASA Astrophysics Data System (ADS)

    Hui, Katrina; Lin, Guang; Pan, Wenxiao

    2013-01-01

    Sickle cell disease (SCD) is an inherited blood disorder characterized by rigid, sickle-shaped red blood cells (RBCs). Because of their rigidity and shape, sickle cells can get stuck in smaller blood vessels, causing blockages and depriving oxygen to tissues. This study develops and applies mathematical models to better understand the mechanism of SCD. Two-dimensional models of RBCs and blood vessels have been constructed by representing them as discrete particles interacting with different forces. The nonlinear, elastic property of healthy RBCs could be adequately reproduced using a cosine angle bending force and a worm-like chain spring force. With the ability to deform, RBCs can squeeze through narrow blood vessels. In modeling sickle cells as rigid bodies and applying repelling and friction forces from the blood vessel, this study shows that geometrical factors (dimensions of the sickle cell and blood vessels) as well as rigidity and adhesiveness of the sickle cell all play an important role in determining how, and if, sickle cells become trapped within narrow blood capillaries. With lack of data to validate the model, this study primarily provides a sensitivity analysis of factors influencing sickle cell occlusion and identified critical data to support future modeling.

  10. RNA 1 and RNA 2 Genomic Segments of Chronic Bee Paralysis Virus Are Infectious and Induce Chronic Bee Paralysis Disease

    PubMed Central

    Youssef, Ibrahim; Schurr, Frank; Goulet, Adeline; Cougoule, Nicolas; Ribière-Chabert, Magali; Darbon, Hervé; Thiéry, Richard; Dubois, Eric

    2015-01-01

    Chronic bee paralysis virus (CBPV) causes an infectious and contagious disease of adult honeybees. Its segmented genome is composed of two major positive single-stranded RNAs, RNA 1 (3,674?nt) and RNA 2 (2,305?nt). Three minor RNAs (about 1,000?nt each) have been described earlier but they were not detected by sequencing of CBPV genome. In this study, the results of in vivo inoculation of the two purified CBPV major RNAs are presented and demonstrate that RNA 1 and RNA 2 are infectious. Honeybees inoculated with 109 RNA copies per bee developed paralysis symptoms within 6 days after inoculation. The number of CBPV RNA copies increased significantly throughout the infection. Moreover, the negative strand of CBPV RNA was detected by RT-PCR, and CBPV particles were visualized by electronic microscopy in inoculated honeybees. Taken together, these results show that CBPV RNA 1 and CBPV RNA 2 segments can induce virus replication and produce CBPV virus particles. Therefore, the three minor RNAs described in early studies are not essential for virus replication. These data are crucial for the development of a reverse genetic system for CBPV. PMID:26583154

  11. IFN? influences type I interferon response and susceptibility to Theiler's virus-induced demyelinating disease.

    PubMed

    Bowen, Jenna L; Olson, Julie K

    2013-08-01

    Theiler's murine encephalomyelitis virus (TMEV) induces a demyelinating disease in susceptible SJL mice that has similarities to multiple sclerosis in humans. TMEV infection of susceptible mice leads to a persistent virus infection of the central nervous system (CNS), which promotes the development of demyelinating disease associated with an inflammatory immune response in the CNS. TMEV infection of resistant C57BL6 mice results in viral clearance without development of demyelinating disease. Interestingly, TMEV infection of resistant mice deficient in IFN? leads to a persistent virus infection in the CNS and development of demyelinating disease. We have previously shown that the innate immune response affects development of TMEV- induced demyelinating disease, thus we wanted to determine the role of IFN? during the innate immune response. TMEV-infected IFN?-deficient mice had an altered innate immune response, including reduced expression of innate immune cytokines, especially type I interferons. Administration of type I interferons, IFN? and IFNß, to TMEV-infected IFN?-deficient mice during the innate immune response restored the expression of innate immune cytokines. Most importantly, administration of type I interferons to IFN?-deficient mice during the innate immune response decreased the virus load in the CNS and decreased development of demyelinating disease. Microglia are the CNS resident immune cells that express innate immune receptors. In TMEV-infected IFN?-deficient mice, microglia had reduced expression of innate immune cytokines, and administration of type I interferons to these mice restored the innate immune response by microglia. In the absence of IFN?, microglia from TMEV-infected mice had reduced expression of some innate immune receptors and signaling molecules, especially IRF1. These results suggest that IFN? plays an important role in the innate immune response to TMEV by enhancing the expression of innate immune cytokines, especially type I interferons, which directly affects the development of demyelinating disease. PMID:23829778

  12. Protective Effect of Curcumin on Pulmonary and Cardiovascular Effects Induced by Repeated Exposure to Diesel Exhaust Particles in Mice

    PubMed Central

    Nemmar, Abderrahim; Subramaniyan, Deepa; Ali, Badreldin H.

    2012-01-01

    Particulate air pollution has been associated with increased risk of cardiopulmonary diseases. However, the underlying mechanisms are not fully understood. We have previously demonstrated that single dose exposure to diesel exhaust particle (DEP) causes lung inflammation and peripheral thrombotic events. Here, we exposed mice with repeated doses of DEP (15µg/animal) every 2nd day for 6 days (a total of 4 exposures), and measured several cardiopulmonary endpoints 48 h after the end of the treatments. Moreover, the potential protective effect of curcumin (the yellow pigment isolated from turmeric) on DEP-induced cardiopulmonary toxicity was assessed. DEP exposure increased macrophage and neutrophil numbers, tumor necrosis factor ? (TNF ?) in the bronchoalveolar lavage (BAL) fluid, and enhanced airway resistance to methacoline measured invasively using Flexivent. DEP also significantly increased plasma C-reactive protein (CRP) and TNF ? concentrations, systolic blood pressure (SBP) as well as the pial arteriolar thrombosis. It also significantly enhanced the plasma D-dimer and plasminogen activator inhibitor-1 (PAI-1). Pretreatment with curcumin by oral gavage (45 mg/kg) 1h before exposure to DEP significantly prevented the influx of inflammatory cells and the increase of TNF ? in BAL, and the increased airway resistance caused by DEP. Likewise, curcumin prevented the increase of SBP, CRP, TNF ?, D-dimer and PAI-1. The thrombosis was partially but significantly mitigated. In conclusion, repeated exposure to DEP induced lung and systemic inflammation characterized by TNF? release, increased SBP, and accelerated coagulation. Our findings indicate that curcumin is a potent anti-inflammatory agent that prevents the release of TNF? and protects against the pulmonary and cardiovascular effects of DEP. PMID:22745783

  13. Current-induced transition from particle-by-particle to concurrent intercalation in phase-separating battery electrodes.

    PubMed

    Li, Yiyang; El Gabaly, Farid; Ferguson, Todd R; Smith, Raymond B; Bartelt, Norman C; Sugar, Joshua D; Fenton, Kyle R; Cogswell, Daniel A; Kilcoyne, A L David; Tyliszczak, Tolek; Bazant, Martin Z; Chueh, William C

    2014-12-01

    Many battery electrodes contain ensembles of nanoparticles that phase-separate on (de)intercalation. In such electrodes, the fraction of actively intercalating particles directly impacts cycle life: a vanishing population concentrates the current in a small number of particles, leading to current hotspots. Reports of the active particle population in the phase-separating electrode lithium iron phosphate (LiFePO4; LFP) vary widely, ranging from near 0% (particle-by-particle) to 100% (concurrent intercalation). Using synchrotron-based X-ray microscopy, we probed the individual state-of-charge for over 3,000 LFP particles. We observed that the active population depends strongly on the cycling current, exhibiting particle-by-particle-like behaviour at low rates and increasingly concurrent behaviour at high rates, consistent with our phase-field porous electrode simulations. Contrary to intuition, the current density, or current per active internal surface area, is nearly invariant with the global electrode cycling rate. Rather, the electrode accommodates higher current by increasing the active particle population. This behaviour results from thermodynamic transformation barriers in LFP, and such a phenomenon probably extends to other phase-separating battery materials. We propose that modifying the transformation barrier and exchange current density can increase the active population and thus the current homogeneity. This could introduce new paradigms to enhance the cycle life of phase-separating battery electrodes. PMID:25218062

  14. Manganese-Induced Parkinsonism and Parkinson’s Disease: Shared and Distinguishable Features

    PubMed Central

    Kwakye, Gunnar F.; Paoliello, Monica M.B.; Mukhopadhyay, Somshuvra; Bowman, Aaron B.; Aschner, Michael

    2015-01-01

    Manganese (Mn) is an essential trace element necessary for physiological processes that support development, growth and neuronal function. Secondary to elevated exposure or decreased excretion, Mn accumulates in the basal ganglia region of the brain and may cause a parkinsonian-like syndrome, referred to as manganism. The present review discusses the advances made in understanding the essentiality and neurotoxicity of Mn. We review occupational Mn-induced parkinsonism and the dynamic modes of Mn transport in biological systems, as well as the detection and pharmacokinetic modeling of Mn trafficking. In addition, we review some of the shared similarities, pathologic and clinical distinctions between Mn-induced parkinsonism and Parkinson’s disease. Where possible, we review the influence of Mn toxicity on dopamine, gamma aminobutyric acid (GABA), and glutamate neurotransmitter levels and function. We conclude with a survey of the preventive and treatment strategies for manganism and idiopathic Parkinson’s disease (PD). PMID:26154659

  15. Ameliorative Potential of Tamarindus indica on High Fat Diet Induced Nonalcoholic Fatty Liver Disease in Rats

    PubMed Central

    Sasidharan, Suja Rani; Anandakumar, Senthilkumar; Venkatesan, Vijayabalaji; Ariyattu Madhavan, Chandrasekharan Nair; Agarwal, Amit

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD), the prevalence of which is rising globally with current upsurge in obesity, is one of the most frequent causes of chronic liver diseases. The present study evaluated the ameliorative effect of extract of Tamarindus indica seed coat (ETS) on high fat diet (HFD) induced NAFLD, after daily administration at 45, 90, and 180?mg/kg body weight dose levels for a period of 6 weeks, in albino Wistar rats. Treatment with ETS at all tested dose levels significantly attenuated the pathological alterations associated with HFD induced NAFLD viz. hepatomegaly, elevated hepatic lipid and lipid peroxides, serum alanine aminotransferase, and free fatty acid levels as well as micro-/macrohepatic steatosis. Moreover, extract treatment markedly reduced body weight and adiposity along with an improvement in insulin resistance index. The study findings, therefore suggested the therapeutic potential of ETS against NAFLD, acting in part through antiobesity, insulin sensitizing, and antioxidant mechanisms. PMID:24688399

  16. Ameliorative potential of Tamarindus indica on high fat diet induced nonalcoholic fatty liver disease in rats.

    PubMed

    Sasidharan, Suja Rani; Joseph, Joshua Allan; Anandakumar, Senthilkumar; Venkatesan, Vijayabalaji; Madhavan, Chandrasekharan Nair Ariyattu; Agarwal, Amit

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD), the prevalence of which is rising globally with current upsurge in obesity, is one of the most frequent causes of chronic liver diseases. The present study evaluated the ameliorative effect of extract of Tamarindus indica seed coat (ETS) on high fat diet (HFD) induced NAFLD, after daily administration at 45, 90, and 180 mg/kg body weight dose levels for a period of 6 weeks, in albino Wistar rats. Treatment with ETS at all tested dose levels significantly attenuated the pathological alterations associated with HFD induced NAFLD viz. hepatomegaly, elevated hepatic lipid and lipid peroxides, serum alanine aminotransferase, and free fatty acid levels as well as micro-/macrohepatic steatosis. Moreover, extract treatment markedly reduced body weight and adiposity along with an improvement in insulin resistance index. The study findings, therefore suggested the therapeutic potential of ETS against NAFLD, acting in part through antiobesity, insulin sensitizing, and antioxidant mechanisms. PMID:24688399

  17. Disease modeling using human induced pluripotent stem cells: Lessons from the liver?

    PubMed Central

    Gieseck, Richard L.; Colquhoun, Jennifer; Hannan, Nicholas R.F.

    2014-01-01

    Human pluripotent stem cells (hPSCs) have the capacity to differentiate into any of the hundreds of distinct cell types that comprise the human body. This unique characteristic has resulted in considerable interest in the field of regenerative medicine, given the potential for these cells to be used to protect, repair, or replace diseased, injured, and aged cells within the human body. In addition to their potential in therapeutics, hPSCs can be used to study the earliest stages of human development and to provide a platform for both drug screening and disease modeling using human cells. Recently, the description of human induced pluripotent stem cells (hIPSCs) has allowed the field of disease modeling to become far more accessible and physiologically relevant, as pluripotent cells can be generated from patients of any genetic background. Disease models derived from hIPSCs that manifest cellular disease phenotypes have been established to study several monogenic diseases; furthermore, hIPSCs can be used for phenotype-based drug screens to investigate complex diseases for which the underlying genetic mechanism is unknown. As a result, the use of stem cells as research tools has seen an unprecedented growth within the last decade as researchers look for in vitro disease models which closely mimic in vivo responses in humans. Here, we discuss the beginnings of hPSCs, starting with isolation of human embryonic stem cells, moving into the development and optimization of hIPSC technology, and ending with the application of hIPSCs towards disease modeling and drug screening applications, with specific examples highlighting the modeling of inherited metabolic disorders of the liver. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics. PMID:24943800

  18. Identification of antigenic proteins associated with trichloroethylene-induced autoimmune disease by serological proteome analysis

    SciTech Connect

    Liu Jianjun; Xing Xiumei; Huang Haiyan; Jiang Yingzhi; He Haowei; Xu Xinyun; Yuan Jianhui; Zhou Li; Yang Linqing; Zhuang Zhixiong

    2009-11-01

    Although many studies indicated that trichloroethylene (TCE) could induce autoimmune diseases and some protein adducts were detected, the proteins were not identified and mechanisms remain unknown. To screen and identify autoantigens which might be involved in TCE-induced autoimmune diseases, three groups of sera were collected from healthy donors (I), patients suffering from TCE-induced exfoliative dermatitis (ED) (II), and the healed ones (III). Serological proteome analysis (SERPA) was performed with total proteins of TCE-treated L-02 liver cells as antigen sources and immunoglobins of the above sera as probes. Highly immunogenic spots (2-fold or above increase compared with group I) in group II and III were submitted to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and tandem mass spectrometry sequencing. Western blot analysis was followed using commercial antibodies and individual serum. Six proteins were identified. Among them, Enoyl Coenzyme A hydratase peroxisoma 1 and lactate dehydrogenase B only showed stronger immunogenicity for group II sera, while Purine nucleoside phosphorylase, ribosomal protein P0 and proteasome activator subunit1 isoform1 also showed stronger immunogenicity for group III sera. Noteworthy, NM23 reacted only with group II sera. Western blot analysis of NM23 expression indicated that all of the individual serum of group II showed immune activity, which confirmed the validity of SERPA result. These findings revealed that there exist autoantibodies in group II and III sera. Besides, autoantibodies of the two stages of disease course were different. These autoantigens might serve as biomarkers to elucidate mechanisms underlying TCE toxicity and are helpful for diagnosis, therapy and prognosis of TCE-induced autoimmune diseases.

  19. FINE AMBIENT AIR PARTICULAR MATTER EXPOSURE INDUCES MOLECULAR ALTERATIONS INDICATIVE OF CARDIOVASCULAR DISEASE PROGRESSION IN ATHEROSCLEROTIC SUSCEPTIBLE MICE

    EPA Science Inventory

    Epidemiological, clinical, and toxicological studies have demonstrated that exposure to ambient air particulate matter (PM) can alter cardiovascular function and may influence cardiovascular disease (CVD). It has been shown that exposure to concentrated ambient air particles (CA...

  20. Surfactant Protein A in Exhaled Endogenous Particles Is Decreased in Chronic Obstructive Pulmonary Disease (COPD) Patients: A Pilot Study

    PubMed Central

    Lärstad, Mona; Almstrand, Ann-Charlotte; Larsson, Per; Bake, Björn; Larsson, Sven; Ljungström, Evert; Mirgorodskaya, Ekaterina; Olin, Anna-Carin

    2015-01-01

    Background Exhaled, endogenous particles are formed from the epithelial lining fluid in small airways, where surfactant protein A (SP-A) plays an important role in pulmonary host defense. Based on the knowledge that chronic obstructive pulmonary disease (COPD) starts in the small airway epithelium, we hypothesized that chronic inflammation modulates peripheral exhaled particle SP-A and albumin levels. The main objective of this explorative study was to compare the SP-A and albumin contents in exhaled particles from patients with COPD and healthy subjects and to determine exhaled particle number concentrations. Methods Patients with stable COPD ranging from moderate to very severe (n = 13), and healthy non-smoking subjects (n = 12) were studied. Subjects performed repeated breath maneuvers allowing for airway closure and re-opening, and exhaled particles were optically counted and collected on a membrane using the novel PExA® instrument setup. Immunoassays were used to quantify SP-A and albumin. Results COPD patients exhibited significantly lower SP-A mass content of the exhaled particles (2.7 vs. 3.9 weight percent, p = 0.036) and lower particle number concentration (p<0.0001) than healthy subjects. Albumin mass contents were similar for both groups. Conclusions Decreased levels of SP-A may lead to impaired host defense functions of surfactant in the airways, contributing to increased susceptibility to COPD exacerbations. SP-A in exhaled particles from small airways may represent a promising non-invasive biomarker of disease in COPD patients. PMID:26656890

  1. FE2O3 PARTICLE-INDUCED PROSTAGLANDIN E2 (PGE2) SYNTHESIS IN ALVEOLAR MACROPHAGES (AM) DETERMINES PARTICULATE INFLAMMATORY POTENTIAL

    EPA Science Inventory

    As shown by epidemiologic studies, acute exposure to ambient particles is associated with exacerbation of pulmonary and cardiovascular diseases. Metals associated with particles are able to mediate lung injury via oxidant-catalyzed reactions. However, the underlying mechanism i...

  2. Acetaminophen-induced liver injury in obesity and nonalcoholic fatty liver disease.

    PubMed

    Michaut, Anaïs; Moreau, Caroline; Robin, Marie-Anne; Fromenty, Bernard

    2014-08-01

    Although acetaminophen (APAP) is usually considered as a safe drug, this painkiller can lead to acute liver failure after overdoses. Moreover, there is evidence that the maximum recommended dosage can induce hepatic cytolysis in some individuals. Several predisposing factors appear to enhance the risk and severity of APAP-induced liver injury including chronic alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions linked to obesity. In contrast, obesity by itself does not seem to be associated with a higher risk of APAP-induced liver injury. Since 1987, seven studies dealt with APAP-induced hepatotoxicity in rodent models of NAFLD and five of them found that this liver disease was associated with higher APAP toxicity. Unfortunately, these studies did not unequivocally established the mechanism(s) whereby NAFLD could favour APAP hepatotoxicity, although some investigations suggested that pre-existent induction of hepatic cytochrome P450 2E1 (CYP2E1) could play a significant role by increasing the generation of N-acetyl-p-benzoquinone imine (NAPQI), the toxic metabolite of APAP. Moreover, pre-existent mitochondrial dysfunction associated with NAFLD could also be involved. In contrast, some investigations suggested that factors that could reduce the risk and severity of APAP hepatotoxicity in obesity and NAFLD include higher hepatic APAP glucuronidation, reduced CYP3A4 activity and increased volume of body distribution. Thus, the occurrence and the outcome of APAP-induced liver injury in an obese individual with NAFLD might depend on a delicate balance between metabolic factors that can be protective and others that favour large hepatic levels of NAPQI. PMID:24575957

  3. Neuroprotective activity of Stereospermum suaveolens DC against 6-OHDA induced Parkinson's disease model

    PubMed Central

    Shalavadi, M. H.; Chandrashekhar, V. M.; Avinash, S. P.; Sowmya, C.; Ramkishan, A.

    2012-01-01

    Objectives: To evaluate the neuroprotective effect of Stereospermum suaveolens DC on 6-hydroxy dopamine induced Parkinson's disease model. Materials and Methods: The study was conducted on Sprague-Dawley rats where parkinson's disease was induced by producing the striatal 6-hydroxy dopamine lesions. The test animals received methanolic extract of Stereospermum suaveolens at dose of 125, 250 and 500 mg/kg for 42 days. Behavioral assessment, spontaneous locomotor activity and muscular coordination were studied. Antioxidant levels, striatal infraction area were assessed and histopathological studies were carried out. Results: The Stereospermum suaveolens DC methanolic extract showed significant dose dependent increase in behavioral activity, improved muscular coordination. Significant reduction of lipid peroxidation (LPO), increased antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT) and non-enzymatic activity of glutathione (GSH) and total thiol levels in extract treated groups was observed in test groups as compared to control group. Striatal infarction area was significantly reduced in extract treated groups as compared to control group. Conclusion: The methanolic extract of Stereospermum suaveolens DC showed neuroprotective activity against 6-hydroxy dopamine induced Parkinson's disease in rats. PMID:23248404

  4. Melatonin prevents apoptosis induced by 6-hydroxydopamine in neuronal cells: implications for Parkinson's disease.

    PubMed

    Mayo, J C; Sainz, R M; Uria, H; Antolin, I; Esteban, M M; Rodriguez, C

    1998-04-01

    It was recently reported that low doses of 6-hydroxydopamine (6-OHDA) induce apoptosis of naive (undifferentiated) and neuronal (differentiated) PC12 cells, and this system has been proposed as an adequate experimental model for the study of Parkinson's disease. The mechanism by which this neurotoxin damages cells is via the production of free radicals. Given that the neurohormone melatonin has been reported 1) to be a highly effective endogenous free radical scavenger, 2) to increase the mRNA levels and the activity of several antioxidant enzymes, and 3) to inhibit apoptosis in other tissues, we have studied the ability of melatonin to prevent the programmed cell death induced by 6-OHDA in PC12 cells. We found that melatonin prevents the apoptosis caused by 6-OHDA in naive and neuronal PC12 cells as estimated by 1) cell viability assays, 2) counting of the number of apoptotic cells, and 3) analysis and quantification of DNA fragmentation. Exploration of the mechanisms used by melatonin to reduce programmed cell death revealed that this chemical mediator prevents the 6-OHDA induced reduction of mRNAs for several antioxidant enzymes. The possibility that melatonin utilized additional mechanisms to prevent apoptosis of these cells is also discussed. Since this endogenous agent has no known side effects and readily crosses the blood-brain-barrier, we consider melatonin to have a high clinical potential in the treatment of Parkinson's disease and possibly other neurodegenerative diseases, although more research on the mechanisms is yet to be done. PMID:9551855

  5. Butyrate Enhances Disease Resistance of Chickens by Inducing Antimicrobial Host Defense Peptide Gene Expression

    PubMed Central

    Sunkara, Lakshmi T.; Achanta, Mallika; Schreiber, Nicole B.; Bommineni, Yugendar R.; Dai, Gan; Jiang, Weiyu; Lamont, Susan; Lillehoj, Hyun S.; Beker, Ali; Teeter, Robert G.; Zhang, Guolong

    2011-01-01

    Host defense peptides (HDPs) constitute a large group of natural broad-spectrum antimicrobials and an important first line of immunity in virtually all forms of life. Specific augmentation of synthesis of endogenous HDPs may represent a promising antibiotic-alternative approach to disease control. In this study, we tested the hypothesis that exogenous administration of butyrate, a major type of short-chain fatty acids derived from bacterial fermentation of undigested dietary fiber, is capable of inducing HDPs and enhancing disease resistance in chickens. We have found that butyrate is a potent inducer of several, but not all, chicken HDPs in HD11 macrophages as well as in primary monocytes, bone marrow cells, and jejuna and cecal explants. In addition, butyrate treatment enhanced the antibacterial activity of chicken monocytes against Salmonella enteritidis, with a minimum impact on inflammatory cytokine production, phagocytosis, and oxidative burst capacities of the cells. Furthermore, feed supplementation with 0.1% butyrate led to a significant increase in HDP gene expression in the intestinal tract of chickens. More importantly, such a feeding strategy resulted in a nearly 10-fold reduction in the bacterial titer in the cecum following experimental infections with S. enteritidis. Collectively, the results indicated that butyrate-induced synthesis of endogenous HDPs is a phylogenetically conserved mechanism of innate host defense shared by mammals and aves, and that dietary supplementation of butyrate has potential for further development as a convenient antibiotic-alternative strategy to enhance host innate immunity and disease resistance. PMID:22073293

  6. Analysis of Clonostachys rosea-Induced Resistance to Tomato Gray Mold Disease in Tomato Leaves

    PubMed Central

    Guan, Xin; Chen, Xiuling; Chen, Hongyu; Zhang, Jian; Zhang, Junfeng; Li, Jingfu; Yang, Yijun; Wang, Aoxue

    2014-01-01

    Tomato gray mold disease, caused by Botrytis cinerea, is a serious disease in tomato. Clonostachys rosea is an antagonistic microorganism to B. cinerea. To investigate the induced resistance mechanism of C. rosea, we examined the effects of these microorganisms on tomato leaves, along with changes in the activities of three defense enzymes (PAL, PPO, GST), second messengers (NO, H2O2, O2?) and phytohormones (IAA, ABA, GA3, ZT, MeJA, SA and C2H4). Compared to the control, all treatments induced higher levels of PAL, PPO and GST activity in tomato leaves and increased NO, SA and GA3 levels. The expression of WRKY and MAPK, two important transcription factors in plant disease resistance, was upregulated in C. rosea- and C. rosea plus B. cinerea-treated samples. Two-dimensional gel electrophoresis analysis showed that two abundant proteins were present in the C. rosea plus B. cinerea-treated samples but not in the other samples. These proteins were determined (by mass spectrum analysis) to be LEXYL2 (?-xylosidase) and ATP synthase CF1 alpha subunit. Therefore, C. rosea plus B. cinerea treatment induces gray mold resistance in tomato. This study provides a basis for elucidating the mechanism of C. rosea as a biocontrol agent. PMID:25061981

  7. Pathogen-induced elicitin production in transgenic tobacco generates a hypersensitive response and nonspecific disease resistance.

    PubMed Central

    Keller, H; Pamboukdjian, N; Ponchet, M; Poupet, A; Delon, R; Verrier, J L; Roby, D; Ricci, P

    1999-01-01

    The rapid and effective activation of disease resistance responses is essential for plant defense against pathogen attack. These responses are initiated when pathogen-derived molecules (elicitors) are recognized by the host. We have developed a strategy for creating novel disease resistance traits whereby transgenic plants respond to infection by a virulent pathogen with the production of an elicitor. To this end, we generated transgenic tobacco plants harboring a fusion between the pathogen-inducible tobacco hsr 203J gene promoter and a Phytophthora cryptogea gene encoding the highly active elicitor cryptogein. Under noninduced conditions, the transgene was silent, and no cryptogein could be detected in the transgenic plants. In contrast, infection by the virulent fungus P. parasitica var nicotianae stimulated cryptogein production that coincided with the fast induction of several defense genes at and around the infection sites. Induced elicitor production resulted in a localized necrosis that resembled a P. cryptogea-induced hypersensitive response and that restricted further growth of the pathogen. The transgenic plants displayed enhanced resistance to fungal pathogens that were unrelated to Phytophthora species, such as Thielaviopsis basicola, Erysiphe cichoracearum, and Botrytis cinerea. Thus, broad-spectrum disease resistance of a plant can be generated without the constitutive synthesis of a transgene product. PMID:9927640

  8. Diesel Exhaust Particles Induce Cysteine Oxidation and S-Glutathionylation in House Dust Mite Induced Murine Asthma

    PubMed Central

    Lee, Gerald B.; Brandt, Eric B.; Xiao, Chang; Gibson, Aaron M.; Le Cras, Timothy D.; Brown, Lou Ann S.; Fitzpatrick, Anne M.; Khurana Hershey, Gurjit K.

