WorldWideScience

Sample records for endogenous protection mechanisms

  1. Role of endogenous thiols in protection

    Science.gov (United States)

    Vos, O.

    Aminothiols represent the most important group of radioprotective compounds. The most effective compounds administered at an optimal dose and time before irradiation are able to provide a protection in mice with a dose reduction factor (DRF) of about 2-2.5. The working mechanism can partly be explained as a scavenging process of radicals induced in water and partly as a chemical repair process of injured DNA. The endogenous aminothiol which has far-out the highest intracellular concentration is glutathione (GSH). The importance of intracellular GSH in determining cellular radiosensitivity has been shown by irradiating cells that had very low GSH levels. Such cells appear to have a high radiosensitivity, especially in hypoxic conditions. On the other hand, it has been demonstrated that induction of a high GSH level (100-200% above the normal level) provides only a small protection. In vitro experiments with DNA indicate that thiols with a high positive charge condense in the vicinity of DNA and are effective protectors, whereas thiols with a negative charge are kep away from it and are poor protectors. In comparison with the most effective exogenous aminothiols like cysteamine and WR1065, GSH is not an effective radioprotector. Putative explanations for this relatively poor protective ability of GSH are presented.

  2. [Mechanisms of leukocyte formation of endogenous pyrogen].

    Science.gov (United States)

    Rybakina, E G; Sorokin, A V

    1982-06-01

    A study was made of the kinetics of endogenous pyrogen production by rabbit blood and exudate leukocytes and possible role played by the products of activated leukocytes in autoregulation of the process. It was established that accumulation of endogenous pyrogen in the cell precedes its release by stimulated cells. Then the processes of active pyrogen formation and release gel interdependent: pyrogen formed releases from the cell; the lowering of pyrogen concentration in the cell is accompanied by the decrease of its content in the medium. No stimulating effect of the products activated during leukocyte inflammation on pyrogen formation by blood leukocytes was discovered.

  3. Endogenous erythropoietin protects neuroretinal function in ischemic retinopathy.

    Science.gov (United States)

    Mowat, Freya M; Gonzalez, Francisco; Luhmann, Ulrich F O; Lange, Clemens A; Duran, Yanai; Smith, Alexander J; Maxwell, Patrick H; Ali, Robin R; Bainbridge, James W B

    2012-04-01

    Because retinal ischemia is a common cause of vision loss, we sought to determine the effects of ischemia on neuroretinal function and survival in murine oxygen-induced retinopathy (OIR) and to define the role of endogenous erythropoietin (EPO) in this model. OIR is a reproducible model of ischemia-induced retinal neovascularization; it is used commonly to develop antiangiogenic strategies. We investigated the effects of ischemia in murine OIR on retinal function and neurodegeneration by electroretinography and detailed morphology. OIR was associated with significant neuroretinal dysfunction, with reduced photopic and scotopic ERG responses and reduced b-wave/a-wave ratios consistent with specific inner-retinal dysfunction. OIR resulted in significantly increased apoptosis and atrophy of the inner retina in areas of ischemia. EPO deficiency in heterozygous Epo-Tag transgenic mice was associated with more profound retinal dysfunction after OIR, indicated by a significantly greater suppression of ERG amplitudes, but had no measurable effect on the extent of retinal ischemia, preretinal neovascularization, or neuroretinal degeneration in OIR. Systemic administration of recombinant EPO protected EPO-deficient mice against this additional suppression, but EPO supplementation in wild-type animals with OIR did not rescue neuroretinal dysfunction or degeneration. Murine OIR offers a valuable model of ischemic neuroretinal dysfunction and degeneration in which to investigate adaptive tissue responses and evaluate novel therapeutic approaches. Endogenous EPO can protect neuroretinal function in ischemic retinopathy. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. Endogenous glutathione protects human skin fibroblasts against the cytotoxic action of UVB, UVA and near-visible radiations

    International Nuclear Information System (INIS)

    Tyrell, R.M.; Pidoux, Mireille

    1986-01-01

    Both the UVB (290-320 nm) and UVA (320-380 nm) regions of sunlight damage human skin cells but, particularly at the longer wavelengths, information is scant concerning the mechanism(s) of damage induction and the roles of cellular defense mechanisms. Following extensive glutathione depletion of cultured human skin fibroblasts, the cells become strongly sensitized to the cytotoxic action of near-visible (405 nm), UVA (334 nm, 365 nm) and UVB (313 nm) but not UVC (254 nm) radiations. In the critical UVB region, the magnitude of the protection afforded by endogenous glutathione approaches that of the protection provided by excision repair. The results suggest that a significant fraction of even UVB damage can be mediated by free radical attack and that a major role of glutathione in human skin cells is to protect them from the cytotoxic action of sunlight. (author)

  5. MnTM-4-PyP modulates endogenous antioxidant responses and protects primary cortical neurons against oxidative stress.

    Science.gov (United States)

    Cheng, Kuo-Yuan; Guo, Fei; Lu, Jia-Qi; Cao, Yuan-Zhao; Wang, Tian-Chang; Yang, Qi; Xia, Qing

    2015-05-01

    Oxidative stress is a direct cause of injury in various neural diseases. Manganese porphyrins (MnPs), a large category of superoxide dismutase (SOD) mimics, shown universally to have effects in numerous neural disease models in vivo. Given their complex intracellular redox activities, detailed mechanisms underlying the biomedical efficacies are not fully elucidated. This study sought to investigate the regulation of endogenous antioxidant systems by a MnP (MnTM-4-PyP) and its role in the protection against neural oxidative stress. Primary cortical neurons were treated with MnTM-4-PyP prior to hydrogen peroxide-induced oxidative stress. MnTM-4-PyP increased cell viability, reduced intracellular level of reactive oxygen species, inhibited mitochondrial apoptotic pathway, and ameliorated endoplasmic reticulum function. The protein levels and activities of endogenous SODs were elevated, but not those of catalase. SOD2 transcription was promoted in a transcription factor-specific manner. Additionally, we found FOXO3A and Sirt3 levels also increased. These effects were not observed with MnTM-4-PyP alone. Induction of various levels of endogenous antioxidant responses by MnTM-4-PyP has indispensable functions in its protection for cortical neurons against hydrogen peroxide-induced oxidative stress. © 2014 John Wiley & Sons Ltd.

  6. [Protective effects of endogenous carbon monoxide against myocardial ischemia-reperfusion injury in rats].

    Science.gov (United States)

    Zhou, Zhen; Ma, Shuang; Liu, Jie; Ji, Qiao-Rong; Cao, Cheng-Zhu; Li, Xiao-Na; Tang, Feng; Zhang, Wei

    2018-04-25

    The present study is aimed to explore the effects of endogenous carbon monoxide on the ischemia-reperfusion in rats. Wistar rats were intraperitoneally injected with protoporphyrin cobalt chloride (CoPP, an endogenous carbon monoxide agonist, 5 mg/kg), zinc protoporphyrin (ZnPP, an endogenous carbon monoxide inhibitor, 5 mg/kg) or saline. Twenty-four hours after injection, the myocardial ischemia-reperfusion model was made by Langendorff isolated cardiac perfusion system, and cardiac function parameters were collected. Myocardial cGMP content was measured by ELISA, and the endogenous carbon monoxide in plasma and myocardial enzymes in perfusate at 10 min after reperfusion were measured by colorimetry. The results showed that before ischemia the cardiac functions of CoPP, ZnPP and control groups were stable, and there were no significant differences. After reperfusion, cardiac functions had significant differences among the three groups (P endogenous carbon monoxide can maintain cardiac function, shorten the time of cardiac function recovery, and play a protective role in cardiac ischemia-reperfusion.

  7. Role of endogenous serotonin in the mechanism of action of radioprotective substances

    International Nuclear Information System (INIS)

    Konstantinova, M.M.; Nekrasova, I.V.; Gusareva, Eh.V.; Dontsova, G.V.

    1978-01-01

    A study is made of a correlation between radiomodifying activity of noradrenaline (NA), N-ethylmaleimide (NEM) and a combination of these agents and their effect on the content of endogenous serotonin in cells of Ehrlich's ascites tumor and E. coli B. There is no uniformity in the response of different cells and uniform direction of the changes in their radioresistance and endogenous serotonin content both under the effect of the substances (NA and NEM) given separately and under a combined effect of the protector and the agent, which removes the protective effect or prevents realization of the latter (NEM). This enables us to arrive at a conclusion that endogenous serotonin is not the only factor responsible for the radioprotective effect of the protective substances. At the same time, it is not excluded that endogenous serotonin is involved in the chain of reactions which are necessary for the radioprotective effect to come into play

  8. Ischemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke.

    Science.gov (United States)

    Wang, Yuechun; Reis, Cesar; Applegate, Richard; Stier, Gary; Martin, Robert; Zhang, John H

    2015-10-01

    In the area of brain injury and neurodegenerative diseases, a plethora of experimental and clinical evidence strongly indicates the promise of therapeutically exploiting the endogenous adaptive system at various levels like triggers, mediators and the end-effectors to stimulate and mobilize intrinsic protective capacities against brain injuries. It is believed that ischemic pre-conditioning and post-conditioning are actually the strongest known interventions to stimulate the innate neuroprotective mechanism to prevent or reverse neurodegenerative diseases including stroke and traumatic brain injury. Recently, studies showed the effectiveness of ischemic per-conditioning in some organs. Therefore the term ischemic conditioning, including all interventions applied pre-, per- and post-ischemia, which spans therapeutic windows in 3 time periods, has recently been broadly accepted by scientific communities. In addition, it is extensively acknowledged that ischemia-mediated protection not only affects the neurons but also all the components of the neurovascular network (consisting of neurons, glial cells, vascular endothelial cells, pericytes, smooth muscle cells, and venule/veins). The concept of cerebroprotection has been widely used in place of neuroprotection. Intensive studies on the cellular signaling pathways involved in ischemic conditioning have improved the mechanistic understanding of tolerance to cerebral ischemia. This has added impetus to exploration for potential pharmacologic mimetics, which could possibly induce and maximize inherent protective capacities. However, most of these studies were performed in rodents, and the efficacy of these mimetics remains to be evaluated in human patients. Several classical signaling pathways involving apoptosis, inflammation, or oxidation have been elaborated in the past decades. Newly characterized mechanisms are emerging with the advances in biotechnology and conceptual renewal. In this review we are going to focus on

  9. Mechanisms in endogenous leukemia virus induction by radiation and chemicals

    International Nuclear Information System (INIS)

    Tennant, R.W.; Rascati, R.J.; Lavelle, G.C.

    1976-01-01

    A model of endogenous leukemia virus induction in AKR strain mouse cells based on two distinct types of alterations in cellular or proviral DNA is presented. The first type are non-repairable alterations, such as those caused by the incorporation of halogenated pyrimidines; the second type are repairable lesions, such as those caused by irradiation or certain other chemicals. The production of non-repairable lesions leads to the formation of a stable, proviral state which is dependent upon cell division for complete virus expression. A stable provirus intermediate state is not demonstrable in cells induced by treatments which cause repairable lesions, since replication of damaged or altered DNA must occur before the lesions are removed by repair synthesis. Experimental support for this model is presented

  10. Endogenous protection derived from activin A/Smads transduction loop stimulated via ischemic injury in PC12 cells.

    Science.gov (United States)

    Mang, Jing; Mei, Chun-Li; Wang, Jiao-Qi; Li, Zong-Shu; Chu, Ting-Ting; He, Jin-Ting; Xu, Zhong-Xin

    2013-10-17

    Activin A (ActA), a member of transforming growth factor-beta (TGF-b) super- family, affects many cellular processes, including ischemic stroke. Though the neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD) injury have already been reported by us, the endogenous role of ActA remains poorly understood. To further define the role and mechanism of endogenous ActA and its signaling in response to acute ischemic damage, we used an OGD model in PC12 cells to simulate ischemic injury on neurons in vitro. Cells were pre-treated by monoclonal antibody against activin receptor type IIA (ActRII-Ab). We found that ActRII-Ab augments ischemic injury in PC12 cells. Further, the extracellular secretion of ActA as well as phosphorylation of smad3 in PC12 cells was also up-regulated by OGD, but suppressed by ActRII-Ab. Taken together, our results show that ActRII-Ab may augment ischemic injury via blocking of transmembrane signal transduction of ActA, which confirmed the existence of endogenous neuroprotective effects derived from the ActA/Smads pathway. ActRIIA plays an important role in transferring neuronal protective signals inside. It is highly possible that ActA transmembrance signaling is a part of the positive feed-back loop for extracellular ActA secretion.

  11. Endogenous Protection Derived from Activin A/Smads Transduction Loop Stimulated via Ischemic Injury in PC12 Cells

    Directory of Open Access Journals (Sweden)

    Zhong-Xin Xu

    2013-10-01

    Full Text Available Activin A (ActA, a member of transforming growth factor-beta (TGF-b super- family, affects many cellular processes, including ischemic stroke. Though the neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD injury have already been reported by us, the endogenous role of ActA remains poorly understood. To further define the role and mechanism of endogenous ActA and its signaling in response to acute ischemic damage, we used an OGD model in PC12 cells to simulate ischemic injury on neurons in vitro. Cells were pre-treated by monoclonal antibody against activin receptor type IIA (ActRII-Ab. We found that ActRII-Ab augments ischemic injury in PC12 cells. Further, the extracellular secretion of ActA as well as phosphorylation of smad3 in PC12 cells was also up-regulated by OGD, but suppressed by ActRII-Ab. Taken together, our results show that ActRII-Ab may augment ischemic injury via blocking of transmembrane signal transduction of ActA, which confirmed the existence of endogenous neuroprotective effects derived from the ActA/Smads pathway. ActRIIA plays an important role in transferring neuronal protective signals inside. It is highly possible that ActA transmembrance signaling is a part of the positive feed-back loop for extracellular ActA secretion.

  12. Collateral blood flow in different cerebrovascular hierarchy provides endogenous protection in cerebral ischemia.

    Science.gov (United States)

    Luo, Chuanming; Liang, Fengyin; Ren, Huixia; Yao, Xiaoli; Liu, Qiang; Li, Mingyue; Qin, Dajiang; Yuan, Ti-Fei; Pei, Zhong; Su, Huanxing

    2017-11-01

    Collateral blood flow as vascular adaptions to focal cerebral ischemia is well recognized. However, few studies directly investigate the dynamics of collateral vessel recruitment in vivo and little is known about the effect of collateral blood flow in different cerebrovascular hierarchy on the neuropathology after focal ischemic stroke. Here, we report that collateral blood flow is critically involved in blood vessel compensations following regional ischemia. We occluded a pial arteriole using femtosecond laser ablating under the intact thinned skull and documented the changes of collateral flow around the surface communication network and between the surface communication network and subsurface microcirculation network using in vivo two photon microscopy imaging. Occlusion of the pial arteriole apparently increased the diameter and collateral blood flow of its leptomeningeal anastomoses, which significantly reduced the cortical infarction size. This result suggests that the collateral flow via surface communicating network connected with leptomeningeal anastomoses could greatly impact on the extent of infarction. We then further occluded the target pial arteriole and all of its leptomeningeal anastomoses. Notably, this type of occlusion led to reversals of blood flow in the penetrating arterioles mainly proximal to the occluded pial arteriole in a direction from the subsurface microcirculation network to surface arterioles. Interesting, the cell death in the area of ischemic penumbra was accelerated when we performed occlusion to cease the reversed blood flow in those penetrating arterioles, suggesting that the collateral blood flow from subsurface microcirculation network exerts protective roles in delaying cell death in the ischemic penumbra. In conclusion, we provide the first experimental evidence that collateral blood vessels at different cerebrovascular hierarchy are endogenously compensatory mechanisms in brain ischemia. © 2016 International Society of

  13. Novel protective role of endogenous cardiac myocyte P2X4 receptors in heart failure.

    Science.gov (United States)

    Yang, Tiehong; Shen, Jian-bing; Yang, Ronghua; Redden, John; Dodge-Kafka, Kimberly; Grady, James; Jacobson, Kenneth A; Liang, Bruce T

    2014-05-01

    Heart failure (HF), despite continuing progress, remains a leading cause of mortality and morbidity. P2X4 receptors (P2X4R) have emerged as potentially important molecules in regulating cardiac function and as potential targets for HF therapy. Transgenic P2X4R overexpression can protect against HF, but this does not explain the role of native cardiac P2X4R. Our goal is to define the physiological role of endogenous cardiac myocyte P2X4R under basal conditions and during HF induced by myocardial infarction or pressure overload. Mice established with conditional cardiac-specific P2X4R knockout were subjected to left anterior descending coronary artery ligation-induced postinfarct or transverse aorta constriction-induced pressure overload HF. Knockout cardiac myocytes did not show P2X4R by immunoblotting or by any response to the P2X4R-specific allosteric enhancer ivermectin. Knockout hearts showed normal basal cardiac function but depressed contractile performance in postinfarct and pressure overload models of HF by in vivo echocardiography and ex vivo isolated working heart parameters. P2X4R coimmunoprecipitated and colocalized with nitric oxide synthase 3 (eNOS) in wild-type cardiac myocytes. Mice with cardiac-specific P2X4R overexpression had increased S-nitrosylation, cyclic GMP, NO formation, and were protected from postinfarct and pressure overload HF. Inhibitor of eNOS, L-N(5)-(1-iminoethyl)ornithine hydrochloride, blocked the salutary effect of cardiac P2X4R overexpression in postinfarct and pressure overload HF as did eNOS knockout. This study establishes a new protective role for endogenous cardiac myocyte P2X4R in HF and is the first to demonstrate a physical interaction between the myocyte receptor and eNOS, a mediator of HF protection. © 2014 American Heart Association, Inc.

  14. Effect of Endogenous Androgens on 17β-Estradiol-Mediated Protection after Spinal Cord Injury in Male Rats

    OpenAIRE

    Kachadroka, Supatra; Hall, Alicia M.; Niedzielko, Tracy L.; Chongthammakun, Sukumal; Floyd, Candace L.

    2010-01-01

    Several groups have recently shown that 17β-estradiol is protective in spinal cord injury (SCI). Testosterone can be aromatized to 17β-estradiol and may increase estrogen-mediated protection. Alternatively, testosterone has been shown to increase excitotoxicity in models of central nervous system (CNS) injury. These experiments test the hypothesis that endogenous testosterone in male rats alters 17β-estradiol-mediated protection by evaluating a delayed administration over a clinically relevan...

  15. Repair of endogenous and ionizing radiation-induced DNA damages: mechanisms and biological functions

    International Nuclear Information System (INIS)

    Boiteux, S.

    2002-01-01

    The cellular DNA is continuously exposed to endogenous and exogenous stress. Oxidative stress due to cellular metabolism is the major cause of endogenous DNA damage. On the other hand, ionizing radiation (IR) is an important exogenous stress. Both induce similar DNA damages: damaged bases, abasic sites and strand breakage. Most of these lesions are lethal and/or mutagenic. The survival of the cell is managed by efficient and accurate DNA repair mechanisms that remove lesions before their replication or transcription. DNA repair pathways involved in the removal of IR-induced lesions are briefly described. Base excision repair (BER) is mostly involved in the removal of base damage, abasic sites and single strand breaks. In contrast, DNA double strand breaks are mostly repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). How DNA repair pathways prevent cancer process is also discussed. (author)

  16. Endogenous reward mechanisms and their importance in stress reduction, exercise and the brain.

    Science.gov (United States)

    Esch, Tobias; Stefano, George B

    2010-06-30

    Stress can facilitate disease processes and causes strain on the health care budgets. It is responsible or involved in many human ailments of our time, such as cardiovascular illnesses, particularly related to the psychosocial stressors of daily life, including work. Besides pharmacological or clinical medical treatment options, behavioral stress reduction is much-needed. These latter approaches rely on an endogenous healing potential via life-style modification. Hence, research has suggested different ways and approaches to self-treat stress or buffer against stressors and their impacts. These self-care-centred approaches are sometimes referred to as mind-body medicine or multi-factorial stress management strategies. They consist of various cognitive behavioral techniques, as well as relaxation exercises and nutritional counselling. However, a critical and consistent element of modern effective stress reduction strategies are exercise practices. With regard to underlying neurobiological mechanisms of stress relief, reward and motivation circuitries that are imbedded in the limbic regions of the brain are responsible for the autoregulatory and endogenous processing of stress. Exercise techniques clearly have an impact upon these systems. Thereby, physical activities have a potential to increase mood, i.e., decrease psychological distress by pleasure induction. For doing so, neurobiological signalling molecules such as endogenous morphine and coupled nitric oxide pathways get activated and finely tuned. Evolutionarily, the various activities and autoregulatory pathways are linked together, which can also be demonstrated by the fact that dopamine is endogenously converted into morphine which itself leads to enhanced nitric oxide release by activation of constitutive nitric oxide synthase enzymes. These molecules and mechanisms are clearly stress-reducing.

  17. Antimicrobial activity and mechanism of PDC213, an endogenous peptide from human milk

    International Nuclear Information System (INIS)

    Sun, Yazhou; Zhou, Yahui; Liu, Xiao; Zhang, Fan; Yan, Linping; Chen, Ling; Wang, Xing; Ruan, Hongjie; Ji, Chenbo; Cui, Xianwei; Wang, Jiaqin

    2017-01-01

    Human milk has always been considered an ideal source of elemental nutrients to both preterm and full term infants in order to optimally develop the infant's tissues and organs. Recently, hundreds of endogenous milk peptides were identified in human milk. These peptides exhibited angiotensin-converting enzyme inhibition, immunomodulation, or antimicrobial activity. Here, we report the antimicrobial activity and mechanism of a novel type of human antimicrobial peptide (AMP), termed PDC213 (peptide derived from β-Casein 213-226 aa). PDC213 is an endogenous peptide and is present at higher levels in preterm milk than in full term milk. The inhibitory concentration curve and disk diffusion tests showed that PDC213 had obvious antimicrobial against S. aureus and Y. enterocolitica, the common nosocomial pathogens in neonatal intensive care units (NICUs). Fluorescent dye methods, electron microscopy experiments and DNA-binding activity assays further indicated that PDC213 can permeabilize bacterial membranes and cell walls rather than bind intracellular DNA to kill bacteria. Together, our results suggest that PDC213 is a novel type of AMP that warrants further investigation. - Highlights: • PDC213 is an endogenous peptide presenting higher levels in preterm milk. • PDC213 showed obvious antimicrobial against S. aereus and Y. enterocolitica. • PDC213 can permeabilize bacterial membranes and cell walls to kill bacterias. • PDC213 is a novel type of antimicrobial peptides worthy further investigation.

  18. The role of endogenous and exogenous mechanisms in the formation of R&D networks

    Science.gov (United States)

    Tomasello, Mario V.; Perra, Nicola; Tessone, Claudio J.; Karsai, Márton; Schweitzer, Frank

    2014-01-01

    We develop an agent-based model of strategic link formation in Research and Development (R&D) networks. Empirical evidence has shown that the growth of these networks is driven by mechanisms which are both endogenous to the system (that is, depending on existing alliances patterns) and exogenous (that is, driven by an exploratory search for newcomer firms). Extant research to date has not investigated both mechanisms simultaneously in a comparative manner. To overcome this limitation, we develop a general modeling framework to shed light on the relative importance of these two mechanisms. We test our model against a comprehensive dataset, listing cross-country and cross-sectoral R&D alliances from 1984 to 2009. Our results show that by fitting only three macroscopic properties of the network topology, this framework is able to reproduce a number of micro-level measures, including the distributions of degree, local clustering, path length and component size, and the emergence of network clusters. Furthermore, by estimating the link probabilities towards newcomers and established firms from the data, we find that endogenous mechanisms are predominant over the exogenous ones in the network formation, thus quantifying the importance of existing structures in selecting partner firms. PMID:25022561

  19. The role of endogenous and exogenous mechanisms in the formation of R&D networks

    Science.gov (United States)

    Tomasello, Mario V.; Perra, Nicola; Tessone, Claudio J.; Karsai, Márton; Schweitzer, Frank

    2014-07-01

    We develop an agent-based model of strategic link formation in Research and Development (R&D) networks. Empirical evidence has shown that the growth of these networks is driven by mechanisms which are both endogenous to the system (that is, depending on existing alliances patterns) and exogenous (that is, driven by an exploratory search for newcomer firms). Extant research to date has not investigated both mechanisms simultaneously in a comparative manner. To overcome this limitation, we develop a general modeling framework to shed light on the relative importance of these two mechanisms. We test our model against a comprehensive dataset, listing cross-country and cross-sectoral R&D alliances from 1984 to 2009. Our results show that by fitting only three macroscopic properties of the network topology, this framework is able to reproduce a number of micro-level measures, including the distributions of degree, local clustering, path length and component size, and the emergence of network clusters. Furthermore, by estimating the link probabilities towards newcomers and established firms from the data, we find that endogenous mechanisms are predominant over the exogenous ones in the network formation, thus quantifying the importance of existing structures in selecting partner firms.