    2013-01-01

    Background Diesel exhaust particle (DEP) exposure enhances allergic inflammation and has been linked to the incidence of asthma. Oxidative stress on the thiol molecules cysteine (Cys) and glutathione (GSH) can promote inflammatory host responses. The effect of DEP on the thiol oxidation/reduction (redox) state in the asthmatic lung is unknown. Objective To determine if DEP exposure alters the Cys or GSH redox state in the asthmatic airway. Methods Bronchoalveolar lavage fluid was obtained from a house dust mite (HDM) induced murine asthma model exposed to DEP. GSH, glutathione disulfide (GSSG), Cys, cystine (CySS), and s-glutathionylated cysteine (CySSG) were determined by high pressure liquid chromatography. Results DEP co-administered with HDM, but not DEP or HDM alone, decreased total Cys, increased CySS, and increased CySSG without significantly altering GSH or GSSG. Conclusions DEP exposure promotes oxidation and S-glutathionylation of cysteine amino acids in the asthmatic airway, suggesting a novel mechanism by which DEP may enhance allergic inflammatory responses. PMID:23555996

  9. Effect of surfactants on shear-induced gelation and gel morphology of soft strawberry-like particles.

    PubMed

    Xie, Delong; Arosio, Paolo; Wu, Hua; Morbidelli, Massimo

    2011-06-01

    The role of surfactant type in the aggregation and gelation of strawberry-like particles induced by intense shear without any electrolyte addition is investigated. The particles are composed of a rubbery core, partially covered by a plastic shell, and well stabilized by fixed (sulfate) charges in the end group of the polymer chains originating from the initiator. In the absence of any surfactant, after the system passes through a microchannel at a Peclet number equal to 220 and a particle volume fraction equal to 0.15, not only shear-induced gelation but also partial coalescence among the particles occurs. The same shear-induced aggregation/gelation process has been carried out in the presence of an ionic (sulfonate) surfactant or a nonionic (Tween 20) steric surfactant. It is found that for both surfactants shear-induced gelation does occur at low surfactant surface density but the conversion of the primary particles to the clusters constituting the gel decreases as the surfactant surface density increases. When the surfactant surface density increases above certain critical values, shear-induced gelation and eventually even aggregation do not occur any longer. For the sulfonate surfactant, this was explained in the literature by the non-DLVO, short-range repulsive hydration forces generated by the adsorbed surfactant layer. In this work, it is shown that the steric repulsion generated by the adsorbed Tween 20 layer can also protect particles from aggregation under intense shear. Moreover, the nonionic steric surfactant can also protect the strawberry-like particles from coalescence. This implies a decrease in the fractal dimension of the clusters constituting the gel from 2.76 to 2.45, which cannot be achieved using the ionic sulfonate surfactant. PMID:21542566

  10. Detection of halogenated flame retardants in polyurethane foam by particle induced X-ray emission

    NASA Astrophysics Data System (ADS)

    Maley, Adam M.; Falk, Kyle A.; Hoover, Luke; Earlywine, Elly B.; Seymour, Michael D.; DeYoung, Paul A.; Blum, Arlene; Stapleton, Heather M.; Peaslee, Graham F.

    2015-09-01

    A novel application of particle-induced X-ray emission (PIXE) has been developed to detect the presence of chlorinated and brominated flame retardant chemicals in polyurethane foams. Traditional Gas Chromatography-Mass Spectrometry (GC-MS) methods for the detection and identification of halogenated flame retardants in foams require extensive sample preparation and data acquisition time. The elemental analysis of the halogens in polyurethane foam performed by PIXE offers the opportunity to identify the presence of halogenated flame retardants in a fraction of the time and sample preparation cost. Through comparative GC-MS and PIXE analysis of 215 foam samples, excellent agreement between the two methods was obtained. These results suggest that PIXE could be an ideal rapid screening method for the presence of chlorinated and brominated flame retardants in polyurethane foams.

  11. Water-soluble core/shell nanoparticles for proton therapy through particle-induced radiation

    NASA Astrophysics Data System (ADS)

    Park, Jeong Chan; Jung, Myung-Hwan; Kim, Maeng Jun; Kim, Kye-Ryung

    2015-02-01

    Metallic nanoparticles have been used in biomedical applications such as magnetic resonance imaging (MRI), therapy, and drug delivery systems. Metallic nanoparticles as therapeutic tools have been demonstrated using radio-frequency magnetic fields or near-infrared light. Recently, therapeutic applications of metallic nanomaterials combined with proton beams have been reported. Particle-induced radiation from metallic nanoparticles, which can enhance the therapeutic effects of proton therapy, was released when the nanoparticles were bombarded by a high-energy proton beam. Core/shell nanoparticles, especially Au-coated magnetic nanoparticles, have drawn attention in biological applications due to their attractive characteristics. However, studies on the phase transfer of organic-ligand-based core/shell nanoparticles into water are limited. Herein, we demonstrated that hydrophobic core/shell structured nanomaterials could be successfully dispersed in water through chloroform/surfactant mixtures. The effects of the core/shell nanomaterials and the proton irradiation on Escherichia coli (E. coli) were also explored.

  12. Fiber-optic SERS microfluidic chip based on light-induced gold nano-particle aggregation

    NASA Astrophysics Data System (ADS)

    Liu, Haitao; Liu, Jiansheng; Li, Shaopeng; Chen, Luoyang; Zhou, Hongwen; Zhu, Jinsong; Zheng, Zheng

    2015-10-01

    A novel optofluidic surface-enhanced Raman scattering (SERS) chip was specially designed and fabricated using polydimethylsiloxane (PDMS) and embedded with normal silica multi-mode optical fibers. Unlike in a conventional Raman detection configuration where an angle of 90° is commonly adopted, here the orientations of the excitation fiber and the collection fiber was set at such an obtuse angle so that the light beam from the excitation fiber can illuminate the endface, but is not within the acceptance angle of the collection fiber. It was found that with the laser irradiating on the endface of the collection fiber in the sample solution, the Raman scattering intensity continued to grow and a level about 30-times than its initial intensity was observed, which was understood by light-induced gold nano-particle aggregation. The effects of fibers' coupling angles, positions and laser irradiation power on the aggregation were investigated.

  13. Confinement Induced Plastic Crystal-to-Crystal Transitions in Rodlike Particles with Long-Ranged Repulsion

    NASA Astrophysics Data System (ADS)

    Liu, Bing; Besseling, Thijs H.; van Blaaderen, Alfons; Imhof, Arnout

    2015-08-01

    Colloidal particles in geometrical confinement display a complex variety of packing structures different from their three-dimensional (3D) bulk counterpart. Here, we confined charged rodlike colloids with long-ranged repulsions to a thin wedge-shaped cell and show, by quantitative 3D confocal microscopy, that not only their positional but also their orientational order depends sensitively upon the slit width. Synchronized with transitions in lattice symmetry and number of layers confinement induces plastic crystal-to-crystal transitions. A model analysis suggests that this complex sequence of more or less rotationally ordered states originates from the subtle competition between the electrostatic repulsion of a rod with the wall and with its neighbors.

  14. Lidar remote sensing of laser-induced incandescence on light absorbing particles in the atmosphere.

    PubMed

    Miffre, Alain; Anselmo, Christophe; Geffroy, Sylvain; Fréjafon, Emeric; Rairoux, Patrick

    2015-02-01

    Carbon aerosol is now recognized as a major uncertainty on climate change and public health, and specific instruments are required to address the time and space evolution of this aerosol, which efficiently absorbs light. In this paper, we report an experiment, based on coupling lidar remote sensing with Laser-Induced-Incandescence (LII), which allows, in agreement with Planck's law, to retrieve the vertical profile of very low thermal radiation emitted by light-absorbing particles in an urban atmosphere over several hundred meters altitude. Accordingly, we set the LII-lidar formalism and equation and addressed the main features of LII-lidar in the atmosphere by numerically simulating the LII-lidar signal. We believe atmospheric LII-lidar to be a promising tool for radiative transfer, especially when combined with elastic backscattering lidar, as it may then allow a remote partitioning between strong/less light absorbing carbon aerosols. PMID:25836102

  15. Boron analysis for neutron capture therapy using particle-induced gamma-ray emission.

    PubMed

    Nakai, Kei; Yamamoto, Yohei; Okamoto, Emiko; Yamamoto, Tetsuya; Yoshida, Fumiyo; Matsumura, Akira; Yamada, Naoto; Kitamura, Akane; Koka, Masashi; Satoh, Takahiro

    2015-12-01

    The neutron source of BNCT is currently changing from reactor to accelerator, but peripheral facilities such as a dose-planning system and blood boron analysis have still not been established. To evaluate the potential application of particle-induced gamma-ray emission (PIGE) for boron measurement in clinical boron neutron capture therapy, boronophenylalanine dissolved within a cell culture medium was measured using PIGE. PIGE detected 18?gB/mL f-BPA in the culture medium, and all measurements of any given sample were taken within 20min. Two hours of f-BPA exposure was required to create a boron distribution image. However, even though boron remained in the cells, the boron on the cell membrane could not be distinguished from the boron in the cytoplasm. PMID:26242558

  16. The merits of particle induced X-ray emission in revealing painting techniques

    NASA Astrophysics Data System (ADS)

    Neelmeijer, C.; Mäder, M.

    2002-04-01

    Particle induced X-ray emission (PIXE) at the external proton beam has proved ideal to study individual techniques of creating art objects. In particular, PIXE is suitable for examining paintings because of the low level of background produced by organic components like binders and paper backings. Thus, traces of pigments as deposited from pens on cardboard can be identified by this method. The combination of PIXE with external Rutherford backscattering spectrometry (RBS) allows non-destructive characterisation of near surface and thin film arrangements of paint materials. Thicker but less complex layers of oil paintings can be identified by special procedures of depth-resolved PIXE investigation. In this case, RBS provides additional information on organic coverings like madder lake or varnishes.

  17. Bubbling behavior of a fluidized bed of fine particles caused by vibration-induced air inflow.

    PubMed

    Matsusaka, Shuji; Kobayakawa, Murino; Mizutani, Megumi; Imran, Mohd; Yasuda, Masatoshi

    2013-01-01

    We demonstrate that a vibration-induced air inflow can cause vigorous bubbling in a bed of fine particles and report the mechanism by which this phenomenon occurs. When convective flow occurs in a powder bed as a result of vibrations, the upper powder layer with a high void ratio moves downward and is compressed. This process forces the air in the powder layer out, which leads to the formation of bubbles that rise and eventually burst at the top surface of the powder bed. A negative pressure is created below the rising bubbles. A narrow opening at the bottom allows the outside air to flow into the powder bed, which produces a vigorously bubbling fluidized bed that does not require the use of an external air supply system. PMID:23378921

  18. Pathogenic Role of B Cells in Anti-CD40-Induced Necroinflammatory Liver Disease

    PubMed Central

    Kimura, Kiminori; Moriwaki, Hisataka; Nagaki, Masahito; Saio, Masanao; Nakamoto, Yasunari; Naito, Makoto; Kuwata, Kazuo; Chisari, Francis V.

    2006-01-01

    Activated B cells function in antibody production and antigen presentation, but whether they perform any pathophysiological functions at sites of inflammation is not fully understood. Here, we report that intravenous injection of an agonistic anti-CD40 monoclonal antibody (?CD40) causes a biphasic inflammatory liver disease in inbred mice. The late phase of disease was suppressed in B-cell-deficient mice and by the depletion of macrophages, but not T cells or natural killer cells. We also report that SCID mice were not susceptible to ?CD40-induced liver disease unless they were reconstituted with normal B cells and that B cells as well as macrophages played key roles in ?CD40-induced late phase of liver inflammation. Finally, liver disease and the recruitment of inflammatory cells into the liver were mediated by interferon-? and tumor necrosis factor-?, but not by Fas. In conclusion, these results indicate that CD40 ligation can trigger a B-cell-mediated inflammatory response that can have pathogenic consequences for the liver. PMID:16507894

  19. Lesion bacterial communities in American lobsters with diet-induced shell disease.

    PubMed

    Quinn, Robert A; Metzler, Anita; Tlusty, Michael; Smolowitz, Roxanna M; Leberg, Paul; Chistoserdov, Andrei Y

    2012-04-26

    In southern New England, USA, shell disease affects the profitability of the American lobster Homarus americanus fishery. In laboratory trials using juvenile lobsters, exclusive feeding of herring Clupea harengus induces shell disease typified initially by small melanized spots that progress into distinct lesions. Amongst a cohabitated, but segregated, cohort of 11 juvenile lobsters fed exclusively herring, bacterial communities colonizing spots and lesions were investigated by denaturing gradient gel electrophoresis of 16S rDNA amplified using 1 group-specific and 2 universal primer sets. The Bacteroidetes and Proteobacteria predominated in both spots and lesions and included members of the orders Flavobacteriales (Bacteriodetes), Rhodobacterales, Rhodospirillales and Rhizobiales (Alphaproteobacteria), Xanthomonadales (Gammaproteobacteria) and unclassified Gammaproteobacteria. Bacterial communities in spot lesions displayed more diversity than communities with larger (older) lesions, indicating that the lesion communities stabilize over time. At least 8 bacterial types persisted as lesions developed from spots. Aquimarina 'homaria', a species commonly cultured from lesions present on wild lobsters with epizootic shell disease, was found ubiquitously in spots and lesions, as was the 'Candidatus Kopriimonas aquarianus', implicating putative roles of these species in diet-induced shell disease of captive lobsters. PMID:22535872

  20. Impaired neural differentiation of induced pluripotent stem cells generated from a mouse model of Sandhoff disease.

    PubMed

    Ogawa, Yasuhiro; Tanaka, Makoto; Tanabe, Miho; Suzuki, Toshihiro; Togawa, Tadayasu; Fukushige, Tomoko; Kanekura, Takuro; Sakuraba, Hitoshi; Oishi, Kazuhiko

    2013-01-01

    Sandhoff disease (SD) is a glycosphingolipid storage disease that arises from mutations in the Hexb gene and the resultant deficiency in ?-hexosaminidase activity. This deficiency results in aberrant lysosomal accumulation of the ganglioside GM2 and related glycolipids, and progressive deterioration of the central nervous system. Dysfunctional glycolipid storage causes severe neurodegeneration through a poorly understood pathogenic mechanism. Induced pluripotent stem cell (iPSC) technology offers new opportunities for both elucidation of the pathogenesis of diseases and the development of stem cell-based therapies. Here, we report the generation of disease-specific iPSCs from a mouse model of SD. These mouse model-derived iPSCs (SD-iPSCs) exhibited pluripotent stem cell properties and significant accumulation of GM2 ganglioside. In lineage-directed differentiation studies using the stromal cell-derived inducing activity method, SD-iPSCs showed an impaired ability to differentiate into early stage neural precursors. Moreover, fewer neurons differentiated from neural precursors in SD-iPSCs than in the case of the wild type. Recovery of the Hexb gene in SD-iPSCs improved this impairment of neuronal differentiation. These results provide new insights as to understanding the complex pathogenic mechanisms of SD. PMID:23383290

  1. Impaired Neural Differentiation of Induced Pluripotent Stem Cells Generated from a Mouse Model of Sandhoff Disease

    PubMed Central

    Ogawa, Yasuhiro; Tanaka, Makoto; Tanabe, Miho; Suzuki, Toshihiro; Togawa, Tadayasu; Fukushige, Tomoko; Kanekura, Takuro; Sakuraba, Hitoshi; Oishi, Kazuhiko

    2013-01-01

    Sandhoff disease (SD) is a glycosphingolipid storage disease that arises from mutations in the Hexb gene and the resultant deficiency in ?-hexosaminidase activity. This deficiency results in aberrant lysosomal accumulation of the ganglioside GM2 and related glycolipids, and progressive deterioration of the central nervous system. Dysfunctional glycolipid storage causes severe neurodegeneration through a poorly understood pathogenic mechanism. Induced pluripotent stem cell (iPSC) technology offers new opportunities for both elucidation of the pathogenesis of diseases and the development of stem cell-based therapies. Here, we report the generation of disease-specific iPSCs from a mouse model of SD. These mouse model-derived iPSCs (SD-iPSCs) exhibited pluripotent stem cell properties and significant accumulation of GM2 ganglioside. In lineage-directed differentiation studies using the stromal cell-derived inducing activity method, SD-iPSCs showed an impaired ability to differentiate into early stage neural precursors. Moreover, fewer neurons differentiated from neural precursors in SD-iPSCs than in the case of the wild type. Recovery of the Hexb gene in SD-iPSCs improved this impairment of neuronal differentiation. These results provide new insights as to understanding the complex pathogenic mechanisms of SD. PMID:23383290

  2. A Doxycycline-Inducible System for Genetic Correction of iPSC Disease Models.

    PubMed

    Sim, Xiuli; Cardenas-Diaz, Fabian L; French, Deborah L; Gadue, Paul

    2016-01-01

    Patient-derived induced pluripotent stem cells (iPSCs) are valuable tools for the study of developmental biology and disease modeling. In both applications, genetic correction of patient iPSCs is a powerful method to understand the specific contribution of a gene(s) in development or diseased state(s). Here, we describe a protocol for the targeted integration of a doxycycline-inducible transgene expression system in a safe harbor site in iPSCs. Our gene targeting strategy uses zinc finger nucleases (ZFNs) to enhance homologous recombination at the AAVS1 safe harbor locus, thus increasing the efficiency of the site-specific integration of the two targeting vectors that make up the doxycycline-inducible system. Importantly, the use of dual-drug selection in our system increases the efficiency of positive selection for double-targeted clones to >50 %, permitting a less laborious screening process. If desired, this protocol can also be adapted to allow the use of tissue-specific promoters to drive gene expression instead of the doxycycline-inducible promoter (TRE). Additionally, this protocol is also compatible with the use of Transcription-Activator-Like Effector Nucleases (TALENs) or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 system in place of ZFNs. PMID:25630922

  3. The lasting effect of limonene-induced particle formation on air quality in a genuine indoor environment.

    PubMed

    Rösch, Carolin; Wissenbach, Dirk K; von Bergen, Martin; Franck, Ulrich; Wendisch, Manfred; Schlink, Uwe

    2015-09-01

    Atmospheric ozone-terpene reactions, which form secondary organic aerosol (SOA) particles, can affect indoor air quality when outdoor air mixes with indoor air during ventilation. This study, conducted in Leipzig, Germany, focused on limonene-induced particle formation in a genuine indoor environment (24 m(3)). Particle number, limonene and ozone concentrations were monitored during the whole experimental period. After manual ventilation for 30 min, during which indoor ozone levels reached up to 22.7 ppb, limonene was introduced into the room at concentrations of approximately 180 to 250 ?g m(-3). We observed strong particle formation and growth within a diameter range of 9 to 50 nm under real-room conditions. Larger particles with diameters above 100 nm were less affected by limonene introduction. The total particle number concentrations (TPNCs) after limonene introduction clearly exceed outdoor values by a factor of 4.5 to 41 reaching maximum concentrations of up to 267,000 particles cm(-3). The formation strength was influenced by background particles, which attenuated the formation of new SOA with increasing concentration, and by ozone levels, an increase of which by 10 ppb will result in a six times higher TPNC. This study emphasizes indoor environments to be preferred locations for particle formation and growth after ventilation events. As a consequence, SOA formation can produce significantly higher amounts of particles than transported by ventilation into the indoor air. PMID:25966888

  4. A new setup for elastic recoil analysis using ion induced electron emission for particle identification

    NASA Astrophysics Data System (ADS)

    Steinbauer, E.; Benka, O.; Steinbatz, M.

    1998-03-01

    We describe a new setup for elastic recoil detection analysis (ERDA) using our recently developed particle identification method. Before the ions and elastic recoil atoms from the target reach a silicon surface barrier detector for energy analysis, they penetrate a set of thin foils (e.g. carbon). The ion induced electron emission yield from the foils depends on the nuclear charge of the penetrating ion and it is roughly proportional to the energy loss in the foil. The emitted electrons are accelerated towards a microchannel plate (MCP), which gives a signal amplitude proportional to the number of emitted electrons. This signal is measured in coincidence with the energy signal from the surface barrier detector using our dual-parameter multichannel analyzer system M2D. Since the energy resolution is not measurably deteriorated by the particle identification our setup offers optimum depth resolution for light elements. Due to the compact design large solid angles for high sensitivity can be achieved. A new measuring chamber has been built which offers considerable improvements. The ERDA scattering angle (30° or 45°) and the target orientation can be selected for optimum depth resolution or sensitivity. Element separation for light elements has been enhanced by several improvements: A new geometry of the foil setup improves the collection efficiency for ion induced electrons onto the MCP, coating of the carbon foils with insulators enhances the electron emission yield. Finally, a new data evaluation procedure has been developed in which the pulse height spectrum of the MCP is considered to be a linear combination of individual spectra from the incident ion and of the recoil atoms. The normalized shapes of these spectra are taken from calibration measurements, the intensities are then calculated using a linear fitting algorithm and finally give the depth profiles of the elements in the target. For hydrogen in near surface layers even isotopic separation is possible. Examples for 1H and 2H in a Be matrix will be given.

  5. C - Reactive Protein Induced Rearrangement of Phosphatidylcholine on Nanoparticle Mimics of Lipoprotein Particles

    PubMed Central

    Mackiewicz, Marilyn R.; Hodges, Heather L.

    2010-01-01

    Lipid-coated metal nanoparticles are developed here as a mimic of low-density lipoprotein (LDL) particles and used to study C-reactive protein (CRP) binding to highly curved lipid membranes. A 12 nm shift in the localized surface plasmon resonance (LSPR) was observed when CRP was added to the lipid-coated gold nanoparticles. Transmission electron microscopy (TEM) revealed that CRP induced a structural change to the lipids, resulting in clusters of nanoparticles. This clustering provides a visualization of how CRP could cause the aggregation of LDL particles, which is a key step in atherosclerosis. The cluster formation and resultant LSPR shift requires the presence of both CRP and calcium. Fluorescence anisotropy, using a CRP-specific, fluorophore-labeled aptamer confirmed that CRP was bound to the lipid-coated nanoparticles. An increase in the fluorescence anisotropy (?r = +0.261 ± 0.004) of the aptamer probe occurs in the presence of CRP, PC-coated nanoparticles, and calcium. Subsequent sequestration of calcium by EDTA leads to a decrease in the anisotropy (?r = -0.233 ± 0.011), however, there is no change in the LSPR and no change to the cluster structure observed by TEM. This indicates that CRP binds to the PC membrane on the nanoparticle surface reversibly through a calcium bridging mechanism while changing the underlying membrane structure irreversibly as a result of binding. PMID:20364851

  6. Mechanism of vibration-induced repulsion force on a particle in a viscous fluid cell.

    PubMed

    Saadatmand, Mehrrad; Kawaji, Masahiro

    2013-08-01

    Space platforms such as the Space Shuttle and International Space Station have been considered an ideal environment for production of protein and semiconductor crystals of superior quality due to the negligible gravity-induced convection. Although it was believed that under microgravity environment diffusive mass transport would dominate the growth of the crystals, some related experiments have not shown satisfactory results possibly due to the movement of the growing crystals in fluid cells caused by small vibrations present in the space platforms called g-jitter. In ground-based experiments, there have been clear observations of attraction and repulsion of a solid particle with respect to a nearby wall of the fluid cell due to small vibrations. The present work is a numerical investigation on the physical mechanisms responsible for the repulsion force, which has been predicted to increase with the cell vibration frequency and amplitude, as well as the fluid viscosity. Moreover, the simulations have revealed that the repulsion force occurs mostly due to the increased pressure in the narrow gap between the particle and the nearest wall. PMID:24032936

  7. Modeling particle-induced electron emission in a simplified plasma Test Cell

    SciTech Connect

    Giuliano, Paul N.; Boyd, Iain D.

    2013-03-21

    Particle-induced electron emission (PIE) is modeled in a simplified, well-characterized plasma Test Cell operated at UCLA. In order for PIE to be a useful model in this environment, its governing equations are first reduced to lower-order models which can be implemented in a direct simulation Monte Carlo and Particle-in-Cell framework. These reduced-order models are described in full and presented as semi-empirical models. The models are implemented to analyze the interaction of low- and high-energy ({approx}1-2 keV) xenon ions and atoms with the stainless steel electrodes of the Test Cell in order to gain insight into the emission and transport of secondary electrons. Furthermore, there is a lack of data for xenon-stainless steel atom- and ion-surface interactions for similar environments. Using experimental data as a reference, both total yields and emitted electron energy distribution functions can be deduced by observing sensitivities of current collection results to these numerical models and their parameters.

  8. Spatial learning and memory deficits induced by exposure to iron-56-particle radiation

    NASA Technical Reports Server (NTRS)

    Shukitt-Hale, B.; Casadesus, G.; McEwen, J. J.; Rabin, B. M.; Joseph, J. A.

    2000-01-01

    It has previously been shown that exposing rats to particles of high energy and charge (HZE) disrupts the functioning of the dopaminergic system and behaviors mediated by this system, such as motor performance and an amphetamine-induced conditioned taste aversion; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, spatial learning and memory were assessed in the Morris water maze 1 month after whole-body irradiation with 1.5 Gy of 1 GeV/nucleon high-energy (56)Fe particles, to test the cognitive behavioral consequences of radiation exposure. Irradiated rats demonstrated cognitive impairment compared to the control group as seen in their increased latencies to find the hidden platform, particularly on the reversal day when the platform was moved to the opposite quadrant. Also, the irradiated group used nonspatial strategies during the probe trials (swim with no platform), i.e. less time spent in the platform quadrant, fewer crossings of and less time spent in the previous platform location, and longer latencies to the previous platform location. These findings are similar to those seen in aged rats, suggesting that an increased release of reactive oxygen species may be responsible for the induction of radiation- and age-related cognitive deficits. If these decrements in behavior also occur in humans, they may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere.

  9. Salt-induced reentrant stability of polyion-decorated particles with tunable surface charge density

    E-print Network

    Simona Sennato; Laura Carlini; Domenico Truzzolillo; Federico Bordi

    2015-03-10

    The electrostatic complexation between DOTAP-DOPC unilamellar liposomes and an oppositely charged polyelectrolyte (NaPA) has been investigated in a wide range of the liposome surface charge density. We systematically characterized the "reentrant condensation" and the charge inversion of polyelectrolyte-decorated liposomes by means of dynamic light scattering and electrophoresis. We explored the stability of this model polyelectrolyte/colloid system by fixing each time the charge of the bare liposomes and by changing two independent control parameters of the suspensions: the polyelectrolyte/colloid charge ratio and the ionic strength of the aqueous suspending medium. The progressive addition of neutral DOPC lipid within the liposome membrane gave rise to a new intriguing phenomenon: the stability diagram of the suspensions showed a novel reentrance due to the crossing of the desorption threshold of the polyelectrolyte. Indeed, at fixed charge density of the bare DOTAP/DOPC liposomes and for a wide range of polyion concentrations, we showed that the simple electrolyte addition first (low salt regime) destabilizes the suspensions because of the enhanced screening of the residual repulsion between the complexes, and then (high salt regime) determines the onset of a new stable phase, originated by the absence of polyelectrolyte adsorption on the particle surfaces. We show that the observed phenomenology can be rationalized within the Velegol-Thwar model for heterogeneously charged particles and that the polyelectrolyte desorption fits well the predictions of the adsorption theory of Winkler and Cherstvy. Our findings unambiguously support the picture of the reentrant condensation as driven by the correlated adsorption of the polyelectrolyte chains on the particle surface, providing interesting insights into possible mechanisms for tailoring complex colloids via salt-induced effects.

  10. Energetic-particle-driven instabilities and induced fast-ion transport in a reversed field pinch

    SciTech Connect

    Lin, L.; Brower, D. L.; Ding, W. X.; Anderson, J. K.; Capecchi, W.; Eilerman, S.; Forest, C. B.; Koliner, J. J.; Nornberg, M. D.; Reusch, J.; Sarff, J. S.; Liu, D.

    2014-05-15

    Multiple bursty energetic-particle (EP) driven modes with fishbone-like structure are observed during 1?MW tangential neutral-beam injection in a reversed field pinch (RFP) device. The distinguishing features of the RFP, including large magnetic shear (tending to add stability) and weak toroidal magnetic field (leading to stronger drive), provide a complementary environment to tokamak and stellarator configurations for exploring basic understanding of EP instabilities. Detailed measurements of the EP mode characteristics and temporal-spatial dynamics reveal their influence on fast ion transport. Density fluctuations exhibit a dynamically evolving, inboard-outboard asymmetric spatial structure that peaks in the core where fast ions reside. The measured mode frequencies are close to the computed shear Alfvén frequency, a feature consistent with continuum modes destabilized by strong drive. The frequency pattern of the dominant mode depends on the fast-ion species. Multiple frequencies occur with deuterium fast ions compared to single frequency for hydrogen fast ions. Furthermore, as the safety factor (q) decreases, the toroidal mode number of the dominant EP mode transits from n=5 to n=6 while retaining the same poloidal mode number m=1. The transition occurs when the m=1, n=5 wave-particle resonance condition cannot be satisfied as the fast-ion safety factor (q{sub fi}) decreases. The fast-ion temporal dynamics, measured by a neutral particle analyzer, resemble a classical predator-prey relaxation oscillation. It contains a slow-growth phase arising from the beam fueling followed by a rapid drop when the EP modes peak, indicating that the fluctuation-induced transport maintains a stiff fast-ion density profile. The inferred transport rate is strongly enhanced with the onset of multiple EP modes.

  11. Salt-induced reentrant stability of polyion-decorated particles with tunable surface charge density.

    PubMed

    Sennato, Simona; Carlini, Laura; Truzzolillo, Domenico; Bordi, Federico

    2016-01-01

    The electrostatic complexation between DOTAP/DOPC unilamellar liposomes and an oppositely charged polyelectrolyte (NaPA) has been investigated in a wide range of the liposome surface charge density. We systematically characterized the reentrant condensation and the charge inversion of polyelectrolyte-decorated liposomes by means of dynamic light scattering and electrophoresis. We explored the stability of this model polyelectrolyte/colloid system at different values of the surface charge of the bare liposomes and by changing two independent control parameters of the suspensions: the polyelectrolyte/colloid charge ratio and the ionic strength of the aqueous suspending medium. The progressive addition of neutral DOPC lipid within the liposome membrane gave rise to an interesting phenomenon which has not been observed previously: the stability diagram of the suspensions showed a novel reentrance due to the crossing of the desorption threshold of the polyelectrolyte. Indeed, at fixed charge density of the bare DOTAP/DOPC liposomes and for a wide range of polyion concentrations, we showed that the simple electrolyte addition first (low salt regime) destabilizes the suspensions because of the enhanced screening of the residual repulsion between the complexes, and then (high salt regime) determines the onset of a new stable phase, originated by the absence of polyelectrolyte adsorption on the particle surfaces. We show that the observed phenomenology can be rationalized within the modified Velegol-Thwar model for heterogeneously charged particles and that the polyelectrolyte desorption fits well the predictions of the adsorption theory of Winkler and Cherstvy [1]. Our findings unambiguously support the picture of the reentrant condensation as driven by the correlated adsorption of the polyelectrolyte chains on the particle surface, providing interesting insights into possible mechanisms for tailoring complex colloids via salt-induced effects. PMID:26117503

  12. Exposure to wear particles generated from studded tires and pavement induces inflammatory cytokine release from human macrophages.

    PubMed

    Lindbom, John; Gustafsson, Mats; Blomqvist, Göran; Dahl, Andreas; Gudmundsson, Anders; Swietlicki, Erik; Ljungman, Anders G

    2006-04-01

    Health risks associated with exposure to airborne particulate matter (PM) have been shown epidemiologically as well as experimentally, pointing to both respiratory and cardiovascular effects. Lately, wear particles generated from traffic have been recognized to be a major contributing source to the overall particle load, especially in the Nordic countries were studded tires are used. In this work, we investigated the inflammatory effect of PM10 generated from the wear of studded tires on two different types of pavement. As comparison, we also investigated PM10 from a traffic-intensive street, a subway station, and diesel exhaust particles (DEP). Human monocyte-derived macrophages, nasal epithelial cells (RPMI 2650), and bronchial epithelial cells (BEAS-2B) were exposed to the different types of particles, and the secretion of IL-6, IL-8, IL-10, and TNF-alpha into the culture medium was measured. The results show a significant release of cytokines from macrophages after exposure for all types of particles. When particles generated from asphalt/granite pavement were compared to asphalt/quartzite pavement, the granite pavement had a significantly higher capacity to induce the release of cytokines. The granite pavement particles induced cytokine release at the same magnitude as the street particles did, which was higher than what particles from both a subway station and DEP did. Exposure of epithelial cells to PM10 resulted in a significant increase of TNF-alpha secreted from BEAS-2B cells for all types of particles used (DEP was not tested), and the highest levels were induced by subway particles. None of the particle types were able to evoke detectable cytokine release from RPMI 2650 cells. The results indicate that PM10 generated by the wear of studded tires on the street surface is a large contributor to the cytokine-releasing ability of particles in traffic-intensive areas and that the type of pavement used is important for the level of this contribution. Furthermore, the airway inflammatory potential of wear particles from tires and pavement might be of a greater magnitude than that of DEP. PMID:16608163

  13. Galactomannan and Zymosan Block the Epinephrine-Induced Particle Transport in Tracheal Epithelium

    PubMed Central

    Weiterer, Sebastian; Kohlen, Thomas; Veit, Florian; Sachs, Lydia; Uhle, Florian; Lichtenstern, Christoph; Weigand, Markus A.; Henrich, Michael

    2015-01-01

    Background Ciliary beating by respiratory epithelial cells continuously purges pathogens from the lower airways. Here we investigated the effect of the fungal cell wall polysaccharides Galactomannan (GM) and Zymosan (Zym) on the adrenergic activated particle transport velocity (PTV) of tracheal epithelium. Methods Experiments were performed using tracheae isolated from male C57BL/6J mice. Transport velocity of the cilia bearing epithelial cells was measured by analysing recorded image sequences. Generation of reactive oxygen species (ROS) were determined using Amplex Red reagents. PCR experiments were performed on isolated tracheal epithelium to identify adrenergic receptor mRNA. Results The adrenergic receptors ?1D, ?2A, ?1 and ?2 have been identified in isolated tracheal epithelium. We found epinephrine responsible for an increase in PTV, which could only be reduced by selective ?-receptor-inhibition. In addition, either GM or Zym prevented the epinephrine induced PTV increase. Furthermore, we observed a strong ROS generation evoked by GM or Zym. However, epinephrine induced increase in PTV recovered in the presence of GM and Zym after application of ROS scavengers. Conclusion Both GM or Zym trigger reversible ROS generation in tracheal tissue leading to inhibition of the ?-adrenergic increase in PTV. PMID:26571499

  14. Induced pluripotent stem cell-based studies of Parkinson's disease: challenges and promises.

    PubMed

    Sanchez-Danes, Adriana; Benzoni, Patrizia; Memo, Maurizio; Dell'Era, Patrizia; Raya, Angel; Consiglio, Antonella

    2013-12-01

    A critical step in the development of effective therapeutics to treat Parkinson's disease (PD) is the identification of molecular pathogenic mechanisms underlying this chronically progressive neurodegenerative disease. However, while animal models have provided valuable information about the molecular basis of PD, the lack of faithful cellular and animal models that recapitulate human pathophysiology is delaying the development of new therapeutics. The reprogramming of somatic cells to induced pluripotent stem cells (iPSC) using delivery of defined combinations of transcription factors is a groundbreaking discovery that opens great opportunities for modeling human diseases, including PD, since iPSC can be generated from patients and differentiated into disease-relevant cell types, which would capture the patients' genetic complexity. Furthermore, human iPSC-derived neuronal models offer unprecedented access to early stages of the disease, allowing the investigation of the events that initiate the pathologic process in PD. Recently, human iPSC-derived neurons from patients with familial and sporadic PD have been generated and importantly they recapitulate some PD-related cell phenotypes, including abnormal ?-synuclein accumulation in vitro, and alterations in the autophagy machinery. This review highlights the current PD iPSC-based models and discusses the potential future research directions of this field. PMID:24040813

  15. Interspecific transmission and recovery of TCBS-induced disease between Acanthaster planci and Linckia guildingi.

    PubMed

    Caballes, C F; Schupp, P J; Pratchett, M S; Rivera-Posada, J A

    2012-09-12

    The susceptibility of the coral-feeding crown-of-thorns starfish Acanthaster planci to disease may provide an avenue with which to effectively control population outbreaks that have caused severe and widespread coral loss in the Indo-Pacific. Injecting thiosulfate-citrate-bile-sucrose (TCBS) agar into A. planci tissues induced a disease characterized by dermal lesions, loss of skin turgor, collapsed spines, and accumulation of mucus on spine tips. Moreover, the symptoms (and presumably the agent) of this disease would spread rapidly intraspecifically, but interspecific transmission (to other species of echinoderms) is yet to be examined. Vibrio rotiferianus, which was previously reported as a pathogen isolated from lesions of experimentally infected A. planci, was also recovered from Linckia guildingi lesions after several days of direct contact with diseased A. planci, demonstrating disease transmission. However, all L. guildingi fully recovered after 31 ± 16 d. Further studies are in progress to understand the ecology of Vibrio infection in A. planci and the potential transmission risk to corals, fishes, and other echinoderms to evaluate whether injections of TCBS could be a viable tool for controlling A. planci outbreaks. PMID:22968793

  16. Continuum- and particle-based modeling of shapes and dynamics of red blood cells in health and disease

    PubMed Central

    Li,, Xuejin; Vlahovska, Petia M.

    2012-01-01

    We review recent advances in multiscale modeling of the mechanics of healthy and diseased red blood cells (RBCs), and blood flow in the microcirculation. We cover the traditional continuum-based methods but also particle-based methods used to model both the RBCs and the blood plasma. We highlight examples of successful simulations of blood flow including malaria and sickle cell anemia. PMID:23230450

  17. Merging the geological and biological sciences: An integrated approach to the study of mineral-induced pulmonary diseases

    SciTech Connect

    Guthrie, G.D. Jr.; Mossman, B.T.

    1993-12-31

    Most natural solids are minerals, ubiquitous on the surface of the Earth. Each of us is exposed to minerals daily. Unfortunately, several minerals are known to induce a variety of pulmonary diseases following inhalation. Research on the initiation of diseases by minerals has progressed rapidly over the last century to the point of addressing the question of what are the mechanisms by which a mineral can induce disease. The identification of the mineralogical, geochemical, and biochemical mechanisms important in mineral-induced pathogenesis requires an interdiciplinary approach. This book presents much of the basic information necessary to facilatate this interaction. The first chapters cover some of the important geological mineralogical and geochemical concepts necessary for individuals interested in studying mineral-induced pathogenesis. The second half of the book contains several chapter covering some of the epidemiological, pathological, biological and biochemical concepts underlying mineral-induced pathogenesis. The final chapter covers the regulatory aspects of minerals. 2 refs., 1 fig.

  18. [The Role of Adoptive Transfer of Immune Cells in Helminth- induced Regulation of Allergy and Autoimmune Diseases].

    PubMed

    Ding, Yi-han; Zhou, Rui; Yang, Xiao-di; Zhang, Li-li

    2015-08-01

    Parasitic worms (helminth) or their derivates can inhibit allergy and autoimmune diseases by inducing the activation of immune cells and thus the release of regulatory factors. A large number of animal experiments have shown that adoptive transfer of lymphocytes can protect against immune deregulation and have potential clinical applications. In this review, we discuss the research progress on the role of adoptive transfer of immune cells in worm-induced regulation of allergy and autoimmune diseases. PMID:26672222

  19. Intracellular influx of calcium induced by quartz particles in alveolar macrophages

    SciTech Connect

    Feng Tian; Tong Zhu; Yu Shang

    2010-01-15

    Historical studies report that cellular injury and silicosis are related to cytosolic free calcium (Ca{sup 2+}). Moreover, reactive oxygen species (ROS) have been linked to cellular injury. However, the detail mechanism of the increase in [Ca{sup 2+}]{sub i} and the relationship between [Ca{sup 2+}]{sub i} and ROS production remains unknown. Quartz particle has been found to increase [Ca{sup 2+}]{sub i} and activate the generation of ROS. Our hypothesis is that [Ca{sup 2+}]{sub i} increase induced by quartz particle is from extracellular Ca{sup 2+} through the Ca{sup 2+} channel, and [Ca{sup 2+}]{sub i} increase is believed to activate ROS production. In order to examine this hypothesis, we treated rat alveolar macrophages with quartz (SiO{sub 2}) particles and used laser scanning confocal microscopy to measure [Ca{sup 2+}]{sub i} and the fluorescence intensity of ROS. Time- and dose-dependent increases in [Ca{sup 2+}]{sub I} and ROS in macrophages as well as cell viability were observed. Through chelating extracellular Ca{sup 2+} with ethylene glycol tetraacetic acid and releasing intracellular Ca{sup 2+} with thapsigargin, we found that 72.7% of the [Ca{sup 2+}]{sub i} increase was due to the influx of Ca{sup 2+} from the extracellular environment, via Ca{sup 2+} channels in the plasma membrane. By adding mannitol to scavenge hydroxyl radicals (OH.), and removing surface iron from the quartz particles to reduce OH. generation, we observed a reduced level of ROS generation, whereas the increase in [Ca{sup 2+}]{sub i} was unaffected. When using EGTA to reduce [Ca{sup 2+}]{sub i}, we observed a decrease in ROS production. This study suggests that the [Ca{sup 2+}]{sub i} influx was independent of OH. production, and the [Ca{sup 2+}]{sub i} increase resulted in ROS production. These results further indicate that there is a strong relationship between cytosolic free Ca{sup 2+} content and cellular injury as well as silica exposure.

  20. Neonatal capsaicin treatment in rats induces chronic hyperthermia resulting in infectious disease

    PubMed Central

    JEONG, KEUN-YEONG; KIM, HWAN MOOK

    2015-01-01

    Treatment of neonatal animals with capsaicin has previously been associated with long-lasting hyperthermia and severe cutaneous lesions. The present study analyzed the effects of capsaicin-induced hyperthermia on the occurrence of infectious disease and pruritic dermatitis in a rat model. Pregnant Sprague-Dawley (SD) rats were obtained 1 week prior to parturition. Pups from each litter were randomly assigned to the following experimental groups: Capsaicin-treated (cap-treated; n=10) or vehicle-treated (n=5). Capsaicin (50 mg/kg) or vehicle were systemically administered to the SD rat pups (age, 48 h), after which body temperature was measured using a biotelemetry system, and the effects of hyperthermia on the ability of the rat pups to resist bacterial infection were analyzed. Furthermore, pruritus-induced scratching behavior and dermatitis were assessed, and changes in interleukin (IL)-4- and IL-13-induced immunoglobulin E expression were measured. Treatment of neonatal rats with capsaicin resulted in chronic hyperthermia, which had negative effects on the host immune defense response. The expression levels of T-helper type 2 cell-associated cytokines were significantly increased (P<0.01) in the cap-treated rats following bacterial infection with Staphylococcus aureus or Streptococcus agalactiae. Furthermore, cap-treated rats exhibited pruritus-induced scratching behavior and dermatitis. The results of the present study suggested that treatment of neonatal rats with capsaicin induces chronic hyperthermia and decreases the effectiveness of the host defense system. Therefore, a cap-treated neonatal rat model may be considered useful when investigating the association between hyperthermia and infectious disease. PMID:26668650

  1. Does methylmercury-induced hypercholesterolemia play a causal role in its neurotoxicity and cardiovascular disease?

    PubMed

    Moreira, Eduardo Luiz; de Oliveira, Jade; Dutra, Márcio Ferreira; Santos, Danúbia Bonfanti; Gonçalves, Carlos Alberto; Goldfeder, Eliane Maria; de Bem, Andreza Fabro; Prediger, Rui Daniel; Aschner, Michael; Farina, Marcelo

    2012-12-01

    Methylmercury (MeHg) is an environmental pollutant that biomagnifies throughout the aquatic food chain, thus representing a toxicological concern for humans subsiding on fish for their dietary intake. Although the developing brain is considered the critical target organ of MeHg toxicity, recent evidence indicates that the cardiovascular system may be the most sensitive in adults. However, data on the mechanisms mediating MeHg-induced cardiovascular toxicity are scarce. Based on the close relationship between cardiovascular disease and dyslipidemia, this study was designed to investigate the effects of long-term MeHg exposure on plasma lipid levels in mice, as well as their underlying mechanisms and potential relationships to MeHg-induced neurotoxicity. Our major finding was that long-term MeHg exposure induced dyslipidemia in rodents. Specifically, Swiss and C57BL/6 mice treated for 21 days with a drinking solution of MeHg (40 mg/l, ad libitum) diluted in tap water showed increased total and non-HDL plasma cholesterol levels. MeHg-induced hypercholesterolemia was also observed in low-density lipoprotein receptor knockout (LDLr?/?) mice, indicating that this effect was not related to decreased LDLr-mediated cholesterol transport from blood to other tissues. Although the hepatic synthesis of cholesterol was unchanged, significant signs of nephrotoxicity (glomerular shrinkage, tubular vacuolization, and changed urea levels) were observed in MeHg-exposed mice, indicating that the involvement of nephropathy in MeHg-induced lipid dyshomeostasis may not be ruled out. Notably, Probucol (a lipid-lowering drug) prevented the development of hypercholesterolemia when coadministered with MeHg. Finally, hypercholesterolemic LDLr?/? mice were more susceptible to MeHg-induced cerebellar glial activation, suggesting that hypercholesterolemia in itself may pose a risk factor in MeHg-induced neurotoxicity. Overall, based on the strong and graded positive association between total as well as LDL cholesterol and risk of cardiovascular diseases, our data support the concept of MeHg-induced cardiovascular toxicity. PMID:22903822

  2. Concentrated ambient ultrafine particle exposure induces cardiac change in young healthy volunteers

    EPA Science Inventory

    Exposure to ambient ultrafine particles has been associated with cardiopulmonary toxicity and mortality. Adverse effects specifically linked to ultrafine particles include loss of sympathovagal balance and altered hemostasis. To characterize the effects of ultrafine particles in ...

  3. Susceptibility of inflamed ariway and alveolar epithelial cells to injury induced by diesel exhaust particles of varying organic carbon content

    EPA Science Inventory

    Exposure to traffic-related ambient air pollution, such as diesel exhaust particles (DEP), is associated with adverse health outcomes, especially in individuals with preexisting inflammatory respiratory diseases. Using an analogous in vitro system to model both the healthy and a...

  4. Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis.

    PubMed

    Monin, Leticia; Griffiths, Kristin L; Lam, Wing Y; Gopal, Radha; Kang, Dongwan D; Ahmed, Mushtaq; Rajamanickam, Anuradha; Cruz-Lagunas, Alfredo; Zúñiga, Joaquín; Babu, Subash; Kolls, Jay K; Mitreva, Makedonka; Rosa, Bruce A; Ramos-Payan, Rosalio; Morrison, Thomas E; Murray, Peter J; Rangel-Moreno, Javier; Pearce, Edward J; Khader, Shabaana A

    2015-12-01

    Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1-expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1-expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB. PMID:26571397

  5. Radiation-induced cardiovascular diseases: Is the epidemiologic evidence compatible with the radiobiologic data?

    SciTech Connect

    Schultz-Hector, Susanne . E-mail: susanne.schultz-hector@helmholtz.de; Trott, Klaus-Ruediger Prof.

    2007-01-01

    The Life Span Study of Japanese atomic bomb survivors demonstrates that radiation exposure significantly increased the risk of developing ischemic heart disease, in particular myocardial infarction. Similarly, epidemiologic investigations in very large populations of patients who had received postoperative radiotherapy for breast cancer or for peptic ulcer demonstrate that radiation exposure of the heart with an average equivalent single dose of approximately 2 Gy significantly increased the risk of developing ischemic heart disease more than 10 years after irradiation. These epidemiologic findings are compatible with radiobiologic data on the pathogenesis of radiation-induced heart disease in experimental animals. The critical target structure appears to be the endothelial lining of blood vessels, in particular arteries, leading to early functional alterations such as pro-inflammatory responses and other changes, which are slowly progressive. Research should concentrate on the interaction of these radiation-induced endothelial changes with the early stages of age-related atherosclerosis to develop criteria for optimizing treatment plans in radiotherapy and also potential interventional strategies.

  6. Pneumolysin Expression by Streptococcus pneumoniae Protects Colonized Mice from Influenza Virus-induced Disease

    PubMed Central

    Wolf, Amaya I.; Strauman, Maura C.; Mozdzanowska, Krystyna; Williams, Katie L.; Osborne, Lisa C.; Shen, Hao; Liu, Qin; Garlick, David; Artis, David; Hensley, Scott E.; Caton, Andrew J.; Weiser, Jeffrey N.; Erikson, Jan

    2014-01-01

    The response to influenza virus (IAV) infection and severity of disease is highly variable in humans. We hypothesized that one factor contributing to this variability is the presence of specific respiratory tract (RT) microbes. One such microbe is Streptococcus pneumoniae (Sp) that is carried asymptomatically in the RT of many humans. In a mouse co-infection model we found that in contrast to secondary bacterial infection that exacerbates disease, Sp colonization 10 days prior to IAV protects from virus-induced morbidity and lung pathology. Using mutant Sp strains, we identified a critical role for the bacterial virulence factor pneumolysin (PLY) in mediating this protection. Colonization with the PLY-sufficient Sp strain induces expression of the immune-suppressive enzyme arginase 1 in alveolar macrophages (aMø) and correlates with attenuated recruitment and function of pulmonary inflammatory cells. Our study demonstrates a novel role for PLY in Sp-mediated protection by maintaining aMø as "gatekeepers" against virus-induced immunopathology. PMID:24999050

  7. A lysosomal storage disease induced by Ipomoea carnea in goats in Mozambique.

    PubMed

    de Balogh, K K; Dimande, A P; van der Lugt, J J; Molyneux, R J; Naudé, T W; Welman, W G

    1999-05-01

    A novel plant-induced lysosomal storage disease was observed in goats from a village in Mozambique. Affected animals were ataxic, with head tremors and nystagmus. Because of a lack of suitable feed, the animals consumed an exotic hedge plant growing in the village that was identified as Ipomoea carnea (shrubby morning glory, Convolvulaceae). The toxicosis was reproduced by feeding I. carnea plant material to goats. In acute cases, histologic changes in the brain and spinal cord comprised widespread cytoplasmic vacuolation of neurons and glial cells in association with axonal spheroid formation. Ultrastructurally, cytoplasmic storage vacuoles in neurons were membrane bound and consistent with lysosomes. Cytoplasmic vacuolation was also found in neurons in the submucosal and mesenteric plexuses in the small intestine, in renal tubular epithelial cells, and in macrophage-phagocytic cells in the spleen and lymph nodes in acute cases. Residual alterations in the brain in chronic cases revealed predominantly cerebellar lesions characterized by loss of Purkinje neurons and gliosis of the Purkinje cell layer. Analysis of I. carnea plant material by gas chromatography-mass spectrometry established the presence of the mannosidase inhibitor swainsonine and 2 glycosidase inhibitors, calystegine B2 and calystegine C1, consistent with a plant-induced alpha-mannosidosis in the goats. The described storage disorder is analogous to the lysosomal storage diseases induced by ingestion of locoweeds (Astragalus and Oxytropis) and poison peas (Swainsona). PMID:10353359

  8. Fast Particle Finite Orbit Width and Larmor Radius Effects on Lown Toroidicity induced Alfv'en Eigenmode Excitation

    E-print Network

    ) and finite Larmor radius (FLR) of fast particles on the stability of low­n toroidicity­induced Alfv­ tion. It is shown that both FOW and FLR effects are typically stabilizing: the TAE growth rate can (FOW) and finite Larmor radius (FLR) comparable to the TAE mode scale length. A large radial

  9. LONG-TERM CHANGES IN AMPHETAMINE-INDUCED REINFORCEMENT AND AVERSION IN RATS FOLLOWING EXPOSURE TO 56FE PARTICLES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exposing rats to heavy particles produces alterations in the functioning of dopaminergic neurons and in the behaviors that depend upon the integrity of the dopaminergic system. Two of these dopamine-dependent behaviors include amphetamine-induced reinforcement, measured using the conditioned place ...

  10. Pressure induced increase of particle size and resulting weakening of elastic stiffness of CeO2 nanocrystals

    E-print Network

    Downs, Robert T.

    Pressure induced increase of particle size and resulting weakening of elastic stiffness of CeO2 10 nm increases at pressures above 20 GPa. At ambient pressure, CeO2 nanocrystals exhibit larger cell, above 20 GPa, the bulk modulus is reduced to 230 10 GPa. Thus, a critical pressure of 20 GPa

  11. Amphetamine-Induced Taste Aversion Learning in Young and Old F-344 Rats Following Exposure to 56Fe Particles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exposure to 56Fe particles produces changes in dopaminergic function and in dopamine dependent behaviors, including amphetamine-induced conditioned taste aversion (CTA) learning. Because many of these changes are characteristic of the changes that accompany the aging process, the present study was ...

  12. particles

    NASA Astrophysics Data System (ADS)

    Xia, Yu; Chen, Zhihong; Zhang, Zhengguo; Fang, Xiaoming; Liang, Guozheng

    2014-05-01

    We explore a facile and nontoxic hydrothermal route for synthesis of a Cu2ZnSnS4 nanocrystalline material by using l-cysteine as the sulfur source and ethylenediaminetetraacetic acid (EDTA) as the complexing agent. The effects of the amount of EDTA, the mole ratio of the three metal ions, and the hydrothermal temperature and time on the phase composition of the obtained product have been systematically investigated. The addition of EDTA and an excessive dose of ZnCl2 in the hydrothermal reaction system favor the generation of kesterite Cu2ZnSnS4. Pure kesterite Cu2ZnSnS4 has been synthesized at 180°C for 12 h from the reaction system containing 2 mmol of EDTA at 2:2:1 of Cu/Zn/Sn. It is confirmed by Raman spectroscopy that those binary and ternary phases are absent in the kesterite Cu2ZnSnS4 product. The kesterite Cu2ZnSnS4 material synthesized by the hydrothermal process consists of flower-like particles with 250 to 400 nm in size. It is revealed that the flower-like particles are assembled from single-crystal Cu2ZnSnS4 nanoflakes with ca. 20 nm in size. The band gap of the Cu2ZnSnS4 nanocrystalline material is estimated to be 1.55 eV. The films fabricated from the hierarchical Cu2ZnSnS4 particles exhibit fast photocurrent responses under intermittent visible-light irradiation, implying that they show potentials for use in solar cells and photocatalysis.

  13. GENOMIC IDENTIFICATION OF POTENTIAL RISK FACTORS DURING ACETAMINOPHEN-INDUCED LIVER DISEASE IN SUSCEPTIBLE AND RESISTANT STRAINS OF MICE

    EPA Science Inventory

    Drug-induced liver disease (DILD) continues to cause significant morbidity and mortality and impair new drug development. Mounting evidence suggests that DILD is a complex, multifactorial disease in which no one factor is likely to be an absolute indicator of susceptibility. As a...

  14. Effects of heavy particle irradiation and diet on amphetamine- and lithium chloride-induced taste avoidance learning in rats

    NASA Technical Reports Server (NTRS)

    Rabin, Bernard M.; Shukitt-Hale, Barbara; Szprengiel, Aleksandra; Joseph, James A.

    2002-01-01

    Rats were maintained on diets containing either 2% blueberry or strawberry extract or a control diet for 8 weeks prior to being exposed to 1.5 Gy of 56Fe particles in the Alternating Gradient Synchrotron at Brookhaven National Laboratory. Three days following irradiation, the rats were tested for the effects of irradiation on the acquisition of an amphetamine- or lithium chloride-induced (LiCl) conditioned taste avoidance (CTA). The rats maintained on the control diet failed to show the acquisition of a CTA following injection of amphetamine. In contrast, the rats maintained on antioxidant diets (strawberry or blueberry extract) continued to show the development of an amphetamine-induced CTA following exposure to 56Fe particles. Neither irradiation nor diet had an effect on the acquisition of a LiCl-induced CTA. The results are interpreted as indicating that oxidative stress following exposure to 56Fe particles may be responsible for the disruption of the dopamine-mediated amphetamine-induced CTA in rats fed control diets; and that a reduction in oxidative stress produced by the antioxidant diets functions to reinstate the dopamine-mediated CTA. The failure of either irradiation or diet to influence LiCl-induced responding suggests that oxidative stress may not be involved in CTA learning following injection of LiCl.

  15. Role of Cardiovascular Disease-associated iron overload in Libby amphibole-induced acute pulmonary injury and inflammation

    EPA Science Inventory

    Pulmonary toxicity induced by asbestos is thought to be mediated through redox-cycling of fiber-bound and bioavailable iron (Fe). We hypothesized that Libby amphibole (LA)-induced cute lung injury will be exacerbated in rat models of cardiovascular disease (CVD)-associated Fe-ove...