  20. Endogenous molecular network reveals two mechanisms of heterogeneity within gastric cancer

    Science.gov (United States)

    Li, Site; Zhu, Xiaomei; Liu, Bingya; Wang, Gaowei; Ao, Ping

    2015-01-01

    Intratumor heterogeneity is a common phenomenon and impedes cancer therapy and research. Gastric cancer (GC) cells have generally been classified into two heterogeneous cellular phenotypes, the gastric and intestinal types, yet the mechanisms of maintaining two phenotypes and controlling phenotypic transition are largely unknown. A qualitative systematic framework, the endogenous molecular network hypothesis, has recently been proposed to understand cancer genesis and progression. Here, a minimal network corresponding to such framework was found for GC and was quantified via a stochastic nonlinear dynamical system. We then further extended the framework to address the important question of intratumor heterogeneity quantitatively. The working network characterized main known features of normal gastric epithelial and GC cell phenotypes. Our results demonstrated that four positive feedback loops in the network are critical for GC cell phenotypes. Moreover, two mechanisms that contribute to GC cell heterogeneity were identified: particular positive feedback loops are responsible for the maintenance of intestinal and gastric phenotypes; GC cell progression routes that were revealed by the dynamical behaviors of individual key components are heterogeneous. In this work, we constructed an endogenous molecular network of GC that can be expanded in the future and would broaden the known mechanisms of intratumor heterogeneity. PMID:25962957

  1. Studies on the pathogenesis of fever. IX. Characteristics of endogenous serum pyrogen and mechanisms governing its release.

    Science.gov (United States)

    PETERSDORF, R G; KEENE, W R; BENNETT, I L

    1957-12-01

    The "endogenous serum pyrogen" that appears in the circulating blood after a single intravenous injection of endotoxin does not produce leukopenia in normal animals, fails to provoke the local Shwartzman reaction, and elicits no "tolerance" when injected daily. Suppression of the febrile response to endotoxin by prednisone does not prevent the appearance of pyrogen in the blood. Animals given large amounts of endotoxin daily continue to respond with high fevers despite failure of endogenous serum pyrogen to appear in detectable amounts after the first two or three injections. Analysis of the response to daily injections shows clearly that the fever during the first 2 hours after administration of endotoxin is unrelated to levels of endogenous serum pyrogen; in contrast, the magnitude of the fever after the 2nd hour correlates well with endogenous pyrogen in some instances. The leukopenic response to endotoxin could not be correlated with the appearance of endogenous serum pyrogen. The differences between endotoxin and endogenous pyrogen and the similarities between leukocyte extracts (sterile exudates) and endogenous pyrogen are summarized and discussed. Dissociation of the febrile response to bacterial endotoxin and levels of endogenous serum pyrogen are discussed and it is concluded that a mechanism involving both direct and indirect action of endotoxins offers the best explanation for the pyrogenic action of these bacterial products.

  2. Endogenous Protection Derived from Activin A/Smads Transduction Loop Stimulated via Ischemic Injury in PC12 Cells

    OpenAIRE

    Mang, Jing; Mei, Chun-Li; Wang, Jiao-Qi; Li, Zong-Shu; Chu, Ting-Ting; He, Jin-Ting; Xu, Zhong-Xin

    2013-01-01

    Activin A (ActA), a member of transforming growth factor-beta (TGF-b) super- family, affects many cellular processes, including ischemic stroke. Though the neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD) injury have already been reported by us, the endogenous role of ActA remains poorly understood. To further define the role and mechanism of endogenous ActA and its signaling in response to acute ischemic damage, we used an OGD model in PC12 cells to simulate isch...

  3. Mechanical design and protection of superconducting magnets

    CERN Document Server

    Asner, Alfred M

    1978-01-01

    The principles of the mechanical design of superconducting magnets of concentric configuration, with iron low-temperature and room- temperature screening, are outlined. Measures for protection of such magnets against quench forces, are considered. (4 refs).

  4. A quantum protective mechanism in photosynthesis

    NARCIS (Netherlands)

    Marais, A.; Sinayskiy, I.; Petruccione, F.; van Grondelle, R.

    2015-01-01

    Since the emergence of oxygenic photosynthesis, living systems have developed protective mechanisms against reactive oxygen species. During charge separation in photosynthetic reaction centres, triplet states can react with molecular oxygen generating destructive singlet oxygen. The triplet product

  5. Endogenous Control Mechanisms of FAK and PYK2 and Their Relevance to Cancer Development and Therapy

    KAUST Repository

    Naser, Rayan Mohammad Mahmoud

    2018-05-10

    Focal adhesion kinase (FAK) and its close paralogue, proline-rich tyrosine kinase 2 (PYK2), are key regulators of aggressive spreading and metastasis of cancer cells. While targeted small-molecule inhibitors of FAK and PYK2 are showing promising antitumor activity, their clinical long-term efficacy may be undermined by the strong capacity of cancer cells to evade anti-kinase drugs. In healthy cells, the expression and/or function of FAK and PYK2 is tightly controlled through modulation of gene expression, competing alternatively spliced forms, non-coding RNAs, and proteins that directly or indirectly affect kinase activation or protein stability. The molecular factors involved are frequently deregulated in cancer cells. Here, we review the endogenous mechanisms controlling FAK and PYK2, and discuss how these mechanisms could inspire or improve anticancer therapies.

  6. Endogenous Control Mechanisms of FAK and PYK2 and Their Relevance to Cancer Development and Therapy

    KAUST Repository

    Naser, Rayan Mohammad Mahmoud; Aldehaiman, Abdullah; Diaz Galicia, Miriam Escarlet; Arold, Stefan T.

    2018-01-01

    Focal adhesion kinase (FAK) and its close paralogue, proline-rich tyrosine kinase 2 (PYK2), are key regulators of aggressive spreading and metastasis of cancer cells. While targeted small-molecule inhibitors of FAK and PYK2 are showing promising antitumor activity, their clinical long-term efficacy may be undermined by the strong capacity of cancer cells to evade anti-kinase drugs. In healthy cells, the expression and/or function of FAK and PYK2 is tightly controlled through modulation of gene expression, competing alternatively spliced forms, non-coding RNAs, and proteins that directly or indirectly affect kinase activation or protein stability. The molecular factors involved are frequently deregulated in cancer cells. Here, we review the endogenous mechanisms controlling FAK and PYK2, and discuss how these mechanisms could inspire or improve anticancer therapies.

  7. (Some) Cellular Mechanisms Influencing the Transcription of Human Endogenous Retrovirus, HERV-Fc1

    DEFF Research Database (Denmark)

    Laska, Magdalena Janina; Nissen, Kari Konstantin; Nexø, Bjørn Andersen

    2013-01-01

    DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. DNA methylation is considered an important mechanism for silencing of retroelements in the mammalian genome. However, the methylation of human endogenous retroviruses (HERVs) is not well...... investigated. The aim of this study was to investigate the transcriptional potential of HERV-Fc1 proviral 5'LTR in more detail, and examined the specific influence of CpG methylation on this LTR in number of cell lines. Specifically, the role of demethylating chemicals e.g. 5-aza-2' deoxycytidine...... and Trichostatin-A, in inducing or reactivating expression of HERV-Fc1 specific sequences and the mechanisms were investigated. In our present study, 5-aza-dC is shown to be a powerful inducer of HERV-Fc1, and at the same time it strongly inhibits methylation of DNA. Treatment with this demethylating agent 5-aza...

  8. Ethanol extract of Portulaca oleracea L. protects against hypoxia-induced neuro damage through modulating endogenous erythropoietin expression.

    Science.gov (United States)

    Wanyin, Wang; Liwei, Dong; Lin, Jia; Hailiang, Xin; Changquan, Ling; Min, Li

    2012-04-01

    In addition to its role in erythropoiesis, erythropoietin is also appreciated for its neuroprotective effects, and it has been suggested for treatment of some ischemic-hypoxic neurovascular diseases. The protective effects of endogenous erythropoietin in the brain give rise to the hypothesis that modulating erythropoietin expression might be a better way for treatment of ischemia-hypoxia neurovascular diseases. We have found that ethanol extract of Portulaca oleracea L. (EEPO) could increase erythropoietin expression in hypoxic mouse brain in our previous study. The present study is to investigate whether EEPO exerts its neuroprotective effects against hypoxia injury through regulating endogenous erythropoietin expression. The results demonstrated that EEPO decreased the serum neuron specific enolase level in hypoxia mice and the activity of caspase-3 in neuron, increased the neuron viability and attenuated the pathological damages caused by the hypoxia condition. Importantly, we also found that EEPO stimulated the endogenous erythropoietin expression at both mRNA and protein levels. Using the conditioned medium containing soluble erythropoietin receptor, we found that the neuroprotective effects of EEPO were dependent, at least partly, on erythropoietin expression. Although EEPO did not affect transcription of hypoxia inducible factor-1α (HIF-1α), it did stabilize expression of HIF-1α. It is concluded that EEPO has neuroprotective effects against hypoxia injury, which is at least partly through stimulating endogenous erythropoietin expression by stabilizing HIF-1α. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Prebiotics: Definition and protective mechanisms.

    Science.gov (United States)

    Valcheva, Rosica; Dieleman, Levinus A

    2016-02-01

    The increase in chronic metabolic and immunologic disorders in the modern society is linked to major changes in the dietary patterns. These chronic conditions are associated with intestinal microbiota dysbiosis where important groups of carbohydrate fermenting, short-chain fatty acids-producing bacteria are reduced. Dietary prebiotics are defined as a selectively fermented ingredients that result in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health. Application of prebiotics may then restore the gut microbiota diversity and activity. Unlike the previously accepted prebiotics definition, where a limited number of bacterial species are involved in the prebiotic activity, new data from community-wide microbiome analysis demonstrated a broader affect of the prebiotics on the intestinal microbiota. These new findings require a revision of the current definition. In addition, prebiotics may exert immunomodulatory effects through microbiota-independent mechanisms that will require future investigations involving germ-free animal disease models. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Effect of endogenous androgens on 17beta-estradiol-mediated protection after spinal cord injury in male rats.

    Science.gov (United States)

    Kachadroka, Supatra; Hall, Alicia M; Niedzielko, Tracy L; Chongthammakun, Sukumal; Floyd, Candace L

    2010-03-01

    Several groups have recently shown that 17beta-estradiol is protective in spinal cord injury (SCI). Testosterone can be aromatized to 17beta-estradiol and may increase estrogen-mediated protection. Alternatively, testosterone has been shown to increase excitotoxicity in models of central nervous system (CNS) injury. These experiments test the hypothesis that endogenous testosterone in male rats alters 17beta-estradiol-mediated protection by evaluating a delayed administration over a clinically relevant dose range and manipulating testicular-derived testosterone. Adult male Sprague Dawley rats were either gonadectomized or left gonad-intact prior to SCI. SCI was produced by a midthoracic crush injury. At 30 min post SCI, animals received a subcutaneous pellet of 0.0, 0.05, 0.5, or 5.0 mg of 17beta-estradiol, released over 21 days. Hindlimb locomotion was analyzed weekly in the open field. Spinal cords were collected and analyzed for cell death, expression of Bcl-family proteins, and white-matter sparing. Post-SCI administration of the 0.5- or 5.0-mg pellet improved hindlimb locomotion, reduced urinary bladder size, increased neuronal survival, reduced apoptosis, improved the Bax/Bcl-xL protein ratio, and increased white-matter sparing. In the absence of endogenous testicular-derived androgens, SCI induced greater apoptosis, yet 17beta-estradiol administration reduced apoptosis to the same extent in gonadectomized and gonad-intact male rats. These data suggest that delayed post-SCI administration of a clinically relevant dose of 17beta-estradiol is protective in male rats, and endogenous androgens do not alter estrogen-mediated protection. These data suggest that 17beta-estradiol is an effective therapeutic intervention for reducing secondary damage after SCI in males, which could be readily translated to clinical trials.

  11. Protection of honeybee Apis mellifera by its endogenous and exogenous lactic flora against bacterial infections

    Directory of Open Access Journals (Sweden)

    Irakli Janashia

    2016-09-01

    Three exogenous bacteriocin-producing LAB strains were tested against the same pathogens and against 25 endogenous bacterial isolates representing 11 different LAB species. The screening showed that all the tested exogenous bacteriocin-producing strains inhibited the tested P. larvae strains. The endogenous LAB strains exhibited varied sensitivity profiles when treated with bacteriocin-producing strains. This raises similar challenges to those observed in antibiotic applications leading to dysbacteriosis, even though the efficacy of these bacteriocins against P. larvae in an in vitro system is evident.

  12. Study on distribution of reservoir endogenous microbe and oil displacement mechanism

    Directory of Open Access Journals (Sweden)

    Ming Yue

    2017-02-01

    Full Text Available In order to research oil displacement mechanism by indigenous microbial communities under reservoir conditions, indigenous microbial flooding experiments using the endogenous mixed bacterium from Shengli Oilfield were carried out. Through microscopic simulation visual model, observation and analysis of distribution and flow of the remaining oil in the process of water flooding and microbial oil displacement were conducted under high temperature and high pressure conditions. Research has shown that compared with atmospheric conditions, the growth of the microorganism metabolism and attenuation is slowly under high pressure conditions, and the existence of the porous medium for microbial provides good adhesion, also makes its growth cycle extension. The microbial activities can effectively launch all kinds of residual oil, and can together with metabolites, enter the blind holes off which water flooding, polymer flooding and gas flooding can’t sweep, then swap out remaining oil, increase liquidity of the crude oil and remarkably improve oil displacement effect.

  13. Quinolinic Acid, an Endogenous Molecule Combining Excitotoxicity, Oxidative Stress and Other Toxic Mechanisms

    Directory of Open Access Journals (Sweden)

    Verónica Pérez-De La Cruz

    2012-01-01

    Full Text Available Quinolinic acid (QUIN, an endogenous metabolite of the kynurenine pathway, is involved in several neurological disorders, including Huntington's disease, Alzheimer's disease, schizophrenia, HIV associated dementia (HAD etc. QUIN toxicity involves several mechanisms which trigger various metabolic pathways and transcription factors. The primary mechanism exerted by this excitotoxin in the central nervous system (CNS has been largely related with the overactivation of N-methyl-D-aspartate receptors and increased cytosolic Ca 2+ concentrations, followed by mitochondrial dysfunction, cytochrome c release, ATP exhaustion, free radical formation and oxidative damage. As a result, this toxic pattern is responsible for selective loss of middle size striatal spiny GABAergic neurons and motor alterations in lesioned animals. This toxin has recently gained attention in biomedical research as, in addition to its proven excitotoxic profile, a considerable amount of evidence suggests that oxidative stress and energetic disturbances are major constituents of its toxic pattern in the CNS. Hence, this profile has changed our perception of how QUIN-related disorders combine different toxic mechanisms resulting in brain damage. This review will focus on the description and integration of recent evidence supporting old and suggesting new mechanisms to explain QUIN toxicity.

  14. Endogenous Cholinergic Inputs and Local Circuit Mechanisms Govern the Phasic Mesolimbic Dopamine Response to Nicotine

    Science.gov (United States)

    Graupner, Michael; Maex, Reinoud; Gutkin, Boris

    2013-01-01

    Nicotine exerts its reinforcing action by stimulating nicotinic acetylcholine receptors (nAChRs) and boosting dopamine (DA) output from the ventral tegmental area (VTA). Recent data have led to a debate about the principal pathway of nicotine action: direct stimulation of the DAergic cells through nAChR activation, or disinhibition mediated through desensitization of nAChRs on GABAergic interneurons. We use a computational model of the VTA circuitry and nAChR function to shed light on this issue. Our model illustrates that the α4β2-containing nAChRs either on DA or GABA cells can mediate the acute effects of nicotine. We account for in vitro as well as in vivo data, and predict the conditions necessary for either direct stimulation or disinhibition to be at the origin of DA activity increases. We propose key experiments to disentangle the contribution of both mechanisms. We show that the rate of endogenous acetylcholine input crucially determines the evoked DA response for both mechanisms. Together our results delineate the mechanisms by which the VTA mediates the acute rewarding properties of nicotine and suggest an acetylcholine dependence hypothesis for nicotine reinforcement. PMID:23966848

  15. Endogenous S-sulfhydration of PTEN helps protect against modification by nitric oxide

    International Nuclear Information System (INIS)

    Ohno, Kazuki; Okuda, Kosaku; Uehara, Takashi

    2015-01-01

    Highlights: • PTEN is S-sulfhydrated endogenously in SH-SY5Y human neuroblastoma cells. • Preventing this modification by knocking down CBS renders PTEN sensitive to NO. • pAkt levels are increased significantly in CBS siRNA-transfected cells. • H 2 S functions as an endogenous regulator of PTEN in neuronal cells. - Abstract: Hydrogen sulfide (H 2 S) is a gaseous regulatory factor produced by several enzymes, and plays a pivotal role in processes such as proliferation or vasodilation. Recent reports demonstrated the physiological and pathophysiological functions of H 2 S in neurons. PTEN is a target of nitric oxide (NO) or hydrogen peroxide, and the oxidative modification of cysteine (Cys) residue(s) attenuates its enzymatic activity. In the present study, we assessed the effect of H 2 S on the direct modification of PTEN and the resulting downstream signaling. A modified biotin switch assay in SH-SY5Y human neuroblastoma cells revealed that PTEN is S-sulfhydrated endogenously. Subsequently, site-directed mutagenesis demonstrated that both Cys71 and Cys124 in PTEN are targets for S-sulfhydration. Further, the knockdown of cystathionine β-synthetase (CBS) using siRNA decreased this modification in a manner that was correlated to amount of H 2 S. PTEN was more sensitive to NO under these conditions. These results suggest that the endogenous S-sulfhydration of PTEN via CBS/H 2 S plays a role in preventing the S-nitrosylation that would inhibition its enzymatic activity under physiological conditions

  16. Endogenous S-sulfhydration of PTEN helps protect against modification by nitric oxide

    Energy Technology Data Exchange (ETDEWEB)

    Ohno, Kazuki; Okuda, Kosaku; Uehara, Takashi, E-mail: uehara@pharm.okayama-u.ac.jp

    2015-01-02

    Highlights: • PTEN is S-sulfhydrated endogenously in SH-SY5Y human neuroblastoma cells. • Preventing this modification by knocking down CBS renders PTEN sensitive to NO. • pAkt levels are increased significantly in CBS siRNA-transfected cells. • H{sub 2}S functions as an endogenous regulator of PTEN in neuronal cells. - Abstract: Hydrogen sulfide (H{sub 2}S) is a gaseous regulatory factor produced by several enzymes, and plays a pivotal role in processes such as proliferation or vasodilation. Recent reports demonstrated the physiological and pathophysiological functions of H{sub 2}S in neurons. PTEN is a target of nitric oxide (NO) or hydrogen peroxide, and the oxidative modification of cysteine (Cys) residue(s) attenuates its enzymatic activity. In the present study, we assessed the effect of H{sub 2}S on the direct modification of PTEN and the resulting downstream signaling. A modified biotin switch assay in SH-SY5Y human neuroblastoma cells revealed that PTEN is S-sulfhydrated endogenously. Subsequently, site-directed mutagenesis demonstrated that both Cys71 and Cys124 in PTEN are targets for S-sulfhydration. Further, the knockdown of cystathionine β-synthetase (CBS) using siRNA decreased this modification in a manner that was correlated to amount of H{sub 2}S. PTEN was more sensitive to NO under these conditions. These results suggest that the endogenous S-sulfhydration of PTEN via CBS/H{sub 2}S plays a role in preventing the S-nitrosylation that would inhibition its enzymatic activity under physiological conditions.

  17. Resveratrol protects the ovary against chromium-toxicity by enhancing endogenous antioxidant enzymes and inhibiting metabolic clearance of estradiol

    International Nuclear Information System (INIS)

    Banu, Sakhila K.; Stanley, Jone A.; Sivakumar, Kirthiram K.; Arosh, Joe A.; Burghardt, Robert C.

    2016-01-01

    Resveratrol (RVT), a polyphenolic component in grapes and red wine, has been known for its cytoprotective actions against several diseases. However, beneficial effects of RVT against early exposure to endocrine disrupting chemicals (EDCs) have not been understood. EDCs are linked to several ovarian diseases such as premature ovarian failure, polycystic ovary syndrome, early menopause and infertility in women. Hexavalent chromium (CrVI) is a heavy metal EDC, and widely used in > 50 industries. Environmental contamination with CrVI in the US is rapidly increasing, predisposing the human to several illnesses including cancers and still birth. Our lab has been involved in determining the molecular mechanism of CrVI-induced female infertility and intervention strategies to mitigate CrVI effects. Lactating mother rats were exposed to CrVI (50 ppm potassium dichromate) from postpartum days 1–21 through drinking water with or without RVT (10 mg/kg body wt., through oral gavage daily). During this time, F1 females received respective treatments through mother's milk. On postnatal day (PND) 25, blood and the ovary, kidney and liver were collected from the F1 females for analyses. CrVI increased atresia of follicles by increasing cytochrome C and cleaved caspase-3; decreasing antiapoptotic proteins; decreasing estradiol (E 2 ) biosynthesis and enhancing metabolic clearance of E 2 , increasing oxidative stress and decreasing endogenous antioxidants. RVT mitigated the effects of CrVI by upregulating cell survival proteins and AOXs; and restored E 2 levels by inhibiting hydroxylation, glucuronidation and sulphation of E 2 . This is the first study to report the protective effects of RVT against any toxicant in the ovary. - Highlights: • Resveratrol (RVT) protects the ovary against CrVI-toxicity. • RVT mitigated CrVI-induced apoptosis and follicle atresia. • RVT restored estradiol level against CrVI-toxicity. • RVT inhibited metabolic clearance of estradiol in the

  18. Resveratrol protects the ovary against chromium-toxicity by enhancing endogenous antioxidant enzymes and inhibiting metabolic clearance of estradiol

    Energy Technology Data Exchange (ETDEWEB)

    Banu, Sakhila K., E-mail: skbanu@cvm.tamu.edu; Stanley, Jone A.; Sivakumar, Kirthiram K.; Arosh, Joe A.; Burghardt, Robert C.

    2016-07-15

    Resveratrol (RVT), a polyphenolic component in grapes and red wine, has been known for its cytoprotective actions against several diseases. However, beneficial effects of RVT against early exposure to endocrine disrupting chemicals (EDCs) have not been understood. EDCs are linked to several ovarian diseases such as premature ovarian failure, polycystic ovary syndrome, early menopause and infertility in women. Hexavalent chromium (CrVI) is a heavy metal EDC, and widely used in > 50 industries. Environmental contamination with CrVI in the US is rapidly increasing, predisposing the human to several illnesses including cancers and still birth. Our lab has been involved in determining the molecular mechanism of CrVI-induced female infertility and intervention strategies to mitigate CrVI effects. Lactating mother rats were exposed to CrVI (50 ppm potassium dichromate) from postpartum days 1–21 through drinking water with or without RVT (10 mg/kg body wt., through oral gavage daily). During this time, F1 females received respective treatments through mother's milk. On postnatal day (PND) 25, blood and the ovary, kidney and liver were collected from the F1 females for analyses. CrVI increased atresia of follicles by increasing cytochrome C and cleaved caspase-3; decreasing antiapoptotic proteins; decreasing estradiol (E{sub 2}) biosynthesis and enhancing metabolic clearance of E{sub 2}, increasing oxidative stress and decreasing endogenous antioxidants. RVT mitigated the effects of CrVI by upregulating cell survival proteins and AOXs; and restored E{sub 2} levels by inhibiting hydroxylation, glucuronidation and sulphation of E{sub 2}. This is the first study to report the protective effects of RVT against any toxicant in the ovary. - Highlights: • Resveratrol (RVT) protects the ovary against CrVI-toxicity. • RVT mitigated CrVI-induced apoptosis and follicle atresia. • RVT restored estradiol level against CrVI-toxicity. • RVT inhibited metabolic clearance of

  19. Economic transactions, opportunistic behavior and protective mechanisms

    DEFF Research Database (Denmark)

    Koch, Carsten Allan

    Whenever actors participate in transactions they expose themselves to risks of various kinds. Some of these risks are attributable to events outside the control of the participants and are unavoidable. Others originate in, or are aggrevated by, opportunistic actions undertaken by contract partners...... and other co-operators. This paper is concerned with the latter type of risk and the protection against it. Six protective mechanisms, which may serve as safeguards against opportunistic behavior, are presented and discussed. Special attention is paid to reputation effects. It is noted that such effects may...... account for the lack of opportunistic behavior with which networks are often credited. No protective mechanism is, however, effective under all circumstances....

  20. A quantum protective mechanism in photosynthesis

    Science.gov (United States)

    Marais, Adriana; Sinayskiy, Ilya; Petruccione, Francesco; van Grondelle, Rienk

    2015-03-01

    Since the emergence of oxygenic photosynthesis, living systems have developed protective mechanisms against reactive oxygen species. During charge separation in photosynthetic reaction centres, triplet states can react with molecular oxygen generating destructive singlet oxygen. The triplet product yield in bacteria is observed to be reduced by weak magnetic fields. Reaction centres from plants' photosystem II share many features with bacterial reaction centres, including a high-spin iron whose function has remained obscure. To explain observations that the magnetic field effect is reduced by the iron, we propose that its fast-relaxing spin plays a protective role in photosynthesis by generating an effective magnetic field. We consider a simple model of the system, derive an analytical expression for the effective magnetic field and analyse the resulting triplet yield reduction. The protective mechanism is robust for realistic parameter ranges, constituting a clear example of a quantum effect playing a macroscopic role vital for life.

  1. Quality of protection evaluation of security mechanisms.

    Science.gov (United States)

    Ksiezopolski, Bogdan; Zurek, Tomasz; Mokkas, Michail

    2014-01-01

    Recent research indicates that during the design of teleinformatic system the tradeoff between the systems performance and the system protection should be made. The traditional approach assumes that the best way is to apply the strongest possible security measures. Unfortunately, the overestimation of security measures can lead to the unreasonable increase of system load. This is especially important in multimedia systems where the performance has critical character. In many cases determination of the required level of protection and adjustment of some security measures to these requirements increase system efficiency. Such an approach is achieved by means of the quality of protection models where the security measures are evaluated according to their influence on the system security. In the paper, we propose a model for QoP evaluation of security mechanisms. Owing to this model, one can quantify the influence of particular security mechanisms on ensuring security attributes. The methodology of our model preparation is described and based on it the case study analysis is presented. We support our method by the tool where the models can be defined and QoP evaluation can be performed. Finally, we have modelled TLS cryptographic protocol and presented the QoP security mechanisms evaluation for the selected versions of this protocol.