  16. Adalimumab-induced psoriatic alopecia/alopecia areata-like reaction in a patient with Crohn's disease.

    PubMed

    Toda-Brito, H; Lopes, L; Soares-Almeida, L; Filipe, P

    2015-01-01

    Anti-tumor necrosis factor (anti-TNF) agents have been successfully used to treat both chronic idiopathic inflammatory bowel disease and other immune-mediated chronic diseases, but they can also induce a wide array of cutaneous reactions, including new-onset psoriasis and alopecia. We report a case of alopecia associated with psoriasiform skin lesions in a patient on adalimumab treatment for Crohn's disease. PMID:26632930

  17. Energetic-particle-driven instabilities and induced fast-ion transport in a reversed field pinch

    NASA Astrophysics Data System (ADS)

    Lin, Liang

    2013-10-01

    Multiple bursty energetic-particle (EP) modes with fishbone-like structures are observed during 1 MW tangential neutral-beam injection into MST reversed field pinch (RFP) plasmas. The distinguishing features of the RFP, including large magnetic shear (tending to add stability) and weak toroidal magnetic field (leading to large fast ion beta and stronger drive), provide a complementary environment to tokamak and stellarator configurations for exploring basic understanding of these instabilities. Detailed measurements of the EP mode characteristics and temporal-spatial dynamics reveal their influence on fast ion transport and interaction with global tearing modes. Internal magnetic field fluctuations associated with the EP modes are directly observed for the first time by Faraday-effect polarimetry (frequency ~ 90 kHz and amplitude ~ 2 G). Simultaneously measured density fluctuations exhibit a dynamically evolving and asymmetric spatial structure that peaks near the core where fast ions reside and shifts outward as the instability evolves. Furthermore, the EP mode frequencies appear at ~k?VA , consistent with continuum modes destabilized by strong drive. The fast-ion temporal dynamics, measured by a neutral particle analyzer, resemble a classical predator-prey relaxation oscillation. It contains a slow-growing phase arising from the beam fueling followed by a rapid drop (~ 15 %) when the EP modes peak, indicating the fluctuation-induced transport maintains a stiff fast-ion density profile. The inferred transport rate is strongly enhanced (× 2) with the onset of multiple nonlinearly-interacting EP modes. The fast ions also impact global tearing modes, reducing their amplitudes by up to 65%. This mode reduction is lessened following the EP-bursts, further evidence for fast ion redistribution that weakens the suppression mechanism. Possible tearing mode suppression mechanisms will be discussed. Work supported by US DoE.

  18. Modeling climate impact on an emerging disease, the Phytophthora alni-induced alder decline.

    PubMed

    Aguayo, Jaime; Elegbede, Fabrice; Husson, Claude; Saintonge, François-Xavier; Marçais, Benoît

    2014-10-01

    Alder decline caused by Phytophthora alni is one of the most important emerging diseases in natural ecosystems in Europe, where it has threatened riparian ecosystems for the past 20 years. Environmental factors, such as mean site temperature and soil characteristics, play an important role in the occurrence of the disease. The objective of the present work was to model and forecast the effect of environment on the severity of alder Phytophthora outbreaks, and to determine whether recent climate change might explain the disease emergence. Two alder sites networks in NE and SW France were surveyed to assess the crown health of trees; the oomycete soil inoculum was also monitored in the NE network. The main factors explaining the temporal annual variation in alder crown decline or crown recovery were the mean previous winter and previous summer temperatures. Both low winter temperatures and high summer temperatures were unfavorable to the disease. Cold winters promoted tree recovery because of poor survival of the pathogen, while hot summer temperature limited the incidence of tree decline. An SIS model explaining the dynamics of the P. alni-induced alder decline was developed using the data of the NE site network and validated using the SW site network. This model was then used to simulate the frequency of declining alder over time with historical climate data. The last 40 years' weather conditions have been generally favorable to the establishment of the disease, indicating that others factors may be implicated in its emergence. The model, however, showed that the climate of SW France was much more favorable for the disease than that of the Northeast, because it seldom limited the overwintering of the pathogen. Depending on the European area, climate change could either enhance or decrease the severity of the alder decline. PMID:24729529

  19. Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease

    PubMed Central

    Jiang, Hong; Schiffer, Eric; Song, Zhangfa; Wang, Jianwei; Zürbig, Petra; Thedieck, Kathrin; Moes, Suzette; Bantel, Heike; Saal, Nadja; Jantos, Justyna; Brecht, Meiken; Jenö, Paul; Hall, Michael N.; Hager, Klaus; Manns, Michael P.; Hecker, Hartmut; Ganser, Arnold; Döhner, Konstanze; Bartke, Andrzej; Meissner, Christoph; Mischak, Harald; Ju, Zhenyu; Rudolph, K. Lenhard

    2008-01-01

    Telomere dysfunction limits the proliferative capacity of human cells by activation of DNA damage responses, inducing senescence or apoptosis. In humans, telomere shortening occurs in the vast majority of tissues during aging, and telomere shortening is accelerated in chronic diseases that increase the rate of cell turnover. Yet, the functional role of telomere dysfunction and DNA damage in human aging and diseases remains under debate. Here, we identified marker proteins (i.e., CRAMP, stathmin, EF-1?, and chitinase) that are secreted from telomere-dysfunctional bone-marrow cells of late generation telomerase knockout mice (G4mTerc?/?). The expression levels of these proteins increase in blood and in various tissues of aging G4mTerc?/? mice but not in aging mice with long telomere reserves. Orthologs of these proteins are up-regulated in late-passage presenescent human fibroblasts and in early passage human cells in response to ?-irradiation. The study shows that the expression level of these marker proteins increases in the blood plasma of aging humans and shows a further increase in geriatric patients with aging-associated diseases. Moreover, there was a significant increase in the expression of the biomarkers in the blood plasma of patients with chronic diseases that are associated with increased rates of cell turnover and telomere shortening, such as cirrhosis and myelodysplastic syndromes (MDS). Analysis of blinded test samples validated the effectiveness of the biomarkers to discriminate between young and old, and between disease groups (MDS, cirrhosis) and healthy controls. These results support the concept that telomere dysfunction and DNA damage are interconnected pathways that are activated during human aging and disease. PMID:18695223

  20. MECHANISMS OF ACTION OF INHALED FIBERS, PARTICLES AND NANOPARTICLES IN LUNG AND CARDIOVASCULAR DISEASES

    EPA Science Inventory

    ABSTRACT: A symposium on the mechanisms of action of inhaled airborne particulate matter (PM),pathogenic particles and fibers such as silica and asbestos, and nanomaterials, defined as synthetic particles or fibers less than 100 nm in diameter, was held on October 27 and 28,
    ...

  1. Dopaminergic induced changes in cognitive and motor processing in Parkinson's disease: an electrophysiological investigation.

    PubMed Central

    Prasher, D; Findley, L

    1991-01-01

    Event-related potentials and reaction time measures to auditory discrimination tasks of graded difficulty were used to separate cognitive from motor processing time in 27 patients with newly diagnosed, previously untreated Parkinson's disease and later on optimal levodopa treatment. Before treatment event-related potential P3 and task performance were normal but the reaction time was prolonged compared with age matched controls. After treatment P3 latency was significantly prolonged and the reaction time reduced suggesting a dopamine induced dissociation between cognitive and motor processing. In early Parkinson's disease cognitive processing time remains normal but the motor processing time is prolonged. Dopamine replacement is followed by significantly reduced motor processing time despite increased cognitive processing time. Motor processing may reflect the dopamine status of the putamen whereas dopaminergic over-stimulation of other regions may adversely affect cognitive processing in patients treated with levodopa. PMID:1895125

  2. Asymptomatic presentation of mesalamine-induced lung injury in an adolescent with Crohn disease

    PubMed Central

    Cilloniz, Rafael; Chesrown, Sarah Elizabeth; Gonzalez-Peralta, Regino P

    2009-01-01

    The present report describes the case of a 14-year-old boy receiving mesalamine for Crohn disease who was discovered to have incidental pulmonary infiltrates on chest radiograph and CT scan shortly after increasing the dose of this medication. Despite the significant radiographic abnormalities, he had no respiratory symptoms. He had normal oxygenation and normal pulmonary function tests including spirometry, lung volumes and diffusion capacity. Transbronchial biopsies showed patchy interstitial fibrosis with ill-defined non-necrotising granulomas and lymphoid aggregates. Pulmonary infiltrates resolved within 6 weeks of discontinuation of mesalamine and the addition of low-dose daily corticosteroids. This case likely represents an asymptomatic “early stage” of mesalamine-induced lung injury preceding the onset of symptoms. Alternatively, mesalamine may induce asymptomatic lung injury more commonly than is presently suspected. To the best of our knowledge this is the first time this complication has been reported without respiratory symptoms. PMID:21686567

  3. Impact of Rhesus disease on the global problem of bilirubin-induced neurologic dysfunction.

    PubMed

    Zipursky, Alvin; Bhutani, Vinod K

    2015-02-01

    Clinical experience with Rhesus (Rh) disease and its post-icteric sequelae is limited among high-income countries because of nearly over four decades of effective prevention care. We hypothesized that Rh disease is prevalent in other regions of the world because it is likely that protection is limited or non-existent. Following a worldwide study, it has been concluded that Rh hemolytic disease is a significant public health problem resulting in stillbirths and neonatal deaths, and is a major cause of severe hyperbilirubinemia with its sequelae, kernicterus and bilirubin-induced neurologic dysfunction. Knowing that effective Rh-disease prophylaxis depends on maternal blood-type screening, healthcare afforded to the high-risk mothers needs to be free of bottlenecks and coupled with unfettered access to effective Rh-immunoglobulin. Future studies that match the universal identification of Rh-negative status of women and targeted use of immunoprophylaxis to prevent childhood bilirubin neurotoxicity are within reach, based on vast prior experiences. PMID:25582277

  4. Inflammatory Gene Expression Upon TGF-?1-Induced p38 Activation in Primary Dupuytren's Disease Fibroblasts

    PubMed Central

    Bujak, Maro; Ratkaj, Ivana; Markova-Car, Elitza; Juriši?, Davor; Horvati?, Anita; Vu?ini?, Sr?an; Lerga, Jonatan; Baus-Lon?ar, Mirela; Paveli?, Krešimir; Kraljevi? Paveli?, Sandra

    2015-01-01

    Objectives: Inflammation is an underlying mechanism behind fibrotic processes and differentiation of cells into myofibroblasts. Presented study therefore provides new data on activation of autoimmune and inflammatory immune response genes that accompany activation of p38 and cell differentiation in primary cells derived from Dupuytren's disease (DD) patients. Methods: Primary non-Dupuytren's disease cells (ND) were isolated from macroscopically unaffected palmar fascia adjacent to diseased tissue obtained from patients diagnosed with the last stage of DD and cultured in vitro. Gene expression, collagen gel contraction assay and analysis of secreted proteins were performed in ND cells treated with TGF-?1 and/or inhibitor of p38 phosphorylation. Results: During differentiation of ND fibroblasts, increased expression of immune response genes PAI-1, TIMP-1, CCL11, and IL-6 was found. These changes were accompanied by increased cell contractility and activation of p38 and its target kinase MK2. Inhibition of p38 phosphorylation reversed these processes in vitro. Conclusions: TGF-?1 induced p38 phosphorylation in ND cells grown from macroscopically unaffected palmar fascia adjacent to diseased tissue from DD patients. This was accompanied by activation of the cytokine genes CCL-11 and IL-6 and secretion of extracellular matrix regulatory proteins PAI-1 and TIMP-1. A combined approach directed toward inflammation and p38 MAPK-mediated processes in DD might be considered for improving management of DD patients and prevention of recurrence. PMID:26697433

  5. Levodopa-induced dyskinesias in Parkinson’s disease: emerging treatments

    PubMed Central

    Bargiotas, Panagiotis; Konitsiotis, Spyridon

    2013-01-01

    Parkinson’s disease therapy is still focused on the use of L-3,4-dihydroxyphenylalanine (levodopa or L-dopa) for the symptomatic treatment of the main clinical features of the disease, despite intensive pharmacological research in the last few decades. However, regardless of its effectiveness, the long-term use of levodopa causes, in combination with disease progression, the development of motor complications termed levodopa-induced dyskinesias (LIDs). LIDs are the result of profound modifications in the functional organization of the basal ganglia circuitry, possibly related to the chronic and pulsatile stimulation of striatal dopaminergic receptors by levodopa. Hence, for decades the key feature of a potentially effective agent against LIDs has been its ability to ensure more continuous dopaminergic stimulation in the brain. The growing knowledge regarding the pathophysiology of LIDs and the increasing evidence on involvement of nondopaminergic systems raises the possibility of more promising therapeutic approaches in the future. In the current review, we focus on novel therapies for LIDs in Parkinson’s disease, based mainly on agents that interfere with glutamatergic, serotonergic, adenosine, adrenergic, and cholinergic neurotransmission that are currently in testing or clinical development. PMID:24174877

  6. Curcumin modulates the immune response associated with LPS-induced periodontal disease in rats.

    PubMed

    Guimarães, Morgana R; de Aquino, Sabrina Garcia; Coimbra, Leila S; Spolidorio, Luis C; Kirkwood, Keith L; Rossa, Carlos

    2012-02-01

    Curcumin is a plant-derived dietary spice ascribed various biological activities. Curcumin therapeutic applications have been studied in a variety of conditions, but not on periodontal disease. Periodontal disease is a chronic inflammatory condition initiated by an immune response to micro-organisms of the dental biofilm. Experimental periodontal disease was induced in rats by injecting LPS in the gingival tissues on the palatal aspect of upper first molars (30 µg LPS, 3 times/week for 2 weeks). Curcumin was administered to rats daily via oral gavage at 30 and 100 mg/kg body weight. Reverse transcriptase-qPCR and ELISA were used to determine the expression of IL-6, TNF-? and prostaglandin E(2) synthase on the gingival tissues. The inflammatory status was evaluated by stereometric and descriptive analysis on hematoxylin/eosin-stained sections, whereas modulation of p38 MAPK and NK-?B signaling was assessed by Western blot. Curcumin effectively inhibited cytokine gene expression at mRNA and protein levels, but NF-?B was inhibited only with the lower dose of curcumin, whereas p38 MAPK activation was not affected. Curcumin produced a significant reduction on the inflammatory infiltrate and increased collagen content and fibroblastic cell numbers. Curcumin potently inhibits innate immune responses associated with periodontal disease, suggesting a therapeutic potential in this chronic inflammatory condition. PMID:21242275

  7. Using human induced pluripotent stem cells to model cerebellar disease: Hope and hype

    PubMed Central

    Wiethoff, Sarah; Arber, Charles; Li, Abi; Wray, Selina; Houlden, Henry; Patani, Rickie

    2015-01-01

    The cerebellum forms a highly ordered and indispensible component of motor function within the adult neuraxis, consisting of several distinct cellular subtypes. Cerebellar disease, through a variety of genetic and acquired causes, results in the loss of function of defined subclasses of neurons, and remains a significant and untreatable health care burden. The scarcity of therapies in this arena can partially be explained by unresolved disease mechanisms due to inaccessibility of human cerebellar neurons in a relevant experimental context where initiating disease mechanisms could be functionally elucidated, or drug screens conducted. In this review we discuss the potential promise of human induced pluripotent stem cells (hiPSCs) for regenerative neurology, with a particular emphasis on in vitro modelling of cerebellar degeneration. We discuss progress made thus far using hiPSC-based models of neurodegeneration, noting the relatively slower pace of discovery made in modelling cerebellar dysfunction. We conclude by speculating how strategies attempting cerebellar differentiation from hiPSCs can be refined to allow the generation of accurate disease models. This in turn will permit a greater understanding of cerebellar pathophysiology to inform mechanistically rationalised therapies, which are desperately needed in this field. PMID:25985846

  8. Chimeric GII.4 Norovirus Virus-Like-Particle-Based Vaccines Induce Broadly Blocking Immune Responses

    PubMed Central

    Debbink, Kari; Lindesmith, Lisa C.; Donaldson, Eric F.; Swanstrom, Jesica

    2014-01-01

    ABSTRACT There is currently no licensed vaccine for noroviruses, and development is hindered, in part, by an incomplete understanding of the host adaptive immune response to these highly heterogeneous viruses and rapid GII.4 norovirus molecular evolution. Emergence of a new predominant GII.4 norovirus strain occurs every 2 to 4 years. To address the problem of GII.4 antigenic variation, we tested the hypothesis that chimeric virus-like particle (VLP)-based vaccine platforms, which incorporate antigenic determinants from multiple strains into a single genetic background, will elicit a broader immune response against contemporary and emergent strains. Here, we compare the immune response generated by chimeric VLPs to that of parental strains and a multivalent VLP cocktail. Results demonstrate that chimeric VLPs induce a more broadly cross-blocking immune response than single parental VLPs and a similar response to a multivalent GII.4 VLP cocktail. Furthermore, we show that incorporating epitope site A alone from one strain into the background of another is sufficient to induce a blockade response against the strain donating epitope site A. This suggests a mechanism by which population-wide surveillance of mutations in a single epitope could be used to evaluate antigenic changes in order to identify potential emergent strains and quickly reformulate vaccines against future epidemic strains as they emerge in human populations. IMPORTANCE Noroviruses are gastrointestinal pathogens that infect an estimated 21 million people per year in the United States alone. GII.4 noroviruses account for >70% of all outbreaks, making them the most clinically important genotype. GII.4 noroviruses undergo a pattern of epochal evolution, resulting in the emergence of new strains with altered antigenicity over time, complicating vaccine design. This work is relevant to norovirus vaccine design as it demonstrates the potential for development of a chimeric VLP-based vaccine platform that may broaden the protective response against multiple GII.4 strains and proposes a potential reformulation strategy to control newly emergent strains in the human population. PMID:24741081

  9. Tauroursodeoxycholic acid prevents MPTP-induced dopaminergic cell death in a mouse model of Parkinson's disease.

    PubMed

    Castro-Caldas, M; Carvalho, A Neves; Rodrigues, E; Henderson, C J; Wolf, C R; Rodrigues, C M P; Gama, M J

    2012-10-01

    Mitochondrial dysfunction and oxidative stress are implicated in the neurodegenerative process in Parkinson's disease (PD). Moreover, c-Jun N-terminal kinase (JNK) plays an important role in dopaminergic neuronal death in substantia nigra pars compacta. Tauroursodeoxycholic acid (TUDCA) acts as a mitochondrial stabilizer and anti-apoptotic agent in several models of neurodegenerative diseases. Here, we investigated the role of TUDCA in preventing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration in a mouse model of PD. We evaluated whether TUDCA modulates MPTP-induced degeneration of dopaminergic neurons in the nigrostriatal axis, and if that can be explained by regulation of JNK phosphorylation, reactive oxygen species (ROS) production, glutathione S-transferase (GST) catalytic activation, and Akt signaling, using C57BL/6 glutathione S-transferase pi (GSTP) null mice. TUDCA efficiently protected against MPTP-induced dopaminergic degeneration. We have previously demonstrated that exacerbated JNK activation in GSTP null mice resulted in increased susceptibility to MPTP neurotoxicity. Interestingly, pre-treatment with TUDCA prevented MPTP-induced JNK phosphorylation in mouse midbrain and striatum. Moreover, the anti-oxidative role of TUDCA was demonstrated in vivo by impairment of ROS production in the presence of MPTP. Finally, results herein suggest that the survival pathway activated by TUDCA involves Akt signaling, including downstream Bad phosphorylation and NF-?B activation. We conclude that TUDCA is neuroprotective in an in vivo model of PD, acting mainly by modulation of JNK activity and cellular redox thresholds, together with activation of the Akt pro-survival pathway. These results open new perspectives for the pharmacological use of TUDCA, as a modulator of neurodegeneration in PD. PMID:22773138

  10. Picosecond laser induced fragmentation of coarse Cu2O particles into nanoparticles in liquid media

    NASA Astrophysics Data System (ADS)

    Ali, Mokhtar; Remalli, Nagarjuna; Yehya, Fahem; Chaudhary, Anil Kumar; Srikanth, Vadali V. S. S.

    2015-12-01

    Micron sized cuprous oxide (Cu2O) particles are easily fragmented into nanosized (5-10 nm) particles using picosecond (ps) laser (wavelength = 532 nm) pulses. The coarse Cu2O particles are first synthesized by reducing copper chloride with the aid of honey. These particles are then dispersed in liquid media (double distilled water or ethanol) and exposed to ps laser pulses to obtain well-dispersed nanosized Cu2O particles. By using this method of fragmentation, morphology of the particles can be altered while retaining their crystal structure. The innate nature of this method allows continuous production of nanoparticles from coarser particles.

  11. Gravitational perturbation of the BTZ black hole induced by test particles and weak cosmic censorship in AdS spacetime

    SciTech Connect

    Rocha, Jorge V.; Cardoso, Vitor

    2011-05-15

    We analyze the gravitational perturbations induced by particles falling into a three dimensional, asymptotically AdS black hole geometry. More specifically, we solve the linearized perturbation equations obtained from the geodesic motion of a ringlike distribution of test particles in the BTZ background. This setup ensures that the U(1) symmetry of the background is preserved. The nonasymptotic flatness of the background raises difficulties in attributing the significance of energy and angular momentum to the conserved quantities of the test particles. This issue is well known but, to the best of our knowledge, has never been addressed in the literature. We confirm that the naive expressions for energy and angular momentum are the correct definitions. Finally, we put an asymptotically AdS version of the weak cosmic censorship to a test: by attempting to overspin the BTZ black hole with test particles it is found that the black hole cannot be spun-up past its extremal limit.

  12. Underwater pressure amplification of laser-induced plasma shock waves for particle removal applications

    SciTech Connect

    Dunbar, Thomas J.; Cetinkaya, Cetin

    2007-07-30

    Underwater amplification of laser-induced plasma (LIP)-generated transient pressure waves using shock tubes is introduced and demonstrated. Previously, it has been shown that LIP for noncontact particle removal is possible on the sub-100-nm level. This is now enhanced through shock tube utilization in a medium such as water by substantially increasing shock wave pressure for the same pulse energy. A shock tube constrains the volume and changes the propagation direction of the expanding plasma core by focusing a pulsed-laser beam inside a tube with a blind end, thus increasing the wave front pressure generated. Current amplification approach can reduce radiation exposure of the substrate from the shock wave because of the increased distance from the LIP core to the substrate provided by the increased pressure per unit pulse energy. For the same pulsed laser, with the aid of a shock tube, substantial levels of pressure amplitude amplification (8.95) and maximum pressure (6.48 MPa) are observed and reported.

  13. Transition-Edge Sensors for Particle Induced X-ray Emission Measurements

    NASA Astrophysics Data System (ADS)

    Palosaari, M. R. J.; Kinnunen, K. M.; Julin, J.; Laitinen, M.; Napari, M.; Sajavaara, T.; Doriese, W. B.; Fowler, J.; Reintsema, C.; Swetz, D.; Schmidt, D.; Ullom, J.; Maasilta, I. J.

    2014-08-01

    In this paper we present a new measurement setup, where a transition-edge sensor detector array is used to detect X-rays in particle induced X-ray emission (PIXE) measurements with a 2 MeV proton beam. Transition-edge sensors offer orders of magnitude improvement in energy resolution compared to conventional silicon or germanium detectors, making it possible to recognize spectral lines in materials analysis that have previously been impossible to resolve, and to get chemical information from the elements. Our sensors are cooled to the operation temperature (65 mK) with a cryogen-free adiabatic demagnetization refrigerator, which houses a specially designed X-ray snout that has a vacuum tight window to couple in the radiation. For the best pixel, the measured instrumental energy resolution was 3.06 eV full width at half maximum at 5.9 keV. We discuss the current status of the project, benefits of transition-edge sensors when used in PIXE spectroscopy, and the results from the first measurements.

  14. Signal-sequence induced conformational changes in the signal recognition particle

    PubMed Central

    Hainzl, Tobias; Sauer-Eriksson, A. Elisabeth

    2015-01-01

    Co-translational protein targeting is an essential, evolutionarily conserved pathway for delivering nascent proteins to the proper cellular membrane. In this pathway, the signal recognition particle (SRP) first recognizes the N-terminal signal sequence of nascent proteins and subsequently interacts with the SRP receptor. For this, signal sequence binding in the SRP54 M domain must be effectively communicated to the SRP54 NG domain that interacts with the receptor. Here we present the 2.9?Å crystal structure of unbound- and signal sequence bound SRP forms, both present in the asymmetric unit. The structures provide evidence for a coupled binding and folding mechanism in which signal sequence binding induces the concerted folding of the GM linker helix, the finger loop, and the C-terminal alpha helix ?M6. This mechanism allows for a high degree of structural adaptability of the binding site and suggests how signal sequence binding in the M domain is coupled to repositioning of the NG domain. PMID:26051119

  15. Signal-sequence induced conformational changes in the signal recognition particle

    NASA Astrophysics Data System (ADS)

    Hainzl, Tobias; Sauer-Eriksson, A. Elisabeth

    2015-06-01

    Co-translational protein targeting is an essential, evolutionarily conserved pathway for delivering nascent proteins to the proper cellular membrane. In this pathway, the signal recognition particle (SRP) first recognizes the N-terminal signal sequence of nascent proteins and subsequently interacts with the SRP receptor. For this, signal sequence binding in the SRP54 M domain must be effectively communicated to the SRP54 NG domain that interacts with the receptor. Here we present the 2.9 Å crystal structure of unbound- and signal sequence bound SRP forms, both present in the asymmetric unit. The structures provide evidence for a coupled binding and folding mechanism in which signal sequence binding induces the concerted folding of the GM linker helix, the finger loop, and the C-terminal alpha helix ?M6. This mechanism allows for a high degree of structural adaptability of the binding site and suggests how signal sequence binding in the M domain is coupled to repositioning of the NG domain.

  16. Strain-induced transformation of amorphous spherical precipitates into platelets: Application to oxide particles in silicon

    SciTech Connect

    Voronkov, V. V.; Falster, R.

    2001-06-01

    The spherical shape of an amorphous precipitate becomes unstable if the combination P{sup 2}R of precipitate radius R and pressure P exceeds some critical value. This critical value was found to be about 4.44 G{sigma}, where G is the matrix shear modulus and {sigma} is the specific energy of the precipitate/matrix interface. Once this instability criterion is fulfilled, the initially spherical particle will reduce the total free energy (the sum of strain energy and the surface energy) by becoming a thin oblate spheroid (effectively, a platelet). The actual pressure P in the course of oxygen precipitation in silicon is controlled by a high self-interstitial supersaturation caused by emission of self-interstitials by growing precipitates. The duration of annealing necessary to reach the stage of collapse of spheres into platelets is calculated as a function of temperature and the precipitate density. Calculated results are compatible with the experimentally observed annealing conditions for platelet formation. Another important example of sphere to platelet transformation is microdefect formation in vacancy-type silicon. In this case a large negative value of P is sufficient to induce collapse. {copyright} 2001 American Institute of Physics.

  17. Search for wave-induced particle precipitation from lightning and transmitter sources. Master's thesis

    SciTech Connect

    Lundberg, J.E.

    1988-01-01

    Wave-induced particle precipitation is introduced and examined for whistlers whose sources are within the plasmapause. The possible correlation between lightning strokes that carry positive charge to the ground and the observed Trimpi events is discussed, sudden phase and/or amplitude shifts of a received VLF signal with gradual return to predisturbed values. The thunderstorm charging mechanisms that lead to the observed charge distribution and the advection of the positively charged cirrus anvil away from the body of the thunderstorm are briefly examined. The comparative current strengths and the relative frequency of positive and negative strokes is studied for different types of thunderstorms. The magnetospheric ducting of the lightning-generated whistler wave and the interaction with trapped electrons is examined. The detectable effects the precipitating electrons have on the ionosphere is introduced. Included are testing and design of the x-ray detector and balloon-launch considerations. The problems encountered during the x-ray-detector's balloon flights are examined. The riometer and x-ray-detector data-analysis methods are mentioned. The results were negative for the data analyzed, but the limiting factors severely restricted the usable data. Possible experimental methods are mentioned.

  18. Low-density lipoprotein particle size and coronary artery disease in a childhood-onset type 1 diabetes population.

    PubMed

    Erbey, J R; Robbins, D; Forrest, K Y; Orchard, T J

    1999-04-01

    Low-density lipoprotein (LDL) cholesterol has been widely recognized as a strong predictor of coronary artery disease (CAD). Recently, studies have examined the influence of LDL particle size (an integral part of the insulin resistance syndrome) on the development of CAD in the general population. This report examines the correlates of LDL particle size and its association with CAD in a type 1 diabetes population. We evaluated the interrelationships between LDL particle size and the presence of CAD in a cohort of childhood-onset type 1 diabetic subjects using the Pittsburgh Epidemiology of Diabetes Complications (EDC) study. LDL particle size was measured in 337 subjects (mean age, 35.6 years; mean diabetes duration, 27.2 years) who underwent the 8-year follow-up examination. LDL particle size was determined by vertical polyacrylamide gel (2% to 16%) electrophoresis. Subjects with the small dense LDL particle phenotype (<235.5 angstroms) [corrected] had a longer diabetes duration, higher cholesterol, triglyceride, LDL, fibrinogen, waist to hip ratio (WHR), and hemoglobin A1 (HbA1), and lower high-density lipoprotein (HDL) cholesterol compared with subjects with the large LDL particle phenotype (>257 angstroms) [corrected]. Males were also more likely to have an increased body mass index (BMI) and CAD, while females were more likely to have hypertension and a family history of type 2 diabetes (a potential marker of insulin resistance and CAD risk). The odds ratio ([OR] 95% confidence, interval [CI]) using logistic regression analysis for LDL particle size in association with CAD was 0.79 (0.60 to 1.04). Multivariate modeling indicated that the duration of type 1 diabetes, depressive symptomatology, and triglycerides were independently associated with the presence of CAD. We conclude that although small dense LDL particle size is associated with CAD in our type 1 diabetes population, its borderline association can largely be explained by the triglyceride concentration. However, as in the general population, LDL particle size is associated with many elements of the insulin resistance syndrome, including a family history of type 2 diabetes, and is likely an important element in the contribution of insulin resistance to the development of CAD in type 1 diabetes. PMID:10206450

  19. Results and perspectives of the investigation of traditional and thermal stress induced thermophoresis of particles in gas in microgravity

    NASA Astrophysics Data System (ADS)

    Vedernikov, Andrei; Balapanov, Daniyar; Beresnev, Sergey; Queeckers, Patrick

    Thermophoretic motion of particles suspended in a gas has been a subject of extensive theoretical and experimental investigations for many years because of its wide spread in nature, significance for fundamental and applied aerosol physic. Negative thermophoresis, i.e. solid particle motion towards hotter region in a gas and not as usually from hotter region, was predicted more than 40 years ago and remains an unsolved problem for a choice between different models treating main driving mechanisms -- thermal slip and thermal stress induced gas motion. For a problem of negative thermophoresis, we present experimental evidences in favor of the latter mechanism based on direct observation of particle motion at microgravity; Knudsen particle number 2\\cdot 10(-3) (Kn being the ratio of the molecular mean free path to the particle size); particle-to-gas heat conductivity ratios 2\\cdot 10(4) for copper solid particles and 1.8 for glass bubbles. For both types of particles the experimental results fit well the gas kinetic model of Beresnev and Chernyak [1]. We present characteristics of a set-up and procedures that are able to provide sufficient accuracy and volume of experimental data for testing any model of particle thermophoresis. High quality microgravity is a necessity for such investigations. The short duration microgravity of drop towers suits well this requirement. The sign and value of the thermophoretic force strongly depends on the Knudsen number, particle-to-gas heat conductivity ratio and accommodation coefficients, all of which vary within several decimal orders of magnitude. In order to make crucial conclusions on the choice of the adequate model, there should be hundreds of short duration microgravity experiments. The European Space Agency scientific project Interaction in Cosmic and Atmospheric Particle Systems (ICAPS) [2] planned for the International Space Station, provides complementary opportunities for the investigation of thermophoresis at large and very large Knudsen numbers for single particles and large clusters of particles under wide range of experimental parameters, i.e. different particle sizes, shapes, materials; different properties of gases; several types of additional forces and their time-space variation. ESA PRODEX Program, Belgian Federal Science Policy Office and Bremen Drop Tower Operation and Service Company ZARM FABmbH (Germany) are greatly acknowledged for their support. [1] Beresnev S., Chernyak V. Thermophoresis of a spherical particle in a rarefied gas: Numerical analysis based on the model kinetic equations // Phys. Fluids. 1995. V.7. P.1743. [2] Blum, J. et al. "Dust in Space", Europhysicsnews, Vol. 39, pp. 27-29, 2008.

  20. Light induced heterogeneous ozone processing on the pesticides adsorbed on silica particles

    NASA Astrophysics Data System (ADS)

    Socorro, J.; Désert, M.; Quivet, E.; Gligorovski, S.; Wortham, H.

    2013-12-01

    In France, in 2010, the sales of pesticides reached 1.8 billion euros for 61 900 tons of active ingredients, positioning France as a first European consumer of pesticides, as reported by the European Crop Protection Association. About 19 million hectares of crops are sprayed annually with pesticides, i.e., 35% of the total surface area of France. This corresponds to an average pesticide dose of 3.2 kg ha-1. The consumption of herbicide and fungicide is favoured in comparison to the use of insecticides in France and the other European countries, as well. The partitioning of pesticides between the gas and particulate phases influences the atmospheric fate of these compounds such as their photo-chemical degradation. There is much uncertainty concerning the behavior of the pesticides in the atmosphere. Especially, there is a gap of knowledge concerning the degradation of the pesticides induced by heterogeneous reactions in absence and especially in presence of solar light. Considering that most of the pesticides currently used are semi-volatile, it is of crucial importance to investigate the heterogeneous reactivity of particulate pesticides with light and with atmospheric oxidants such as ozone and OH radical. The aim of the present work is to evaluate the light induced heterogeneous ozonation of suspended pesticide particles. 8 pesticides (cyprodinil, deltamethrin, difenoconazole, fipronil, oxadiazon, pendimethalin, permethrin and tetraconazole) were chosen for their physico-chemical properties and their concentration levels in the PACA (Région Provence-Alpes-Côte d'Azur) region, France. Silica particles with well-known properties were chosen as model particles of atmospheric relevance. Kinetic rate constants were determined to allow estimate the atmospheric lifetimes relating to ozone. The rate constants were determined as follows: k = (6.6 × 0.2) 10-19, (7.2 × 0.3) 10-19, (5.1 × 0.5) 10-19, (3.9 × 0.3) 10-19 [cm3 molecules-1 s-1] for Cyprodinil, delthamethrine, permethrine and pendimethaline, respectively. Concerning the other four pesticides under study i.e. difenoconazole, fipronil, oxadiazon and tetraconazole the obtained rate constants were extremely slow, < 3.9 10-19 [cm3 molecules-1 s-1]. In addition, we identified the condensed phase products in such heterogeneous reactions of ozone with the particulate pesticides by GC-MS coupled with the derivatization technique. The gas-phase products were followed on-line by PTR-MS-TOF. The obtained results will allow to recognize the impact of the pesticides and their degradation products on the human health, and to make recommendations in order to reduce population exposure to the pesticide plume. The results of this work will contribute to better describe and understand the pollution by phyto-sanitary products on the regional scale, which constitutes a necessary step in the development of environmental strategies. As a result the obtained results will help in the development of future environmental strategies to better understand and control phyto-sanitary product application and human exposure.

  1. Studying human respiratory disease in animals - role of induced and naturally occurring models.

    PubMed

    Williams, Kurt; Roman, Jesse

    2016-01-01

    Respiratory disorders like asthma, emphysema, and pulmonary fibrosis affect millions of Americans and many more worldwide. Despite advancements in medical research that have led to improved understanding of the pathophysiology of these conditions and sometimes to new therapeutic interventions, these disorders are for the most part chronic and progressive; current interventions are not curative and do not halt disease progression. A major obstacle to further advancements relates to the absence of animal models that exactly resemble the human condition, which delays the elucidation of relevant mechanisms of action, the unveiling of biomarkers of disease progression, and identification of new targets for intervention in patients. There are currently many induced animal models of human respiratory disease available for study, and even though they mimic features of human disease, discoveries in these models have not always translated into safe and effective treatments in humans. A major obstacle relates to the genetic, anatomical, and functional variations amongst species, which represents the major challenge to overcome when searching for appropriate models of respiratory disease. Nevertheless, rodents, in particular mice, have become the most common species used for experimentation, due to their relatively low cost, size, and adequate understanding of murine genetics, among other advantages. Less well known is the fact that domestic animals also suffer from respiratory illnesses similar to those found in humans. Asthma, bronchitis, pneumonia, and pulmonary fibrosis are among the many disorders occurring naturally in dogs, cats, and horses, among other species. These models might better resemble the human condition and are emphasized here, but further investigations are needed to determine their relevance. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:26467890

  2. BCG Vaccine-Induced Neuroprotection in a Mouse Model of Parkinson's Disease

    PubMed Central

    Yong, Jing; Lacan, Goran; Dang, Hoa; Hsieh, Terry; Middleton, Blake; Wasserfall, Clive; Tian, Jide; Melega, William P.; Kaufman, Daniel L.

    2011-01-01

    There is a growing interest in using vaccination with CNS antigens to induce autoreactive T cell responses that home to damaged areas in the CNS and ameliorate neurodegenerative disease. Neuroprotective vaccine studies have focused on administering oligodendrocyte antigens or Copaxone® in complete Freund's adjuvant (CFA). Theoretical considerations, however, suggest that vaccination with a neuronal antigen may induce more robust neuroprotective immune responses. We assessed the neuroprotective potential of vaccines containing tyrosine hydroxylase (a neuronal protein involved in dopamine synthesis) or Copaxone® in CFA in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Surprisingly, we observed that the main beneficial factor in these vaccines was the CFA. Since the major immunogenic component in CFA is Mycobacterium tuberculosis, which closely related to the bacille Calmette-Guérin (BCG) that is used in human vaccines, we tested BCG vaccination in the MPTP mouse model. We observed that BCG vaccination partially preserved markers of striatal dopamine system integrity and prevented an increase in activated microglia in the substantia nigra of MPTP-treated mice. These results support a new neuroprotective vaccine paradigm in which general (nonself-reactive) immune stimulation in the periphery can limit potentially deleterious microglial responses to a neuronal insult and exert a neurorestorative effect in the CNS. Accordingly, BCG vaccination may provide a new strategy to augment current treatments for a wide range of neuropathological conditions. PMID:21304945

  3. BCG vaccine-induced neuroprotection in a mouse model of Parkinson's disease.

    PubMed

    Yong, Jing; Lacan, Goran; Dang, Hoa; Hsieh, Terry; Middleton, Blake; Wasserfall, Clive; Tian, Jide; Melega, William P; Kaufman, Daniel L

    2011-01-01

    There is a growing interest in using vaccination with CNS antigens to induce autoreactive T cell responses that home to damaged areas in the CNS and ameliorate neurodegenerative disease. Neuroprotective vaccine studies have focused on administering oligodendrocyte antigens or Copaxone® in complete Freund's adjuvant (CFA). Theoretical considerations, however, suggest that vaccination with a neuronal antigen may induce more robust neuroprotective immune responses. We assessed the neuroprotective potential of vaccines containing tyrosine hydroxylase (a neuronal protein involved in dopamine synthesis) or Copaxone® in CFA in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Surprisingly, we observed that the main beneficial factor in these vaccines was the CFA. Since the major immunogenic component in CFA is Mycobacterium tuberculosis, which closely related to the bacille Calmette-Guérin (BCG) that is used in human vaccines, we tested BCG vaccination in the MPTP mouse model. We observed that BCG vaccination partially preserved markers of striatal dopamine system integrity and prevented an increase in activated microglia in the substantia nigra of MPTP-treated mice. These results support a new neuroprotective vaccine paradigm in which general (nonself-reactive) immune stimulation in the periphery can limit potentially deleterious microglial responses to a neuronal insult and exert a neurorestorative effect in the CNS. Accordingly, BCG vaccination may provide a new strategy to augment current treatments for a wide range of neuropathological conditions. PMID:21304945

  4. Solving the puzzle of Parkinson's disease using induced pluripotent stem cells.

    PubMed

    Zhao, Ping; Luo, Zhiwei; Tian, Weihua; Yang, Jiayin; Ibáñez, David P; Huang, Zhijian; Tortorella, Micky D; Esteban, Miguel A; Fan, Wenxia

    2014-11-01

    The prevalence and incidence of Parkinson's disease (PD) is increasing due to a prolonged life expectancy. This highlights the need for a better mechanistic understanding and new therapeutic approaches. However, traditional in vitro and in vivo experimental models to study PD are suboptimal, thus hampering the progress in the field. The epigenetic reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) offers a unique way to overcome this problem, as these cells share many properties of embryonic stem cells (ESCs) including the potential to be transformed into different lineages. PD modeling with iPSCs is nowadays facilitated by the growing availability of high-efficiency neural-specific differentiation protocols and the possibility to correct or induce mutations as well as creating marker cell lines using designer nucleases. These technologies, together with steady advances in human genetics, will likely introduce profound changes in the way we interpret PD and develop new treatments. Here, we summarize the different PD iPSCs reported so far and discuss the challenges for disease modeling using these cell lines. PMID:24939824

  5. Prostaglandins in the perilymph of guinea pig with type II collagen induced ear diseases

    SciTech Connect

    Takeda, T.; Chiang, T.; Kitano, H.; Sudo, N.; Kim, S.Y.; Ha, S.; Woo, V.; Wolf, B.; Floyd, R.; Yoo, T.J.

    1986-03-01

    The authors have studied the prostaglandins (PGs) in the perilymph from guinea pig with type II collagen induced autoimmune ear disease. Hartly guinea pigs were immunized with type II collagen in CFA and auditory brain stem responses (ABR) were measured at 2, 3, 4, and 6 months after initial immunization perilymph was obtained and the levels of PGE2 and 6 keto-PGFl..cap alpha.. were measured by radioimmunoassays. Temporal bones were examined for the histopathologic changes. Immunized guinea pigs showed the evidence of hearing loss by ABR. The temporal bones showed the following changes: spiral ganglia degeneration, mild to moderate degree of degeneration in organ of Corti, infrequent very mild endolymphatic hydrops and labrynthitis. The perilymph from immunized animals contained about 5 times more PGE2 and about 3 times more 6 keto-PGFl..cap alpha.. than control animals. However, between these two groups, there was no difference in the CSF and sera levels of PGE2 and 6 keto-PGFl..cap alpha... Thus, this study suggests that these inflammatory mediators might be involved in the pathogenesis of collagen induced autoimmune inner ear disease.

  6. Protective Effects of Curcumin Against Rotenone and Salsolinol Induced Toxicity: Implications for Parkinson’s Disease

    PubMed Central

    Qualls, Zakiya; Brown, Dwayne; Ramlochansingh, Carlana; Hurley, Laura L.; Tizabi, Yousef

    2013-01-01

    Parkinson’s disease (PD) is a debilitating neurodegenerative disorder that results from the loss of or damage to dopaminergic cells in the substantia nigra. Exposure to either the pesticide rotenone or the endogenous neurotoxin salsolinol has been shown to mimic this dopaminergic cell loss. In this study we first sought to determine whether combination of rotenone and salsolinol would result in an additive or synergistic toxicity. For this purpose we utilized SH-SY5Y cells, a human neuroblastoma cell line that is commonly used to model dopaminergic neurodegeneration. We then tested whether curcumin, a natural plant compound with known health benefits including potential neuroprotective properties, could also protect against rotenone and/or salsolinol induced toxicity. Moreover, since apoptotic mechanism has been implicated in toxicity of these compounds the anti-apoptotic effect of curcumin was also evaluated. Our results indicate a synergistic toxicity of low concentrations of rotenone (1 and 5 uM) and salsolinol (25 and 50 mM) that was associated with apoptosis as determined by cell flow cytometry. There was also an increase in caspase-3 levels. Pretreatment with curcumin (1-10 uM) dose-dependently attenuated rotenone and/or salsolinol induced toxicity and the associated apoptosis. These results suggest that exposure to a combination of rotenone and salsolinol may contribute to the pathology of PD, and that curcumin has a therapeutic potential in this disease. PMID:24122264

  7. Use of a soluble epoxide hydrolase inhibitor in smoke-induced chronic obstructive pulmonary disease.

    PubMed

    Wang, Lei; Yang, Jun; Guo, Lei; Uyeminami, Dale; Dong, Hua; Hammock, Bruce D; Pinkerton, Kent E

    2012-05-01

    Tobacco smoke-induced chronic obstructive pulmonary disease (COPD) is a prolonged inflammatory condition of the lungs characterized by progressive and largely irreversible airflow limitation attributable to a number of pathologic mechanisms, including bronchitis, bronchiolitis, emphysema, mucus plugging, pulmonary hypertension, and small-airway obstruction. Soluble epoxide hydrolase inhibitors (sEHIs) demonstrated anti-inflammatory properties in a rat model after acute exposure to tobacco smoke. We compared the efficacy of sEHI t-TUCB (trans-4-{4-[3-(4-trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid) and the phosphodiesterase-4 (PDE4) inhibitor Rolipram (Biomol International, Enzo Life Sciences, Farmingdale, NY) to reduce lung injury and inflammation after subacute exposure to tobacco smoke over a period of 4 weeks. Pulmonary physiology, bronchoalveolar lavage, cytokine production, and histopathology were analyzed to determine the efficacy of sEHI and Rolipram to ameliorate tobacco smoke-induced inflammation and injury in the spontaneously hypertensive rat. Both t-TUCB and Rolipram inhibited neutrophil elevation in bronchoalveolar lavage. sEHI t-TUCB suppressed IFN-?, while improving lung function by reducing tobacco smoke-induced total respiratory resistance and tissue damping (small-airway and peripheral tissue resistance). Increases in tobacco smoke-induced alveolar airspace size were attenuated by t-TUCB. Rolipram inhibited the production of airway mucus. Both t-TUCB and Rolipram inhibited vascular remodeling-related growth factor. These findings suggest that sEHI t-TUCB has therapeutic potential for treating COPD by improving lung function and attenuating the lung inflammation and emphysematous changes caused by tobacco smoke. To the best of our knowledge, this is the first report to demonstrate that sEHI exerts significant protective effects after repeated, subacute tobacco smoke-induced lung injury in a rat model of COPD. PMID:22180869

  8. Hyperosmolar Stress Induces Neutrophil Extracellular Trap Formation: Implications for Dry Eye Disease

    PubMed Central

    Tibrewal, Sapna; Ivanir, Yair; Sarkar, Joy; Nayeb-Hashemi, Neema; Bouchard, Charles S.; Kim, Eunjae; Jain, Sandeep

    2014-01-01

    Purpose. To determine if hyperosmolar stress can stimulate human neutrophils to form neutrophil extracellular traps (NETs) and to investigate potential strategies to reduce formation of NETs (NETosis) in a hyperosmolar environment. Methods. Neutrophils were isolated from peripheral venous blood of healthy subjects and incubated in iso-osmolar (280 mOsM) or hyperosmolar (420 mOsM) media for 4 hours. Neutrophil extracellular traps were quantified using a PicoGreen dye assay to measure extracellular DNA. Two known inhibitors of NETosis, staurosporine and anti-?2 integrin blocking antibody, and two proresolution formyl peptide receptor 2 (FPR2) agonists, annexin/lipocortin-1 mimetic peptide and 15-epi-lipoxin A4, were evaluated as possible strategies to reduce hyperosmolarity-induced NETosis. Results. The amount of NETs induced by hyperosmolar medium (420 mOsM) increased linearly over time to 3.2 ± 0.3 times that induced by iso-osmolar medium at 4 hours (P < 0.05). NETosis increased exponentially with increasing osmolarity and was independent of the stimulus used to increase osmolarity. Upon neutrophil exposure to hyperosmolar stress, restoration of iso-osmolar conditions decreased NET formation by 52.7% ± 5% (P < 0.05) but did not completely abrogate it. Among the strategies tested to reduce NETosis in a hyperosmolar environment, annexin-1 peptide was the most efficacious. Conclusions. Hyperosmolarity induces formation of NETs by neutrophils. This NETosis mechanism may explain the presence of excessive NETs on the ocular surface of patients with dry eye disease. Because they reduce hyperosmolarity-induced NETosis, FPR2 agonists may have therapeutic potential in these patients. PMID:25406284

  9. Proceedings: Consideration of Genetics in the Design of Induced Pluripotent Stem Cell-Based Models of Complex Disease

    PubMed Central

    Shepard, Kelly A.

    2014-01-01

    SUMMARY The goal of exploiting induced pluripotent stem cell (iPSC) technology for the discovery of new mechanisms and treatments of disease is being pursued by many laboratories, and analyses of rare monogenic diseases have already provided ample evidence that this approach has merit. Considering the enormous medical burden imposed by common chronic diseases, successful implementation of iPSC-based models has the potential for major impact on these diseases as well. Since common diseases represent complex traits with varying genetic and environmental contributions to disease manifestation, the use of iPSC technology poses unique challenges. In this perspective, we will consider how the genetics of complex disease and mechanisms underlying phenotypic variation affect experimental design. PMID:25359995

  10. Elevated Endothelial Hypoxia-Inducible Factor-1? Contributes to Glomerular Injury and Promotes Hypertensive Chronic Kidney Disease.

    PubMed

    Luo, Renna; Zhang, Weiru; Zhao, Cheng; Zhang, Yujin; Wu, Hongyu; Jin, Jianping; Zhang, Wenzheng; Grenz, Almut; Eltzschig, Holger K; Tao, Lijian; Kellems, Rodney E; Xia, Yang

    2015-07-01

    Hypertensive chronic kidney disease is one of the most prevalent medical conditions with high morbidity and mortality in the United States and worldwide. However, early events initiating the progression to hypertensive chronic kidney disease are poorly understood. We hypothesized that elevated endothelial hypoxia-inducible factor-1? (HIF-1?) is a common early insult triggering initial glomerular injury leading to hypertensive chronic kidney disease. To test our hypothesis, we used an angiotensin II infusion model of hypertensive chronic kidney disease to determine the specific cell type and mechanisms responsible for elevation of HIF-1? and its role in the progression of hypertensive chronic kidney disease. Genetic studies coupled with reverse transcription polymerase chain reaction profiling revealed that elevated endothelial HIF-1? is essential to initiate glomerular injury and progression to renal fibrosis by the transcriptional activation of genes encoding multiple vasoactive proteins. Mechanistically, we found that endothelial HIF-1? gene expression was induced by angiotensin II in a nuclear factor-?B-dependent manner. Finally, we discovered reciprocal positive transcriptional regulation of endothelial Hif-1? and Nf-?b genes is a key driving force for their persistent activation and disease progression. Overall, our findings revealed that the stimulation of HIF-1? gene expression in endothelial cells is detrimental to induce kidney injury, hypertension, and disease progression. Our findings highlight early diagnostic opportunities and therapeutic approaches for hypertensive chronic kidney disease. PMID:25987665

  11. Nrf2 Is a Protective Factor against Oxidative Stresses Induced by Diesel Exhaust Particle in Allergic Asthma

    PubMed Central

    Kawada, Tomoyuki; Azuma, Arata

    2013-01-01

    Epidemiological studies have shown that air pollutants, such as diesel exhaust particle (DEP), are implicated in the increased incidence of allergic airway disorders. In vitro studies of molecular mechanisms have focused on the role of reactive oxygen species generated directly and indirectly by the exposure to DEP. Antioxidants effectively reduce the allergic inflammatory effects induced by DEP both in vitro and in vivo. On the other hand, Nrf2 is a transcription factor essential for the inducible and/or constitutive expression of phase II and antioxidant enzymes. Disruption of Nrf2 enhances susceptibility to airway inflammatory responses and exacerbation of allergic inflammation induced by DEP in mice. Host responses to DEP are regulated by a balance between antioxidants and proinflammatory responses. Nrf2 may be an important protective factor against oxidative stresses induced by DEP in airway inflammation and allergic asthma and is expected to contribute to chemoprevention against DEP health effects in susceptible individuals. PMID:23738037

  12. Effect of Subthalamic Deep Brain Stimulation on Levodopa-Induced Dyskinesia in Parkinson's Disease

    PubMed Central

    Kim, Ji Hee; Chang, Won Seok; Jung, Hyun Ho

    2015-01-01

    Purpose To evaluate the effect of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on levodopa-induced peak-dose dyskinesia in patients with Parkinson's disease (PD). Materials and Methods A retrospective review was conducted on patients who underwent STN DBS for PD from May 2000 to July 2012. Only patients with levodopa-induced dyskinesia prior to surgery and more than 1 year of available follow-up data after DBS were included. The outcome measures included the dyskinesia subscore of the Unified Parkinson's Disease Rating Scale (UPDRS) part IV (items 32 to 34 of UPDRS part IV) and the levodopa equivalent daily dose (LEDD). The patients were divided into two groups based on preoperative to postoperative LEDD change at 12 months after the surgery: Group 1, LEDD decrease >15%; Group 2, all other patients. Group 2 was further divided by the location of DBS leads. Results Of the 100 patients enrolled, 67 were in Group 1, while those remaining were in Group 2. Twelve months after STN DBS, Groups 1 and 2 showed improvements of 61.90% and 57.14%, respectively, in the dyskinesia subscore. Group 1 was more likely to experience dyskinesia suppression; however, the association between the groups and dyskinesia suppression was not statistically significant (p=0.619). In Group 2, dyskinesia was significantly decreased by stimulation of the area above the STN in 18 patients compared to stimulation of the STN in 15 patients (p=0.048). Conclusion Levodopa-induced dyskinesia is attenuated by STN DBS without reducing the levodopa dosage. PMID:26256974

  13. Emerging mechanistic targets in lung injury induced by combustion-generated particles.

    EPA Science Inventory

    ABSTRACT The mechanism for biological effect following pulmonary exposure to combustion-generated particles is incompletely defined. Transient receptor potential (TRP) cation channels were identified as “particle sensors” in that their activation was coupled with the initiation ...

  14. Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery

    PubMed Central

    Singh, Vimal K.; Kalsan, Manisha; Kumar, Neeraj; Saini, Abhishek; Chandra, Ramesh

    2015-01-01

    Recent progresses in the field of Induced Pluripotent Stem Cells (iPSCs) have opened up many gateways for the research in therapeutics. iPSCs are the cells which are reprogrammed from somatic cells using different transcription factors. iPSCs possess unique properties of self renewal and differentiation to many types of cell lineage. Hence could replace the use of embryonic stem cells (ESC), and may overcome the various ethical issues regarding the use of embryos in research and clinics. Overwhelming responses prompted worldwide by a large number of researchers about the use of iPSCs evoked a large number of peple to establish more authentic methods for iPSC generation. This would require understanding the underlying mechanism in a detailed manner. There have been a large number of reports showing potential role of different molecules as putative regulators of iPSC generating methods. The molecular mechanisms that play role in reprogramming to generate iPSCs from different types of somatic cell sources involves a plethora of molecules including miRNAs, DNA modifying agents (viz. DNA methyl transferases), NANOG, etc. While promising a number of important roles in various clinical/research studies, iPSCs could also be of great use in studying molecular mechanism of many diseases. There are various diseases that have been modeled by uing iPSCs for better understanding of their etiology which maybe further utilized for developing putative treatments for these diseases. In addition, iPSCs are used for the production of patient-specific cells which can be transplanted to the site of injury or the site of tissue degeneration due to various disease conditions. The use of iPSCs may eliminate the chances of immune rejection as patient specific cells may be used for transplantation in various engraftment processes. Moreover, iPSC technology has been employed in various diseases for disease modeling and gene therapy. The technique offers benefits over other similar techniques such as animal models. Many toxic compounds (different chemical compounds, pharmaceutical drugs, other hazardous chemicals, or environmental conditions) which are encountered by humans and newly designed drugs may be evaluated for toxicity and effects by using iPSCs. Thus, the applications of iPSCs in regenerative medicine, disease modeling, and drug discovery are enormous and should be explored in a more comprehensive manner. PMID:25699255

  15. Induced Pluripotency and Gene Editing in Disease Modelling: Perspectives and Challenges

    PubMed Central

    Seah, Yu Fen Samantha; EL Farran, Chadi A.; Warrier, Tushar; Xu, Jian; Loh, Yuin-Han

    2015-01-01

    Embryonic stem cells (ESCs) are chiefly characterized by their ability to self-renew and to differentiate into any cell type derived from the three main germ layers. It was demonstrated that somatic cells could be reprogrammed to form induced pluripotent stem cells (iPSCs) via various strategies. Gene editing is a technique that can be used to make targeted changes in the genome, and the efficiency of this process has been significantly enhanced by recent advancements. The use of engineered endonucleases, such as homing endonucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and Cas9 of the CRISPR system, has significantly enhanced the efficiency of gene editing. The combination of somatic cell reprogramming with gene editing enables us to model human diseases in vitro, in a manner considered superior to animal disease models. In this review, we discuss the various strategies of reprogramming and gene targeting with an emphasis on the current advancements and challenges of using these techniques to model human diseases. PMID:26633382

  16. Redox reactions induced by nitrosative stress mediate protein misfolding and mitochondrial dysfunction in neurodegenerative diseases.