  2. Quality of Protection Evaluation of Security Mechanisms

    Science.gov (United States)

    Ksiezopolski, Bogdan; Zurek, Tomasz; Mokkas, Michail

    2014-01-01

    Recent research indicates that during the design of teleinformatic system the tradeoff between the systems performance and the system protection should be made. The traditional approach assumes that the best way is to apply the strongest possible security measures. Unfortunately, the overestimation of security measures can lead to the unreasonable increase of system load. This is especially important in multimedia systems where the performance has critical character. In many cases determination of the required level of protection and adjustment of some security measures to these requirements increase system efficiency. Such an approach is achieved by means of the quality of protection models where the security measures are evaluated according to their influence on the system security. In the paper, we propose a model for QoP evaluation of security mechanisms. Owing to this model, one can quantify the influence of particular security mechanisms on ensuring security attributes. The methodology of our model preparation is described and based on it the case study analysis is presented. We support our method by the tool where the models can be defined and QoP evaluation can be performed. Finally, we have modelled TLS cryptographic protocol and presented the QoP security mechanisms evaluation for the selected versions of this protocol. PMID:25136683

  3. Disease protection and interleukin-10 induction by endogenous interferon-β in multiple sclerosis?

    DEFF Research Database (Denmark)

    Hesse, D.; Krakauer, M.; Lund, H

    2011-01-01

    with increased spontaneous MX1 expression also had increased expression of other genes induced by regular IFN-ß treatment of MS. MX1 expression correlated with FOXP3 and IL10 expression, and IL10 expression correlated negatively with disease activity on magnetic resonance imaging. Further, in vivo IL10...... expression was lower in NAb-positive patients than in untreated patients with MS and healthy controls. Finally, ex vivo treatment of mononuclear blood cells with IFN-ß induced the expression of IL10, and this was blocked by the addition of serum from NAb-positive patients with MS. CONCLUSION: Our findings...... suggest that endogenous IFN-ß may induce the expression of immunoregulatory IL10 in MS and that this might be associated with dampening of inflammatory disease activity....

  4. BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity

    DEFF Research Database (Denmark)

    Rasmussen, Rikke D.; Gajjar, Madhavsai K.; Tuckova, Lucie

    2016-01-01

    Oncogene-evoked replication stress (RS) fuels genomic instability in diverse cancer types. Here we report that BRCA1, traditionally regarded a tumour suppressor, plays an unexpected tumour-promoting role in glioblastoma (GBM), safeguarding a protective response to supraphysiological RS levels. Hi...

  5. Mechanism of stimulation of endogenous fermentation in yeast by carbonyl cyanide m-chlorophenylhydrazone

    NARCIS (Netherlands)

    Noshiro, A.; Purwin, C.; Laux, M.; Nicolaij, K.; Scheffers, W.A.; Holzer, H.

    1987-01-01

    Addition of the uncoupler and protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) to starved yeast cells starts endogenous alcoholic fermentation lasting about 20 min. Hexose 6-phosphates, fructose 2,6-bisphosphate, and pyruvate accumulate in less than 2 min after addition of CCCP from

  6. Separate Mechanisms Recruited by Exogenous and Endogenous Spatial Cues: Evidence from a Spatial Stroop Paradigm

    Science.gov (United States)

    Funes, Maria Jesus; Lupianez, Juan; Milliken, Bruce

    2007-01-01

    The present experiments tested whether endogenous and exogenous cues produce separate effects on target processing. In Experiment 1, participants discriminated whether an arrow presented left or right of fixation pointed to the left or right. For 1 group, the arrow was preceded by a peripheral noninformative cue. For the other group, the arrow was…

  7. Neurobiological mechanisms involved in nicotine dependence and reward: participation of the endogenous opioid system

    Science.gov (United States)

    Berrendero, Fernando; Robledo, Patricia; Trigo, José Manuel; Martín-García, Elena; Maldonado, Rafael

    2010-01-01

    Nicotine is the primary component of tobacco that maintains the smoking habit and develops addiction. The adaptive changes of nicotinic acetylcholine receptors produced by repeated exposure to nicotine play a crucial role in the establishment of dependence. However, other neurochemical systems also participate in the addictive effects of nicotine including glutamate, cannabinoids, GABA and opioids. This review will cover the involvement of these neurotransmitters in nicotine addictive properties, with a special emphasis on the endogenous opioid system. Thus, endogenous enkephalins and beta-endorphins acting on mu-opioid receptors are involved in nicotine rewarding effects, whereas opioid peptides derived from prodynorphin participate in nicotine aversive responses. An upregulation of mu-opioid receptors has been reported after chronic nicotine treatment that could counteract the development of nicotine tolerance, whereas the downregulation induced on kappa-opioid receptors seems to facilitate nicotine tolerance. Endogenous enkephalins acting on mu-opioid receptors also play a role in the development of physical dependence to nicotine. In agreement with these actions of the endogenous opioid system, the opioid antagonist naltrexone has shown to be effective for smoking cessation in certain subpopulations of smokers. PMID:20170672

  8. Silver resistance in Gram-negative bacteria: a dissection of endogenous and exogenous mechanisms.

    Science.gov (United States)

    Randall, Christopher P; Gupta, Arya; Jackson, Nicole; Busse, David; O'Neill, Alex J

    2015-04-01

    To gain a more detailed understanding of endogenous (mutational) and exogenous (horizontally acquired) resistance to silver in Gram-negative pathogens, with an emphasis on clarifying the genetic bases for resistance. A suite of microbiological and molecular genetic techniques was employed to select and characterize endogenous and exogenous silver resistance in several Gram-negative species. In Escherichia coli, endogenous resistance arose after 6 days of exposure to silver, a consequence of two point mutations that were both necessary and sufficient for the phenotype. These mutations, in ompR and cusS, respectively conferred loss of the OmpC/F porins and derepression of the CusCFBA efflux transporter, both phenotypic changes previously linked to reduced intracellular accumulation of silver. Exogenous resistance involved derepression of the SilCFBA efflux transporter as a consequence of mutation in silS, but was additionally contingent on expression of the periplasmic silver-sequestration protein SilE. Silver resistance could be selected at high frequency (>10(-9)) from Enterobacteriaceae lacking OmpC/F porins or harbouring the sil operon and both endogenous and exogenous resistance were associated with modest fitness costs in vitro. Both endogenous and exogenous silver resistance are dependent on the derepressed expression of closely related efflux transporters and are therefore mechanistically similar phenotypes. The ease with which silver resistance can become selected in some bacterial pathogens in vitro suggests that there would be benefit in improved surveillance for silver-resistant isolates in the clinic, along with greater control over use of silver-containing products, in order to best preserve the clinical utility of silver. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

  9. Endogenous jasmonic and salicylic acids levels in the Cd-hyperaccumulator Noccaea (Thlaspi) praecox exposed to fungal infection and/or mechanical stress.

    Science.gov (United States)

    Llugany, M; Martin, S R; Barceló, J; Poschenrieder, C

    2013-08-01

    Sensitivity to Erysiphe in Noccaea praecox with low metal supply is related to the failure in enhancing SA. Cadmium protects against fungal-infection by direct toxicity and/or enhanced fungal-induced JA signaling. Metal-based defense against biotic stress is an attractive hypothesis on evolutionary advantages of plant metal hyperaccumulation. Metals may compensate for a defect in biotic stress signaling in hyperaccumulators (metal-therapy) by either or both direct toxicity to pathogens and by metal-induced alternative signaling pathways. Jasmonic acid (JA) and salicylic acid (SA) are well-established components of stress signaling pathways. However, few studies evaluate the influence of metals on endogenous concentrations of these defense-related hormones. Even less data are available for metal hyperaccumulators. To further test the metal-therapy hypothesis we analyzed endogenous SA and JA concentrations in Noccaea praecox, a cadmium (Cd) hyperaccumulator. Plants treated or not with Cd, were exposed to mechanical wounding, expected to enhance JA signaling, and/or to infection by biotrophic fungus Erysiphe cruciferarum for triggering SA. JA and SA were analyzed in leaf extracts using LC-ESI(-)-MS/MS. Plants without Cd were more susceptible to fungal attack than plants receiving Cd. Cadmium alone tended to increase leaf SA but not JA. Either or both fungal attack and mechanical wounding decreased SA levels and enhanced JA in the Cd-rich leaves of plants exposed to Cd. High leaf Cd in N. praecox seems to hamper biotic-stress-induced SA, while triggering JA signaling in response to fungal attack and wounding. To the best of our knowledge, this is the first report on the endogenous JA and SA levels in a Cd-hyperaccumulator exposed to different biotic and abiotic stresses. Our results support the view of a defect in SA stress signaling in Cd hyperaccumulating N. praecox.

  10. Protective mechanical ventilation, why use it?

    Science.gov (United States)

    Seiberlich, Emerson; Santana, Jonas Alves; Chaves, Renata de Andrade; Seiberlich, Raquel Carvalho

    2011-01-01

    Mechanical ventilation (MV) strategies have been modified over the last decades with a tendency for increasingly lower tidal volumes (VT). However, in patients without acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) the use of high VTs is still very common. Retrospective studies suggest that this practice can be related to mechanical ventilation-associated ALI. The objective of this review is to search for evidence to guide protective MV in patients with healthy lungs and to suggest strategies to properly ventilate lungs with ALI/ARDS. A review based on the main articles that focus on the use of strategies of mechanical ventilation was performed. Consistent studies to determine which would be the best way to ventilate a patient with healthy lungs are lacking. Expert recommendations and current evidence presented in this article indicate that the use of a VT lower than 10 mL.kg(-1), associated with positive end-expiratory pressure (PEEP) ≥ 5 cmH(2)O without exceeding a pressure plateau of 15 to 20 cmH(2)O could minimize alveolar stretching at the end of inspiration and avoid possible inflammation or alveolar collapse. Copyright © 2011 Elsevier Editora Ltda. All rights reserved.

  11. Native and enzymatically modified wheat (Triticum aestivum L.) endogenous lipids in bread making: a focus on gas cell stabilization mechanisms.

    Science.gov (United States)

    Gerits, Lien R; Pareyt, Bram; Masure, Hanne G; Delcour, Jan A

    2015-04-01

    Lipopan F and Lecitase Ultra lipases were used in straight dough bread making to study how wheat lipids affect bread loaf volume (LV) and crumb structure setting. Lipase effects on LV were dose and dough piece weight dependent. The bread quality improving mechanisms exerted by endogenous lipids were studied in terms of gluten network strengthening, which indirectly stabilizes gas cells, and in terms of direct interfacial gas cell stabilization. Unlike diacetyl tartaric esters of mono- and diacylglycerols (DATEM, used as control), lipase use did not impact dough extensibility. The effect on dough extensibility was therefore related to its lipid composition at the start of mixing. Both lipases and DATEM strongly increase the levels of polar lipids in dough liquor and their availability for and potential accumulation at gas cell interfaces. Lipases form lysolipids that emulsify other lipids. We speculate that DATEM competes with (endogenous) polar lipids for interacting with gluten proteins. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. STUDIES ON TUBERCULIN FEVER. 3. MECHANISMS INVOLVED IN THE RELEASE OF ENDOGENOUS PYROGEN IN VITRO.

    Science.gov (United States)

    ATKINS, E; HEIJN, C

    1965-08-01

    In a search for the source of the circulating endogenous pyrogen (EP) that mediates tuberculin-induced fever, tuberculin was incubated in vitro with various tissues of rabbits sensitized by intravenous infection with BCG. Evidence was obtained that tuberculin specifically stimulates cells in the blood of sensitized rabbits to generate pyrogen in vitro, whereas both lymph node and spleen cells from the same donors were inactive. Since normal blood cells, incubated in plasma of sensitized donors, were similarly activated, it is postulated that circulating antibodies play a role in sensitizing cells (presumably granulocytes) to release pyrogen on contact with tuberculin) both in vitro and in vivo. Release of endogenous pyrogen in vitro may be a sensitive means of detecting immunologic reactions between antigen and specifically sensitized blood cells-in other allergic states accompanied by fever.

  13. Endogenous reward mechanisms and their importance in stress reduction, exercise and the brain

    OpenAIRE

    Esch, Tobias; Stefano, George B.

    2010-01-01

    Stress can facilitate disease processes and causes strain on the health care budgets. It is responsible or involved in many human ailments of our time, such as cardiovascular illnesses, particularly related to the psychosocial stressors of daily life, including work. Besides pharmacological or clinical medical treatment options, behavioral stress reduction is much-needed. These latter approaches rely on an endogenous healing potential via life-style modification. Hence, research has suggested...

  14. [Mechanisms of endogenous drug resistance acquisition by spontaneous chromosomal gene mutation].

    Science.gov (United States)

    Fukuda, H; Hiramatsu, K

    1997-05-01

    Endogenous resistance in bacteria is caused by a change or loss of function and generally genetically recessive. However, this type of resistance acquisition are now prevalent in clinical setting. Chromosomal genes that afford endogenous resistance are the genes correlated with the target of the drug, the drug inactivating enzymes, and permeability of the molecules including the antibacterial agents. Endogenous alteration of the drug target are mediated by the spontaneous mutation of their structural gene. This mutation provides much lower affinity of the drugs for the target. Gene expression of the inactivating enzymes, such as class C beta-lactamase, is generally regulated by regulatory genes. Spontaneous mutations in the regulatory genes cause constitutive enzyme production and provides the resistant to the agent which is usually stable for such enzymes. Spontaneous mutation in the structural gene gives the enzyme extra-spectrum substrate specificity, like ESBL (Extra-Spectrum-beta-Lactamase). Expression of structural genes encoding the permeability systems are also regulated by some regulatory genes. The spontaneous mutation of the regulatory genes reduce an amount of porin protein. This mutation causes much lower influx of the drug in the cell. Spontaneous mutation in promoter region of the structural gene of efflux protein was observed. This mutation raised the gene transcription and overproduced efflux protein. This protein progresses the drug efflux from the cell.

  15. Benzodiazepine receptor ligand influences on learning: an endogenous modulatory mechanism mediated by benzodiazepines possibly of alimentary origin

    Directory of Open Access Journals (Sweden)

    I. Izquierdo

    1991-01-01

    Full Text Available In rats pre-but not post-training ip administration of either flumazenil, a central benzodiazepine (BSD receptor antagonist, or of n-butyl-B-carboline-carboxylate (BCCB, an inverse agonist, enhanced retention of inhibitory avoidance learning. Flumazenil vlocked the enhancing effect of BCCB, and the inhibitory effect of the BZD agonists clonazepam and diazepam also given pre-training. Post-training administration of these drugs had no effects. The peripheral BZD receptor agonist/chloride channel blocker Ro5-4864 had no effect on the inhibitory avoidance task when given ip prior to training, buth it caused enhancement when given immediately post-training either ip or icv. This effect was blocked by PK11195, a competitive antagonist of Ro5-4864. These results suggest that ther is an endogenous mechanism mediated by BZD agonists, which is sensitive to inverse agonists and that normally down-regulates the formation of memories through a mechanism involving GABA-A receptors and the corresponding chloride channels. The most likely agonists for the endogenous mechanism suggested are the diazepam-like BZDs found in brain whose origin is possibly alimentary. Levels of these BZDs in the cortex were found to sharply decrease after inhibitory acoidance training or mere exposure to the training apparatus.

  16. Endogenous repair mechanisms enhanced in Parkinson's disease following stem cell therapy

    Directory of Open Access Journals (Sweden)

    Eleonora Napoli

    2017-01-01

    Full Text Available This mini-review highlights the innovative observation that transplanted human neural stem cells can bring about endogenous brain repair through the stimulation of multiple regenerative processes in the neurogenic area (i.e., subventricular zone [SVZ] in an animal model of Parkinson's disease (PD. In addition, we convey that identifying anti-inflammatory cytokines, therapeutic proteomes, and neurotrophic factors within the SVZ may be essential to induce brain repair and behavioral recovery. This work opens up a new area of research for further understanding the pathology and treatment of PD. This paper is a review article. Referred literature in this paper has been listed in the references section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.

  17. Market mechanism based on the endogenous changing of game types such as Minority-Majority games

    Science.gov (United States)

    Ahn, Sanghyun; Lim, Gyuchang; Kim, Sooyong; Kim, Kyungsik

    2010-03-01

    In many social and biological systems agents simultaneously and adaptively compete for limited resources, thereby altering their environment. We propose a evolution function extending Minority-Majority Games that captures the competition between agents to make money. The dynamics changes the ratio of two types of boundedly rational traders, fundamentalists and chartists with the payoff function endogenously. In the previous game theories, the best strategies are not always targeting the minority but are shifting opportunistically between the minority and the majority. And using a mixture of local bifurcation theory and numerical methods, there are possible bifurcation routes to complicated asset price dynamics, chaotic attractors. Hereby we improve the thinking logic of the atoms for attaching the dynamics to the market. This working shows that removing unrealistic features of the game theories leads to models which reproduce a behavior close to what is observed in real markets.

  18. Combined radiation-protective and radiation-sensitizing agents. III. Radiosensitization by misonidazole as a function of concentrations of endogenous glutathione or exogenous thiols

    International Nuclear Information System (INIS)

    Koch, C.J.; Stobbe, C.C.; Baer, K.A.

    1986-01-01

    Radiosensitization of V79 Chinese hamster fibroblasts by 0.5 mM misonidazole is a smooth function of endogenous glutathione (GSH) levels as modulated upwards by pre-incubation in medium containing cysteamine, or downwards by pre-incubation in medium containing buthionine sulfoximine. The enhancement ratio (radiation sensitivity in nitrogen/radiation sensitivity in nitrogen +/- sensitizer or thiol) varies from 1.3 at 12 mM to 2.25 at less than 0.1 mM endogenous GSH. The enhanced radiosensitivity of thiol-depleted hypoxic cells is reversed when exogenous thiols are added, and for equivalent ER, the exogenous thiol concentrations are much lower than the endogenous GSH concentrations. Measurement of intracellular drug concentrations amplified rather than diminished the above discrepancy, since intracellular concentrations of cysteamine were lower and glutathione much lower than the extracellular concentrations. Three possible explanations are addressed: an external membrane component of damage is involved, long-range protection to DNA target radicals is possible from outside the cell (e.g., donation of electrons), and (c) endogenous glutathione is not in a free or exchangeable state (e.g., bound)

  19. Edge forward mechanical protection for porcelain insulators

    Energy Technology Data Exchange (ETDEWEB)

    deCasseres, D.K.

    1987-12-01

    Vandal damage to exposed outdoor insulators of all types has become an increasing problem. Porcelain is susceptible to impact fracture, and Area Boards have frequently found it necessary to protect expensive and often highly vulnerable terminating assemblies from the unwelcome attention of hooligans. Various means of physical protection can be used, but many of these are highly demanding in terms of maintenance. This article discusses the 'state of the art' in insulator protection, and describes the design and development of a new concept in the field-the Shed Protector-a number of which are now installed on 132kV sealing ends throughout the Electricity Supply Industry.

  20. Legal Mechanisms for Protecting Riparian Resource Values

    Science.gov (United States)

    Lamb, Berton L.; Lord, Eric

    1992-04-01

    Riparian resources include the borders of rivers, lakes, ponds, and potholes. These border areas are very important for a number of reasons, including stream channel maintenance, flood control, aesthetics, erosion control, fish and wildlife habitat, recreation, and water quality maintenance. These diverse functions are not well protected by law or policy. We reviewed law and policies regarding endangered species habitat designation, land use planning, grazing management, water allocation, takings, and federal permits and licenses, along with the roles of federal, state, and local governments. We discuss the politics of implementing these policies, focusing on the difficulties in changing entrenched water and land use practices. Our review indicates a lack of direct attention to riparian ecosystem issues in almost all environmental and land use programs at every level of government. Protection of riparian resource values requires a means to integrate existing programs to focus on riparian zones.

  1. Involvement of endogenous antioxidant systems in the protective activity of pituitary adenylate cyclase-activating polypeptide against hydrogen peroxide-induced oxidative damages in cultured rat astrocytes.

    Science.gov (United States)

    Douiri, Salma; Bahdoudi, Seyma; Hamdi, Yosra; Cubì, Roger; Basille, Magali; Fournier, Alain; Vaudry, Hubert; Tonon, Marie-Christine; Amri, Mohamed; Vaudry, David; Masmoudi-Kouki, Olfa

    2016-06-01

    Astroglial cells possess an array of cellular defense mechanisms, including superoxide dismutase (SOD) and catalase antioxidant enzymes, to prevent damages caused by oxidative stress. Nevertheless, astroglial cell viability and functionality can be affected by significant oxidative stress. We have previously shown that pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent glioprotective agent that prevents hydrogen peroxide (H2 O2 )-induced apoptosis in cultured astrocytes. The purpose of this study was to investigate the potential protective effect of PACAP against oxidative-generated alteration of astrocytic antioxidant systems. Incubation of cells with subnanomolar concentrations of PACAP inhibited H2 O2 -evoked reactive oxygen species accumulation, mitochondrial respiratory burst, and caspase-3 mRNA level increase. PACAP also stimulated SOD and catalase activities in a concentration-dependent manner, and counteracted the inhibitory effect of H2 O2 on the activity of these two antioxidant enzymes. The protective action of PACAP against H2 O2 -evoked inhibition of antioxidant systems in astrocytes was protein kinase A, PKC, and MAP-kinase dependent. In the presence of H2 O2 , the SOD blocker NaCN and the catalase inhibitor 3-aminotriazole, both suppressed the protective effects of PACAP on SOD and catalase activities, mitochondrial function, and cell survival. Taken together, these results indicate that the anti-apoptotic effect of PACAP on astroglial cells can account for the activation of endogenous antioxidant enzymes and reduction in respiration rate, thus preserving mitochondrial integrity and preventing caspase-3 expression provoked by oxidative stress. Considering its powerful anti-apoptotic and anti-oxidative properties, the PACAPergic signaling system should thus be considered for the development of new therapeutical approaches to cure various pathologies involving oxidative neurodegeneration. We propose the following cascade for the

  2. Acupuncture Mechanisms: Anesthesia, Analgesia and Protection on Organ Functions

    Directory of Open Access Journals (Sweden)

    Jing Wang

    2015-01-01

    Full Text Available Acupuncture, as a healing art in traditional Chinese medicine, has been widely used to treat various diseases. In the history of acupuncture anesthesia, in the past decades, mechanisms of acupuncture analgesia has been widely investigated, and in recent years, acupuncture protection on organ functions has attracted great interest. This review summarized the research progress on mechanisms of acupuncture for analgesia and its protection against organ function injury in anesthesia, and its perspective of analgesia, immunomodulation, neuroendocrine regulation and multiple organ protection. The current evidence supports that acupuncture analgesia and its organ protection in anesthesia is associated with the integration of neuroendocrine-immune networks in the level of neurotransmitters, cytokines, hormones, neuronal ensembles, lymphocytes, and endocrine cells. Although the mechanisms of acupuncture analgesia and its organ protection are still not completely understood, basic as well as clinic researches on the mechanisms and applications of acupuncture and related techniques are being carried out.

  3. Endogenous Pyrogen Physiology.

    Science.gov (United States)

    Beisel, William R.

    1980-01-01

    Discusses the physiology of endogenous pyrogen (EP), the fever-producing factor of cellular origin. Included are: its hormone-like role, its molecular nature, bioassay procedures, cellular production and mechanisms of EP action. (SA)

  4. Mechanical ventilation drives pneumococcal pneumonia into lung injury and sepsis in mice: protection by adrenomedullin.

    Science.gov (United States)

    Müller-Redetzky, Holger C; Will, Daniel; Hellwig, Katharina; Kummer, Wolfgang; Tschernig, Thomas; Pfeil, Uwe; Paddenberg, Renate; Menger, Michael D; Kershaw, Olivia; Gruber, Achim D; Weissmann, Norbert; Hippenstiel, Stefan; Suttorp, Norbert; Witzenrath, Martin

    2014-04-14

    Ventilator-induced lung injury (VILI) contributes to morbidity and mortality in acute respiratory distress syndrome (ARDS). Particularly pre-injured lungs are susceptible to VILI despite protective ventilation. In a previous study, the endogenous peptide adrenomedullin (AM) protected murine lungs from VILI. We hypothesized that mechanical ventilation (MV) contributes to lung injury and sepsis in pneumonia, and that AM may reduce lung injury and multiple organ failure in ventilated mice with pneumococcal pneumonia. We analyzed in mice the impact of MV in established pneumonia on lung injury, inflammation, bacterial burden, hemodynamics and extrapulmonary organ injury, and assessed the therapeutic potential of AM by starting treatment at intubation. In pneumococcal pneumonia, MV increased lung permeability, and worsened lung mechanics and oxygenation failure. MV dramatically increased lung and blood cytokines but not lung leukocyte counts in pneumonia. MV induced systemic leukocytopenia and liver, gut and kidney injury in mice with pneumonia. Lung and blood bacterial burden was not affected by MV pneumonia and MV increased lung AM expression, whereas receptor activity modifying protein (RAMP) 1-3 expression was increased in pneumonia and reduced by MV. Infusion of AM protected against MV-induced lung injury (66% reduction of pulmonary permeability p protect against development of lung injury, sepsis and extrapulmonary organ injury in mechanically ventilated individuals with severe pneumonia.

  5. Agonist-induced down-regulation of endogenous protein kinase c α through an endolysosomal mechanism.

    Science.gov (United States)

    Lum, Michelle A; Pundt, Krista E; Paluch, Benjamin E; Black, Adrian R; Black, Jennifer D

    2013-05-03

    Protein kinase C (PKC) isozymes undergo down-regulation upon sustained stimulation. Previous studies have pointed to the existence of both proteasome-dependent and -independent pathways of PKCα processing. Here we demonstrate that these down-regulation pathways are engaged in different subcellular compartments; proteasomal degradation occurs mainly at the plasma membrane, whereas non-proteasomal processing occurs in the perinuclear region. Using cholesterol depletion, pharmacological inhibitors, RNA interference, and dominant-negative mutants, we define the mechanisms involved in perinuclear accumulation of PKCα and identify the non-proteasomal mechanism mediating its degradation. We show that intracellular accumulation of PKCα involves at least two clathrin-independent, cholesterol/lipid raft-mediated pathways that do not require ubiquitination of the protein; one is dynamin-dependent and likely involves caveolae, whereas the other is dynamin- and small GTPase-independent. Internalized PKCα traffics through endosomes and is delivered to the lysosome for degradation. Supportive evidence includes (a) detection of the enzyme in EEA1-positive early endosomes, Rab7-positive late endosomes/multivesicular bodies, and LAMP1-positive lysosomes and (b) inhibition of its down-regulation by lysosome-disrupting agents and leupeptin. Only limited dephosphorylation of PKCα occurs during trafficking, with fully mature enzyme being the main target for lysosomal degradation. These studies define a novel and widespread mechanism of desensitization of PKCα signaling that involves endocytic trafficking and lysosome-mediated degradation of the mature, fully phosphorylated protein.

  6. First principles, market failures and endogenous obsolescence: the dynamic approach to capacity mechanisms

    International Nuclear Information System (INIS)

    Keppler, Jan Horst

    2014-11-01

    The theoretical benchmark model arguing that competitive energy-only markets with VOLL pricing can provide sufficient levels of capacity is a coherent starting point also for discussions about capacity remuneration mechanisms (CRMs). Two types of market imperfection, both stemming from the non-storability of electricity and the resultant inelasticity of demand, however require qualification of the benchmark model and can justify CRMs. The first type of market imperfection relates to the existence of security-of-supply externalities as involuntary curbs on demand under VOLL-pricing create disutility beyond the private non-consumption of electricity. In interconnected economies, utility does not only depend on individual electricity consumption but also on the smooth consumption of others. These externalities are captured in the difference between voluntary and involuntary demand response. The second type of market imperfection relates to the asymmetric incentives for investors under imperfect information. Due to the inelasticity of demand and the lumpiness of generating equipment, investors in markets for non-storable goods will err on the side of caution, under-investing at the margin rather than over-investing. There exists thus not an intrinsic, general case but a time- and context-specific case for CRMs depending on the shape of the load-curve, the elasticity of demand and the availability of flexibility resources. The choice of mechanism will depend on the number of hours of potential capacity short-falls and the resulting capital-intensity of the technologies most apt to respond to them. Most importantly, well-designed CRMs will set in motion the very structural dynamics towards more elastic demand, a development that might one day make them obsolete and render the theoretical benchmark model applicable again. CRMs thus require transparent and pre-announced review mechanisms at regular intervals. (authors)

  7. Incentivizing Verifiable Privacy-Protection Mechanisms for Offline Crowdsensing Applications.

    Science.gov (United States)

    Sun, Jiajun; Liu, Ningzhong

    2017-09-04

    Incentive mechanisms of crowdsensing have recently been intensively explored. Most of these mechanisms mainly focus on the standard economical goals like truthfulness and utility maximization. However, enormous privacy and security challenges need to be faced directly in real-life environments, such as cost privacies. In this paper, we investigate offline verifiable privacy-protection crowdsensing issues. We firstly present a general verifiable privacy-protection incentive mechanism for the offline homogeneous and heterogeneous sensing job model. In addition, we also propose a more complex verifiable privacy-protection incentive mechanism for the offline submodular sensing job model. The two mechanisms not only explore the private protection issues of users and platform, but also ensure the verifiable correctness of payments between platform and users. Finally, we demonstrate that the two mechanisms satisfy privacy-protection, verifiable correctness of payments and the same revenue as the generic one without privacy protection. Our experiments also validate that the two mechanisms are both scalable and efficient, and applicable for mobile devices in crowdsensing applications based on auctions, where the main incentive for the user is the remuneration.

  8. Production of endogenous pyrogen.

    Science.gov (United States)

    Dinarello, C A

    1979-01-01

    The production and release of endogenous pyrogen by the host is the first step in the pathogenesis of fever. Endogenous pyrogen is a low-molecular-weight protein released from phagocytic leukocytes in response to several substances of diverse nature. Some of these agents stimulate production of endogenous pyrogen because they are toxic; others act as antigens and interact with either antibody or sensitized lymphocytes in order to induce its production. Some tumors of macrophage origin produce the molecule spontaneously. Whatever the mechanism involved, endogenous pyrogen is synthesized following transcription of new DNA and translation of mRNA into new protein. Once synthesis is completed, the molecule is released without significant intracellular storage. Recent evidence suggests that following release, molecular aggregates form which are biologically active. In its monomer form, endogenous pyrogen is a potent fever-producing substance and mediates fever by its action on the thermoregulatory center.

  9. Mechanisms of protection of information in computer networks and systems

    Directory of Open Access Journals (Sweden)

    Sergey Petrovich Evseev

    2011-10-01

    Full Text Available Protocols of information protection in computer networks and systems are investigated. The basic types of threats of infringement of the protection arising from the use of computer networks are classified. The basic mechanisms, services and variants of realization of cryptosystems for maintaining authentication, integrity and confidentiality of transmitted information are examined. Their advantages and drawbacks are described. Perspective directions of development of cryptographic transformations for the maintenance of information protection in computer networks and systems are defined and analyzed.

  10. Protective mechanism against cancer found in progeria patient cells

    Science.gov (United States)

    NCI scientists have studied cells of patients with an extremely rare genetic disease that is characterized by drastic premature aging and discovered a new protective cellular mechanism against cancer. They found that cells from patients with Hutchinson Gi

  11. Institutional Mechanisms for Human Rights Protection in Nigeria: An ...

    African Journals Online (AJOL)

    Nnamdi Azikiwe University Journal of International Law and Jurisprudence ... This paper has focused on the institutional mechanisms for human rights protection ... is discussed in line with its powers and duties under the law that established it.

  12. Progranulin contributes to endogenous mechanisms of pain defense after nerve injury in mice.

    Science.gov (United States)

    Lim, Hee-Young; Albuquerque, Boris; Häussler, Annett; Myrczek, Thekla; Ding, Aihao; Tegeder, Irmgard

    2012-04-01

    Progranulin haploinsufficiency is associated with frontotemporal dementia in humans. Deficiency of progranulin led to exaggerated inflammation and premature aging in mice. The role of progranulin in adaptations to nerve injury and neuropathic pain are still unknown. Here we found that progranulin is up-regulated after injury of the sciatic nerve in the mouse ipsilateral dorsal root ganglia and spinal cord, most prominently in the microglia surrounding injured motor neurons. Progranulin knockdown by continuous intrathecal spinal delivery of small interfering RNA after sciatic nerve injury intensified neuropathic pain-like behaviour and delayed the recovery of motor functions. Compared to wild-type mice, progranulin-deficient mice developed more intense nociceptive hypersensitivity after nerve injury. The differences escalated with aging. Knockdown of progranulin reduced the survival of dissociated primary neurons and neurite outgrowth, whereas addition of recombinant progranulin rescued primary dorsal root ganglia neurons from cell death induced by nerve growth factor withdrawal. Thus, up-regulation of progranulin after neuronal injury may reduce neuropathic pain and help motor function recovery, at least in part, by promoting survival of injured neurons and supporting regrowth. A deficiency in this mechanism may increase the risk for injury-associated chronic pain. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  13. Hydrogen sulfide: a new endogenous player in an old mechanism of plant tolerance to high salinity

    Directory of Open Access Journals (Sweden)

    Cristiane J. da-Silva

    2017-10-01

    Full Text Available ABSTRACT High salinity affects plants due to stimulation of osmotic stress. Cell signaling triggered by nitric oxide (NO and hydrogen sulfide (H2S activates a cascade of biochemical events that culminate in plant tolerance to abiotic and biotic stresses. For instance, the NO/H2S-stimulated biochemical events that occur in plants during response to high salinity include the control of reactive oxygen species, activation of antioxidant system, accumulation of osmoprotectants in cytosol, induction of K+ uptake and Na+ cell extrusion or its vacuolar compartmentation among others. This review is a compilation of what we have learned in the last 10 years about NO participation during cell signaling in response to high salinity as well as the role of H2S, a new player in the mechanism of plant tolerance to salt stress. The main sources of NO and H2S in plant cells is also discussed together with the evidence of interplay between both signaling molecules during response to stress.

  14. Endogenous antipyretics.

    Science.gov (United States)

    Roth, Joachim

    2006-09-01

    The febrile increase of body temperature is regarded as a component of the complex host response to infection or inflammation that accompanies the activation of the immune system. Late phases of fever appear mediated by pro-inflammatory cytokines called endogenous pyrogens. The rise of body temperature is beneficial because it accelerates several components of the activated immune system. To prevent an excessive and dangerous rise of body temperature the febrile response is controlled, limited in strength and duration, and sometimes even prevented by the actions of endogenous antipyretic substances liberated systemically or within the brain during fever. In most cases the antipyretic effects are achieved by an inhibitory influence on the formation or action of endogenous pyrogens, or by effects on neuronal thermoregulatory circuits that are activated during fever. Endogenous antipyretic substances include steroid hormones, neuropeptides, cytokines and other molecules. It is the purpose of this review to consider the current state in the research on endogenous antipyretic systems.

  15. Resilience in LGB Youths: A Systematic Review of Protection Mechanisms

    Directory of Open Access Journals (Sweden)

    Daniela Fonseca Freitas

    Full Text Available Abstract: Given the mental health disparities among LGB and heterosexual youth, literature has increasingly emphasized the need to identify the mechanisms that promote resilience among sexual minorities. This systematic review sought to answer the question: what are the protection mechanisms against homophobia among LGB youth? Of the 147 references located in the search, 13 studies were analyzed. The identified protection mechanisms were organized by two criteria: specific to sexual orientation or general, and considered to be at the personal, relational and contextual level. Most of the mechanisms revealed to solely promote the positive adjustment in the presence of risk. General protective mechanisms frequently revealed to be more compensatory of the risks than those specific to sexual orientation.

  16. Radiation-protective drugs and their reaction mechanisms

    International Nuclear Information System (INIS)

    Livesey, J.C.; Reed, D.J.; Adamson, L.F.

    1985-01-01

    The objective of this book is to provide the reader with a concise review of radioprotective drugs and their reaction mechanisms. The first chapter reviews the effect of radiation on biological systems at the atomic, molecular, and subcellular levels. The second chapter discusses endogenous factors that influence radioresistance. Chapter 3 presents the main theme of the book, chemical radioprotection and its mechanisms, and examines the basis of natural radioprotection and how it may be affected by exogenous chemicals. Chapter 4, the Therapy of Radiation Damage, is a very brief general discussion that only touches on some of the experimental approaches to therapy. Chapter 5 contains recommendations for future research. The two appendices list research in progress in the United States and some radioprotective compounds of possible investigational interest. Also included is a brief discussion of structure-activity relationships

  17. Heliox Improves Carbon Dioxide Removal during Lung Protective Mechanical Ventilation

    NARCIS (Netherlands)

    Beurskens, Charlotte J.; Brevoord, Daniel; Lagrand, Wim K.; van den Bergh, Walter M.; Vroom, Margreeth B.; Preckel, Benedikt; Horn, Janneke; Juffermans, Nicole P.

    2014-01-01

    Introduction. Helium is a noble gas with low density and increased carbon dioxide (CO2) diffusion capacity. This allows lower driving pressures in mechanical ventilation and increased CO2 diffusion. We hypothesized that heliox facilitates ventilation in patients during lung-protective mechanical

  18. Endogenous anticancer mechanism: differentiation.

    Science.gov (United States)

    Werneck, Miriam Bianchi de Frontin

    2012-06-01

    It has been recently shown that within heterogeneous tumor masses a small population of less differentiated transformed cells has the ability to self-renew and regenerate the bulk of the tumor. Their similarities with normal stem cells in terms of gene expression patterns, proliferative capacity and surface markers rendered them the name of cancer stem-like cells (CSC), and these are thought to be the tumor initiating cells (TIC). Their limited susceptibility to classical anti-tumor therapy help explain the high incidence of cancer-treatment relapses observed in selected malignancies. Much effort is being directed towards the understanding of factors that maintain CSC survival and their self-renewal capacity, with the goal that these same signaling pathways can be harnessed for treatments that aim at inducing CSC differentiation. This review will discuss the CSC theory, its implications, potential signaling pathways responsible for maintaining their undifferentiated and pluripotent states, and new venues being explored to target these cells in modern cancer therapy.

  19. Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Mørch, Marlene Thorsen; Holm, Thomas Hellesøe

    2015-01-01

    show elevated levels of Type I IFNs in the central nervous system (CNS), suggesting a role for endogenous Type I IFN during inflammation. However, the therapeutic benefit of Type I IFN produced in the CNS remains to be established. The aim of this study was to examine whether experimentally induced CNS......-endogenous Type I IFN influences EAE. Using IFN-β reporter mice, we showed that direct administration of polyinosinic-polycytidylic acid (poly I:C), a potent inducer of IFN-β, into the cerebrospinal fluid induced increased leukocyte numbers and transient upregulation of IFN-β in CD45/CD11b-positive cells located...... in the meninges and choroid plexus, as well as enhanced IFN-β expression by parenchymal microglial cells. Intrathecal injection of poly I:C to mice showing first symptoms of EAE substantially increased the normal disease-associated expression of IFN-α, IFN-β, interferon regulatory factor-7 and IL-10 in CNS...

  20. Business as a component mechanism of social protection of population

    Directory of Open Access Journals (Sweden)

    Tsintsadze Asie

    2014-01-01

    Full Text Available The social protection of population is a main direction of activities of any government. In modern period social protection of population is proceeding with the help of social policy. Mainly social policy implementation is done by the government. Currently in Georgia the main mechanism for social protection is social insurance, which is carried out by the Ministry of Labor, Health and Social Affairs. In Georgia social subsidy agency is responsible for the health insurance and medical programs. Under condition of marketing economy the limitation of interference of government in economy decreased means of social protection. In the modern conditions social protection mechanism should be developed jointly by the government and private sector measures. It becomes necessary to increase the role of business in the social protection of population, which with the difference of charity requests more social responsibility. The most important goal of any government is the effective employment of its population. The research objective is to explore the role of business in the social protection; to set the problems and find the concrete proposals for solving these problems. It is clear that operation of social policy measures can be entirely imposed on the business. As well as the business can ensure effective functioning of the employment level and thus contribute to the development of their own businesses as well as the social policy of government. This paper formulates proposals is direction of the interaction of business and government, their activities for effective social protection of population.

  1. Molecular mechanisms of lipoapoptosis and metformin protection in GLP-1 secreting cells

    DEFF Research Database (Denmark)

    Kappe, Camilla; Holst, Jens Juul; Zhang, Qimin

    2012-01-01

    Evidence is emerging that elevated serum free fatty acids (hyperlipidemia) contribute to the pathogenesis of type-2-diabetes, and lipotoxicity is observed in many cell types. We recently published data indicating lipotoxic effects of simulated hyperlipidemia also in GLP-1-secreting cells, where...... the antidiabetic drug metformin conferred protection from lipoapoptosis. The aim of the present study was to identify mechanisms involved in mediating lipotoxicity and metformin lipoprotection in GLP-1 secreting cells. These signaling events triggered by simulated hyperlipidemia may underlie reduced GLP-1...... secretion in diabetic subjects, and metformin lipoprotection by metformin could explain elevated plasma GLP-1 levels in diabetic patients on chronic metformin therapy. The present study may thus identify potential molecular targets for increasing endogenous GLP-1 secretion through enhanced viability of GLP...

  2. Trajectory data privacy protection based on differential privacy mechanism

    Science.gov (United States)

    Gu, Ke; Yang, Lihao; Liu, Yongzhi; Liao, Niandong

    2018-05-01

    In this paper, we propose a trajectory data privacy protection scheme based on differential privacy mechanism. In the proposed scheme, the algorithm first selects the protected points from the user’s trajectory data; secondly, the algorithm forms the polygon according to the protected points and the adjacent and high frequent accessed points that are selected from the accessing point database, then the algorithm calculates the polygon centroids; finally, the noises are added to the polygon centroids by the differential privacy method, and the polygon centroids replace the protected points, and then the algorithm constructs and issues the new trajectory data. The experiments show that the running time of the proposed algorithms is fast, the privacy protection of the scheme is effective and the data usability of the scheme is higher.

  3. Ecological mechanisms linking protected areas to surrounding lands.

    Science.gov (United States)

    Hansen, Andrew J; DeFries, Ruth

    2007-06-01

    Land use is expanding and intensifying in the unprotected lands surrounding many of the world's protected areas. The influence of this land use change on ecological processes is poorly understood. The goal of this paper is to draw on ecological theory to provide a synthetic framework for understanding how land use change around protected areas may alter ecological processes and biodiversity within protected areas and to provide a basis for identifying scientifically based management alternatives. We first present a conceptual model of protected areas embedded within larger ecosystems that often include surrounding human land use. Drawing on case studies in this Invited Feature, we then explore a comprehensive set of ecological mechanisms by which land use on surrounding lands may influence ecological processes and biodiversity within reserves. These mechanisms involve changes in ecosystem size, with implications for minimum dynamic area, species-area effect, and trophic structure; altered flows of materials and disturbances into and out of reserves; effects on crucial habitats for seasonal and migration movements and population source/sink dynamics; and exposure to humans through hunting, poaching, exotics species, and disease. These ecological mechanisms provide a basis for assessing the vulnerability of protected areas to land use. They also suggest criteria for designing regional management to sustain protected areas in the context of surrounding human land use. These design criteria include maximizing the area of functional habitats, identifying and maintaining ecological process zones, maintaining key migration and source habitats, and managing human proximity and edge effects.

  4. Organizational and legal mechanism of the environmental protection

    Directory of Open Access Journals (Sweden)

    А. П. Гетьман

    2014-12-01

    Full Text Available Organizational and legal mechanisms of environmental protection are defined by the author of the article as a mechanism of organization and system of activities of state executive power bodies and local self-government bodies in the field of environmental public relations arising in connection with environmental protection and environmental safety provision. The rules of administrative law are its legal basis, alongside with the norms of environmental law. The former designed to reflect the specifics of the subject, objects, subjects and principles of legal regulation of social relations in this area. The latter define common goals, objectives and functions of state public relations management nature.

  5. Heliox Improves Carbon Dioxide Removal during Lung Protective Mechanical Ventilation

    OpenAIRE

    Beurskens, Charlotte J; Brevoord, Daniel; Lagrand, Wim K; van den Bergh, Walter M; Vroom, Margreeth B; Preckel, Benedikt; Horn, Janneke; Juffermans, Nicole P

    2014-01-01

    Introduction. Helium is a noble gas with low density and increased carbon dioxide (CO2) diffusion capacity. This allows lower driving pressures in mechanical ventilation and increased CO2 diffusion. We hypothesized that heliox facilitates ventilation in patients during lung-protective mechanical ventilation using low tidal volumes. Methods. This is an observational cohort substudy of a single arm intervention study. Twenty-four ICU patients were included, who were admitted after a cardiac arr...

  6. Mechanism of protective action of surface carbide layers on titanium

    International Nuclear Information System (INIS)

    Chukalovskaya, T.V.; Chebotareva, N.P.; Tomashov, N.D.

    1990-01-01

    The protective action of surface carbide layer on titanium produced in methane atmosphere at 1000 deg C and under 6.7 kPa pressure in H 2 SO 4 solutions is studied through comparison of microsection metallographic specimens prior to and after corrosion testing (after specimen activation); through comparison of anodic characteristics after partial stripping of the layer up to its complete stripping; through analysis of the behaviour of Ti-TiC galvanic couple, and through investigation of corresponding corrosion diagrams under test conditions. It is shown that screening protective mechanism is primarily got involved in highly agressive media (high temperature and concentration of solution), and in less agressive environment the protection of titanium with carbide layer is primarily ensured by electrochemical mechanism

  7. Antioxidative and proline potentials as a protective mechanism in ...

    African Journals Online (AJOL)

    Stress can define as all negative factors affecting plant growth. One of the most important problems among stress factors is salt stress. Antioxidant responses are tested in Soybean (Glycine max. L.) cv., “A3935” grown under 0, 50, 100 and 150 mM NaCl in order to investigate the plants protective mechanisms against salt ...

  8. Combining Semi-Endogenous and Fully Endogenous Growth: a Generalization.

    OpenAIRE

    Cozzi, Guido

    2017-01-01

    This paper shows that combining the semi-endogenous and the fully endogenous growth mechanisms with a general CES aggregator, either growth process can prevail in the balanced growth path depending on their degree of complementarity/substitutability. Policy-induced long-run economic switches to the fully endogenous steady state as the R&D employment ratio surpasses a positive threshold are possible if the two growth engines are gross substitutes.

  9. Mechanism of Fructus Aurantii Flavonoids Promoting Gastrointestinal Motility: From Organic and Inorganic Endogenous Substances Combination Point of View.

    Science.gov (United States)

    Wang, Shuai; Bao, Yong-Rui; Li, Tian-Jiao; Yu, Ting; Chang, Xin; Yang, Guan-Lin; Meng, Xian-Sheng

    2017-01-01

    Fructus Aurantii (FA) derived from the dried, and unripe fruit of Citrus aurantium L. is one of the commonly used traditional Chinese medicines to treat gastrointestinal motility dysfunction diseases. According to the literature research, FA flavonoids (FAF) are important active ingredients of FA promoting gastrointestinal motility, but the exact material basis and mechanism of action are still not very clear. This experiment was designed to illustrate the material basis of FAF promoting gastrointestinal motility and explore the mechanism of action from an organic and inorganic combination point of view. In this experiment, high-performance liquid chromatography (HPLC) method was used to analyze the composition and content of FAF. Based on the prominent prokinetic effect of FAF on mice, the mechanism of action was speculated through a combination of HPLC coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS) and inductively coupled plasma mass spectrometry (ICP-MS). With the method of HPLC, ten dominating components of FAF including neoeriocitrin, narirutin, rhoifolin, naringin, hesperidin, neohesperidin, neoponcirin, naringenin, hesperetin, and nobiletin accounting for more than 86% of FAF were identified. Combined HPLC-QTOF-MS with ICP-MS, the endogenous substances with difference in the blood of mice were analyzed, in which 4-dimethylallyltryptophan, corticosterone, phytosphingosine, sphinganine, LysoPC (20:4(5Z, 8Z, 11Z, 14Z)), LysoPC(18:2 (9Z, 12Z)), and Ca 2+ , Mg 2+ , Zn 2+ metal ions had significant changes, involving tryptophan metabolism, corticosterone metabolism, sphingolipid metabolism, and other pathways. The results preliminarily elaborated the mechanism of FAF promoting gastrointestinal motility from an organic and inorganic point of view, which provide valuable information for researching and developing new multi-component Chinese medicine curing gastrointestinal underpower associated diseases. Fructus Aurantii flavonoids are one

  10. Induction of radiation resistance and radio-protective mechanism. On the reactive oxygen and free radical

    International Nuclear Information System (INIS)

    Yukawa, Osami

    2003-01-01

    Radical scavenging system for reactive oxygen species (ROS) leading to radio-protection is reviewed on findings in animals, tissues and cells. Protection against oxygen toxicity in evolution can be seen in anaerobes' superoxide dismutase (SOD) over 3500 million years ago. ROS is generated endogenously and also by radiation. However, the intracellular sites of the generated ROS are different depending on its cause. The protection is done through enzymes like SOD, peroxidase, catalase, glutathione-related enzymes and through substances like GSH, α-tocopherol, ascorbic acid etc. Induction of ROS scavenging substances related with radio-resistance includes the responses to the low dose radiation (5-50 cGy) in those enzymes described above; to middle to high dose radiation (1-30 Gy) in a similar and in other unknown mechanisms; to exposure of ROS like H 2 O 2 at low concentration; and to antioxidant treatment. The cross-resistance between radiation and drugs suggests necessity of this induction. (N.I.)

  11. High copy number in human endogenous retrovirus families is associated with copying mechanisms in addition to reinfection

    Czech Academy of Sciences Publication Activity Database

    Belshaw, R.; Katzourakis, A.; Pačes, Jan; Burt, A.; Tristem, M.