    PubMed

    Gu, Zezong; Nakamura, Tomohiro; Lipton, Stuart A

    2010-06-01

    Overstimulation of N-methyl-D-aspartate (NMDA)-type glutamate receptors accounts, at least in part, for excitotoxic neuronal damage, potentially contributing to a wide range of acute and chronic neurologic diseases. Neurodegenerative disorders including Alzheimer's disease (AD) and Parkinson's disease (PD), manifest deposits of misfolded or aggregated proteins, and result from synaptic injury and neuronal death. Recent studies have suggested that nitrosative stress due to generation of excessive nitric oxide (NO) can mediate excitotoxicity in part by triggering protein misfolding and aggregation, and mitochondrial fragmentation in the absence of genetic predisposition. S-Nitrosylation, or covalent reaction of NO with specific protein thiol groups, represents a convergent signal pathway contributing to NO-induced protein misfolding and aggregation, compromised dynamics of mitochondrial fission-fusion process, thus leading to neurotoxicity. Here, we review the effect of S-nitrosylation on protein function under excitotoxic conditions, and present evidence suggesting that NO contributes to protein misfolding and aggregation via S-nitrosylating protein-disulfide isomerase or the E3 ubiquitin ligase parkin, and mitochondrial fragmentation through beta-amyloid-related S-nitrosylation of dynamin-related protein-1. Moreover, we also discuss that inhibition of excessive NMDA receptor activity by memantine, an uncompetitive/fast off-rate (UFO) drug can ameliorate excessive production of NO, protein misfolding and aggregation, mitochondrial fragmentation, and neurodegeneration. PMID:20333559

  17. Induced Pluripotency and Gene Editing in Disease Modelling: Perspectives and Challenges.

    PubMed

    Seah, Yu Fen Samantha; El Farran, Chadi A; Warrier, Tushar; Xu, Jian; Loh, Yuin-Han

    2015-01-01

    Embryonic stem cells (ESCs) are chiefly characterized by their ability to self-renew and to differentiate into any cell type derived from the three main germ layers. It was demonstrated that somatic cells could be reprogrammed to form induced pluripotent stem cells (iPSCs) via various strategies. Gene editing is a technique that can be used to make targeted changes in the genome, and the efficiency of this process has been significantly enhanced by recent advancements. The use of engineered endonucleases, such as homing endonucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and Cas9 of the CRISPR system, has significantly enhanced the efficiency of gene editing. The combination of somatic cell reprogramming with gene editing enables us to model human diseases in vitro, in a manner considered superior to animal disease models. In this review, we discuss the various strategies of reprogramming and gene targeting with an emphasis on the current advancements and challenges of using these techniques to model human diseases. PMID:26633382

  18. Trehalose intake induces chaperone molecules along with autophagy in a mouse model of Lewy body disease.

    PubMed

    Tanji, Kunikazu; Miki, Yasuo; Maruyama, Atsushi; Mimura, Junsei; Matsumiya, Tomoh; Mori, Fumiaki; Imaizumi, Tadaatsu; Itoh, Ken; Wakabayashi, Koichi

    2015-10-01

    The accumulation of mis-folded and/or abnormally modified proteins is a major characteristic of many neurodegenerative diseases. In Lewy body disease (LBD), which includes Parkinson's disease and dementia with Lewy bodies, insoluble ?-synuclein is widely deposited in the presynaptic terminals as well as in the neuronal cytoplasm in distinct brain regions. It is well known that the autophagy-lysosome system serves as an efficient degradation pathway for abnormal molecules within cells. To test the possibility that activated autophagy can degrade abnormal molecules, we investigated the effect of trehalose on abnormal aggregation of ?-synuclein in a model of LBD. Trehalose is a natural disaccharide composed of two glucose units and functions as an autophagy inducer. Consistent with previous studies, trehalose increased level of the autophagosomal protein LC3, especially a lipidated form LC3-II in cultured cells and mice brain. Also, trehalose increased levels of several chaperon molecules, such as HSP90 and SigmaR1, in the brains of LBD model mice. Further studies revealed that level of detergent-insoluble ?-synuclein was suppressed in mice following oral administration of trehalose, despite an apparent alteration was not observed regarding abnormal aggregation of ?-synuclein. These results suggest that the oral intake of trehalose modulates propensity of molecules prior to aggregation formation. PMID:26299928

  19. Induced neural stem/precursor cells for fundamental studies and potential application in neurodegenerative diseases.

    PubMed

    Shen, Ting; Pu, Jiali; Zheng, Tingting; Zhang, Baorong

    2015-10-01

    Recent research has shown that defined sets of exogenous factors are sufficient to convert rodent and human somatic cells directly into induced neural stem cells or neural precursor cells (iNSCs/iNPCs). The process of transdifferentiation bypasses the step of a pluripotent state and reduces the risk of tumorigenesis and genetic instability while retaining the self-renewing capacity. This iNSC/iNPC technology has fueled much excitement in regenerative medicine, as these cells can be differentiated into target cells for re placement therapy for neurodegenerative diseases. Patients' somatic cell-derived iNSCs/iNPCs have also been proposed to serve as disease models with potential value in both fundamental studies and clinical applications. This review focuses on the mechanisms, techniques, and app lications of iNSCs/iNPCs from a series of related studies, as well as further efforts in designing novel strategies using iNSC/iNPC technology and its potential applications in neurodegenerative diseases. PMID:26077704

  20. Donepezil Regulates 1-Methyl-4-phenylpyridinium-Induced Microglial Polarization in Parkinson's Disease.

    PubMed

    Chen, Teng; Hou, Ruihua; Xu, Shujun; Wu, Chengyuan

    2015-10-21

    1-Methyl-4-phenylpyridinium (MPP+) induces microglial activation and degeneration of dopaminergic (DAergic) neurons. Donepezil is a well-known acetylcholinesterase inhibitor used clinically to treat cognitive dysfunction in Alzheimer's disease (AD). In the present study, we tested the hypothesis that MPP+ promotes microglial M1 polarization and suppresses M2 polarization and that this can be restored by donepezil. Results indicate that MPP+ treatment in microglial BV2 cells promotes microglial polarization toward the M1 state. However, pretreatment with donepezil inhibited MPP+-induced M1 polarization in microglia by suppressing the release of interleukin (IL)-6, IL-1?, or tumor necrosis factor (TNF)-?. Importantly, we found that MPP+ inhibited microglial M2 polarization by suppressing expression of Arg-1, Fizz1, and Ym1, which was also rescued by pretreatment with donepezil. In addition, IL-4-mediated induction of anti-inflammatory marker genes IL-10, IL-13, and transforming growth factor-?2 (TGF-?2) were significantly attenuated by MPP+ in BV2 cells, which was restored by pretreatment with donepezil in a concentration-dependent manner. Mechanistically, we found that the addition of MPP+ reduced the intensity of phosphorylated signal transducer and activator of transcription 6 (STAT6) but not total STAT6 in IL-4-stimulated BV2 cells. Importantly, pretreatment of microglial BV2 cells with donepezil 3 h prior to administration of MPP+ rescued the reduction of STAT6 phosphorylation induced by MPP+. PMID:26114860

  1. The Batten disease gene CLN3 confers resistance to endoplasmic reticulum stress induced by tunicamycin

    SciTech Connect

    Wu, Dan; Liu, Jing; Wu, Baiyan; Tu, Bo; Zhu, Weiguo; Luo, Jianyuan

    2014-04-25

    Highlights: • The work reveals a protective properties of CLN3 towards TM-induced apoptosis. • CLN3 regulates expression of the GRP78 and the CHOP in response to the ER stress. • CLN3 plays a specific role in the ERS response. - Abstract: Mutations in CLN3 gene cause juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease), an early-onset neurodegenerative disorder that is characterized by the accumulation of ceroid lipofuscin within lysosomes. The function of the CLN3 protein remains unclear and is presumed to be related to Endoplasmic reticulum (ER) stress. To investigate the function of CLN3 in the ER stress signaling pathway, we measured proliferation and apoptosis in cells transfected with normal and mutant CLN3 after treatment with the ER stress inducer tunicamycin (TM). We found that overexpression of CLN3 was sufficient in conferring increased resistance to ER stress. Wild-type CLN3 protected cells from TM-induced apoptosis and increased cell proliferation. Overexpression of wild-type CLN3 enhanced expression of the ER chaperone protein, glucose-regulated protein 78 (GRP78), and reduced expression of the proapoptotic protein CCAAT/-enhancer-binding protein homologous protein (CHOP). In contrast, overexpression of mutant CLN3 or siRNA knockdown of CLN3 produced the opposite effect. Together, our data suggest that the lack of CLN3 function in cells leads to a failure of management in the response to ER stress and this may be the key deficit in JNCL that causes neuronal degeneration.

  2. Dendritic Cells Induce Autoimmune Diabetes and Maintain Disease via De Novo Formation of Local Lymphoid Tissue

    PubMed Central

    Ludewig, Burkhard; Odermatt, Bernhard; Landmann, Salome; Hengartner, Hans; Zinkernagel, Rolf M.

    1998-01-01

    Activation of autoreactive T cells can lead to autoimmune diseases such as insulin-dependent diabetes mellitus (IDDM). The initiation and maintenance of IDDM by dendritic cells (DC), the most potent professional antigen-presenting cells, were investigated in transgenic mice expressing the lymphocytic choriomeningitis virus glycoprotein (LCMV-GP) under the control of the rat insulin promoter (RIP-GP mice). We show that after adoptive transfer of DC constitutively expressing the immunodominant cytotoxic T lymphocyte (CTL) epitope of the LCMV-GP, RIP-GP mice developed autoimmune diabetes. Kinetic and functional studies of DC-activated CTL revealed that development of IDDM was dependent on dose and timing of antigenic stimulation. Strikingly, repeated CTL activation by DC led to severe destructive mononuclear infiltration of the pancreatic islets but also to de novo formation of islet-associated organized lymphoid structures in the pancreatic parenchyma. In addition, repetitive DC immunization induced IDDM with lymphoid neogenesis also in perforin-deficient RIP-GP mice, illustrating that CD8+ T cell–dependent inflammatory mechanisms independent of perforin could induce IDDM. Thus, DC presenting self-antigens not only are potent inducers of autoreactive T cells, but also help to maintain a peripheral immune response locally; therefore, the induction of autoimmunity against previously ignored autoantigens represents a potential hazard, particularly in DC-based antitumor therapies. PMID:9782126

  3. Aspirin induces IL-4 production: augmented IL-4 production in aspirin-exacerbated respiratory disease

    PubMed Central

    Kong, Su-Kang; Soo Kim, Byung; Gi Uhm, Tae; Soo Chang, Hun; Sook Park, Jong; Woo Park, Sung; Park, Choon-Sik; Chung, Il Yup

    2015-01-01

    Aspirin hypersensitivity is a hallmark of aspirin-exacerbated respiratory disease (AERD), a clinical syndrome characterized by the severe inflammation of the respiratory tract after ingestion of cyclooxygenase-1 inhibitors. We investigated the capacity of aspirin to induce interleukin-4 (IL-4) production in inflammatory cells relevant to AERD pathogenesis and examined the associated biochemical and molecular pathways. We also compared IL-4 production in peripheral blood mononuclear cells (PBMCs) from patients with AERD vs aspirin-tolerant asthma (ATA) upon exposure to aspirin. Aspirin induced IL-4 expression and activated the IL-4 promoter in a report assay. The capacity of aspirin to induce IL-4 expression correlated with its activity to activate mitogen-activated protein kinases, to form DNA–protein complexes on P elements in the IL-4 promoter and to synthesize nuclear factor of activated T cells, critical transcription factors for IL-4 transcription. Of clinical importance, aspirin upregulated IL-4 production twice as much in PBMCs from patients with AERD compared with PBMCs from patients with ATA. Our results suggest that IL-4 is an inflammatory component mediating intolerance reactions to aspirin, and thus is crucial for AERD pathogenesis.

  4. Ameliorative Effect of Chrysin on Adenine-Induced Chronic Kidney Disease in Rats

    PubMed Central

    Ali, Badreldin H.; Adham, Sirin A.; Al Za’abi, Mohammed; Waly, Mostafa I.; Yasin, Javed; Nemmar, Abderrahim; Schupp, Nicole

    2015-01-01

    Chrysin (5, 7- dihydroxyflavone) is a flavonoid with several pharmacological properties that include antioxidant, anti-inflammatory and antiapoptotic activities. in this work, we investigated some effects of three graded oral doses of chrysin (10, 50 and 250 mg/kg) on kidney structure and function in rats with experimental chronic renal disease (CKD) induced by adenine (0.25% w/w in feed for 35 days), which is known to involve inflammation and oxidative stress. Using several indices in plasma, urine and kidney homogenates, adenine was found to impair kidney function as it lowered creatinine clearance and increased plasma concentrations of creatinine, urea, neutrophil gelatinase-associated lipocalin and N-Acetyl-beta-D-glucosaminidase activity. Furthermore, it raised plasma concentrations of the uremic toxin indoxyl sulfate, some inflammatory cytokines and urinary albumin concentration. Renal morphology was severely damaged and histopathological markers of inflammation and fibrosis were especially increased. In renal homogenates, antioxidant indices, including superoxide dismutase and catalase activities, total antioxidant capacity and reduced glutathione were all adversely affected. Most of these adenine – induced actions were moderately and dose -dependently mitigated by chrysin, especially at the highest dose. Chrysin did not cause any overt adverse effect on the treated rats. The results suggest that different doses of chrysin produce variable salutary effects against adenine-induced CKD in rats, and that, pending further pharmacological and toxicological studies, its usability as a possible ameliorative agent in human CKD should be considered. PMID:25909514

  5. Rhinovirus Infection Induces Degradation of Antimicrobial Peptides and Secondary Bacterial Infection in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Mallia, Patrick; Footitt, Joseph; Sotero, Rosa; Jepson, Annette; Contoli, Marco; Trujillo-Torralbo, Maria-Belen; Kebadze, Tatiana; Aniscenko, Julia; Oleszkiewicz, Gregory; Gray, Katrina; Message, Simon D.; Ito, Kazuhiro; Barnes, Peter J.; Adcock, Ian M.; Papi, Alberto; Stanciu, Luminita A.; Elkin, Sarah L.; Kon, Onn M.; Johnson, Malcolm

    2012-01-01

    Rationale: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with virus (mostly rhinovirus) and bacterial infections, but it is not known whether rhinovirus infections precipitate secondary bacterial infections. Objectives: To investigate relationships between rhinovirus infection and bacterial infection and the role of antimicrobial peptides in COPD exacerbations. Methods: We infected subjects with moderate COPD and smokers and nonsmokers with normal lung function with rhinovirus. Induced sputum was collected before and repeatedly after rhinovirus infection and virus and bacterial loads measured with quantitative polymerase chain reaction and culture. The antimicrobial peptides secretory leukoprotease inhibitor (SLPI), elafin, pentraxin, LL-37, ?-defensins and ?-defensin-2, and the protease neutrophil elastase were measured in sputum supernatants. Measurements and Main Results: After rhinovirus infection, secondary bacterial infection was detected in 60% of subjects with COPD, 9.5% of smokers, and 10% of nonsmokers (P < 0.001). Sputum virus load peaked on Days 5–9 and bacterial load on Day 15. Sputum neutrophil elastase was significantly increased and SLPI and elafin significantly reduced after rhinovirus infection exclusively in subjects with COPD with secondary bacterial infections, and SLPI and elafin levels correlated inversely with bacterial load. Conclusions: Rhinovirus infections are frequently followed by secondary bacterial infections in COPD and cleavage of the antimicrobial peptides SLPI and elafin by virus-induced neutrophil elastase may precipitate these secondary bacterial infections. Therapy targeting neutrophil elastase or enhancing innate immunity may be useful novel therapies for prevention of secondary bacterial infections in virus-induced COPD exacerbations. PMID:23024024

  6. Gemcitabine-Induced Pulmonary Toxicity: A Case Report of Pulmonary Veno-Occlusive Disease

    PubMed Central

    Turco, Célia; Jary, Marine; Kim, Stefano; Moltenis, Mélanie; Degano, Bruno; Manzoni, Philippe; Nguyen, Thierry; Genet, Bruno; Rabier, Marie-Blanche Valnet; Heyd, Bruno; Borg, Christophe

    2015-01-01

    INTRODUCTION Gemcitabine is a chemotherapeutic agent frequently used by for the treatment of several malignancies both in the adjuvant and metastatic setting. Although myelosuppression is the most adverse event of this therapy, gemcitabine might induce severe pulmonary toxicities. We describe a case of pulmonary veno-occlusive disease (PVOD) related to gemcitabine. CASE PRESENTATION The patient was an 83-year-old man with a metastatic pancreatic cancer who was treated by gemcitabine as first-line therapy. He was in good health and received no other chemotherapy. A dose of 1000 mg/m2 of gemcitabine was administered over a 30-minute intravenous infusion on days 1, 8, and 15 of a 28-day cycle. After a period of 6 months, a complete response was observed. Nevertheless, the patient developed a severe dyspnea, with arterial hypoxemia and very low lung diffusion for carbon monoxide. A CT scan showed diffuse ground glass opacities with septal lines, bilateral pleural effusion, and lymph node enlargement. On echocardiography, there was a suspicion of pulmonary hypertension with elevated systolic pulmonary artery pressure and normal left ventricular pressures. Right heart catheterization confirmed pulmonary hypertension and normal pulmonary artery occlusion pressure. Diagnosis of PVOD was made, and a gemcitabine-induced toxicity was suspected. A symptomatic treatment was started. At last follow-up, patient was in functional class I with near-normal of CT scan, arterial blood gases, and echocardiography. A gemcitabine-induced PVOD is the more likely diagnosis. PMID:26380562

  7. Neuroprotective effect of curcumin on hippocampal injury in 6-OHDA-induced Parkinson's disease rat.

    PubMed

    Yang, Jiaqing; Song, Shilei; Li, Jian; Liang, Tao

    2014-06-01

    Clinically, Parkinson's disease (PD)-related neuronal lesions commonly occur. The purpose of this study is to investigate potential therapeutic effect of curcumin against hippocampal damage of 6-hydroxydopamine (6-OHDA)-PD rat model. These results showed that curcumin significantly increased the body weight of 6-OHDA-impaired rats (P<0.01), and reversed the anhedonia in rats induced by 6-OHDA impairment (P<0.01). Meanwhile, behavioral manifestations of curcumin-treated PD rats were effectively ameliorated as shown in open field test (P<0.01). In addition, curcumin increased the contents of monoaminergic neurotransmitters (P<0.01), such as dopamine (DA) and norepinephrine (NE), in hippocampal homogenate through high performance liquid chromatography (HPLC) assay. Curcumin effectively alleviated the 6-OHDA-induced hippocampal damage as observed in hematoxylin-eosin (H&E) staining. Furthermore, curcumin obviously up-regulated hippocampal brain derived neurotrophic factor (BDNF), TrkB, phosphatidylinositide 3-kinases (PI3K) protein expressions, respectively as shown in Western blot analysis. These findings demonstrated that curcumin mediated the neuroprotection against 6-OHDA-induced hippocampus neurons in rats, which the underlying mechanism is involved in activating BDNF/TrkB-dependent pathway for promoting neural regeneration of hippocampal tissue. PMID:24642369

  8. Maize Prolamins Could Induce a Gluten-Like Cellular Immune Response in Some Celiac Disease Patients

    PubMed Central

    Ortiz-Sánchez, Juan P.; Cabrera-Chávez, Francisco; Calderón de la Barca, Ana M.

    2013-01-01

    Celiac disease (CD) is an autoimmune-mediated enteropathy triggered by dietary gluten in genetically prone individuals. The current treatment for CD is a strict lifelong gluten-free diet. However, in some CD patients following a strict gluten-free diet, the symptoms do not remit. These cases may be refractory CD or due to gluten contamination; however, the lack of response could be related to other dietary ingredients, such as maize, which is one of the most common alternatives to wheat used in the gluten-free diet. In some CD patients, as a rare event, peptides from maize prolamins could induce a celiac-like immune response by similar or alternative pathogenic mechanisms to those used by wheat gluten peptides. This is supported by several shared features between wheat and maize prolamins and by some experimental results. Given that gluten peptides induce an immune response of the intestinal mucosa both in vivo and in vitro, peptides from maize prolamins could also be tested to determine whether they also induce a cellular immune response. Hypothetically, maize prolamins could be harmful for a very limited subgroup of CD patients, especially those that are non-responsive, and if it is confirmed, they should follow, in addition to a gluten-free, a maize-free diet. PMID:24152750

  9. Loss of Polo ameliorates APP-induced Alzheimer's disease-like symptoms in Drosophila.

    PubMed

    Peng, Fei; Zhao, Yu; Huang, Xirui; Chen, Changyan; Sun, Lili; Zhuang, Luming; Xue, Lei

    2015-01-01

    The amyloid precursor protein (APP) has been implicated in the pathogenesis of Alzheimer's disease (AD). Despite extensive studies, little is known about the regulation of APP's functions in vivo. Here we report that expression of human APP in Drosophila, in the same temporal-spatial pattern as its homolog APPL, induced morphological defects in wings and larval NMJ, larva and adult locomotion dysfunctions, male choice disorder and lifespan shortening. To identify additional genes that modulate APP functions, we performed a genetic screen and found that loss of Polo, a key regulator of cell cycle, partially suppressed APP-induced morphological and behavioral defects in larval and adult stages. Finally, we showed that eye-specific expression of APP induced retina degeneration and cell cycle re-entry, both phenotypes were mildly ameliorated by loss of Polo. These results suggest Polo is an important in vivo regulator of the pathological functions of APP, and provide insight into the role of cell cycle re-entry in AD pathogenesis. PMID:26597721

  10. Loss of Polo ameliorates APP-induced Alzheimer’s disease-like symptoms in Drosophila

    PubMed Central

    Peng, Fei; Zhao, Yu; Huang, Xirui; Chen, Changyan; Sun, Lili; Zhuang, Luming; Xue, Lei

    2015-01-01

    The amyloid precursor protein (APP) has been implicated in the pathogenesis of Alzheimer’s disease (AD). Despite extensive studies, little is known about the regulation of APP’s functions in vivo. Here we report that expression of human APP in Drosophila, in the same temporal-spatial pattern as its homolog APPL, induced morphological defects in wings and larval NMJ, larva and adult locomotion dysfunctions, male choice disorder and lifespan shortening. To identify additional genes that modulate APP functions, we performed a genetic screen and found that loss of Polo, a key regulator of cell cycle, partially suppressed APP-induced morphological and behavioral defects in larval and adult stages. Finally, we showed that eye-specific expression of APP induced retina degeneration and cell cycle re-entry, both phenotypes were mildly ameliorated by loss of Polo. These results suggest Polo is an important in vivo regulator of the pathological functions of APP, and provide insight into the role of cell cycle re-entry in AD pathogenesis. PMID:26597721

  11. Bone Turnover Markers Correlate with Implant fixation in a Rat Model Using LPS Doped Particles to Induced Implant Loosening1

    PubMed Central

    Liu, Shuo; Virdi, Amarjit S.; Sena, Kotaro; Hughes, W. Frank; Sumner, Dale R.

    2011-01-01

    Revision surgery for particle-induced implant loosening in total joint replacement is expected to increase dramatically over the next few decades. This study was designed to investigate if local tissue and serum markers of bone remodeling reflect implant fixation following administration of lipopolysaccharide (LPS)-doped polyethylene (PE) particles in a rat model. 24 rats received bilateral implantation of intramedullary titanium rods in the distal femur, followed by weekly bilateral intra-articular injection of either LPS-doped PE particles (n = 12) or vehicle which contained no particles (n= 12) for 12 weeks. The group in which the particles were injected had increased serum C-terminal telopeptide of type I collagen, decreased serum osteocalcin, increased peri-implant eroded surface, decreased peri-implant bone volume, and decreased mechanical pull-out strength compared to the controls. Implant fixation strength was positively correlated with peri-implant bone volume and serum osteocalcin and inversely correlated with serum C-terminal telopeptide of type I collagen, while energy to yield was positively correlated with serum osteocalcin and inversely correlated with the number of tartrate resistant acid phosphatase positive cells at the interface and the amount of peri-implant eroded surface. There was no effect on trabecular bone volume at a remote site. Thus, the particle-induced impaired fixation in this rat model was directly associated with local and serum markers of elevated bone resorption and depressed bone formation, supporting the rationale of exploring both anti-catabolic and anabolic strategies to treat and prevent particle-related implant osteolysis and loosening and indicating that serum markers may prove useful in tracking implant fixation. PMID:22275163

  12. Inhibition of titanium-particle-induced inflammatory osteolysis after local administration of dopamine and suppression of osteoclastogenesis via D2-like receptor signaling pathway.

    PubMed

    Yang, Huilin; Xu, Yaozeng; Zhu, Mo; Gu, Ye; Zhang, Wen; Shao, Hongguo; Wang, Yijun; Ping, Zichuan; Hu, Xuanyang; Wang, Liangliang; Geng, Dechun

    2016-02-01

    Chronic inflammation and extensive osteoclast formation play critical roles in wear-debris-induced peri-implant osteolysis. We investigated the potential impact of dopamine on titanium-particle-induced inflammatory osteolysis in vivo and in vitro. Twenty-eight C57BL/6J mice were randomly assigned to four groups: sham control (PBS treatment), titanium (titanium/PBS treatment), low- (titanium/2 ?g kg(-1) day(-1) dopamine) and high-dopamine (titanium/10 ?g kg(-1) day(-1) dopamine). After 2 weeks, mouse calvariae were collected for micro-computed tomography (micro-CT) and histomorphometry analysis. Bone-marrow-derived macrophages (BMMs) were isolated to assess osteoclast differentiation. Dopamine significantly reduced titanium-particle-induced osteolysis compared with the titanium group as confirmed by micro-CT and histomorphometric data. Osteoclast numbers were 34.9% and 59.7% (both p < 0.01) lower in the low- and high-dopamine-treatment groups, respectively, than in the titanium group. Additionally, low RANKL, tumor necrosis factor-?, interleukin-1? and interleukin-6 immunochemistry staining were noted in dopamine-treatment groups. Dopamine markedly inhibited osteoclast formation, osteoclastogenesis-related gene expression and pro-inflammatory cytokine expression in BMMs in a dose-dependent manner. Moreover, the resorption area was decreased with 10(-9) M and 10(-8) M dopamine to 40.0% and 14.5% (both p < 0.01), respectively. Furthermore, the inhibitory effect of dopamine was reversed by the D2-like-receptor antagonist haloperidol but not by the D1-like-receptor antagonist SCH23390. These results suggest that dopamine therapy could be developed into an effective and safe method for osteolysis-related disease caused by chronic inflammation and excessive osteoclast formation. PMID:26695376

  13. A comparison of mutations induced by accelerated iron particles versus those induced by low earth orbit space radiation in the FEM-3 gene of Caenorhabditis elegans

    NASA Technical Reports Server (NTRS)

    Hartman, P. S.; Hlavacek, A.; Wilde, H.; Lewicki, D.; Schubert, W.; Kern, R. G.; Kazarians, G. A.; Benton, E. V.; Benton, E. R.; Nelson, G. A.

    2001-01-01

    The fem-3 gene of Caenorhabditis elegans was employed to determine the mutation frequency as well as the nature of mutations induced by low earth orbit space radiation ambient to Space Shuttle flight STS-76. Recovered mutations were compared to those induced by accelerated iron ions generated by the AGS synchrotron accelerator at Brookhaven National Laboratory. For logistical reasons, dauer larvae were prepared at TCU, transported to either Kennedy Space Center or Brookhaven National Laboratory, flown in space or irradiated, returned to TCU and screened for mutants. A total of 25 fem-3 mutants were recovered after the shuttle flight and yielded a mutation frequency of 2.1x10(-5), roughly 3.3-fold higher than the spontaneous rate of 6.3x10(-6). Four of the mutations were homozygous inviable, suggesting that they were large deletions encompassing fem-3 as well as neighboring, essential genes. Southern blot analyses revealed that one of the 25 contained a polymorphism in fem-3, further evidence that space radiation can induce deletions. While no polymorphisms were detected among the iron ion-induced mutations, three of the 15 mutants were homozygous inviable, which is in keeping with previous observations that high LET iron particles generate deficiencies. These data provide evidence, albeit indirect, that an important mutagenic component of ambient space radiation is high LET charged particles such as iron ions.

  14. Direct measurement of the 3-dimensional DNA lesion distribution induced by energetic charged particles in a mouse model tissue

    PubMed Central

    Mirsch, Johanna; Tommasino, Francesco; Frohns, Antonia; Conrad, Sandro; Durante, Marco; Scholz, Michael; Friedrich, Thomas; Löbrich, Markus

    2015-01-01

    Charged particles are increasingly used in cancer radiotherapy and contribute significantly to the natural radiation risk. The difference in the biological effects of high-energy charged particles compared with X-rays or ?-rays is determined largely by the spatial distribution of their energy deposition events. Part of the energy is deposited in a densely ionizing manner in the inner part of the track, with the remainder spread out more sparsely over the outer track region. Our knowledge about the dose distribution is derived solely from modeling approaches and physical measurements in inorganic material. Here we exploited the exceptional sensitivity of ?H2AX foci technology and quantified the spatial distribution of DNA lesions induced by charged particles in a mouse model tissue. We observed that charged particles damage tissue nonhomogenously, with single cells receiving high doses and many other cells exposed to isolated damage resulting from high-energy secondary electrons. Using calibration experiments, we transformed the 3D lesion distribution into a dose distribution and compared it with predictions from modeling approaches. We obtained a radial dose distribution with sub-micrometer resolution that decreased with increasing distance to the particle path following a 1/r2 dependency. The analysis further revealed the existence of a background dose at larger distances from the particle path arising from overlapping dose deposition events from independent particles. Our study provides, to our knowledge, the first quantification of the spatial dose distribution of charged particles in biologically relevant material, and will serve as a benchmark for biophysical models that predict the biological effects of these particles. PMID:26392532

  15. Methotrexate treatment causes early onset of disease in a mouse model of Ross River virus-induced inflammatory disease through increased monocyte production.

    PubMed

    Taylor, Adam; Sheng, Kuo-Ching; Herrero, Lara J; Chen, Weiqiang; Rulli, Nestor E; Mahalingam, Suresh

    2013-01-01

    Part of the Togaviridae family, alphaviruses, including chikungunya virus (CHIKV), Sindbis virus (SINV) and Ross River virus (RRV), are able to cause significant inflammatory pathologies ranging from arthritis to encephalitis. Following symptomatic infection with arthritis-associated alphaviruses, patients often experience severe joint pain, affecting distal and small joints, which can last six months or longer. Recently, methotrexate (MTX), a disease modifying anti-rheumatic drug (DMARD), was used to treat patients experiencing chronic rheumatic symptoms following infection with CHIKV. Here, the effect of MTX on Ross River virus disease (RRVD) in mice was examined to better understand its therapeutic potential for alphaviral-induced musculoskeletal disease and to further our knowledge of the development of alphaviral pathologies. Using a mouse model, we analyzed the effect of MTX on RRVD. RRV disease pathogenesis in response to MTX treatment was determined by measuring levels of proinflammatory factors, cellular infiltrates, viral titer and histological analysis of infected tissues. RRV-infected mice receiving MTX treatment rapidly developed musculoskeletal disease, which correlated with a significant influx of inflammatory cell infiltrates into the skeletal muscle tissue. Although no difference was observed in the level of proinflammatory cytokines and chemokines, the viral load increased at early time points post infection in the serum and quadriceps of MTX treated mice, possibly contributing to disease pathogenesis. Results suggest that MTX treatment of acute RRVD in mice provides no therapeutic benefit and underline the importance of inflammatory monocytes in alphaviral induced arthritides. PMID:23951095

  16. Field-Induced Breakup of Emulsion Droplets Stabilized by Colloidal Particles

    E-print Network

    E. Grace Kim; Kevin Stratford; Paul S. Clegg; Michael E. Cates

    2012-03-02

    We simulate the response of a particle-stabilized emulsion droplet in an external force field, such as gravity, acting equally on all $N$ particles. We show that the field strength required for breakup (at fixed initial area fraction) decreases markedly with droplet size, because the forces act cumulatively, not individually, to detach the interfacial particles. The breakup mode involves the collective destabilization of a solidified particle raft occupying the lower part of the droplet, leading to a critical force per particle that scales approximately as $N^{-1/2}$.

  17. Differential proinflammatory responses induced by diesel exhaust particles with contrasting PAH and metal content.

    PubMed

    Totlandsdal, Annike I; Låg, Marit; Lilleaas, Edel; Cassee, Flemming; Schwarze, Per

    2015-02-01

    Exposure to diesel engine exhaust particles (DEPs), representing a complex and variable mixture of components, has been linked with cellular production and release of several types of mediators related to pulmonary inflammation. A key challenge is to identify the specific components, which may be responsible for these effects. The aim of this study was to compare the proinflammatory potential of two DEP-samples with contrasting contents of polycyclic aromatic hydrocarbons (PAHs) and metals. The DEP-samples were compared with respect to their ability to induce cytotoxicity, expression and release of proinflammatory mediators (IL-6, IL-8), activation of mitogen-activated protein kinases (MAPKs) and expression of CYP1A1 and heme oxygenase-1 (HO-1) in human bronchial epithelial (BEAS-2B) cells. In addition, dithiothreitol and ascorbic acid assays were performed in order to examine the oxidative potential of the PM samples. The DEP-sample with the highest PAH and lowest metal content was more potent with respect to cytotoxicity and expression and release of proinflammatory mediators, CYP1A1 and HO-1 expression and MAPK activation, than the DEP-sample with lower PAH and higher metal content. The DEP-sample with the highest PAH and lowest metal content also possessed a greater oxidative potential. The present results indicate that the content of organic components may be determinant for the proinflammatory effects of DEP. The findings underscore the importance of considering the chemical composition of particulate matter-emissions, when evaluating the potential health impact and implementation of air pollution regulations. PMID:23900936

  18. Search for neutrino-induced particle showers with IceCube-40

    NASA Astrophysics Data System (ADS)

    Aartsen, M. G.; Abbasi, R.; Ackermann, M.; Adams, J.; Aguilar, J. A.; Ahlers, M.; Altmann, D.; Arguelles, C.; Arlen, T. C.; Auffenberg, J.; Bai, X.; Baker, M.; Barwick, S. W.; Baum, V.; Bay, R.; Beatty, J. J.; Becker Tjus, J.; Becker, K.-H.; BenZvi, S.; Berghaus, P.; Berley, D.; Bernardini, E.; Bernhard, A.; Besson, D. Z.; Binder, G.; Bindig, D.; Bissok, M.; Blaufuss, E.; Blumenthal, J.; Boersma, D. J.; Bohm, C.; Bose, D.; Böser, S.; Botner, O.; Brayeur, L.; Bretz, H.-P.; Brown, A. M.; Bruijn, R.; Casey, J.; Casier, M.; Chirkin, D.; Christov, A.; Christy, B.; Clark, K.; Classen, L.; Clevermann, F.; Coenders, S.; Cohen, S.; Cowen, D. F.; Cruz Silva, A. H.; Danninger, M.; Daughhetee, J.; Davis, J. C.; Day, M.; de André, J. P. A. M.; De Clercq, C.; De Ridder, S.; Desiati, P.; de Vries, K. D.; de With, M.; DeYoung, T.; Díaz-Vélez, J. C.; Dunkman, M.; Eagan, R.; Eberhardt, B.; Eichmann, B.; Eisch, J.; Euler, S.; Evenson, P. A.; Fadiran, O.; Fazely, A. R.; Fedynitch, A.; Feintzeig, J.; Feusels, T.; Filimonov, K.; Finley, C.; Fischer-Wasels, T.; Flis, S.; Franckowiak, A.; Frantzen, K.; Fuchs, T.; Gaisser, T. K.; Gallagher, J.; Gerhardt, L.; Gladstone, L.; Glüsenkamp, T.; Goldschmidt, A.; Golup, G.; Gonzalez, J. G.; Goodman, J. A.; Góra, D.; Grandmont, D. T.; Grant, D.; Gretskov, P.; Groh, J. C.; Groß, A.; Ha, C.; Haj Ismail, A.; Hallen, P.; Hallgren, A.; Halzen, F.; Hanson, K.; Hebecker, D.; Heereman, D.; Heinen, D.; Helbing, K.; Hellauer, R.; Hickford, S.; Hill, G. C.; Hoffman, K. D.; Hoffmann, R.; Homeier, A.; Hoshina, K.; Huang, F.; Huelsnitz, W.; Hulth, P. O.; Hultqvist, K.; Hussain, S.; Ishihara, A.; Jacobi, E.; Jacobsen, J.; Jagielski, K.; Japaridze, G. S.; Jero, K.; Jlelati, O.; Kaminsky, B.; Kappes, A.; Karg, T.; Karle, A.; Kauer, M.; Kelley, J. L.; Kiryluk, J.; Kläs, J.; Klein, S. R.; Köhne, J.-H.; Kohnen, G.; Kolanoski, H.; Köpke, L.; Kopper, C.; Kopper, S.; Koskinen, D. J.; Kowalski, M.; Krasberg, M.; Kriesten, A.; Krings, K.; Kroll, G.; Kunnen, J.; Kurahashi, N.; Kuwabara, T.; Labare, M.; Landsman, H.; Larson, M. J.; Lesiak-Bzdak, M.; Leuermann, M.; Leute, J.; Lünemann, J.; Macías, O.; Madsen, J.; Maggi, G.; Maruyama, R.; Mase, K.; Matis, H. S.; McNally, F.; Meagher, K.; Merck, M.; Meures, T.; Miarecki, S.; Middell, E.; Milke, N.; Miller, J.; Mohrmann, L.; Montaruli, T.; Morse, R.; Nahnhauer, R.; Naumann, U.; Niederhausen, H.; Nowicki, S. C.; Nygren, D. R.; Obertacke, A.; Odrowski, S.; Olivas, A.; Omairat, A.; O'Murchadha, A.; Palczewski, T.; Paul, L.; Pepper, J. A.; Pérez de los Heros, C.; Pfendner, C.; Pieloth, D.; Pinat, E.; Posselt, J.; Price, P. B.; Przybylski, G. T.; Quinnan, M.; Rädel, L.; Rameez, M.; Rawlins, K.; Redl, P.; Reimann, R.; Resconi, E.; Rhode, W.; Ribordy, M.; Richman, M.; Riedel, B.; Robertson, S.; Rodrigues, J. P.; Rott, C.; Ruhe, T.; Ruzybayev, B.; Ryckbosch, D.; Saba, S. M.; Sander, H.-G.; Santander, M.; Sarkar, S.; Schatto, K.; Scheriau, F.; Schmidt, T.; Schmitz, M.; Schoenen, S.; Schöneberg, S.; Schönwald, A.; Schukraft, A.; Schulte, L.; Schulz, O.; Seckel, D.; Sestayo, Y.; Seunarine, S.; Shanidze, R.; Sheremata, C.; Smith, M. W. E.; Soldin, D.; Spiczak, G. M.; Spiering, C.; Stamatikos, M.; Stanev, T.; Stanisha, N. A.; Stasik, A.; Stezelberger, T.; Stokstad, R. G.; Stößl, A.; Strahler, E. A.; Ström, R.; Strotjohann, N. L.; Sullivan, G. W.; Taavola, H.; Taboada, I.; Tamburro, A.; Tepe, A.; Ter-Antonyan, S.; Teši?, G.; Tilav, S.; Toale, P. A.; Tobin, M. N.; Toscano, S.; Tselengidou, M.; Unger, E.; Usner, M.; Vallecorsa, S.; van Eijndhoven, N.; Van Overloop, A.; van Santen, J.; Vehring, M.; Voge, M.; Vraeghe, M.; Walck, C.; Waldenmaier, T.; Wallraff, M.; Weaver, Ch.; Wellons, M.; Wendt, C.; Westerhoff, S.; Whelan, B.; Whitehorn, N.; Wiebe, K.; Wiebusch, C. H.; Williams, D. R.; Wissing, H.; Wolf, M.; Wood, T. R.; Woschnagg, K.; Xu, D. L.; Xu, X. W.; Yanez, J. P.; Yodh, G.; Yoshida, S.; Zarzhitsky, P.; Ziemann, J.; Zierke, S.; Zoll, M.; IceCube Collaboration

    2014-05-01

    We report on the search for neutrino-induced particle showers, so-called cascades, in the IceCube-40 detector. The data for this search were collected between April 2008 and May 2009 when the first 40 IceCube strings were deployed and operational. Three complementary searches were performed, each optimized for different energy regimes. The analysis with the lowest energy threshold (2 TeV) targeted atmospheric neutrinos. A total of 67 events were found, consistent with the expectation of 41 atmospheric muons and 30 atmospheric neutrino events. The two other analyses targeted a harder, astrophysical neutrino flux. The analysis with an intermediate threshold of 25 TeV leads to the observation of 14 cascadelike events, again consistent with the prediction of 3.0 atmospheric neutrino and 7.7 atmospheric muon events. We hence set an upper limit of E2?lim?7.46×10-8 GeV sr-1 s-1 cm-2 (90% C.L.) on the diffuse flux from astrophysical neutrinos of all neutrino flavors, applicable to the energy range 25 TeV to 5 PeV, assuming an E?-2 spectrum and a neutrino flavor ratio of 1?1?1 at the Earth. The third analysis utilized a larger and optimized sample of atmospheric muon background simulation, leading to a higher energy threshold of 100 TeV. Three events were found over a background prediction of 0.04 atmospheric muon events and 0.21 events from the flux of conventional and prompt atmospheric neutrinos. Including systematic errors this corresponds to a 2.7? excess with respect to the background-only hypothesis. Our observation of neutrino event candidates above 100 TeV complements IceCube's recently observed evidence for high-energy astrophysical neutrinos.

  19. Energetic-particle-induced electromagnetic geodesic acoustic mode in tokamak plasmas

    SciTech Connect

    Wang, Lingfeng He, Zhixiong; He, Hongda; Shen, Y.; Dong, J. Q.

    2014-07-15

    Energetic-particle-induced kinetic electromagnetic geodesic acoustic modes (EKEGAMs) are numerically studied in low ? (=plasma pressure/magnetic pressure) tokamak plasmas. The parallel component of the perturbed vector potential is considered along with the electrostatic potential perturbation. The effects of finite Larmor radius and finite orbit width of the bulk and energetic ions as well as electron parallel dynamics are all taken into account in the dispersion relation. Systematic harmonic and ordering analysis are performed for frequency and growth rate spectra of the EKEGAMs, assuming (k?{sub i})?q{sup ?3}???1, where q, k, and ?{sub i} are the safety factor, radial component of the EKEGAMs wave vector, and the Larmor radius of the ions, respectively. It is found that there exist critical ?{sub h}/?{sub i} values, which depend, in particular, on pitch angle of energetic ions and safety factor, for the mode to be driven unstable. The EKEGAMs may also be unstable for pitch angle ?{sub 0}B<0.4 in certain parameter regions. Finite ? effect of the bulk ions is shown to have damping effect on the EKEGAMs. Modes with higher radial wave vectors have higher growth rates. The damping from electron dynamics is found decreasing with decrease of the temperature ratio T{sub e}/T{sub i}. The modes are easily to be driven unstable in low safety factor q region and high temperature ratio T{sub h}/T{sub i} region. The harmonic features of the EKEGAMs are discussed as well.

  20. Role of Exopolysaccharide in Aggregatibacter actinomycetemcomitans–Induced Bone Resorption in a Rat Model for Periodontal Disease

    PubMed Central

    Shanmugam, Mayilvahanan; Gopal, Prerna; El Abbar, Faiha; Schreiner, Helen C.; Kaplan, Jeffrey B.; Fine, Daniel H.; Ramasubbu, Narayanan

    2015-01-01

    Aggregatibacter actinomycetemcomitans a causative agent of periodontal disease in humans, forms biofilm on biotic and abiotic surfaces. A. actinomycetemcomitans biofilm is heterogeneous in nature and is composed of proteins, extracellular DNA and exopolysaccharide. To explore the role played by the exopolysaccharide in the colonization and disease progression, we employed genetic reduction approach using our rat model of A. actinomycetemcomitans-induced periodontitis. To this end, a genetically modified strain of A. actinomycetemcomitans lacking the pga operon was compared with the wild-type strain in the rat infection model. The parent and mutant strains were primarily evaluated for bone resorption and disease. Our study showed that colonization, bone resorption/disease and antibody response were all elevated in the wild-type fed rats. The bone resorption/disease caused by the pga mutant strain, lacking the exopolysaccharide, was significantly less (P < 0.05) than the bone resorption/disease caused by the wild-type strain. Further analysis of the expression levels of selected virulence genes through RT-PCR showed that the decrease in colonization, bone resorption and antibody titer in the absence of the exopolysaccharide might be due to attenuated levels of colonization genes, flp-1, apiA and aae in the mutant strain. This study demonstrates that the effect exerted by the exopolysaccharide in A. actinomycetemcomitans-induced bone resorption has hitherto not been recognized and underscores the role played by the exopolysaccharide in A. actinomycetemcomitans-induced disease. PMID:25706999

  1. Trophic cascades following the disease-induced decline of an apex predator, the Tasmanian devil.

    PubMed

    Hollings, Tracey; Jones, Menna; Mooney, Nick; McCallum, Hamish

    2014-02-01

    As apex predators disappear worldwide, there is escalating evidence of their importance in maintaining the integrity and diversity of the ecosystems they inhabit. The largest extant marsupial carnivore, the Tasmanian devil (Sarcophilus harrisii) is threatened with extinction from a transmissible cancer, devil facial tumor disease (DFTD). The disease, first observed in 1996, has led to apparent population declines in excess of 95% in some areas and has spread to more than 80% of their range. We analyzed a long-term Tasmania-wide data set derived from wildlife spotlighting surveys to assess the effects of DFTD-induced devil decline on populations of other mammals and to examine the relative strength of top-down and bottom-up control of mesopredators between 2 regions with different environmental conditions. Collection of the data began >10 years before DFTD was first observed. A decrease in devil populations was immediate across diseased regions following DFTD arrival, and there has been no indication of population recovery. Feral cats (Felis catus) increased in areas where the disease was present the longest, and feral cat occurrence was significantly and negatively associated with devils. The smallest mesopredator, the eastern quoll (Dasyurus viverrinus), declined rapidly following DFTD arrival. This result suggests the species was indirectly protected by devils through the suppression of larger predators. Rainfall deficiency was also a significant predictor of their decline. Environmental variables determined the relative importance of top-down control in the population regulation of mesopredators. In landscapes of low rainfall and relatively higher proportions of agriculture and human settlement, top-down forces were dampened and bottom-up forces had the most effect on mesopredators. For herbivore prey species, there was evidence of population differences after DFTD arrival, but undetected environmental factors had greater effects. The unique opportunity to assess population changes over extensive temporal and spatial scales following apex predator loss further demonstrated their role in structuring ecosystems and of productivity in determining the strength of top-down control. PMID:24024987

  2. Cardiac disease modeling using induced pluripotent stem cell-derived human cardiomyocytes

    PubMed Central

    Dell’Era, Patrizia; Benzoni, Patrizia; Crescini, Elisabetta; Valle, Matteo; Xia, Er; Consiglio, Antonella; Memo, Maurizio

    2015-01-01

    Causative mutations and variants associated with cardiac diseases have been found in genes encoding cardiac ion channels, accessory proteins, cytoskeletal components, junctional proteins, and signaling molecules. In most cases the functional evaluation of the genetic alteration has been carried out by expressing the mutated proteins in in-vitro heterologous systems. While these studies have provided a wealth of functional details that have greatly enhanced the understanding of the pathological mechanisms, it has always been clear that heterologous expression of the mutant protein bears the intrinsic limitation of the lack of a proper intracellular environment and the lack of pathological remodeling. The results obtained from the application of the next generation sequencing technique to patients suffering from cardiac diseases have identified several loci, mostly in non-coding DNA regions, which still await functional analysis. The isolation and culture of human embryonic stem cells has initially provided a constant source of cells from which cardiomyocytes (CMs) can be obtained by differentiation. Furthermore, the possibility to reprogram cellular fate to a pluripotent state, has opened this process to the study of genetic diseases. Thus induced pluripotent stem cells (iPSCs) represent a completely new cellular model that overcomes the limitations of heterologous studies. Importantly, due to the possibility to keep spontaneously beating CMs in culture for several months, during which they show a certain degree of maturation/aging, this approach will also provide a system in which to address the effect of long-term expression of the mutated proteins or any other DNA mutation, in terms of electrophysiological remodeling. Moreover, since iPSC preserve the entire patients’ genetic context, the system will help the physicians in identifying the most appropriate pharmacological intervention to correct the functional alteration. This article summarizes the current knowledge of cardiac genetic diseases modelled with iPSC. PMID:25815118

  3. Neuroprotective effect of physical exercise in a mouse model of Alzheimer's disease induced by ?-amyloid???? peptide.

    PubMed

    Souza, Leandro C; Filho, Carlos B; Goes, André T R; Fabbro, Lucian Del; de Gomes, Marcelo G; Savegnago, Lucielli; Oliveira, Mauro Schneider; Jesse, Cristiano R

    2013-08-01

    This study was designed to investigate the potential neuroprotective effect of exercise in a mouse model of Alzheimer's disease (AD) induced by intracerebroventricular (i.c.v.) injection of beta-amyloid???? (A?????) peptide. For this aim, male Swiss Albino mice were submitted to swimming training (ST) with progressive increase in intensity and duration for 8 weeks before A????? administration (400 pmol/animal; 3 ?l/site, i.c.v. route). The cognitive behavioral, oxidative stress, and neuroinflammatory markers in hippocampus and prefrontal cortex of mice were assessed 7 days after A????? administration. Our results demonstrated that ST was effective in preventing impairment in short- and long-term memories in the object recognition test. ST attenuated the increased levels of reactive species and decreased non-protein thiol levels in hippocampus and prefrontal cortex induced by A?????. Also, A????? inhibited superoxide dismutase activity and increased glutathione peroxidase, glutathione reductase, and glutathione S-transferase activities in hippocampus and prefrontal cortex-alterations that were mitigated by ST. In addition, ST was effective against the increase of tumor necrosis factor-alpha and interleukin-1 beta levels and the decrease of interleukin-10 levels in hippocampus and prefrontal cortex. This study confirmed the hypothesis that exercise is able to protect against some mechanisms of A?????-induced neurotoxicity. In conclusion, we suggest that exercise can prevent the cognitive decline, oxidative stress, and neuroinflammation induced by A????? in mice supporting the hypothesis that exercise can be used as a non-pharmacological tool to reduce the symptoms of AD. PMID:23307759

  4. Designing experimental setup and procedures for studying alpha-particle-induced adaptive response in zebrafish embryos in vivo

    E-print Network

    Yu, Peter K.N.

    in zebrafish embryos in vivo V.W.Y. Choi a , R.K.K. Lam a , E.Y.W. Chong a , S.H. Cheng b , K.N. Yu a track detector PADC Biological effects Adaptive response Zebrafish embryos a b s t r a c t The present-particle-induced adaptive response in zebrafish embryos in vivo. Thin PADC films with a thickness of 16 lm were fabricated

  5. Low doses of alpha particles do not induce sister chromatid exchanges in bystander Chinese hamster cells defective in homologous recombination

    SciTech Connect

    Nagasawa, H; Wilson, P F; Chen, D J; Thompson, L H; Bedford, J S; Little, J B

    2007-10-26

    We reported previously that the homologous recombinational repair (HRR)-deficient Chinese hamster mutant cell line irs3 (deficient in the Rad51 paralog Rad51C) showed only a 50% spontaneous frequency of sister chromatid exchange (SCE) as compared to parental wild-type V79 cells. Furthermore, when irradiated with very low doses of alpha particles, SCEs were not induced in irs3 cells, as compared to a prominent bystander effect observed in V79 cells (Nagasawa et al., Radiat. Res. 164, 141-147, 2005). In the present study, we examined additional Chinese hamster cell lines deficient in the Rad51 paralogs Rad51C, Rad51D, Xrcc2, and Xrcc3 as well as another essential HRR protein, Brca2. Spontaneous SCE frequencies in non-irradiated wild-type cell lines CHO, AA8 and V79 were 0.33 SCE/chromosome, whereas two Rad51C-deficient cell lines showed only 0.16 SCE/chromosome. Spontaneous SCE frequencies in cell lines defective in Rad51D, Xrcc2, Xrcc3, and Brca2 ranged from 0.23-0.33 SCE/chromosome, 0-30% lower than wild-type cells. SCEs were induced significantly 20-50% above spontaneous levels in wild-type cells exposed to a mean dose of 1.3 mGy of alpha particles (<1% of nuclei traversed by an alpha particle). However, induction of SCEs above spontaneous levels was minimal or absent after {alpha}-particle irradiation in all of the HRR-deficient cell lines. These data suggest that Brca2 and the Rad51 paralogs contribute to DNA damage repair processes induced in bystander cells (presumably oxidative damage repair in S-phase cells) following irradiation with very low doses of alpha particles.

  6. COX-2 expression induced by diesel particles involves chromatin modification and degradation of HDAC1

    EPA Science Inventory

    Cyclooxygenase-2 (COX-2) plays an important role in the inflammatory response induced by physiologic and stress stimuli. Exposure to diesel exhaust particulate matter (DEP) has been shown to induce pulmonary inflammation and exacerbate asthma and chronic obstructive pulmonary dis...

  7. Tau missorting and spastin-induced microtubule disruption in neurodegeneration: Alzheimer Disease and Hereditary Spastic Paraplegia.

    PubMed

    Zempel, Hans; Mandelkow, Eva-Maria

    2015-01-01

    In Alzheimer Disease (AD), the mechanistic connection of the two major pathological hallmarks, namely deposition of Amyloid-beta (A?) in the form of extracellular plaques, and the pathological changes of the intracellular protein Tau (such as phosphorylation, missorting, aggregation), is not well understood. Genetic evidence from AD and Down Syndrome (Trisomy 21), and animal models thereof, suggests that aberrant production of A? is upstream of Tau aggregation, but also points to Tau as a critical effector in the pathological process. Yet, the cascade of events leading from increased levels of A? to Tau-dependent toxicity remains a matter of debate.Using primary neurons exposed to oligomeric forms of A?, we have found that Tau becomes mislocalized (missorted) into the somatodendritic compartment. Missorting of Tau correlates with loss of microtubules and downstream consequences such as loss of mature spines, loss of synaptic activity, and mislocalization of mitochondria.In this cascade, missorting of Tau induces mislocalization of TTLL6 (Tubulin-Tyrosine-Ligase-Like 6) into the dendrites. TTLL6 induces polyglutamylation of microtubules, which acts as a trigger for spastin mediated severing of dendritic microtubules. Loss of microtubules makes cells unable to maintain transport of mitochondria, which in turn results in synaptic dysfunction and loss of mature spines. These pathological changes are absent in TauKO derived primary neurons. Thus, Tau mediated mislocalization of TTLL6 and spastin activation reveals a pathological gain of function for Tau and spastin in this cellular model system of AD.In contrast, in hereditary spastic paraplegia (HSP) caused by mutations of the gene encoding spastin (spg4 alias SPAST), spastin function in terms of microtubule severing is decreased at least for the gene product of the mutated allele, resulting in overstable microtubules in disease model systems. Whether total spastin severing activity or microtubule stability in human disease is also affected is not yet clear. No human disease has been associated so far with the long-chain polyglutamylation enzyme TTLL6, or the other TTLLs (1,5,11) possibly involved.Here we review the findings supporting a role for Tau, spastin and TTLL6 in AD and other tauopathies, HSP and neurodegeneration, and summarize possible therapeutic approaches for AD and HSP. PMID:26691836

  8. Unconventional Maturation of Dendritic Cells Induced by Particles from the Laminated Layer of Larval Echinococcus granulosus

    PubMed Central

    Casaravilla, Cecilia; Pittini, Álvaro; Rückerl, Dominik; Seoane, Paula I.; Jenkins, Stephen J.; MacDonald, Andrew S.; Ferreira, Ana M.; Allen, Judith E.