    2005-01-01

    Roč. 22, č. 4 (2005), s. 814-817 ISSN 0737-4038 R&D Projects: GA MŠk(CZ) 1M0520 Institutional research plan: CEZ:AV0Z50520514 Keywords : human endogenous retrovirus * reinfection * retrotransposition Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.233, year: 2005

  12. Heliox Improves Carbon Dioxide Removal during Lung Protective Mechanical Ventilation.

    Science.gov (United States)

    Beurskens, Charlotte J; Brevoord, Daniel; Lagrand, Wim K; van den Bergh, Walter M; Vroom, Margreeth B; Preckel, Benedikt; Horn, Janneke; Juffermans, Nicole P

    2014-01-01

    Introduction. Helium is a noble gas with low density and increased carbon dioxide (CO2) diffusion capacity. This allows lower driving pressures in mechanical ventilation and increased CO2 diffusion. We hypothesized that heliox facilitates ventilation in patients during lung-protective mechanical ventilation using low tidal volumes. Methods. This is an observational cohort substudy of a single arm intervention study. Twenty-four ICU patients were included, who were admitted after a cardiac arrest and mechanically ventilated for 3 hours with heliox (50% helium; 50% oxygen). A fixed protective ventilation protocol (6 mL/kg) was used, with prospective observation for changes in lung mechanics and gas exchange. Statistics was by Bonferroni post-hoc correction with statistical significance set at P ventilation, respiratory rate decreased (25 ± 4 versus 23 ± 5 breaths min(-1), P = 0.010). Minute volume ventilation showed a trend to decrease compared to baseline (11.1 ± 1.9 versus 9.9 ± 2.1 L min(-1), P = 0.026), while reducing PaCO2 levels (5.0 ± 0.6 versus 4.5 ± 0.6 kPa, P = 0.011) and peak pressures (21.1 ± 3.3 versus 19.8 ± 3.2 cm H2O, P = 0.024). Conclusions. Heliox improved CO2 elimination while allowing reduced minute volume ventilation in adult patients during protective mechanical ventilation.

  13. The mechanisms of protection of antioxidants on Nostoc sphaeroides against UV-B radiation

    Science.gov (United States)

    Wang, G. H.

    UV radiation is one of space harmful factor for earth organisms in space exploration In the present work we studied on the role of antioxidant system in Nostoc sphaeroides K u tz Cyanobacteria and the effects of exogenous antioxidant molecules on its photosynthetic rate under UV-B radiation It was found that UV-B radiation decreased the photosynthetic activity of cyanobacterium but promoted the activity of antioxidant system to protect photosystem II PSII and exogenous antioxidant sodium nitroprusside SNP N-acetylcysteine NAC had an obvious protection on PSII activity under UV-B radiation The activity of SOD Superoxide Dismutase EC 1 15 1 1 CAT Catalase EC 1 11 1 6 POD Peroxidase EC 1 11 1 7 and content of MDA and ASC were improved by 0 5mM and 1mM SNP but 0 1mM SNP decreased the activity of antioxide system Exogenous NAC addition decreased the activity of SOD POD CAT and the content MDA and ASC but exogenous NAC addition increased the content of GSH The results suggested that exogenous SNP and NAC may protect algae by different mechanisms in which SNP maybe play double roles as sources of reactive free radicals or ROS scavengers in formation of algae s protection of PSII under UV-B radiation while NAC does function as antioxidant reagent or precursor of glutathione which could protect PSII directly from UV-B radiation Keyword antioxidant system exogenous or endogenous antioxidant Nostoc sphaeroides photosynthesis UV-B radiation

  14. Environmental toxin acrolein alters levels of endogenous lipids, including TRP agonists: A potential mechanism for headache driven by TRPA1 activation

    Directory of Open Access Journals (Sweden)

    Emma Leishman

    2017-01-01

    Full Text Available Exposure to airborne toxins can trigger headaches, but the mechanisms are not well understood. Some environmental toxins, such as acrolein, activate transient receptor potential ankyrin 1 (TRPA1, a receptor involved in pain sensation that is highly expressed in the trigeminovascular system. It has been shown in rat models that repeated exposure to acrolein induces trigeminovascular sensitization to both TRPA1 and TRP vanilloid 1 (TRPV1 agonists, a phenomenon linked to headache. In this study, we test the hypothesis that the sensitization of trigeminovascular responses in rats after acrolein exposure via inhalation is associated with changes in levels of endogenous lipids, including TRPV1 agonists, in the trigeminal ganglia, trigeminal nucleus, and cerebellum. Lipidomics analysis of 80 lipids was performed on each tissue after acute acrolein, chronic acrolein, or room air control. Both acute and chronic acrolein exposure drove widespread alterations in lipid levels. After chronic acrolein exposure, levels of all 6 N-acyl ethanolamines in the screening library, including the endogenous cannabinoid and TRPV1 agonist, N-arachidonoyl ethanolamine, were elevated in trigeminal tissue and in the cerebellum. This increase in TRPV1 ligands by acrolein exposure may indicate further downstream signaling, in that we also show here that a combination of these TRPV1 endogenous agonists increases the potency of the individual ligands in TRPV1-HEK cells. In addition to these TRPV1 agonists, 3 TRPV3 antagonists, 4 TRPV4 agonists, and 25 orphan lipids were up and down regulated after acrolein exposure. These data support the hypothesis that lipid signaling may represent a mechanism by which repeated exposure to the TRPA1 agonist and environmental toxin, acrolein, drives trigeminovascular sensitization. Keywords: Lipidomics, Endogenous cannabinoid, TRPA1, TRPV1, Lipoamine, Acrolein, Migraine

  15. Endogene CGRP

    OpenAIRE

    Höfer, Martina

    2010-01-01

    Hintergrund und Ziele Die vorliegende tierexperimentelle Arbeit beschäftigt sich mit der Frage, welche Rolle endogenes Calcitonin-gene related peptide (CGRP) in der Niere spielt. Hierbei untersuchten wir die renale CGRP Freisetzung aus renalen Afferenzen in vitro anhand von gesunden Tieren und einem pathologischen Modell der Glomerulonephritis. Man weiß bereits, dass sowohl sympathische als auch primär sensorische Neuronen die Entzündung und die Immunantwort in der Peripherie regulieren (68)....

  16. Heliox Improves Carbon Dioxide Removal during Lung Protective Mechanical Ventilation

    Directory of Open Access Journals (Sweden)

    Charlotte J. Beurskens

    2014-01-01

    Full Text Available Introduction. Helium is a noble gas with low density and increased carbon dioxide (CO2 diffusion capacity. This allows lower driving pressures in mechanical ventilation and increased CO2 diffusion. We hypothesized that heliox facilitates ventilation in patients during lung-protective mechanical ventilation using low tidal volumes. Methods. This is an observational cohort substudy of a single arm intervention study. Twenty-four ICU patients were included, who were admitted after a cardiac arrest and mechanically ventilated for 3 hours with heliox (50% helium; 50% oxygen. A fixed protective ventilation protocol (6 mL/kg was used, with prospective observation for changes in lung mechanics and gas exchange. Statistics was by Bonferroni post-hoc correction with statistical significance set at P<0.017. Results. During heliox ventilation, respiratory rate decreased (25±4 versus 23±5 breaths min−1, P=0.010. Minute volume ventilation showed a trend to decrease compared to baseline (11.1±1.9 versus 9.9±2.1 L min−1, P=0.026, while reducing PaCO2 levels (5.0±0.6 versus 4.5±0.6 kPa, P=0.011 and peak pressures (21.1±3.3 versus 19.8±3.2 cm H2O, P=0.024. Conclusions. Heliox improved CO2 elimination while allowing reduced minute volume ventilation in adult patients during protective mechanical ventilation.

  17. Normal pregnancy: mechanisms underlying the paradox of a ouabain-resistant state with elevated endogenous ouabain, suppressed arterial sodium calcium exchange, and low blood pressure

    Science.gov (United States)

    Jacobs, Brandiese E.; Liu, Yong; Pulina, Maria V.; Golovina, Vera A.

    2012-01-01

    Endogenous cardiotonic steroids (CTS) raise blood pressure (BP) via vascular sodium calcium exchange (NCX1.3) and transient receptor-operated channels (TRPCs). Circulating CTS are superelevated in pregnancy-induced hypertension and preeclampsia. However, their significance in normal pregnancy, where BP is low, is paradoxical. Here we test the hypothesis that vascular resistance to endogenous ouabain (EO) develops in normal pregnancy and is mediated by reduced expression of NCX1.3 and TRPCs. We determined plasma and adrenal levels of EO and the impact of exogenous ouabain in pregnancy on arterial expression of Na+ pumps, NCX1.3, TRPC3, and TRPC6 and BP. Pregnant (embryonic day 4) and nonpregnant rats received infusions of ouabain or vehicle. At 14–16 days, tissues and plasma were collected for blotting and EO assay by radioimmunoassay (RIA), liquid chromatography (LC)-RIA, and LC-multidimensional mass spectrometry (MS3). BP (−8 mmHg; P vs. nonpregnant (0.6 ± 0.08 nM; P endogenous and exogenous ouabain is mediated by suppressed NCX1.3 and reduced sensitivity of events downstream of Ca2+ entry. The mechanisms of EO resistance and the impaired fetal and placental growth due to elevated ouabain may be important in pregnancy-induced hypertension (PIH) and preeclampsia (PE). PMID:22245773

  18. Protection against β-amyloid neurotoxicity by a non-toxic endogenous N-terminal β-amyloid fragment and its active hexapeptide core sequence.

    Science.gov (United States)

    Forest, Kelly H; Alfulaij, Naghum; Arora, Komal; Taketa, Ruth; Sherrin, Tessi; Todorovic, Cedomir; Lawrence, James L M; Yoshikawa, Gene T; Ng, Ho-Leung; Hruby, Victor J; Nichols, Robert A

    2018-01-01

    High levels (μM) of beta amyloid (Aβ) oligomers are known to trigger neurotoxic effects, leading to synaptic impairment, behavioral deficits, and apoptotic cell death. The hydrophobic C-terminal domain of Aβ, together with sequences critical for oligomer formation, is essential for this neurotoxicity. However, Aβ at low levels (pM-nM) has been shown to function as a positive neuromodulator and this activity resides in the hydrophilic N-terminal domain of Aβ. An N-terminal Aβ fragment (1-15/16), found in cerebrospinal fluid, was also shown to be a highly active neuromodulator and to reverse Aβ-induced impairments of long-term potentiation. Here, we show the impact of this N-terminal Aβ fragment and a shorter hexapeptide core sequence in the Aβ fragment (Aβcore: 10-15) to protect or reverse Aβ-induced neuronal toxicity, fear memory deficits and apoptotic death. The neuroprotective effects of the N-terminal Aβ fragment and Aβcore on Aβ-induced changes in mitochondrial function, oxidative stress, and apoptotic neuronal death were demonstrated via mitochondrial membrane potential, live reactive oxygen species, DNA fragmentation and cell survival assays using a model neuroblastoma cell line (differentiated NG108-15) and mouse hippocampal neuron cultures. The protective action of the N-terminal Aβ fragment and Aβcore against spatial memory processing deficits in amyloid precursor protein/PSEN1 (5XFAD) mice was demonstrated in contextual fear conditioning. Stabilized derivatives of the N-terminal Aβcore were also shown to be fully protective against Aβ-triggered oxidative stress. Together, these findings indicate an endogenous neuroprotective role for the N-terminal Aβ fragment, while active stabilized N-terminal Aβcore derivatives offer the potential for therapeutic application. © 2017 International Society for Neurochemistry.

  19. Soluble factor(s) from bone marrow cells can rescue lethally irradiated mice by protecting endogenous hematopoietic stem cells.

    Science.gov (United States)

    Zhao, Yi; Zhan, Yuxia; Burke, Kathleen A; Anderson, W French

    2005-04-01

    Ionizing radiation-induced myeloablation can be rescued via bone marrow transplantation (BMT) or administration of cytokines if given within 2 hours after radiation exposure. There is no evidence for the existence of soluble factors that can rescue an animal after a lethal dose of radiation when administered several hours postradiation. We established a system that could test the possibility for the existence of soluble factors that could be used more than 2 hours postirradiation to rescue animals. Animals with an implanted TheraCyte immunoisolation device (TID) received lethal-dose radiation and then normal bone marrow Lin- cells were loaded into the device (thereby preventing direct interaction between donor and recipient cells). Animal survival was evaluated and stem cell activity was tested with secondary bone marrow transplantation and flow cytometry analysis. Donor cell gene expression of five antiapoptotic cytokines was examined. Bone marrow Lin- cells rescued lethally irradiated animals via soluble factor(s). Bone marrow cells from the rescued animals can rescue and repopulate secondary lethally irradiated animals. Within the first 6 hours post-lethal-dose radiation, there is no significant change of gene expression of the known radioprotective factors TPO, SCF, IL-3, Flt-3 ligand, and SDF-1. Hematopoietic stem cells can be protected in lethally irradiated animals by soluble factors produced by bone marrow Lin- cells.

  20. RPA and Rad51 constitute a cell intrinsic mechanism to protect the cytosol from self DNA.

    Science.gov (United States)

    Wolf, Christine; Rapp, Alexander; Berndt, Nicole; Staroske, Wolfgang; Schuster, Max; Dobrick-Mattheuer, Manuela; Kretschmer, Stefanie; König, Nadja; Kurth, Thomas; Wieczorek, Dagmar; Kast, Karin; Cardoso, M Cristina; Günther, Claudia; Lee-Kirsch, Min Ae

    2016-05-27

    Immune recognition of cytosolic DNA represents a central antiviral defence mechanism. Within the host, short single-stranded DNA (ssDNA) continuously arises during the repair of DNA damage induced by endogenous and environmental genotoxic stress. Here we show that short ssDNA traverses the nuclear membrane, but is drawn into the nucleus by binding to the DNA replication and repair factors RPA and Rad51. Knockdown of RPA and Rad51 enhances cytosolic leakage of ssDNA resulting in cGAS-dependent type I IFN activation. Mutations in the exonuclease TREX1 cause type I IFN-dependent autoinflammation and autoimmunity. We demonstrate that TREX1 is anchored within the outer nuclear membrane to ensure immediate degradation of ssDNA leaking into the cytosol. In TREX1-deficient fibroblasts, accumulating ssDNA causes exhaustion of RPA and Rad51 resulting in replication stress and activation of p53 and type I IFN. Thus, the ssDNA-binding capacity of RPA and Rad51 constitutes a cell intrinsic mechanism to protect the cytosol from self DNA.

  1. Fisetin Protects DNA Against Oxidative Damage and Its Possible Mechanism.

    Science.gov (United States)

    Wang, Tingting; Lin, Huajuan; Tu, Qian; Liu, Jingjing; Li, Xican

    2016-06-01

    The paper tries to assess the protective effect of fisetin against •OH-induced DNA damage, then to investigate the possible mechanism. The protective effect was evaluated based on the content of malondialdehyde (MDA). The possible mechanism was analyzed using various antioxidant methods in vitro, including •OH scavenging (deoxyribose degradation), •O2 (-) scavenging (pyrogallol autoxidation), DPPH• scavenging, ABTS•(+) scavenging, and Cu(2+)-reducing power assays. Fisetin increased dose-dependently its protective percentages against •OH-induced DNA damage (IC50 value =1535.00±29.60 µM). It also increased its radical-scavenging percentages in a dose-dependent manner in various antioxidants assays. Its IC50 values in •OH scavenging, •O2(-) scavenging, DPPH• scavenging, ABTS•(+) scavenging, and Cu(2+)-reducing power assays, were 47.41±4.50 µM, 34.05±0.87 µM, 9.69±0.53 µM, 2.43±0.14 µM, and 1.49±0.16 µM, respectively. Fisetin can effectively protect DNA against •OH-induced oxidative damage possibly via reactive oxygen species (ROS) scavenging approach, which is assumed to be hydrogen atom (H•) and/or single electron (e) donation (HAT/SET) pathways. In the HAT pathway, the 3',4'-dihydroxyl moiety in B ring of fisetin is thought to play an important role, because it can be ultimately oxidized to a stable ortho-benzoquinone form.

  2. Protection of mechanized timberings on beds dangerous for mine impacts

    Energy Technology Data Exchange (ETDEWEB)

    Budirsky, S

    1982-01-01

    In some stoping faces on beds which are dangerous for mine impacts, mechanized timbering is successfully used which is not equipped with protection from the effect of these dynamic phenomena. This generated the idea that in the indicated conditions, mechanized timbering may not be equipped with protective devices against dynamic loads. Theoretical studies have shown that the effects of mine impacts depends on the total energy of the impact, distance of this stoping face from the epicenter of the impact, as well as the capacity of the rock massif to transmit and absorb energy of the mine impact. This means that the effect of the mine impact under different conditions is not the same, the mine impacts of lower energy under definite conditions can result in greater damages to the mechanized timbering than mine impact with higher energy. It is believed that the effect of absorption of energy of the mine impact depends on the method of control of the roofing in the stoping face, the presence of hydraulic fill quarantees absorption of up to 80% of its energy. The experience of working beds which are dangerous for mine impacts in the upper Silesia coal basin indicated that the designs of the mechanized timbering, especially shield, in which the stands are not rigidly connected to the roof timber, during operation on beds with thickness 2.5-4 m withstand mine impacts with energy 10/sup 7/ J without significant disorders (mine impacts with this energy occur very frequently . For energy of mine impact of 108 J (impacts with this energy are observed comparatively rarely), the mechanized timberings are considerably damaged.

  3. Mechanical Testing of Carbon Based Woven Thermal Protection Materials

    Science.gov (United States)

    Pham, John; Agrawal, Parul; Arnold, James O.; Peterson, Keith; Venkatapathy, Ethiraj

    2013-01-01

    Three Dimensional Woven thermal protection system (TPS) materials are one of the enabling technologies for mechanically deployable hypersonic decelerator systems. These materials have been shown capable of serving a dual purpose as TPS and as structural load bearing members during entry and descent operations. In order to ensure successful structural performance, it is important to characterize the mechanical properties of these materials prior to and post exposure to entry-like heating conditions. This research focuses on the changes in load bearing capacity of woven TPS materials after being subjected to arcjet simulations of entry heating. Preliminary testing of arcjet tested materials [1] has shown a mechanical degradation. However, their residual strength is significantly more than the requirements for a mission to Venus [2]. A systematic investigation at the macro and microstructural scales is reported here to explore the potential causes of this degradation. The effects of heating on the sizing (an epoxy resin coating used to reduce friction and wear during fiber handling) are discussed as one of the possible causes for the decrease in mechanical properties. This investigation also provides valuable guidelines for margin policies for future mechanically deployable entry systems.

  4. Overexpression of Endogenous Anti-Oxidants with Selenium Supplementation Protects Trophoblast Cells from Reactive Oxygen Species-Induced Apoptosis in a Bcl-2-Dependent Manner.

    Science.gov (United States)

    Khera, Alisha; Vanderlelie, Jessica J; Holland, Olivia; Perkins, Anthony V

    2017-06-01

    The human placenta provides life support for the developing foetus, and a healthy placenta is a prerequisite to a healthy start to life. Placental tissue is subject to oxidative stress which can lead to pathological conditions of pregnancy such as preeclampsia, preterm labour and intrauterine growth restriction. Up-regulation of endogenous anti-oxidants may alleviate placental oxidative stress and provide a therapy for these complications of pregnancy. In this study, selenium supplementation, as inorganic sodium selenite (NaSel) or organic selenomethionine (SeMet), was used to increase the protein production and cellular activity of the important redox active proteins glutathione peroxidase (GPx) and thioredoxin reductase (Thx-Red). Placental trophoblast cell lines, BeWo, JEG-3 and Swan-71, were cultured in various concentrations of NaSel or SeMet for 24 h and cell extracts prepared for western blots and enzyme assays. Rotenone and antimycin were used to stimulate mitochondrial reactive oxygen species (ROS) production and induce apoptosis. Trophoblast cells supplemented with 100 nM NaSel and 500 nM SeMet exhibited significantly enhanced expression and activity of both GPx and Thx-Red. Antimycin and rotenone were found to generate ROS when measured by 2',7'-dichlorofluorescein diacetate (DCFDA) assay, and selenium supplementation was shown to reduce ROS production in a dose-dependent manner. Rotenone, 100 μM treatment for 4 h, caused trophoblast cell apoptosis as evidenced by increased Annexin V binding and decreased expression of Bcl-2. In both assays of apoptosis, selenium supplementation was able to prevent apoptosis, preserve Bcl-2 expression and protect trophoblast cells from mitochondrial oxidative stress. This data suggests that selenoproteins such as GPx and Thx-Red have an important role in protecting trophoblast cells from mitochondrial oxidative stress and that selenium supplementation may be important in treating some placental pathologies.

  5. Meniscal repair following meniscectomy: Mechanism and protective effect

    International Nuclear Information System (INIS)

    Berjon, J.J.; Munuera, L.; Calvo, M.

    1990-01-01

    Meniscal repair was studied to evaluate the mechanism and its potential protective effects on the articular cartilage in an experimental model consisting of 68 knees of adult dogs on which five different types of medial meniscectomy were performed. The results were assessed by macroscopic, microangiographic, and histological methods, after a sequential follow-up period of 10-450 days. Two different mechanisms of meniscal repair were observed, depending on whether meniscal section had been performed in vascular (total meniscectomy) or avascular (subtotal or partial meniscectomy) zones. It was also observed that the repaired meniscal tissue does not prevent articular cartilage degeneration. This is more closely related to the size of the meniscal fragment preserved at meniscetomy. Due to the biomechanical importance of the meniscus and the lack of functional relevance of the repaired meniscal tissue, the most conservative approach possible to meniscectomy is recommended. (orig.)

  6. Mechanisms of radiation oncogenesis and their implications for radiological protection

    International Nuclear Information System (INIS)

    Cox, R.

    1992-01-01

    Studies on the genetics, cytogenetics, biochemistry and molecular biology of neoplasia are now beginning to provide us with an increasingly coherent picture of cancer induction and development. Some of the genes involved in this complex multi-step cellular process have been isolated and characterized and in a few instances it is possible to identify target genes for the initiation of specific neoplasms and how these genes are mutated by environmental carcinogens. Knowledge of molecular mechanisms of mammalian DNA repair and mutagenesis has similarly increased and, together with limited studies of molecular mechanisms of radiation oncogenesis in animal systems, allows specific comment on the molecular nature of radiation-induced initiating events for neoplasia. These data are discussed with an emphasis on their possible implications for radiological protection. (author)

  7. Thermal assault and polyurethane foam-evaluating protective mechanisms

    International Nuclear Information System (INIS)

    Williamson, C.L.; Iams, Z.L.

    2004-01-01

    Rigid polyurethane foam utilizes a variety of mechanisms to mitigate the thermal assault of a ''regulatory burn''. Polymer specific heat and foam k-factor are of limited usefulness in predicting payload protection. Properly formulated rigid polyurethane foam provides additional safeguards by employing ablative mechanisms which are effective even when the foam has been crushed or fractured as a result of trauma. The dissociative transitions from polymer to gas and char, and the gas transport of heat from inside the package out into the environment are also thermal mitigators. Additionally, the in-situ production of an intumescent, insulative, carbonaceous char, confers thermal protection even when a package's outer steel skin has been breached. In this test program, 19 liter, ''Five gallon'' steel pails are exposed on one end to the flame of an ''Oil Burner'' as described in the US Federal Aviation Administration (FAA) ''Aircraft Materials Fire Test Handbook''. When burning 2 diesel at a nominal rate of 8.39 kg (18.5 pounds)/hr, the burner generates a high emissivity flame that impinges on the pail face with the thermal intensity of a full scale pool-fire environment. Results of these tests, TGA and MDSC analysis on the subject foams are reported, and their relevance to full size packages and pool fires are discussed

  8. Redox cycling of endogenous copper by ferulic acid leads to cellular DNA breakage and consequent cell death: A putative cancer chemotherapy mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Sarwar, Tarique [Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, UP 202002 (India); Zafaryab, Md [Genome Biology Lab, Department of Biosciences, Jamia Millia Islamia, Central University, New Delhi 110025 (India); Husain, Mohammed Amir; Ishqi, Hassan Mubarak; Rehman, Sayeed Ur [Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, UP 202002 (India); Moshahid Alam Rizvi, M. [Genome Biology Lab, Department of Biosciences, Jamia Millia Islamia, Central University, New Delhi 110025 (India); Tabish, Mohammad, E-mail: tabish.bcmlab@gmail.com [Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, UP 202002 (India)

    2015-12-01

    Ferulic acid (FA) is a plant polyphenol showing diverse therapeutic effects against cancer, diabetes, cardiovascular and neurodegenerative diseases. FA is a known antioxidant at lower concentrations, however at higher concentrations or in the presence of metal ions such as copper, it may act as a pro-oxidant. It has been reported that copper levels are significantly raised in different malignancies. Cancer cells are under increased oxidative stress as compared to normal cells. Certain therapeutic substances like polyphenols can further increase this oxidative stress and kill cancer cells without affecting the proliferation of normal cells. Through various in vitro experiments we have shown that the pro-oxidant properties of FA are enhanced in the presence of copper. Comet assay demonstrated the ability of FA to cause oxidative DNA breakage in human peripheral lymphocytes which was ameliorated by specific copper-chelating agent such as neocuproine and scavengers of ROS. This suggested the mobilization of endogenous copper in ROS generation and consequent DNA damage. These results were further validated through cytotoxicity experiments involving different cell lines. Thus, we conclude that such a pro-oxidant mechanism involving endogenous copper better explains the anticancer activities of FA. This would be an alternate non-enzymatic, and copper-mediated pathway for the cytotoxic activities of FA where it can selectively target cancer cells with elevated levels of copper and ROS. - Highlights: • Pro-oxidant properties of ferulic acid are enhanced in presence of copper. • Ferulic acid causes oxidative DNA damage in lymphocytes as observed by comet assay. • DNA damage was ameliorated by copper chelating agent neocuproine and ROS scavengers. • Endogenous copper is involved in ROS generation causing DNA damage. • Ferulic acid exerts cancer cell specific cytotoxicity as observed by MTT assay.