    2014-01-01

    The larval stage of the cestode parasite Echinococcus granulosus causes hydatid disease in humans and livestock. This infection is characterized by the growth in internal organ parenchymae of fluid-filled structures (hydatids) that elicit surprisingly little inflammation in spite of their massive size and persistence. Hydatids are protected by a millimeter-thick layer of mucin-based extracellular matrix, termed the laminated layer (LL), which is thought to be a major factor determining the host response to the infection. Host cells can interact both with the LL surface and with materials that are shed from it to allow parasite growth. In this work, we analyzed the response of dendritic cells (DCs) to microscopic pieces of the native mucin-based gel of the LL (pLL). In vitro, this material induced an unusual activation state characterized by upregulation of CD86 without concomitant upregulation of CD40 or secretion of cytokines (interleukin 12 [IL-12], IL-10, tumor necrosis factor alpha [TNF-?], and IL-6). When added to Toll-like receptor (TLR) agonists, pLL-potentiated CD86 upregulation and IL-10 secretion while inhibiting CD40 upregulation and IL-12 secretion. In vivo, pLL also caused upregulation of CD86 and inhibited CD40 upregulation in DCs. Contrary to expectations, oxidation of the mucin glycans in pLL with periodate did not abrogate the effects on cells. Reduction of disulfide bonds, which are known to be important for LL structure, strongly diminished the impact of pLL on DCs without altering the particulate nature of the material. In summary, DCs respond to the LL mucin meshwork with a “semimature” activation phenotype, both in vitro and in vivo. PMID:24842926

  9. HN Protein of Newcastle Disease Virus Induces Apoptosis Through SAPK/JNK Pathway.

    PubMed

    Rajmani, R S; Gandham, Ravi Kumar; Gupta, Shishir Kumar; Sahoo, A P; Singh, Prafull Kumar; Kumar, Rajiv; Saxena, Shikha; Chaturvedi, Uttara; Tiwari, Ashok K

    2015-10-01

    Many viral proteins are responsible for causing induction of apoptosis in the target cells. Hemagglutinin neuraminidase (HN), a multifunctional protein of Newcastle disease virus (NDV), is one of such proteins. The present study was undertaken to determine the apoptotic potential of the HN gene in cultured human cervical cancer cell line (HeLa cell) and to elucidate the molecular mechanisms involved. The results of the study indicate that HN protein causes apoptosis in HeLa cells, as observed by the translocation of Phosphatidylserine, activation of caspases, cleavage of poly (ADP-ribose) polymerase (PARP), and DNA fragmentation. Further, we report that expression of HN protein upregulates the SAPK/JNK pathway leading to transactivation of c-Jun which in turn activates apoptosis signaling. The results of our study provide an insight into the mechanism through which HN induces apoptosis. PMID:26306526

  10. Rituximab-induced interstitial lung disease in a patient with follicular lymphoma: A rare case report

    PubMed Central

    Aagre, Suhas; Patel, Apurva; Kendre, Pradip; Anand, Asha

    2015-01-01

    Rituximab is a chimeric monoclonal antibody that targets CD-20 antigen expressed in more than 90% of all B cell non-Hodgkin's lymphoma (NHL). We report a case of 33-year-old female without any comorbidities, newly diagnosed with stage IIIB follicular lymphoma treated with rituximab-based chemotherapy. Patient developed exertional dyspnea and dry cough after the fourth cycle of rituximab-based chemotherapy. Diagnostic high-resolution computed tomography (HRCT) of the lungs revealed bilateral patchy ground glass opacities suggestive of interstitial lung disease (ILD). It was managed successfully with supplemental oxygen and corticosteroids with discontinuation of the Rituximab. Extensive review of the literature did not reveal ample of material on rituximab-induced ILD (RTX-ILD).

  11. Probing the secrets of Alzheimer's disease using human-induced pluripotent stem cell technology.

    PubMed

    Goldstein, Lawrence S B; Reyna, Sol; Woodruff, Grace

    2015-01-01

    Our understanding of Alzheimer's disease (AD) is still incomplete and, as a result, we lack effective therapies. Reprogramming to generate human-induced pluripotent stem cells provides a new approach to the generation of human neurons that carry the genomes of people with familial or sporadic AD. Differentiation of such stem cells to human neurons is already providing new insights into AD and molecular pathways that may provide new targets for effective therapy. These pathways include typical amyloid response pathways, as well as pathways leading from altered behavior of amyloid precursor protein to the elevated phosphorylation of tau protein. There is also a need for standardization of models so that isogenic lines differing only in the familial AD mutation can be compared. PMID:25534395

  12. Aggregate-Depleted Brain Fails to Induce A? Deposition in a Mouse Model of Alzheimer's Disease

    PubMed Central

    Duran-Aniotz, Claudia; Morales, Rodrigo; Moreno-Gonzalez, Ines; Hu, Ping Ping; Fedynyshyn, Joseph; Soto, Claudio

    2014-01-01

    Recent studies in animal models of Alzheimer's disease (AD) show that amyloid-beta (A?) misfolding can be transmissible; however, the mechanisms by which this process occurs have not been fully explored. The goal of this study was to analyze whether depletion of aggregates from an AD brain suppresses its in vivo “seeding” capability. Removal of aggregates was performed by using the Aggregate Specific Reagent 1 (ASR1) compound which has been previously described to specifically bind misfolded species. Our results show that pre-treatment with ASR1-coupled magnetic beads reduces the in vivo misfolding inducing capability of an AD brain extract. These findings shed light respect to the active principle responsible for the prion-like spreading of Alzheimer's amyloid pathology and open the possibility of using seeds-capturing reagents as a promising target for AD treatment. PMID:24533166

  13. Animal-induced injuries and disease, neonatal jaundice, immunizations, and viral infections.

    PubMed

    Gerson, W T

    1996-08-01

    Highlights from the past years' literature on the topics of animal-induced injuries and diseases, neonatal jaundice, immunizations, and viral infections are discussed from the perspective of the general pediatrician. An effort is made to place recent advances in care or understanding of clinical problems into the context of the pediatric office practice. The current reality of health care-be it managed care, care for the underserved, or the recent pressures on academic and hospital-based medicine-does not alter the importance of the delivery of quality care at the office level. Although it is now popular to define quality of health care in cute advertising copy, as if we are selling durable goods, excellence in pediatric office-based practice continues to require broad strokes of medical knowledge coupled with a unswerving commitment to and advocacy for the needs and well-being of infants, children, and young adults. PMID:8954278

  14. Boundary deformation induced by the inhomogeneous redistribution of enclosed active particles

    E-print Network

    Wen-de Tian; Kang Chen; Yu-qiang Ma

    2015-11-27

    We simulate a two dimensional model of self-propelled particles confined by a deformable boundary. The particles tend to accumulate near the boundary and the shape of the boundary deforms upon the collisions. We find that there are two typical stages in the variation of the morphology with the increase of active force. One is at small force characterized by radially inhomogeneous redistribution of particles and suppression of local fluctuations of the boundary. The other is at large force featured by angularly redistribution of particles and global shape deformation of the boundary. The last two processes are strongly cooperative. We also find different mechanisms in the particle redistribution and opposite force-dependences of the rate of the shape variation at low and high particle concentrations.

  15. The TIM-3 pathway ameliorates Theiler's murine encephalomyelitis virus-induced demyelinating disease.

    PubMed

    Kaneyama, Tomoki; Tomiki, Hiroki; Tsugane, Sayaka; Inaba, Yuji; Ichikawa, Motoki; Akiba, Hisaya; Yagita, Hideo; Kim, Byung S; Koh, Chang-Sung

    2014-07-01

    Infection by Theiler's murine encephalomyelitis virus (TMEV) in the central nervous system (CNS) induces an immune-mediated demyelinating disease in susceptible mouse strains and serves as a relevant infection model for human multiple sclerosis. T-cell immunoglobulin and mucin domain-3 (TIM-3) has been demonstrated to play a crucial role in the maintenance of peripheral tolerance. In this study, we examined the regulatory role of the TIM-3 pathway in the development of TMEV-induced demyelinating disease (TMEV-IDD). The expression of TIM-3 was increased at both protein and mRNA levels in the spinal cords of mice with TMEV-IDD compared with naive controls. In addition, by utilizing a blocking mAb, we demonstrate that TIM-3 negatively regulates TMEV-specific ex vivo production of IFN-? and IL-10 by CD4(+) T cells and IFN-? by CD8(+) T cells from the CNS of mice with TMEV-IDD at 36 days post-infection (dpi). In vivo blockade of TIM-3 by using the anti-TIM-3 mAb resulted in significant exacerbation of the development of TMEV-IDD both clinically and histologically. The number of infiltrating mononuclear cells in the CNS was also increased in mice administered with anti-TIM-3 mAb both at the induction phase (10 dpi) and at the effector phase (36 dpi). Flow cytometric analysis of intracellular cytokines revealed that the number of CD4(+) T cells producing TNF, IL-4, IL-10 and IL-17 was significantly increased at the effector phase in the CNS of anti-TIM-3 mAb-treated mice. These results suggest that the TIM-3 pathway plays a critical role in the regulation of TMEV-IDD. PMID:24486565

  16. Pramipexole-Induced Increased Probabilistic Discounting: Comparison Between a Rodent Model of Parkinson's Disease and Controls

    PubMed Central

    Rokosik, Sandra L; Napier, T Celeste

    2012-01-01

    The dopamine agonist pramipexole (PPX) can increase impulsiveness, and PPX therapy for neurological diseases (Parkinson's disease (PD) and restless leg syndrome) is associated with impulse control disorders (ICDs) in subpopulations of treated patients. A commonly reported ICD is pathological gambling of which risk taking is a prominent feature. Probability discounting is a measurable aspect of risk taking. We recently developed a probability discounting paradigm wherein intracranial self-stimulation (ICSS) serves as the positive reinforcer. Here we used this paradigm to determine the effects of PPX on discounting. We included assessments of a rodent model of PD, wherein 6-OHDA was injected into the dorsolateral striatum of both hemispheres, which produced persistent PD-like deficits in posture adjustment. Rats were trained to perform ICSS-mediated probability discounting, in which PD-like and control groups exhibited similar profiles. Rats were treated twice daily for 2 weeks with 2?mg/kg (±)PPX (ie, 1?mg/kg of the active form), a dose that improved lesion-induced motor deficits. In both groups, (±)PPX increased discounting; preference for the large reinforcer was enhanced 30–45% at the most uncertain probabilities. Tolerance did not develop with repeated treatments. Increased discounting subsided within 2 weeks of (±)PPX cessation, and re-exposure to (±)PPX reinstated heightened discounting. Such findings emulate the clinical scenario; therefore, ICSS for discounting assessments in rats exhibited high face validity. This model should prove useful in medication development where assessment of the propensity of a putative therapy to induce risk-taking behaviors is of interest. PMID:22257895

  17. Characterization of inducible models of Tay-Sachs and related disease.

    PubMed

    Sargeant, Timothy J; Drage, Deborah J; Wang, Susan; Apostolakis, Apostolos A; Cox, Timothy M; Cachón-González, M Begoña

    2012-09-01

    Tay-Sachs and Sandhoff diseases are lethal inborn errors of acid ?-N-acetylhexosaminidase activity, characterized by lysosomal storage of GM2 ganglioside and related glycoconjugates in the nervous system. The molecular events that lead to irreversible neuronal injury accompanied by gliosis are unknown; but gene transfer, when undertaken before neurological signs are manifest, effectively rescues the acute neurodegenerative illness in Hexb-/- (Sandhoff) mice that lack ?-hexosaminidases A and B. To define determinants of therapeutic efficacy and establish a dynamic experimental platform to systematically investigate cellular pathogenesis of GM2 gangliosidosis, we generated two inducible experimental models. Reversible transgenic expression of ?-hexosaminidase directed by two promoters, mouse Hexb and human Synapsin 1 promoters, permitted progression of GM2 gangliosidosis in Sandhoff mice to be modified at pre-defined ages. A single auto-regulatory tetracycline-sensitive expression cassette controlled expression of transgenic Hexb in the brain of Hexb-/- mice and provided long-term rescue from the acute neuronopathic disorder, as well as the accompanying pathological storage of glycoconjugates and gliosis in most parts of the brain. Ultimately, late-onset brainstem and ventral spinal cord pathology occurred and was associated with increased tone in the limbs. Silencing transgenic Hexb expression in five-week-old mice induced stereotypic signs and progression of Sandhoff disease, including tremor, bradykinesia, and hind-limb paralysis. As in germline Hexb-/- mice, these neurodegenerative manifestations advanced rapidly, indicating that the pathogenesis and progression of GM2 gangliosidosis is not influenced by developmental events in the maturing nervous system. PMID:23028353

  18. Enterovirus-71 Virus-Like Particles Induce the Activation and Maturation of Human Monocyte-Derived Dendritic Cells through TLR4 Signaling

    PubMed Central

    Lin, Yu-Li; Hu, Yu-Chen; Liang, Cheng-Chao; Lin, Shih-Yeh; Liang, Yu-Chih; Yuan, Hui-Ping; Chiang, Bor-Luen

    2014-01-01

    Enterovirus 71 (EV71) causes seasonal epidemics of hand-foot-and-mouth disease and has a high mortality rate among young children. We recently demonstrated potent induction of the humoral and cell-mediated immune response in monkeys immunized with EV71 virus-like particles (VLPs), with a morphology resembling that of infectious EV71 virions but not containing a viral genome, which could potentially be safe as a vaccine for EV71. To elucidate the mechanisms through which EV71 VLPs induce cell-mediated immunity, we studied the immunomodulatory effects of EV71 VLPs on human monocyte-derived dendritic cells (DCs), which bind to and incorporate EV71 VLPs. DC treatment with EV71 VLPs enhanced the expression of CD80, CD86, CD83, CD40, CD54, and HLA-DR on the cell surface; increased the production of interleukin (IL)-12 p40, IL-12 p70, and IL-10 by DCs; and suppressed the capacity of DCs for endocytosis. Treatment with EV71 VLPs also enhanced the ability of DCs to stimulate naïve T cells and induced secretion of interferon (IFN)-? by T cells and Th1 cell responses. Neutralization with antibodies against Toll-like receptor (TLR) 4 suppressed the capacity of EV71 VLPs to induce the production of IL-12 p40, IL-12 p70, and IL-10 by DCs and inhibited EV71 VLPs binding to DCs. Our study findings clarified the important role for TLR4 signaling in DCs in response to EV71 VLPs and showed that EV71 VLPs induced inhibitor of kappaB alpha (I?B?) degradation and nuclear factor of kappaB (NF-?B) activation. PMID:25360749

  19. Photoelectric charging of dust particles: Effect of spontaneous and light induced field emission of electrons

    SciTech Connect

    Sodha, M. S.; Dixit, A.

    2009-09-07

    The authors have analyzed the charging of dust particles in a plasma, taking into account the electron/ion currents to the particles, electron/ion generation and recombination, electric field emission, photoelectric emission and photoelectric field emission of electrons under the influence of light irradiation; the irradiance has been assumed to be at a level, which lets the particles retain the negative sign of the charge. Numerical results and discussion conclude the papers.

  20. Numerical investigations of mismatch induced halos in intense charged particle beams

    SciTech Connect

    Papadopoulos, C.; Haber, I.; Kishek, R. A.; O'Shea, P. G.

    2009-01-22

    In this paper, we discuss the parametric resonance model of halo creation, and compare it with self consistent simulation results. In particular, we employ two different initial distribution functions, and we find agreement with the particle-core model, within the limitations of the latter. Furthermore, using a simple particle tracking algorithm, we are able to follow the trajectories of the halo particles, noting that a large number of them go through the core and re-emerge later.

  1. Hydrogen absorption induced metal deposition on palladium and palladium-alloy particles

    DOEpatents

    Wang, Jia X. (East Setauket, NY); Adzic, Radoslav R. (East Setauket, NY)

    2009-03-24

    The present invention relates to methods for producing metal-coated palladium or palladium-alloy particles. The method includes contacting hydrogen-absorbed palladium or palladium-alloy particles with one or more metal salts to produce a sub-monoatomic or monoatomic metal- or metal-alloy coating on the surface of the hydrogen-absorbed palladium or palladium-alloy particles. The invention also relates to methods for producing catalysts and methods for producing electrical energy using the metal-coated palladium or palladium-alloy particles of the present invention.

  2. The Role of Oxidative Stress in Ambient Particulate Matter-induced Lung Diseases and Its Implications in the Toxicity of Engineered Nanoparticles

    PubMed Central

    Li, Ning; Xia, Tian; Nel, Andre E.

    2008-01-01

    Ambient particulate matter (PM) is an environmental factor that has been associated with increased respiratory morbidity and mortality. The major effect of ambient PM on the pulmonary system is the exacerbation of inflammation, especially in susceptible people. One of the mechanisms by which ambient PM exerts its proinflammatory effects is the generation of oxidative stress by its chemical compounds and metals. Cellular responses to PM-induced oxidative stress include activation of antioxidant defense, inflammation, and toxicity. The pro-inflammatory effect of PM in the lung is characterized by increased cytokine/chemokine production and adhesion molecule expression. Moreover, there is evidence that ambient PM can act as an adjuvant for allergic sensitization, which raises the possibility that long-term PM exposure may lead to increased prevalence of asthma. In addition to ambient PM, rapid expansion of nanotechnology has introduced the potential that engineered NP may also become airborne and may contribute to pulmonary diseases by novel mechanisms that could include oxidant injury. Currently, little is known about the potential adverse health effect of these particles. In this communication, the mechanisms by which particulate pollutants, including ambient PM and engineered NP, exert their adverse effects through the generation of oxidative stress and the impacts of oxidant injury in the respiratory tract will be reviewed. The importance of cellular antioxidant and detoxification pathways in protecting against particle-induced lung damage will also be discussed. PMID:18313407

  3. Impaired GAPDH-induced mitophagy contributes to the pathology of Huntington’s disease

    PubMed Central

    Hwang, Sunhee; Disatnik, Marie-Hélène; Mochly-Rosen, Daria

    2015-01-01

    Mitochondrial dysfunction is implicated in multiple neurodegenerative diseases. In order to maintain a healthy population of functional mitochondria in cells, defective mitochondria must be properly eliminated by lysosomal machinery in a process referred to as mitophagy. Here, we uncover a new molecular mechanism underlying mitophagy driven by glyceraldehyde-3-phosphate dehydrogenase (GAPDH) under the pathological condition of Huntington’s disease (HD) caused by expansion of polyglutamine repeats. Expression of expanded polyglutamine tracts catalytically inactivates GAPDH (iGAPDH), which triggers its selective association with damaged mitochondria in several cell culture models of HD. Through this mechanism, iGAPDH serves as a signaling molecule to induce direct engulfment of damaged mitochondria into lysosomes (micro-mitophagy). However, abnormal interaction of mitochondrial GAPDH with long polyglutamine tracts stalled GAPDH-mediated mitophagy, leading to accumulation of damaged mitochondria, and increased cell death. We further demonstrated that overexpression of inactive GAPDH rescues this blunted process and enhances mitochondrial function and cell survival, indicating a role for GAPDH-driven mitophagy in the pathology of HD. PMID:26268247

  4. Drug-induced diseases (DIDs): An experience of a tertiary care teaching hospital from India

    PubMed Central

    Tandon, Vishal R.; Khajuria, Vijay; Mahajan, Vivek; Sharma, Aman; Gillani, Zahid; Mahajan, Annil

    2015-01-01

    Background & objectives: Drug-induced diseases (DIDs) are well known but least studied. Data on DIDs from India are not available. Hence, this retrospective cross-sectional study was undertaken using suspected adverse drug reaction (ADR) data collected form Pharmacovigilance Programme of India (PvPI) to evaluate profile of DIDs over two years, in a tertiary care teaching hospital from north India. Methods: The suspected ADRs in the form of DID were evaluated for drug and disease related variables and were classified in terms of causality. Results: DID rate was 38.80 per cent. Mean duration of developing DIDs was 26.05 ± 9.6 days; 25.16 per cent had more than one co-morbid condition. Geriatric population (53.99%) accounted for maximum DIDs followed by adult (37.79%) and paediatric (8.21%). Maximum events were probable (93.98%) followed by possible (6.04%). All DIDs required intervention. Gastritis (7.43%), diarrhoea (5.92%), anaemia (4.79%), hypotension (2.77%), hepatic dysfunction (2.69%), hypertension (1.51%), myalgia (1.05%), and renal dysfunction (1.01%) were some of the DIDs. Anti tubercular treatment (ATT), anti retroviral treatment (ART), ceftriaxone injection, steroids, non-steroidal anti-inflammatory drugs, antimicrobials and anticancer drugs were found as commonly offending drugs. Interpretation & conclusions: Our findings show that DIDs are a significant health problem in our country, which need more attention. PMID:26261164

  5. Amiodarone-induced hepatic phospholipidosis: a morphological alteration independent of pseudoalcoholic liver disease

    SciTech Connect

    Guigui, B.; Perrot, S.; Berry, J.P.; Fleury-Feith, J.; Martin, N.; Metreau, J.M.; Dhumeaux, D.; Zafrani, E.S.

    1988-09-01

    In order to study the relationship between amiodarone-induced hepatic phospholipidosis and liver disease, liver biopsies obtained from 13 patients treated with amiodarone for 4 months to 15 years were investigated by light and electron microscopy. Light microscopy showed pseudoalcoholic liver lesions that were probably related to amiodarone in four cases, various alterations (i.e. cirrhosis, three cases; steatosis and fibrosis, two cases; chronic venous congestion, one case; acute hepatitis, one case) that could be explained by another cause than amiodarone in seven cases and normal liver in two cases. In all cases, electron microscopy showed intralysosomal myelin figures suggestive of phospholipidosis. These myelin figures were associated with intralysosomal electron-dense deposits. In the four cases in which analysis by electron microprobe was performed, it demonstrated large amounts of iodine in the electron-dense deposit-containing lysosomes, indicating the accumulation of amiodarone. These results show that hepatic phospholipidosis is constantly observed in amiodarone-treated patients, whether or not pseudoalcoholic liver lesions are present. This phospholipidosis, which could be only a morphological marker of intrahepatic accumulation of the drug, should not therefore be considered grounds for attributing liver disease to the drug.

  6. Lipoic acid protects dopaminergic neurons in LPS-induced Parkinson's disease model.

    PubMed

    Li, Yan-Hua; He, Qing; Yu, Jie-zhong; Liu, Chun-yun; Feng, Ling; Chai, Zhi; Wang, Qing; Zhang, Hong-zhen; Zhang, Guang-Xian; Xiao, Bao-guo; Ma, Cun-gen

    2015-10-01

    Parkinson's disease (PD) is a chronic neurodegenerative disease of the central nervous system (CNS), characterized by a loss of dopaminergic neurons, which is thought to be caused by both genetic and environmental factors. Recent findings suggest that neuroinflammation may be a pathogenic factor in the onset and progression of sporadic PD. Here we explore the potential therapeutic effect of lipoic acid (LA) on a lipolysaccharide (LPS)-induced inflammatory PD model. Our results for the first time showed that LA administration improved motor dysfunction, protected dopaminergic neurons loss, and decreased ?-synuclein accumulation in the substantia nigra (SN) area of brain. Further, LA inhibited the activation of nuclear factor-?B (NF-?B) and expression of pro-inflammatory molecules in M1 microglia. Taken together, these results suggest that LA may exert a profound neuroprotective effect and is thus a promising anti-neuroinflammatory and anti-oxidative agent for halting the progression of PD. Interventions aimed at either blocking microglia-derived inflammatory mediators or modulating the polarization of microglia may be potentially useful therapies that are worth further investigation. PMID:26084861

  7. Rabbit Hemorrhagic Disease Virus Variant Recombinant VP60 Protein Induces Protective Immunogenicity.

    PubMed

    Yang, Dong-Kun; Kim, Ha-Hyun; Nah, Jin-Ju; Song, Jae-Young

    2015-11-28

    Rabbit hemorrhagic disease virus (RHDV) is highly contagious and often causes fatal disease that affects both wild and domestic rabbits of the species Oryctolagus cuniculus. A highly pathogenic RHDV variant (RHDVa) has been circulation in the Korean rabbit population since 2007 and has a devastating effect on the rabbit industry in Korea. A highly pathogenic RHDVa was isolated from naturally infected rabbits, and the gene encoding the VP60 protein was cloned into a baculovirus transfer vector and expressed in insect cells. The hemagglutination titer of the Sf-9 cell lysate infected with recombinant VP60 baculovirus was 131,072 units/50 ?l and of the supernatant 4,096 units/50 ?l. Guinea pigs immunized twice intramuscularly with a trial inactivated RHDVa vaccine containing recombinant VP60 contained 2,152 hemagglutination inhibition (HI) geometric mean titers. The 8-week-old white rabbits inoculated with one vaccine dose were challenged with a lethal RHDVa 21 days later and showed 100% survival rates. The recombinant VP60 protein expressed in a baculovirus system induced high HI titers in guinea pigs and rendered complete protection, which led to the development of a novel inactivated RHDVa vaccine. PMID:26198122

  8. Glycopolymers as Antiadhesives of E. coli Strains Inducing Inflammatory Bowel Diseases.

    PubMed

    Yan, Xibo; Sivignon, Adeline; Yamakawa, Nao; Crepet, Agnes; Travelet, Christophe; Borsali, Redouane; Dumych, Tetiana; Li, Zhaoli; Bilyy, Rostyslav; Deniaud, David; Fleury, Etienne; Barnich, Nicolas; Darfeuille-Michaud, Arlette; Gouin, Sébastien G; Bouckaert, Julie; Bernard, Julien

    2015-06-01

    n-Heptyl ?-d-mannose (HM) is a nanomolar antagonist of FimH, a virulence factor of E. coli. Herein we report on the construction of multivalent HM-based glycopolymers as potent antiadhesives of type 1 piliated E. coli. We investigate glycopolymer/FimH and glycopolymer/bacteria interactions and show that HM-based glycopolymers efficiently inhibit bacterial adhesion and disrupt established cell-bacteria interactions in vitro at very low concentration (0.1 ?M on a mannose unit basis). On a valency-corrected basis, HM-based glycopolymers are, respectively, 10(2) and 10(6) times more potent than HM and d-mannose for their capacity to disrupt the binding of adherent-invasive E. coli to T84 intestinal epithelial cells. Finally, we demonstrate that the antiadhesive capacities of HM-based glycopolymers are preserved ex vivo in the colonic loop of a transgenic mouse model of Crohn's disease. All together, these results underline the promising scope of HM-based macromolecular ligands for the antiadhesive treatment of E. coli induced inflammatory bowel diseases. PMID:25961760

  9. Regulation of Smooth Muscle by Inducible Nitric Oxide Synthase and NADPHoxidase in Vascular Proliferative Diseases

    PubMed Central

    Ginnan, Roman; Guikema, Benjamin J.; Halligan, Katharine E.; Singer, Harold A.; Jourd’heuil, David

    2008-01-01

    Inflammation plays a critical role in promoting smooth muscle migration and proliferation during vascular diseases such as post-angioplasty restenosis and atherosclerosis. Another common feature of many vascular diseases is the contribution of reactive oxygen (ROS) and nitrogen (RNS) species to vascular injury. Primary sources of ROS and RNS in smooth muscle are several isoforms of NADPH oxidase (Nox) and the cytokine-regulated inducible nitric oxide (NO) synthase (iNOS). One important example of the interaction between NO and ROS is the reaction of NO with superoxide to yield peroxynitrite, which may contribute to the pathogenesis of hypertension. In this review, we discuss the literature that supports an alternate possibility: Nox-derived ROS modulate NO bioavailability by altering the expression of iNOS. We highlight data showing co-expression of iNOS and Nox in vascular smooth muscle and demonstrating the functional consequences of iNOS and Nox during vascular injury. We describe the relevant literature demonstrating that the mitogen activated protein kinases (MAP kinases) are important modulators of pro-inflammatory cytokine-dependent expression of iNOS. A central hypothesis discussed is that ROS-dependent regulation of the serine/threonine kinase protein kinase C? (PKC?) is essential to understanding how Nox may regulate signaling pathways leading to iNOS expression. Overall, the integration of non-phagocytic NADPHoxidase with cytokine signaling in general and in vascular smooth muscle in particular is poorly understood and merit further investigation. PMID:18211830

  10. Dysfunction of peroxisomes in twitcher mice brain: A possible mechanism of psychosine-induced disease

    SciTech Connect

    Haq, Ehtishamul;