  9. 5-HT3 and 5-HT4 antagonists inhibit peristaltic contractions in guinea-pig distal colon by mechanisms independent of endogenous 5-HT

    Directory of Open Access Journals (Sweden)

    Tiong Cheng Sia

    2013-08-01

    Full Text Available Recent studies have shown that endogenous serotonin is not required for colonic peristalsis in vitro, nor gastrointestinal (GI transit in vivo. However, antagonists of 5-Hydroxytryptamine (5-HT receptors can inhibit peristalsis and GI-transit in mammals, including humans. This raises the question of how these antagonists inhibit GI-motility and transit, if depletion of endogenous 5-HT does not cause any significant inhibitory changes to either GI-motility or transit ? We investigated the mechanism by which 5-HT3 and 5-HT4 antagonists inhibit distension-evoked peristaltic contractions in guinea-pig distal colon. In control animals, repetitive peristaltic contractions of the circular muscle were evoked in response to fixed fecal pellet distension. Distension-evoked peristaltic contractions were unaffected in animals with mucosa and submucosal plexus removed, that were also treated with reserpine (to deplete neuronal 5-HT. In control animals, peristaltic contractions were blocked temporarily by ondansetron (1-10µM and SDZ-205-557 (1-10µM in many animals. Interestingly, after this temporary blockade, and whilst in the continued presence of these antagonists, peristaltic contractions recovered, with characteristics no different from controls. Surprisingly, similar effects were seen in mucosa-free preparations, which had no detectable 5-HT, as detected by mass spectrometry. In summary, distension-evoked peristaltic reflex contractions of the circular muscle layer of the guinea-pig colon can be inhibited temporarily, or permanently, in the same preparation by selective 5-HT3 and 5-HT4 antagonists, depending on the concentration of the antagonists applied. These effects also occur in preparations that lack any detectable 5-HT. We suggest caution should be exercised when interpreting the effects of 5-HT3 and 5-HT4 antagonists; and the role of endogenous 5-HT, in the generation of distension-evoked colonic peristalsis.

  10. The mechanical integrity and protective performance of silica coatings

    International Nuclear Information System (INIS)

    Crouch, A.G.; Dooley, R.B.

    1976-01-01

    Silica coatings have been developed to reduce the oxidation rates of 9Cr and other steels in high temperature environments. An important aspect of their performance is their ability to withstand the mechanical and thermal strains likely to be encountered in practical applications. This has been examined. Silica-coated 9 Cr steel specimens were deformed in tension and coating failure was detected by scanning electron microscope observations of the oxide stringers which delineated the strain-induced cracks on subsequent exidation. Coating fracture was shown to occur in the strain range 0.27 to 0.45%. The crack separation at constant coating thickness decresed with strain and at constant strain was approximately proportional to the square root of the coating thickness. The implications of these results for the protection of the underlying alloy by a cracked coating are considered. (author)

  11. Financial protection mechanisms for inpatients at selected Philippine hospitals.

    Science.gov (United States)

    Caballes, Alvin B; Söllner, Walter; Nañagas, Juan

    2012-11-01

    The study was undertaken to determine, from the patient's perspective, the comparative effectiveness of locally established financial protection mechanisms particularly for indigent and severely-ill hospitalized patients. Data was obtained from a survey conducted in 2010 in Philippine provinces which were part of the Health Systems Development Project and involved 449 patients from selected private and public hospitals. Direct medical expenses incurred during the confinement period, whether already paid for prior to or only billed upon discharge, were initially considered. Expenses were found to be generally larger for the more severely ill and lower for the poor. Hospital-provided discounts and social health insurance (PhilHealth) reimbursements were the financial protection mechanisms evaluated in this study. In average terms, only up to 46% of inpatient expenses were potentially covered by the combined financial support. Depending on the hospital type, 28-42% of submitted PhilHealth claims were invalidated. Multiple linear regression analysis was utilized to determine the relationship of the same set of patients' demographic characteristics, socioeconomic status, severity of illness, and hospital assignments with selected expense categories and financial protection measures. Pre-discharge expenditures were significantly higher in public hospitals. The very ill also faced significantly larger expenses, including those for final hospital charges. Hospital-derived discounts provided significantly more support for indigent as well as very sick patients. The amounts for verified PhilHealth claims were significantly greater for the moderately-ill and, incongruously, the financially better-off patients. Sponsored Program members, supposed indigents enjoying fully-subsidized PhilHealth enrollment, qualified for higher mean reimbursements. However, there was a weak correlation between such patients and those identified as poor by the hospital social service staff. Thus

  12. α-Linolenic Acid, A Nutraceutical with Pleiotropic Properties That Targets Endogenous Neuroprotective Pathways to Protect against Organophosphate Nerve Agent-Induced Neuropathology

    Directory of Open Access Journals (Sweden)

    Tetsade Piermartiri

    2015-11-01

    Full Text Available α-Linolenic acid (ALA is a nutraceutical found in vegetable products such as flax and walnuts. The pleiotropic properties of ALA target endogenous neuroprotective and neurorestorative pathways in brain and involve the transcription factor nuclear factor kappa B (NF-κB, brain-derived neurotrophic factor (BDNF, a major neuroprotective protein in brain, and downstream signaling pathways likely mediated via activation of TrkB, the cognate receptor of BDNF. In this review, we discuss possible mechanisms of ALA efficacy against the highly toxic OP nerve agent soman. Organophosphate (OP nerve agents are highly toxic chemical warfare agents and a threat to military and civilian populations. Once considered only for battlefield use, these agents are now used by terrorists to inflict mass casualties. OP nerve agents inhibit the critical enzyme acetylcholinesterase (AChE that rapidly leads to a cholinergic crisis involving multiple organs. Status epilepticus results from the excessive accumulation of synaptic acetylcholine which in turn leads to the overactivation of muscarinic receptors; prolonged seizures cause the neuropathology and long-term consequences in survivors. Current countermeasures mitigate symptoms and signs as well as reduce brain damage, but must be given within minutes after exposure to OP nerve agents supporting interest in newer and more effective therapies. The pleiotropic properties of ALA result in a coordinated molecular and cellular program to restore neuronal networks and improve cognitive function in soman-exposed animals. Collectively, ALA should be brought to the clinic to treat the long-term consequences of nerve agents in survivors. ALA may be an effective therapy for other acute and chronic neurodegenerative disorders.

  13. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

  14. Inflation gifts and endogenous growth through learning-by-doing

    OpenAIRE

    Andrea Vaona

    2013-01-01

    We investigate the link between inflation, growth and unemployment nesting a model of fair wages into one of endogenous growth of learning by doing and assuming that firms protect wages' purchasing power against inflation in exchange of worker's effort. Unemployment decreases with higher inflation and real growth rates. These effects tends to vanish as inflation and growth increase. Depending on the assumptions on learning-by-doing mechanisms, the effect of inflation on growth can be either n...

  15. SPARC/osteonectin, an endogenous mechanism for targeting albumin to the blood-cerebrospinal fluid interface during brain development

    DEFF Research Database (Denmark)

    Liddelow, S A; Dziegielewska, K M; Møllgård, K

    2011-01-01

    Specialized populations of choroid plexus epithelial cells have previously been shown to be responsible for the transfer of individual plasma proteins from blood to the cerebrospinal fluid (CSF), contributing to their characteristically high concentrations in CSF of the developing brain. The mech......Specialized populations of choroid plexus epithelial cells have previously been shown to be responsible for the transfer of individual plasma proteins from blood to the cerebrospinal fluid (CSF), contributing to their characteristically high concentrations in CSF of the developing brain....... The mechanism of this protein transfer remains elusive. Using a marsupial, Monodelphis domestica, we demonstrate that the albumin-binding protein SPARC (osteonectin/BM-40/culture-shock protein) is present in a subset of choroid plexus epithelial cells from its first appearance, throughout development...

  16. Mechanization of hand labour in special protective works

    International Nuclear Information System (INIS)

    Zhukov, O.A.; Arnol'd, V.V.; Gavritenkov, I.A.; Selyanko, V.G.

    1986-01-01

    New high-efficient technologies introduced in Souzehnergozashchita unit corporation are described in short. The corporation deals with mounting of setting and thermal insulation as well as with works on corrosion protection of TPP and NPP equipment. The innovations include the introduction of polymeric coatings of floors, epoxide enamels for construction structure protection, polymeric materials for which a flame plating technology has been developed

  17. Studies on the Protective Effects of Scutellarein against Neuronal Injury by Ischemia through the Analysis of Endogenous Amino Acids and Ca2+ Concentration Together with Ca2+-ATPase Activity

    Directory of Open Access Journals (Sweden)

    Hao Tang

    2015-01-01

    Full Text Available Scutellarin, which is extracted from the dried plant of Erigeron breviscapus, has been reported to protect the neural injury against excitotoxicity induced by ischemia. However, there are a few studies on the protective effects of scutellarein, which is the main metabolite of scutellarin in vivo. Thus, this study investigated the neuroprotective effects of scutellarein on cerebral ischemia/reperfusion in rats by bilateral common carotid artery occlusion (BCCAO model, through the analysis of endogenous amino acids using HILIC-MS/MS, and evaluation of Ca2+ concentration together with Ca2+-ATPase activity. The results showed that scutellarein having good protective effects on cerebral ischemia/reperfusion might by decreasing the excitatory amino acids, increasing the inhibitory amino acids, lowing intracellular Ca2+ level, and improving Ca2+-ATPase activity, which suggested that scutellarein might be a promising potent agent for the therapy of ischemic cerebrovascular disease.

  18. Anti-ulcerogenic mechanisms of the sesquiterpene lactone onopordopicrin-enriched fraction from Arctium lappa L. (Asteraceae): role of somatostatin, gastrin, and endogenous sulfhydryls and nitric oxide.

    Science.gov (United States)

    de Almeida, Ana Beatriz Albino; Luiz-Ferreira, Anderson; Cola, Maíra; Di Pietro Magri, Luciana; Batista, Leonia Maria; de Paiva, Joseilson Alves; Trigo, José Roberto; Souza-Brito, Alba R M

    2012-04-01

    Arctium lappa L. has been used in folk medicine as a diuretic, depurative, and digestive stimulant and in dermatological conditions. The mechanisms involved in the anti-ulcerogenic activity of the sesquiterpene onopordopicrin (ONP)-enriched fraction (termed the ONP fraction), obtained from A. lappa leaves, were studied. The gastroprotective mechanism of the ONP fraction was evaluated in experimental in vivo models in rodents, mimicking this disease in humans. ONP fraction (50 mg/kg, p.o.) significantly inhibited the mucosal injury induced by ethanol/HCl solution (75%), indomethacin/bethanecol (68.9%), and stress (58.3%). When the ONP fraction was investigated in pylorus ligature, it did not induce alteration in the gastric volume but did modify the pH and total acid concentration of gastric juice. ONP fraction significantly increased serum somatostatin levels (82.1±4.1 vs. control group 12.7±4 pmol/L) and decreased serum gastrin levels (62.6±6.04 vs. control group 361.5±8.2 μU/mL). Mucus production was not significantly altered by the ONP fraction. Gastroprotection by the ONP fraction was completely inhibited by N-ethylmaleimide treatment and did not modify the effect in the animals pretreated with l-N(G)-nitroarginine methyl ester. These results suggest an antisecretory mechanism involved with the antiulcerogenic effect of the ONP fraction. However, only endogenous sulfhydryls play an important role in gastroprotection of the ONP fraction.

  19. Incentive mechanisms for ecosystem protection on private lands

    International Nuclear Information System (INIS)

    Cooper, J.; Perali, F.; Veronesi, M.

    2008-01-01

    This study has the objective to bring to the fore the importance of appropriate incentive schemes for the protection of biodiversity and ecosystems on private lands. The analysis describes the effectiveness of the regulations implemented in advanced countries. In particular, first the study presents some examples and discusses the implications of the actual legislation in developed countries for the protection of biodiversity and ecosystem services. Then, the study analyses the legal doctrine regarding compensation, and the available economic instruments for ecosystem services protection. Finally, the study presents the best economic tools capable to align private behavior with the social goals of protecting the services offered by the ecosystems and favoring the participation of private owners to projects for sustainable production and conservation. Special attention is paid to the institution of Community Foundations using as models those implemented in the United States. [it

  20. Protective Mechanisms of Nitrone Antioxidants in Kanic Acid Induced Neurodegeneration

    Science.gov (United States)

    2004-01-01

    Shin, E.J., Suh, J.H., Floyd, R.A., Bing, G. (1999) Protection of methamphetamine nigrostriatal toxicity by dietary selenium. Brain Res. 851:76-86...HC, and Bing, GY. (2004) Interleukin-10 protects against lipopolysaccharide-mediated neurotoxicity in substantia nigra Neurosci. Abstr. 29:677.18. 71...2004) Roles of the cyclooxygenase-2 and oxidative stress in the methamphetamine - induced neurotoxicity Neurosci. Abstr. 29:235.4.

  1. Studies on the mechanism of endogenous pyrogen production. II. Role of cell products in the regulation of pyrogen release from blood leukocytes.

    Science.gov (United States)

    Bodel, P

    1974-09-01

    Some characteristics of the process by which endogenous pyrogen (EP), the mediator of fever, is released from cells were examined by using human blood leukocytes incubated in vitro. Studies were designed to examine a possible role for leukocyte products, including EP, in the induction, augmentation, or suppression of pyrogen release by blood leukocytes. Products of stimulated leukocytes, including a partially purified preparation of EP, did not induce significant activation of nonstimulated cells. Also, no evidence was obtained that stimulated cell products either augment or inhibit pyrogen production by other stimulated cells. A feedback control of EP production was thus not observed. A crude preparation of EP, containing other products of activated cells, maintained its pyrogenicity when incubated at pH 7.4 but not at pH 5.0. These studies thus provide no support for hypothesized control mechanisms regulating production of EP by blood leukocytes. By contrast, local inactivation of EP at inflammatory sites may modify the amount of EP entering the blood, and hence fever.

  2. Endogenous Lunar Volatiles

    Science.gov (United States)

    McCubbin, F. M.; Liu, Y.; Barnes, J. J.; Anand, M.; Boyce, J. W.; Burney, D.; Day, J. M. D.; Elardo, S. M.; Hui, H.; Klima, R. L.; Magna, T.; Ni, P.; Steenstra, E.; Tartèse, R.; Vander Kaaden, K. E.

    2018-04-01

    This abstract discusses numerous outstanding questions on the topic of endogenous lunar volatiles that will need to be addressed in the coming years. Although substantial insights into endogenous lunar volatiles have been gained, more work remains.

  3. E.S.R. studies of mechanisms of radiation protection effect by cysteine and cystine

    International Nuclear Information System (INIS)

    Xue-Peng, L.; Tie-Cheng, T.; Nian-Yun, L.

    1981-01-01

    By means of E.S.R. the repair mechanism of radiation induced spin transfer from dTMP to cysteine in binary system dTMP-cysteine has been confirmed. Furthermore, a new marked radiation protection effect, exerted by cysteine or cystine on thymine irradiated and observed at low temperature, has been detected. Another sort of fast protection mechanism, including electron transfer and excitation transfer, has been proposed, based on recent advances of primary radiation process of pyrimidine bases and analysed by molecular orbital theory. This fast radiation protection mechanism provides the possibility to utilize electrophilic sulfhydryl protectors for realizing excellent protection effect. (author)

  4. institutional mechanisms for human rights protection in nigeria

    African Journals Online (AJOL)

    Mofasony

    Commission, the Public Complaints Commission and the Truth and .... The Legislative and Institutional Framework of Environmental Protection in the Oil … ... includes strategies targeted at promoting democracy and good governance, rights of ... administrative action of any public authority and companies or their officials ...

  5. Formation, adhesion and mechanical/chemical properties of protective coatings

    International Nuclear Information System (INIS)

    Mattox, D.M.

    1979-01-01

    Some general considerations for protective coatings are discussed. It is suggested that ceramic coatings may provide a class of coatings applicable to high temperature turbine blades for use in a corrosive/erosive environment. In particular, the ceraming glass materials would seem to hold promise, but little or nothing has been done on depositing these materials by vacuum processes

  6. High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice

    Directory of Open Access Journals (Sweden)

    Do Hyeong Gwon

    2017-09-01

    Full Text Available Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI. Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs from ω6-Polyunsaturated fatty acids (ω6-PUFAs without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt were divided into four groups: wt sham (n = 10, fat-1 sham (n = 10, wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15, and fat-1 IRI (n = 15. Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR. Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

  7. High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice.

    Science.gov (United States)

    Gwon, Do Hyeong; Hwang, Tae Woong; Ro, Ju-Ye; Kang, Yoon-Joong; Jeong, Jin Young; Kim, Do-Kyung; Lim, Kyu; Kim, Dong Woon; Choi, Dae Eun; Kim, Jwa-Jin

    2017-09-30

    Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs) from ω6-Polyunsaturated fatty acids (ω6-PUFAs) without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham ( n = 10), fat-1 sham ( n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI ( n = 15). Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK) activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

  8. Endogenous and Exogenous Natural Adjuvants for Vaccine Development.

    Science.gov (United States)

    Bolhassani, Azam; Talebi, Somayeh; Anvar, Ali

    2017-01-01

    Objective & Background: Various adjuvants are usually co-injected with an antigen for stimulation of effective immune responses. Adjuvants are able to elicit innate immune responses at the injection site. Depending on the activated type of innate responses, adjuvants can modify the quality and quantity of adaptive immune responses. Their mechanisms of action in vaccine development include: a) enhancement of the total antibody titers; b) reduction of the antigen dose; c) induction of potent cell-mediated immunity; d) increase in the speed and duration of the protective response; e) stimulation of mucosal immunity; and f) cross-protection. Up to now, different exogenous adjuvants have been identified to boost immune responses including inorganic compounds, mineral oil, bacterial products, non-bacterial organics, detergents or Quil A, plant saponins, Freund's complete or incomplete adjuvants, and delivery systems. However, some immune responses can be generated in the absence of the exogenous adjuvants. Indeed, endogenous adjuvants released from the cells were known as the danger signals and immunogenic compounds. Several main endogenous adjuvants contain cytokines, chemokines, alarmins, dendritic cells (DCs), toll like receptor (TLR) ligands or agonists, and antibodies. In this review, the immune activities of the natural adjuvants especially endogenous adjuvants and their mechanisms of action are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Presynaptic nicotinic α7 and non-α7 receptors stimulate endogenous GABA release from rat hippocampal synaptosomes through two mechanisms of action.

    Directory of Open Access Journals (Sweden)

    Stefania Zappettini

    Full Text Available BACKGROUND: Although converging evidence has suggested that nicotinic acetylcholine receptors (nAChR play a role in the modulation of GABA release in rat hippocampus, the specific involvement of different nAChR subtypes at presynaptic level is still a matter of debate. In the present work we investigated, using selective α7 and α4β2 nAChR agonists, the presence of different nAChR subtypes on hippocampal GABA nerve endings to assess to what extent and through which mechanisms they stimulate endogenous GABA release. METHODOLOGY/FINDINGS: All agonists elicited GABA overflow. Choline (Ch-evoked GABA overflow was dependent to external Ca(2+, but unaltered in the presence of Cd(2+, tetrodotoxin (TTX, dihydro-β-erythroidine (DHβE and 1-(4,4-Diphenyl-3-butenyl-3-piperidinecarboxylic acid hydrochloride SKF 89976A. The effect of Ch was blocked by methyllycaconitine (MLA, α-bungarotoxin (α-BTX, dantrolene, thapsigargin and xestospongin C, suggesting that GABA release might be triggered by Ca(2+ entry into synaptosomes through the α7 nAChR channel with the involvement of calcium from intracellular stores. Additionally, 5-Iodo-A-85380 dihydrochloride (5IA85380 elicited GABA overflow, which was Ca(2+ dependent, blocked by Cd(2+, and significantly inhibited by TTX and DHβE, but unaffected by MLA, SKF 89976A, thapsigargin and xestospongin C and dantrolene. These findings confirm the involvement of α4β2 nAChR in 5IA85380-induced GABA release that seems to occur following membrane depolarization and opening calcium channels. CONCLUSIONS/SIGNIFICANCE: Rat hippocampal synaptosomes possess both α7 and α4β2 nAChR subtypes, which can modulate GABA release via two distinct mechanisms of action. The finding that GABA release evoked by the mixture of sub-maximal concentration of 5IA85380 plus sub-threshold concentrations of Ch was significantly larger than that elicited by the sum of the effects of the two agonists is compatible with the possibility that

  10. Blast mines: physics, injury mechanisms and vehicle protection.

    Science.gov (United States)

    Ramasamy, A; Hill, A M; Hepper, A E; Bull, A M J; Clasper, J C

    2009-12-01

    Since World War II, more vehicles have been lost to land mines than all other threats combined. Anti-vehicular (AV) mines are capable of disabling a heavy vehicle, or completely destroying a lighter vehicle. The most common form of AV mine is the blast mine, which uses a large amount of explosive to directly damage the target. In a conventional military setting, landmines are used as a defensive force-multiplier and to restrict the movements of the opposing force. They are relatively cheap to purchase and easy to acquire, hence landmines are also potent weapons in the insurgents' armamentarium. The stand-offnature of its design has allowed insurgents to cause significant injuries to security forces in current conflicts with little personal risk. As a result, AV mines and improvised explosive devices (IEDs) have become the most common cause of death and injury to Coalition and local security forces operating in Iraq and Afghanistan. Detonation of an AV mine causes an explosive, exothermic reaction which results in the formation of a shockwave followed by a rapid expansion of gases. The shockwave is mainly reflected by the soillair interface and fractures the soil cap overthe mine. The detonation products then vent through the voids in the soil, resulting in a hollow inverse cone which consists of the detonation gases surrounded by the soil ejecta. It is the combination of the detonation products and soil ejecta that interact with the target vehicle and cause injury to the vehicle occupants. A number of different strategies are required to mitigate the blast effects of an explosion. Primary blast effects can be reduced by increasing the standoff distance between the seat of the explosion and the crew compartment. Enhancement of armour on the base of the vehicle, as well as improvements in personal protection can prevent penetration of fragments. Mitigating tertiary effects can be achieved by altering the vehicle geometry and structure, increasing vehicle mass, as

  11. Protective mechanical ventilation during general anesthesia for open abdominal surgery improves postoperative pulmonary function

    NARCIS (Netherlands)

    Severgnini, Paolo; Selmo, Gabriele; Lanza, Christian; Chiesa, Alessandro; Frigerio, Alice; Bacuzzi, Alessandro; Dionigi, Gianlorenzo; Novario, Raffaele; Gregoretti, Cesare; de Abreu, Marcelo Gama; Schultz, Marcus J.; Jaber, Samir; Futier, Emmanuel; Chiaranda, Maurizio; Pelosi, Paolo

    2013-01-01

    The impact of intraoperative ventilation on postoperative pulmonary complications is not defined. The authors aimed at determining the effectiveness of protective mechanical ventilation during open abdominal surgery on a modified Clinical Pulmonary Infection Score as primary outcome and

  12. Case Report of the Use of Mechanical Ventilation Protective Modes in Werdnig-Hoffmann Disease Domiciliary

    Directory of Open Access Journals (Sweden)

    I.V. Gutsul

    2014-08-01

    Full Text Available The article describes our own clinical observation of using mechanical ventilation protective modes in a child with Werdnig-Hoffmann disease and contracture of the upper and lower extremities.

  13. Feedback and education improve physician compliance in use of lung-protective mechanical ventilation

    NARCIS (Netherlands)

    Wolthuis, Esther K.; Korevaar, Johanna C.; Spronk, Peter; Kuiper, Michael A.; Dzoljic, Misa; Vroom, Margreeth B.; Schultz, Marcus J.

    2005-01-01

    Objective: Use of lung-protective mechanical ventilation (MV) by applying lower tidal volumes is recommended in patients suffering from acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Recent data suggest that lung-protective MV may benefit non-ALI/ARDS patients as well. This

  14. Nuclear Technology. Course 30: Mechanical Inspection. Module 30-6, Protective Coating Inspection.

    Science.gov (United States)

    Espy, John

    This sixth in a series of eight modules for a course titled Mechanical Inspection describes the duties of the nuclear quality assurance/quality control technician that are associated with protective coatings, and the national standards that govern the selection, application, and inspection of protective coatings for the reactor containment…

  15. Mechanism of the reaction of ebselen with endogenous thiols : dihydrolipoate is a better cofactor than glutathione in the peroxidase activity of ebselen

    NARCIS (Netherlands)

    Haenen, G R; De Rooij, B M; Vermeulen, N P; Bast, A

    The therapeutic effect of ebselen has been linked to its peroxidase activity. In the present study, the peroxidase activity of ebselen toward H2O2 with the endogenous thiols GSH and dihydrolipoate [L(SH)2] as cofactors was determined. When GSH was used, peroxide removal was described by a ter uni

  16. Mechanisms of Nattokinase in protection of cerebral ischemia.

    Science.gov (United States)

    Ji, Hongrui; Yu, Liang; Liu, Keyu; Yu, Zhigang; Zhang, Qian; Zou, Fengjuan; Liu, Bo

    2014-12-15

    In vivo, the level of cyclic Adenosine Monophosphate (cAMP) and the pathway of the Janus Kinase1/Signal Transducers and Activators of Transcription1 (JAK1/STAT1) were studied. In vitro, the Ca(2+) mobilization in human platelet stimulated by thrombin was observed. In addition, vasomotion of vascular smooth muscle was measured by adding KCl or norepinephrine(NE) under the Ca(2+) contained bath solutions. The effect induced by NE in the presence of N-nitro-L-arginine methyl ester (L-NAME) or indometacin (Indo) was also detected. At last, the levels of tissue plasminogen activator (t-PA) and Plasminogen activator inhibitor-1 (PAI-1) in cultured supernatans in Human umbilical vein endothelial cells (Huvecs) were measured by means of ELISA kit. Results showed that Nattokinase (NK) significantly increased the cAMP level, activated the signal passage of JAK1/STAT1 in injured part and inhibited remarkably the rise of platelet intracellular Ca(2+) ([Ca(2+)]i) in human platelet. Furthermore, NK relaxed rat thoracic aortic artery in the dose-dependent manner and in the endothelium dependent manner and its effect could be attenuated by L-NAME. Also, the secretion of t-PA and PAI-1 were reduced stimulated by Adr on Huvecs. These data indicated that the neuroprotective effect of NK was associated with its antiplatelet activity by elevating cAMP level and attenuating the calcium release from calcium stores; with its anti-apoptotic effect through the activation of JAK1/STAT1 pathway; with its relaxing vascular smooth muscle by promoting synthesis and release of NO, reducing ROC calcium ion influx and with its protection on endothelial cells through increasing fibrinolytic activity and facilitating spontaneous thrombolysis. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Analysis of the selected mechanical parameters of coating of filters protecting against hazardous infrared radiation.

    Science.gov (United States)

    Gralewicz, Grzegorz; Owczarek, Grzegorz; Kubrak, Janusz

    2017-03-01

    This article presents a comparison of the test results of selected mechanical parameters (hardness, Young's modulus, critical force for delamination) for protective filters intended for eye protection against harmful infrared radiation. Filters with reflective metallic films were studied, as well as interference filters developed at the Central Institute for Labour Protection - National Research Institute (CIOP-PIB). The test results of the selected mechanical parameters were compared with the test results, conducted in accordance with a standardised method, of simulating filter surface destruction that occurs during use.

  18. Endogenous pyrogen-like substance produced by reptiles.

    Science.gov (United States)

    Bernheim, H A; Kluger, M J

    1977-06-01

    1. Injection of lizards (Dipsosaurus dorsalis) with rabbit endogenous pyrogen led to a fever. Injections with denatured endogenous pyrogen did not affect body temperature. 2. Injection of lizards with lizard endogenous pyrogen led to a fever of short duration, while injection of denatured lizard endogenous pyrogen produced no change in body temperature. 3. These data support the hypothesis that the febrile mechanism observed in the higher vertebrates has its origins in some primitive vertebrate.

  19. Natural Antioxidants: Multiple Mechanisms to Protect Skin From Solar Radiation

    Directory of Open Access Journals (Sweden)

    Spencer Dunaway

    2018-04-01

    Full Text Available Human skin exposed to solar ultraviolet radiation (UVR results in a dramatic increase in the production of reactive oxygen species (ROS. The sudden increase in ROS shifts the natural balance toward a pro-oxidative state, resulting in oxidative stress. The detrimental effects of oxidative stress occur through multiple mechanisms that involve alterations to proteins and lipids, induction of inflammation, immunosuppression, DNA damage, and activation of signaling pathways that affect gene transcription, cell cycle, proliferation, and apoptosis. All of these alterations promote carcinogenesis and therefore, regulation of ROS levels is critical to the maintenance of normal skin homeostasis. Several botanical products have been found to exhibit potent antioxidant capacity and the ability to counteract UV-induced insults to the skin. These natural products exert their beneficial effects through multiple pathways, including some known to be negatively affected by solar UVR. Aging of the skin is also accelerated by UVR exposure, in particular UVA rays that penetrate deep into the epidermis and the dermis where it causes the degradation of collagen and elastin fibers via oxidative stress and activation of matrix metalloproteinases (MMPs. Because natural compounds are capable of attenuating some of the UV-induced aging effects in the skin, increased attention has been generated in the area of cosmetic sciences. The focus of this review is to cover the most prominent phytoproducts with potential to mitigate the deleterious effects of solar UVR and suitability for use in topical application.

  20. The endogenous and reactive depression subtypes revisited: integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder.

    Science.gov (United States)

    Malki, Karim; Keers, Robert; Tosto, Maria Grazia; Lourdusamy, Anbarasu; Carboni, Lucia; Domenici, Enrico; Uher, Rudolf; McGuffin, Peter; Schalkwyk, Leonard C

    2014-05-07

    Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either 'reactive' or 'endogenous' subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of 'reactive' or 'endogenous' subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of 'reactive' and 'endogenous' depression. We then translated these findings to clinical samples using a human post-mortem mRNA study. Affymetrix mouse whole-genome oligonucleotide arrays were used to measure gene expression from hippocampal tissues of 144 mice from the Genome-based Therapeutic Drugs for Depression (GENDEP) project. The study used four inbred mouse strains and two depressogenic 'stress' protocols (maternal separation and Unpredictable Chronic Mild Stress) to model 'reactive' depression. Stress-related mRNA differences in mouse were compared with a parallel mRNA study using Flinders Sensitive and Resistant rat lines as a model of 'endogenous' depression. Convergent genes differentially expressed across the animal studies were used to inform candidate gene selection in a human mRNA post-mortem case control study from the Stanley Brain Consortium. In the mouse 'reactive' model, the expression of 350 genes changed in response to early stresses and 370 in response to late stresses. A minimal genetic overlap (less than 8.8%) was detected in response to both stress protocols, but 30% of these genes (21) were also differentially regulated in the 'endogenous' rat study. This overlap is significantly greater than expected by chance. The VAMP-2 gene, differentially expressed across the rodent studies, was also significantly altered in the human study after correcting for multiple testing. Our results suggest that 'endogenous' and 'reactive' subtypes of depression are associated with largely

  1. Endogenous Prospect Theory

    OpenAIRE

    Schmidt, Ulrich; Zank, Horst

    2010-01-01

    In previous models of (cumulative) prospect theory reference-dependence of preferences is imposed beforehand and the location of the reference point is exogenously determined. This paper provides an axiomatization of a new specification of cumulative prospect theory, termed endogenous prospect theory, where reference-dependence is derived from preference conditions and a unique reference point arises endogenously.

  2. Are endogenous feline leukemia viruses really endogenous?

    Science.gov (United States)

    Stewart, H; Jarrett, O; Hosie, M J; Willett, B J

    2011-10-15

    Full length endogenous feline leukemia virus (FeLV) proviruses exist within the genomes of many breeds of domestic cat raising the possibility that they may also exist in a transmissible exogenous form. Such viruses would share receptor usage with the recombinant FeLV-B subgroup, a viral subgroup that arises in vivo by recombination between exogenous subgroup A virus (FeLV-A) and endogenous FeLV. Accordingly, all isolates of FeLV-B made to date have contained a "helper" FeLV-A, consistent with their recombinatorial origin. In order to assess whether endogenous viruses are transmitted between cats, we examined primary isolates of FeLV for which the viral subgroup had been determined for the presence of a subgroup B virus that lacked an FeLV-A. Here we describe the identification of two primary field isolates of FeLV (2518 and 4314) that appeared to contain subgroup B virus only by classical interference assays, raising the possibility of between-host transmission of endogenous FeLV. Sequencing of the env gene and U3 region of the 3' long terminal repeat (LTR) confirmed that both viral genomes contained endogenous viral env genes. However the viral 3' LTRs appeared exogenous in origin with a putative 3' recombination breakpoint residing at the 3' end of the env gene. Further, the FeLV-2518 virions also co-packaged a truncated FeLV-A genome containing a defective env gene, termed FeLV-2518(A) whilst no helper subgroup A viral genome was detected in virions of FeLV-4314. The acquisition of an exogenous LTR by the endogenous FeLV in 4314 may have allowed a recombinant FeLV variant to outgrow an exogenous FeLV-A virus that was presumably present during first infection. Given time, a similar evolution may also occur within the 2518 isolate. The data suggest that endogenous FeLVs may be mobilised by acquisition of exogenous LTRs yielding novel viruses that type biologically as FeLV-B. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Endogenous opioid systems: physiological role in the self-limitation of seizures.

    Science.gov (United States)

    Tortella, F C; Long, J B; Holaday, J W

    1985-04-15

    Immediately following a seizure, the severity of subsequent seizures is significantly reduced. The involvement of endogenous opioid systems as a physiological regulator of this postseizure inhibition was studied in rats using repeated maximal electroshock (MES) seizures. Both the opiate antagonist (-)-naloxone and morphine tolerance abolished the progressive seizure protection associated with repeated MES. We propose that endogenous opioids, activated by a prior seizure, provide a central homeostatic inhibitory mechanism which may be responsible for the initiation of a postictal refractory state in the epileptic.

  4. Endogenous Locus Reporter Assays.

    Science.gov (United States)

    Liu, Yaping; Hermes, Jeffrey; Li, Jing; Tudor, Matthew

    2018-01-01

    Reporter gene assays are widely used in high-throughput screening (HTS) to identify compounds that modulate gene expression. Traditionally a reporter gene assay is built by cloning an endogenous promoter sequence or synthetic response elements in the regulatory region of a reporter gene to monitor transcriptional activity of a specific biological process (exogenous reporter assay). In contrast, an endogenous locus reporter has a reporter gene inserted in the endogenous gene locus that allows the reporter gene to be expressed under the control of the same regulatory elements as the endogenous gene, thus more accurately reflecting the changes seen in the regulation of the actual gene. In this chapter, we introduce some of the considerations behind building a reporter gene assay for high-throughput compound screening and describe the methods we have utilized to establish 1536-well format endogenous locus reporter and exogenous reporter assays for the screening of compounds that modulate Myc pathway activity.

  5. An examination of adaptive cellular protective mechanisms using a multi-stage carcinogenesis model

    International Nuclear Information System (INIS)

    Schollnberger, H.; Stewart, R. D.; Mitchel, R. E. J.; Hofmann, W.

    2004-01-01

    A multi-stage cancer model that describes the putative rate-limiting steps in carcinogenesis was developed and used to investigate the potential impact on lung cancer incidence of the hormesis mechanisms suggested by Feinendegen and Pollycove. In this deterministic cancer model, radiation and endogenous processes damage the DNA of target cells in the lung. Some fraction of the misrepaired our unrepaired DNA damage induces genomic instability and, ultimately, leads to the accumulation of malignant cells. The model accounts for cell birth and death processes. Ita also includes a rate of malignant transformation and a lag period for tumour formation. Cellular defence mechanisms are incorporated into the model by postulating dose and dose rate dependent radical scavenging. The accuracy of DNA damage repair also depends on dose and dose rate. Sensitivity studies were conducted to identify critical model inputs and to help define the shapes of the cumulative lung cancer incidence curves that may arise when dose and dose rate dependent cellular defence mechanisms are incorporated into a multi-stage cancer model. For lung cancer, both linear no-threshold (LNT) and non-LNT shaped responses can be obtained. The reported studied clearly show that it is critical to know whether or not and to what extent multiply damaged DNA sites are formed by endogenous processes. Model inputs that give rise to U-shaped responses are consistent with an effective cumulative lung cancer incidence threshold that may be as high as 300 mGy (4 mGy per year for 75 years). (Author) 11 refs

  6. Measurements and modeling for examination of magnitudes and thresholds and transitions of cellular radio-protective mechanisms

    International Nuclear Information System (INIS)

    Leonard, B.

    2007-01-01

    factor of 10 excess dose to connective tissue and organs. Finally, a method for measuring the changes in endogenic cell capabilities to carry-out increased radio-protective processes i.e. separate decreased direct damage (greater ROS scavenging) and the increased repair rates (increased damage recognition, increased damage site location, increased repair mobilization and finally increased repair of the actual damage). This method shows for low LET IDRE no decreased direct damage occurs and significant increased repair occurs. After the 'triggered' threshold and transition of IDRE protection against cell killing, a larger fraction of cell damage produces viable mutations. This suggests that the cells bio-chemically conclude it is senseless to provide protection against potentially mutations in the low dose rate region if all the cells are being killed. Conclusions: The BE does not cause the underground miners high Radon IDRE. Single Specific Energy nucleus hits at very low dose rates activate adaptive response protection of spontaneous neoplastic transformations from mammography X-rays. A dose and dose-rate coupling is modeled. A correlation between the 'triggering' of the transition of the radio-protection for the Hyper-radiosensitivity and dose induced radio-resistance effect (HRS/IRR) and the low LET 'inverse' dose-rate effect (IDRE) as if they are from same radioprotective mechanisms. Possible excess connective tissue and organs damage occurs from low LET IDRE in LDR Brachytherapy treatments with permanent implants.

  7. Novel mechanism of network protection against the new generation of cyber attacks

    Science.gov (United States)

    Milovanov, Alexander; Bukshpun, Leonid; Pradhan, Ranjit

    2012-06-01

    A new intelligent mechanism is presented to protect networks against the new generation of cyber attacks. This mechanism integrates TCP/UDP/IP protocol stack protection and attacker/intruder deception to eliminate existing TCP/UDP/IP protocol stack vulnerabilities. It allows to detect currently undetectable, highly distributed, low-frequency attacks such as distributed denial-of-service (DDoS) attacks, coordinated attacks, botnet, and stealth network reconnaissance. The mechanism also allows insulating attacker/intruder from the network and redirecting the attack to a simulated network acting as a decoy. As a result, network security personnel gain sufficient time to defend the network and collect the attack information. The presented approach can be incorporated into wireless or wired networks that require protection against known and the new generation of cyber attacks.

  8. Upregulation of AMWAP: a novel mechanism for HDAC inhibitors to protect against cisplatin nephrotoxicity.

    Science.gov (United States)

    Tang, Jinhua; Zhuang, Shougang

    2016-02-01

    Histone deacetylases have been reported to protect against renal tubular damage in several animal models of acute renal injury, including cisplatin nephrotoxicity. However, the mechanism involved is not well defined. In this study, Ranganathan et al. identify activated microglia/macrophage WAP domain protein as the novel mediator of histone deacetylase inhibitor-mediated renal protection in a murine model of cisplatin nephrotoxicity. Activated microglia/macrophage WAP-mediated renal protection is associated with suppression of inflammation and renal epithelial cell apoptosis. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  9. Protecting steel from rusting by rust. The mechanism of rust formation and its control

    International Nuclear Information System (INIS)

    Kimura, Masao

    2008-01-01

    Weathering steel, when exposed outdoors for a few years, forms a protective layer resulting in reduction of the corrosion rate. The state of rusts is fundamental for understanding its mechanisms, but the structure and its relationship with the mechanism have not been understood. In this study, a new crystallographic approach was applied to reveal nano-structure of rusts with using of X-ray synchrotron radiation. It has been shown that additional elements alter the corrosion process in its early stage, resulting in formation of protective rusts. (author)

  10. Initial mechanical ventilator settings and lung protective ventilation in the ED.

    Science.gov (United States)

    Wilcox, Susan R; Richards, Jeremy B; Fisher, Daniel F; Sankoff, Jeffrey; Seigel, Todd A

    2016-08-01

    Mechanical ventilation with low tidal volumes has been shown to improve outcomes for patients both with and without acute respiratory distress syndrome. This study aims to characterize mechanically ventilated patients in the emergency department (ED), describe the initial ED ventilator settings, and assess for associations between lung protective ventilation strategies in the ED and outcomes. This was a multicenter, prospective, observational study of mechanical ventilation at 3 academic EDs. We defined lung protective ventilation as a tidal volume of less than or equal to 8 mL/kg of predicted body weight and compared outcomes for patients ventilated with lung protective vs non-lung protective ventilation, including inhospital mortality, ventilator days, intensive care unit length of stay, and hospital length of stay. Data from 433 patients were analyzed. Altered mental status without respiratory pathology was the most common reason for intubation, followed by trauma and respiratory failure. Two hundred sixty-one patients (60.3%) received lung protective ventilation, but most patients were ventilated with a low positive end-expiratory pressure, high fraction of inspired oxygen strategy. Patients were ventilated in the ED for a mean of 5 hours and 7 minutes but had few ventilator adjustments. Outcomes were not significantly different between patients receiving lung protective vs non-lung protective ventilation. Nearly 40% of ED patients were ventilated with non-lung protective ventilation as well as with low positive end-expiratory pressure and high fraction of inspired oxygen. Despite a mean ED ventilation time of more than 5 hours, few patients had adjustments made to their ventilators. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. [Phrenic nerve stimulation protects against mechanical ventilation-induced diaphragmatic dysfunction through myogenic regulatory factors].

    Science.gov (United States)

    An, G H; Chen, M; Zhan, W F; Hu, B; Zhang, H X

    2018-02-12

    Objective: To explore the protective effect of electrical stimulation of phrenic nerve on diaphragmatic function during mechanical ventilation. Methods: Forty healthy adult SD rats were randomly divided into 5 groups: blank control group (BC), spontaneous breathing group (SB), electrical stimulation group (ES), mechanical ventilation group (MV), and electrical stimulation and mechanical ventilation group (MS). The rats in each group were treated for 18 h except for the BC group. After treatment, the diaphragm muscle tissue was obtained and the diaphragm contractility including peak-to-peak value(Vpp) and maximum rate of contraction(+ dT/dt max) were measured. Expression of MyoD and myogenin were detected. Results: Except for the ES and the MS groups, there was a significant difference for peak-to-peak value (Vpp) between each 2 groups ( P mechanical ventilation induced diaphragmatic function damage, and therefore plays a protective effect on the diaphragm.

  12. Development of innovative architecture of the organizational and economic mechanism for the nature protection management

    Science.gov (United States)

    Mikhailov, V. G.; Kiseleva, T. V.; Karasev, V. A.; Mikhailov, G. S.; Skukin, V. A.

    2017-05-01

    The problems of the efficient functioning of environmental and economic systems of various levels on the basis of the adequate organizational and economic management mechanism are considered in the article. The purpose of the study is the analysis and development of theoretical provisions for the formation of a modern, innovative organizational and economic mechanism of the nature protection management. The compliance matrix of the innovative elements presented in the structure of the organizational and economic mechanism of the nature protection management is developed. The main result of the study is the improvement of the existing management mechanism to minimize the negative impact on the environment, including through the incentive system, and to improve the financial performance of the economic entity. The practical component of the study conducted can be recommended to municipal, regional and federal authorities, as well as the industrial enterprises, to support the adoption of the effective, environmentally sound management decisions that are consistent with the global concept of sustainable development.

  13. Mechanisms of saccharide protection against epigallocatechin-3-gallate deterioration in aqueous solutions.

    Science.gov (United States)

    Shpigelman, Avi; Zisapel, Adi; Cohen, Yifat; Livney, Yoav D

    2013-08-15

    We investigated the mechanisms of the protection conferred by sugars to epigallocatechin-3-gallate (EGCG) against deterioration. Additionally, we present a rapid method for evaluating the deterioration rate of EGCG using absorbance spectroscopy. We found that various sugars provided different levels of protection at identical weight percentage, and the combination of sugars and β-lactoglobulin nanocomplexes provided greater protection for EGCG than each protective component alone. We suggest that the concentration-dependent protection by sugars resulted from a combination of mechanisms, including: (1) reduced aqueous O2 solubility, (2) scavenging of reactive oxygen species, and (3) chelation of traces of transition metal ions, which is suggested to be the main reason for the differences among the sugars. The observed protective effect of sugars can be easily applied by the industry in proper selection of sugars for enrichment of syrups or concentrates with EGCG and for the preparation of enriched beverages and foods for health promotion. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Mechanisms of symbiont-conferred protection against natural enemies: an ecological and evolutionary framework.

    Science.gov (United States)

    Gerardo, Nicole M; Parker, Benjamin J

    2014-10-01

    Many vertically-transmitted microbial symbionts protect their insect hosts from natural enemies, including host-targeted pathogens and parasites, and those vectored by insects to other hosts. Protection is often achieved through production of inhibiting toxins, which is not surprising given that toxin production mediates competition in many environments. Classical models of macroecological interactions, however, demonstrate that interspecific competition can be less direct, and recent research indicates that symbiont-protection can be mediated through exploitation of limiting resources, and through activation of host immune mechanisms that then suppress natural enemies. Available data, though limited, suggest that effects of symbionts on vectored pathogens and parasites, as compared to those that are host-targeted, are more likely to result from symbiont activation of the host immune system. We discuss these different mechanisms in light of their potential impact on the evolution of host physiological processes. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Efficiency of inherent protection mechanisms for an improved HTR safety concept

    Energy Technology Data Exchange (ETDEWEB)

    Petersen, K.; Buescher, R.; Gerwin, H.; Schenk, W. [Kernforschungsanlage Juelich G.m.b.H. (Germany, F.R.). Inst. fuer Reaktorentwicklung

    1981-01-15

    For a preliminary design of a 350 MWsub(th) annular core derived from AVR-reactor the efficiency of inherent protection mechanisms is discussed. After-heat removal and auto-shut down potential are demonstrated for intact and complete failure of core heat sinks.

  16. The contribution of the endogenous TRPV1 ligands 9-HODE and 13-HODE to nociceptive processing and their role in peripheral inflammatory pain mechanisms.

    Science.gov (United States)

    Alsalem, Mohammad; Wong, Amy; Millns, Paul; Arya, Pallavi Huma; Chan, Michael Siang Liang; Bennett, Andrew; Barrett, David A; Chapman, Victoria; Kendall, David A

    2013-04-01

    The transient receptor potential vanilloid type 1 (TRPV1) plays a fundamental role in the detection of heat and inflammatory pain responses. Here we investigated the contribution of two potential endogenous ligands [9- and 13- hydroxyoctadecadienoic acid (HODE)] to TRPV1-mediated noxious responses and inflammatory pain responses. 9- and 13-HODE, and their precursor, linoleic acid, were measured in dorsal root ganglion (DRG) neurons and in the hindpaws of control and carrageenan-inflamed rats by liquid chromatography/tandem electrospray mass spectrometry. Calcium imaging studies of DRG neurons were employed to determine the role of TRPV1 in mediating linoleic acid, 9-HODE- and 13-HODE-evoked responses, and the contribution of 15-lipoxygenase to the generation of the HODEs. Behavioural studies investigated the contribution of 9- and 13-HODE and 15-lipoxygenase to inflammatory pain behaviour. 9-HODE (35 ± 7 pmol g(-1)) and 13-HODE (32 ± 6 pmol g(-1)) were detected in hindpaw tissue, but were below the limits of detection in DRGs. Following exposure to linoleic acid, 9- and 13-HODE were detected in DRGs and TRPV1 antagonist-sensitive calcium responses evoked, which were blocked by the 15-lipoxygenase inhibitor PD146176 and an anti-13-HODE antibody. Levels of linoleic acid were significantly increased in the carrageenan-inflamed hindpaw (P PD146176 significantly (P < 0.01) attenuated carrageenan-induced hyperalgesia. This study demonstrates that, although 9- and 13-HODE can activate TRPV1 in DRG cell bodies, the evidence for a role of these lipids as endogenous peripheral TRPV1 ligands in a model of inflammatory pain is at best equivocal. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  17. The Endogenous Exposome

    Science.gov (United States)

    Nakamura, Jun; Mutlu, Esra; Sharma, Vyom; Collins, Leonard; Bodnar, Wanda; Yu, Rui; Lai, Yongquan; Moeller, Benjamin; Lu, Kun; Swenberg, James

    2014-01-01

    The concept of the Exposome, is a compilation of diseases and one’s lifetime exposure to chemicals, whether the exposure comes from environmental, dietary, or occupational exposures; or endogenous chemicals that are formed from normal metabolism, inflammation, oxidative stress, lipid peroxidation, infections, and other natural metabolic processes such as alteration of the gut microbiome. In this review, we have focused on the Endogenous Exposome, the DNA damage that arises from the production of endogenous electrophilic molecules in our cells. It provides quantitative data on endogenous DNA damage and its relationship to mutagenesis, with emphasis on when exogenous chemical exposures that produce identical DNA adducts to those arising from normal metabolism cause significant increases in total identical DNA adducts. We have utilized stable isotope labeled chemical exposures of animals and cells, so that accurate relationships between endogenous and exogenous exposures can be determined. Advances in mass spectrometry have vastly increased both the sensitivity and accuracy of such studies. Furthermore, we have clear evidence of which sources of exposure drive low dose biology that results in mutations and disease. These data provide much needed information to impact quantitative risk assessments, in the hope of moving towards the use of science, rather than default assumptions. PMID:24767943

  18. Formation mechanism of the protective layer in a blast furnace hearth

    Science.gov (United States)

    Jiao, Ke-xin; Zhang, Jian-liang; Liu, Zheng-jian; Xu, Meng; Liu, Feng

    2015-10-01

    A variety of techniques, such as chemical analysis, scanning electron microscopy-energy dispersive spectroscopy, and X-ray diffraction, were applied to characterize the adhesion protective layer formed below the blast furnace taphole level when a certain amount of titanium- bearing burden was used. Samples of the protective layer were extracted to identify the chemical composition, phase assemblage, and distribution. Furthermore, the formation mechanism of the protective layer was determined after clarifying the source of each component. Finally, a technical strategy was proposed for achieving a stable protective layer in the hearth. The results show that the protective layer mainly exists in a bilayer form in the sidewall, namely, a titanium-bearing layer and a graphite layer. Both the layers contain the slag phase whose major crystalline phase is magnesium melilite (Ca2MgSi2O7) and the main source of the slag phase is coke ash. It is clearly determined that solid particles such as graphite, Ti(C,N) and MgAl2O4 play an important role in the formation of the protective layer, and the key factor for promoting the formation of a stable protective layer is reasonable control of the evolution behavior of coke.

  19. Role of endogenous substances in enhancing radioresistance background

    International Nuclear Information System (INIS)

    Goncharenko, E.N.; Gorskaya, T.G.; Graevskaya, E.Eh.; Kozlova, M.A.

    1979-01-01

    Presumable sources of endogenous were studied amines in radiosensitive tissues under the effect of radioprotective agents were studied. The data obtained support the idea that mast cells of rats, having large deposits of biogenous amines, might be one of the reserves contributing to mobilization of endogeneous protective resources of the organism treated with radioprotective agents

  20. On the mechanisms of mobilization of biogenous amines from rats mast cells in conditions of protection against ionizing radiation

    International Nuclear Information System (INIS)

    Goncharenko, E.N.; Graevskaya, E.Eh.; Kravtsov, G.M.; Lomakin, N.N.

    1986-01-01

    A study was made of the role of calcium ions and some other factors in secretion of biogenous amines from rat mast cells. The data obtained indicate that the radioprotective preparations of indolylalkylamine and imidazole series can mobilize endogenous radioprotectors. The process of the mediator release from mast cells under the effect of sulfur-containing radioprotective agents is indirect. The molecular mechanisms of mast cell exocytosis are discussed

  1. Ultraviolet-B-effects on plants: Spectra of harmful effects, primary damage and UV protective mechanisms

    International Nuclear Information System (INIS)

    Wellmann, E.; Beggs, C.; Moehle, B.; Schneider-Ziebert, U.; Steinmetz, V.; Koch, U.

    1986-01-01

    In two model systems of higher plants, damage caused by ultraviolet-B-radiation was analysed as to its mechanism of action and the spectral quantum efficiency. These investigations were to provide information on the relevance of such UV effects in cases of increased ultraviolet-B-irradiation owing to the destruction of ozone. The results indicate the very high tolerance of the plants to ultraviolet-B-radiation which obviously is the result of very effective protective mechanisms, and show at the same time that potential damage must already be reckoned with, given the current share of ultraviolet-B-radiation in solar radiation. Should ultraviolet-B-radiation be increased, then indirect damage to the plant from the destruction of ultraviolet protective mechanisms through UV-B-radiation will probably constitute a particular risk. (orig./MG) [de

  2. Cytokines as endogenous pyrogens.

    Science.gov (United States)

    Dinarello, C A

    1999-03-01

    Cytokines are pleiotropic molecules mediating several pathologic processes. Long before the discovery of cytokines as immune system growth factors or as bone marrow stimulants, investigators learned a great deal about cytokines when they studied them as the endogenous mediators of fever. The terms "granulocytic" or "endogenous pyrogen" were used to describe substances with the biologic property of fever induction. Today, we recognize that pyrogenicity is a fundamental biologic property of several cytokines and hence the clinically recognizeable property of fever links host perturbations during disease with fundamental perturbations in cell biology. In this review, the discoveries made on endogenous pyrogens are revisited, with insights into the importance of the earlier work to the present-day understanding of cytokines in health and in disease.

  3. Protective mechanical ventilation does not exacerbate lung function impairment or lung inflammation following influenza A infection.

    Science.gov (United States)

    Zosky, Graeme R; Cannizzaro, Vincenzo; Hantos, Zoltan; Sly, Peter D

    2009-11-01

    The degree to which mechanical ventilation induces ventilator-associated lung injury is dependent on the initial acute lung injury (ALI). Viral-induced ALI is poorly studied, and this study aimed to determine whether ALI induced by a clinically relevant infection is exacerbated by protective mechanical ventilation. Adult female BALB/c mice were inoculated with 10(4.5) plaque-forming units of influenza A/Mem/1/71 in 50 microl of medium or medium alone. This study used a protective ventilation strategy, whereby mice were anesthetized, tracheostomized, and mechanically ventilated for 2 h. Lung mechanics were measured periodically throughout the ventilation period using a modification of the forced oscillation technique to obtain measures of airway resistance and coefficients of tissue damping and tissue elastance. Thoracic gas volume was measured and used to obtain specific airway resistance, tissue damping, and tissue elastance. At the end of the ventilation period, a bronchoalveolar lavage sample was collected to measure inflammatory cells, macrophage inflammatory protein-2, IL-6, TNF-alpha, and protein leak. Influenza infection caused significant increases in inflammatory cells, protein leak, and deterioration in lung mechanics that were not exacerbated by mechanical ventilation, in contrast to previous studies using bacterial and mouse-specific viral infection. This study highlighted the importance of type and severity of lung injury in determining outcome following mechanical ventilation.

  4. Variability in the Use of Protective Mechanical Ventilation During General Anesthesia.

    Science.gov (United States)

    Ladha, Karim S; Bateman, Brian T; Houle, Timothy T; De Jong, Myrthe A C; Vidal Melo, Marcos F; Huybrechts, Krista F; Kurth, Tobias; Eikermann, Matthias

    2018-02-01

    The purpose of this study was to determine whether significant variation exists in the use of protective ventilation across individual anesthesia providers and whether this difference can be explained by patient, procedure, and provider-related characteristics. The cohort consisted of 262 anesthesia providers treating 57,372 patients at a tertiary care hospital between 2007 and 2014. Protective ventilation was defined as a median positive end-expiratory pressure of 5 cm H2O or more, tidal volume of protective ventilation was modified in sensitivity analyses. In unadjusted analysis, the mean probability of administering protective ventilation was 53.8% (2.5th percentile of provider 19.9%, 97.5th percentile 80.8%). After adjustment for a large number of covariates, there was little change in the results with a mean probability of 51.1% (2.5th percentile 24.7%, 97.5th percentile 77.2%). The variations persisted when the thresholds for protective ventilation were changed. There was significant variability across individual anesthesia providers in the use of intraoperative protective mechanical ventilation. Our data suggest that this variability is highly driven by individual preference, rather than patient, procedure, or provider-related characteristics.

  5. The role of human endogenous retroviruses in brain development and function.

    Science.gov (United States)

    Mortelmans, Kristien; Wang-Johanning, Feng; Johanning, Gary L

    2016-01-01

    Endogenous retroviral sequences are spread throughout the genome of all humans, and make up about 8% of the genome. Despite their prevalence, the function of human endogenous retroviruses (HERVs) in humans is largely unknown. In this review we focus on the brain, and evaluate studies in animal models that address mechanisms of endogenous retrovirus activation in the brain and central nervous system (CNS). One such study in mice found that TRIM28, a protein critical for mouse early development, regulates transcription and silencing of endogenous retroviruses in neural progenitor cells. Another intriguing finding in human brain cells and mouse models was that endogenous retrovirus HERV-K appears to be protective against neurotoxins. We also report on studies that associate HERVs with human diseases of the brain and CNS. There is little doubt of an association between HERVs and a number of CNS diseases. However, a cause and effect relationship between HERVs and these diseases has not yet been established. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  6. Evolution of endogenous analgesia

    NARCIS (Netherlands)

    Niesters, Marieke

    2014-01-01

    Endogenous pain modulation is a complex phenomenon involved in the perception of pain. It consists of top-down inhibitory and facilitatory pathways that originate at higher sites within the central nervous system and converge at dorsal horn neurons in the spinal cord, to modulate incoming afferent

  7. Unemployment and endogenous growth

    NARCIS (Netherlands)

    van Schaik, A.B.T.M.; de Groot, H.L.F.

    1995-01-01

    In this paper we develop a two-sector endogenous growth model with a dual labour market, based on efficiency wages. Growth is driven by intentional R&D performed in the high-tech and high-wage sector. It is examined how a change in rivalry among firms affects simultaneously growth and unemployment.

  8. Protecting cells by protecting their vulnerable lysosomes: Identification of a new mechanism for preserving lysosomal functional integrity upon oxidative stress.

    Science.gov (United States)

    Pascua-Maestro, Raquel; Diez-Hermano, Sergio; Lillo, Concepción; Ganfornina, Maria D; Sanchez, Diego

    2017-02-01

    Environmental insults such as oxidative stress can damage cell membranes. Lysosomes are particularly sensitive to membrane permeabilization since their function depends on intraluminal acidic pH and requires stable membrane-dependent proton gradients. Among the catalog of oxidative stress-responsive genes is the Lipocalin Apolipoprotein D (ApoD), an extracellular lipid binding protein endowed with antioxidant capacity. Within the nervous system, cell types in the defense frontline, such as astrocytes, secrete ApoD to help neurons cope with the challenge. The protecting role of ApoD is known from cellular to organism level, and many of its downstream effects, including optimization of autophagy upon neurodegeneration, have been described. However, we still cannot assign a cellular mechanism to ApoD gene that explains how this protection is accomplished. Here we perform a comprehensive analysis of ApoD intracellular traffic and demonstrate its role in lysosomal pH homeostasis upon paraquat-induced oxidative stress. By combining single-lysosome in vivo pH measurements with immunodetection, we demonstrate that ApoD is endocytosed and targeted to a subset of vulnerable lysosomes in a stress-dependent manner. ApoD is functionally stable in this acidic environment, and its presence is sufficient and necessary for lysosomes to recover from oxidation-induced alkalinization, both in astrocytes and neurons. This function is accomplished by preventing lysosomal membrane permeabilization. Two lysosomal-dependent biological processes, myelin phagocytosis by astrocytes and optimization of neurodegeneration-triggered autophagy in a Drosophila in vivo model, require ApoD-related Lipocalins. Our results uncover a previously unknown biological function of ApoD, member of the finely regulated and evolutionary conserved gene family of extracellular Lipocalins. They set a lipoprotein-mediated regulation of lysosomal membrane integrity as a new mechanism at the hub of many cellular

  9. A procedure for a mechanical evaluation of an undefined osteo-protective material.

    Science.gov (United States)

    Marques, Marco; Terroso, Miguel; Freitas, Ricardo; Marques, AntÓnio Torres; Gabriel, Joaquim; Simoes, Ricardo

    2015-02-01

    Falls represent a major care and cost problem to health and social services world-widely, since 50% of falls result in an injury. In this work, is proposed a methodology to evaluate protective pads materials and geometry performance, in order to reduce impact results in a fall event. Since the material properties and the pad geometry are the key factors to make the protection possible when a fall event occurs, our approach relies on the use of mechanical tests to evaluate the properties of the material and in the study of the pad response during a fall. For this, were used compression, tensile and instrumented falling weight tests, that allow a fully characterization of the materials that can be employed in the protective pads. Likewise, to gather precise information on falls events, in order to study the pad response during a fall, a set of laboratory fall trials were created using a camera-less inertial motion capture (mocap) system. This allow the acquisition of dynamic information of falls, namely acceleration and velocity that can be used to create a finite element analysis (FEA) model, where different segments from the human body can be evaluated when the protective pad is associated to it. Through the proposed methodology, different materials and pad geometries can be studied towards maximizing the performance of protection pads for falls. The mocap system allows the acquisition of fall data, and also the creation of a human body geometrical model, representative of the fall. From the mechanical trials, was showed that the spacer fabric embedded with silicone has the higher ability to reduce the peak force in case of impact when compared with all the other specimens. The compression and the tensile tests allow the mechanical definition of the material, and with this the material definition on the FEA model. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Mechanisms of radiation interaction with DNA: Potential implications for radiation protection

    International Nuclear Information System (INIS)

    Sinclair, W.K.; Fry, R.J.M.

    1987-01-01

    An overview of presentations and discussions which took place at the US Department of Energy/Commission of European Communities (DOE/CEC) workshop on ''Mechanisms of Radiation Interaction with DNA: Potential Implications for Radiation Protection,'' held at San Diego, California, January 21-22, 1987, is provided. The Department has traditionally supported fundamental research on interactions of ionizing radiation with different biological systems and at all levels of biological organization. The aim of this workshop was to review the base of knowledge in the area of mechanisms of radiation action at the DNA level, and to explore ways in which this information can be applied to the development of scientifically sound concepts and procedures for use in the field of radiation protection

  11. QUALITY MANAGEMENT OPERATION MECHANISMS FOR THE PROTECTION OF INFORMATION IN THE INFO-COMMUNICATION SYSTEMS

    Directory of Open Access Journals (Sweden)

    S. V. Belokurov

    2015-01-01

    Full Text Available The article presents the list of facilities and necessary procedures to protect against threats of violation of information availability in terms of exposure to malware in ICT systems and principles conceptual design of mechanisms, antivirus protection, implemented in the form of a component of a software complex for protection of information. This development allows us to formulate the principles of conceptual design of mechanisms, antivirus protection, implemented in the form of a component of a complex of software tools of information security. Special this valuable development for the implementation of procedures for the management of complex organizationaltechnical systems. Streamlining usually has one or any combination of the following objectives (attitudes: rationality, efficiency, improvement of the system. The aim of good governance (e.g. anti-malware is the preservation of the existing structure and system parameters under certain constraints (e.g., constraints on computing resources. If you cannot provide the management on a rational basis, it becomes necessary to change the parameters (parametric synthesis or search for and select the set of admissible structures effective on the criteria of structure (structural synthesis. Note that in this case we are talking about effectiveness for a given period of time, as social and scientific progress inevitably lead to a change of criteria effectiveness evaluation.

  12. Towards understanding the mechanisms and the kinetics of nanoparticle penetration through protective gloves

    International Nuclear Information System (INIS)

    Vinches, L; Boutrigue, N; Zemzem, M; Hallé, S; Peyrot, C; Lemarchand, L; Wilkinson, K J; Tufenkji, N

    2015-01-01

    Parallel to the increased use of engineered nanoparticles (ENP) in the formulation of commercial products or in medicine, numerous health and safety agencies have recommended the application of the precautionary principle to handle ENP; namely, the recommendation to use protective gloves against chemicals. However, recent studies reveal the penetration of titanium dioxide nanoparticles through nitrile rubber protective gloves in conditions simulating occupational use. This project is designed to understand the links between the penetration of gold nanoparticles (nAu) through nitrile rubber protective gloves and the mechanical and physical behaviour of the elastomer material subjected to conditions simulating occupational use (i.e., mechanical deformations (MD) and sweat). Preliminary analyses show that nAu suspensions penetrate selected glove materials after exposure to prolonged (3 hours) dynamic deformations. Significant morphological changes are observed on the outer surface of the glove sample; namely, the number and the surface of the micropores on the surface increase. Moreover, nitrile rubber protective gloves are also shown to be sensitive to the action of nAu suspension and to the action of the saline solution used to simulate sweat (swelling). (paper)

  13. Protective mechanisms and acclimation to solar ultraviolet-B radiation in Oenothera stricta

    Science.gov (United States)

    Robberecht, R.; Caldwell, M. M.

    1981-01-01

    Plant adaptations ameliorating or repairing the damaging effects of ultraviolet-B (UV-B) radiation on plant tissue were investigated. The degree of phenotype plasticity in UV protective mechanisms and acclimation in relation to the natural solar UV-B radiation flux and in an enhanced UV-B irradiance environment was also examined. Mechanisms by which plants avoid radiation, adaptations altering the path of radiation incident on the leaf, and repair processes were considered. Attenuation of UV-B by tissues, UV-B irradiation into the leaf, and the effects of UV-B on photosynthesis were investigated.

  14. Protective mechanisms and acclimation to solar ultraviolet-b radiation in oenothera stricta. Final report

    International Nuclear Information System (INIS)

    Robberecht, R.; Caldwell, M.M.

    1981-12-01

    Plant adaptations ameliorating or repairing the damaging effects of ultraviolet-B (UV-B) radiation on plant tissue were investigated. The degree of phenotype plasticity in UV protective mechanisms and acclimation in relation to the natural solar UV-B radiation flux and in an enhanced UV-B irradiance environment was also examined. Mechanisms by which plants avoid radiation, adaptations altering the path of radiation incident on the leaf, and repair processes were considered. Attenuation of UV-B by tissues, UV-B irradiation into the leaf, and the effects of UV-B on photosynthesis were investigated

  15. A study of the protective effect and mechanism of ketamine on acute lung injury induced by mechanical ventilation.

    Science.gov (United States)

    Wang, W-F; Liu, S; Xu, B

    2017-03-01

    To investigate the protective effects and mechanism of ketamine on acute lung injury induced by mechanical ventilation. 63 patients with acute lung injury caused by mechanical ventilation in our hospital between June 2014 and May 2015 were chosen and divided into three groups: group A, B, and C. Group A (20 cases) received conventional treatment. Group B (21 cases) was treated with propofol and group C (22 cases) with ketamine. The ventilator application time, the success rate of weaning, the mortality rate, inflammation index (IL-1, Caspase-1, and NF-κB), pulmonary function index and oxygen saturation were compared. The ventilator application time and the mortality rate of group B and group C were significantly (p 0.05). After the intervention, the levels of FEV1, FEV1/FVC, FVC and PEER in the three groups increased, but more remarkably in group B and group C (p mechanical ventilation. They shorten the application time of ventilator, improve the success rate of weaning and reduce the mortality rate which is probably related to the reduction of the degree of inflammatory reaction. Ketamine is more effective in reducing inflammatory factors including IL-1β, Caspase-1, and NF-κB than propofol.

  16. Nm23-M2/NDP kinase B induces endogenous c-myc and nm23-M1/NDP kinase A overexpression in BAF3 cells. Both NDP kinases protect the cells from oxidative stress-induced death

    International Nuclear Information System (INIS)

    Arnaud-Dabernat, Sandrine; Masse, Karine; Smani, Moneim; Peuchant, Evelyne; Landry, Marc; Bourbon, Pierre-Marie; Le Floch, Renaud; Daniel, Jean-Yves; Larou, Monique

    2004-01-01

    The nm23 gene family encodes nucleoside diphosphate kinases (NDPKs) which supply the cell with (d)NTPs. The human NDPKB, also known as the PuF protein, binds the c-myc promoter and transactivates the c-myc protooncogene. We have now studied the effects of mouse NDPKA and NDPKB overexpression on endogenous c-myc transactivation in the mouse BAF3 and the rat PC12 cell lines. c-myc transcripts were found to be up-regulated by NDPKB only in the BAF3 line. This suggests that c-myc transcriptional control via NDPKB depends on the presence of cell-specific co-factors. Unexpectedly, NDPKB also induced NDPKA expression. This new effect was found in both cell lines, suggesting that NDPKB-dependent nm23-M1 gene transactivation requires cis and/or trans elements different from those involved in c-myc transactivation. Moreover, the BAF3 cell proliferation capacities were found to be independent of NDPKA or B cell contents. Interestingly, cell death induced by c-myc overexpression or H 2 O 2 exposure was decreased in nm23-transfected compared to control BAF3 cells. These data collectively suggest that NDPKs might improve cell survival by a mechanism coupling DNA repair and transcriptional regulation of genes involved in DNA damage response

  17. In contrast to BOLD: signal enhancement by extravascular water protons as an alternative mechanism of endogenous fMRI signal change.

    Science.gov (United States)

    Figley, Chase R; Leitch, Jordan K; Stroman, Patrick W

    2010-10-01

    Despite the popularity and widespread application of functional magnetic resonance imaging (fMRI) in recent years, the physiological bases of signal change are not yet fully understood. Blood oxygen level-dependant (BOLD) contrast - attributed to local changes in blood flow and oxygenation, and therefore magnetic susceptibility - has become the most prevalent means of functional neuroimaging. However, at short echo times, spin-echo sequences show considerable deviations from the BOLD model, implying a second, non-BOLD component of signal change. This has been dubbed "signal enhancement by extravascular water protons" (SEEP) and is proposed to result from proton-density changes associated with cellular swelling. Given that such changes are independent of magnetic susceptibility, SEEP may offer new and improved opportunities for carrying out fMRI in regions with close proximity to air-tissue and/or bone-tissue interfaces (e.g., the prefrontal cortex and spinal cord), as well as regions close to large blood vessels, which may not be ideally suited for BOLD imaging. However, because of the interdisciplinary nature of the literature, there has yet to be a thorough synthesis, tying together the various and sometimes disparate aspects of SEEP theory. As such, we aim to provide a concise yet comprehensive overview of SEEP, including recent and compelling evidence for its validity, its current applications and its future relevance to the rapidly expanding field of functional neuroimaging. Before presenting the evidence for a non-BOLD component of endogenous functional contrast, and to enable a more critical review for the nonexpert reader, we begin by reviewing the fundamental principles underlying BOLD theory. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Modulation of the release of ( sup 3 H)norepinephrine from the base and body of the rat urinary bladder by endogenous adrenergic and cholinergic mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Somogyi, G.T.; de Groat, W.C. (Univ. of Pittsburgh, PA (USA))

    1990-10-01

    Modulation of (3H)NE release was studied in rat urinary bladder strips prelabeled with (3H)NE. (3H)NE uptake occurred in strips from the bladder base and body, but was very prominent in the base where the noradrenergic innervation is most dense. Electrical field stimulation markedly increased (3H)NE outflow from the superfused tissue. The quantity of (3H)NE release was approximately equal during three consecutive periods of stimulation. Activation of presynaptic muscarinic receptors by 1.0 microM oxotremorine reduced (3H)NE release to 46% of the control. Atropine (1 microM) blocked the effect of oxotremorine and increased the release to 147% of predrug control levels. Activation of presynaptic alpha-2 adrenoceptors by 1 microM clonidine reduced (3H)NE release to 55% of control. Yohimbine blocked the action of clonidine and increased the release to 148% of control. The release of (3H)NE from the bladder base and body was increased by both 1 microM atropine (to 167% and 174% of control, respectively) and 1 microM yohimbine (to 286% and 425% of control, respectively). Atropine and yohimbine administered in combination had similar facilitatory effects as when administered alone. We conclude that the release of (3H)NE from adrenergic nerve endings in electrically stimulated bladder strips is modulated via endogenous transmitters acting on both muscarinic and alpha-2 adrenergic presynaptic receptors and that the latter provide the most prominent control.

  19. Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry study.

    Science.gov (United States)

    Ladha, Karim; Vidal Melo, Marcos F; McLean, Duncan J; Wanderer, Jonathan P; Grabitz, Stephanie D; Kurth, Tobias; Eikermann, Matthias

    2015-07-14

    To evaluate the effects of intraoperative protective ventilation on major postoperative respiratory complications and to define safe intraoperative mechanical ventilator settings that do not translate into an increased risk of postoperative respiratory complications. Hospital based registry study. Academic tertiary care hospital and two affiliated community hospitals in Massachusetts, United States. 69,265 consecutively enrolled patients over the age of 18 who underwent a non-cardiac surgical procedure between January 2007 and August 2014 and required general anesthesia with endotracheal intubation. Protective ventilation, defined as a median positive end expiratory pressure (PEEP) of 5 cmH2O or more, a median tidal volume of less than 10 mL/kg of predicted body weight, and a median plateau pressure of less than 30 cmH2O. Composite outcome of major respiratory complications, including pulmonary edema, respiratory failure, pneumonia, and re-intubation. Of the 69,265 enrolled patients 34,800 (50.2%) received protective ventilation and 34,465 (49.8%) received non-protective ventilation intraoperatively. Protective ventilation was associated with a decreased risk of postoperative respiratory complications in multivariable regression (adjusted odds ratio 0.90, 95% confidence interval 0.82 to 0.98, P=0.013). The results were similar in the propensity score matched cohort (odds ratio 0.89, 95% confidence interval 0.83 to 0.97, P=0.004). A PEEP of 5 cmH2O and median plateau pressures of 16 cmH2O or less were associated with the lowest risk of postoperative respiratory complications. Intraoperative protective ventilation was associated with a decreased risk of postoperative respiratory complications. A PEEP of 5 cmH2O and a plateau pressure of 16 cmH2O or less were identified as protective mechanical ventilator settings. These findings suggest that protective thresholds differ for intraoperative ventilation in patients with normal lungs compared with those used for patients

  20. Endogenous growth and the environment

    NARCIS (Netherlands)

    Withagen, C.A.A.M.; Vellinga, N.

    2001-01-01

    This paper examines the relationship between environmental policy and growth, from the perspective of endogenous growth theory. In particular three standard endogenous growth models are supplemented with environmental issues, such as pollution and exhaustibility of natural resources. It is found

  1. Endogenous growth and environmental policy

    NARCIS (Netherlands)

    Withagen, C.A.A.M.; Vellinga, N.

    2001-01-01

    This paper examines the relationship between environmental policy and growth, from the perspective of endogenous growth theory. In particular three standard endogenous growth models are supplemented with environmental issues, such as pollution and exhaustibility of natural resources. It is found

  2. Protective mechanical ventilation during general anesthesia for open abdominal surgery improves postoperative pulmonary function.

    Science.gov (United States)

    Severgnini, Paolo; Selmo, Gabriele; Lanza, Christian; Chiesa, Alessandro; Frigerio, Alice; Bacuzzi, Alessandro; Dionigi, Gianlorenzo; Novario, Raffaele; Gregoretti, Cesare; de Abreu, Marcelo Gama; Schultz, Marcus J; Jaber, Samir; Futier, Emmanuel; Chiaranda, Maurizio; Pelosi, Paolo

    2013-06-01

    The impact of intraoperative ventilation on postoperative pulmonary complications is not defined. The authors aimed at determining the effectiveness of protective mechanical ventilation during open abdominal surgery on a modified Clinical Pulmonary Infection Score as primary outcome and postoperative pulmonary function. Prospective randomized, open-label, clinical trial performed in 56 patients scheduled to undergo elective open abdominal surgery lasting more than 2 h. Patients were assigned by envelopes to mechanical ventilation with tidal volume of 9 ml/kg ideal body weight and zero-positive end-expiratory pressure (standard ventilation strategy) or tidal volumes of 7 ml/kg ideal body weight, 10 cm H2O positive end-expiratory pressure, and recruitment maneuvers (protective ventilation strategy). Modified Clinical Pulmonary Infection Score, gas exchange, and pulmonary functional tests were measured preoperatively, as well as at days 1, 3, and 5 after surgery. Patients ventilated protectively showed better pulmonary functional tests up to day 5, fewer alterations on chest x-ray up to day 3 and higher arterial oxygenation in air at days 1, 3, and 5 (mmHg; mean ± SD): 77.1 ± 13.0 versus 64.9 ± 11.3 (P = 0.0006), 80.5 ± 10.1 versus 69.7 ± 9.3 (P = 0.0002), and 82.1 ± 10.7 versus 78.5 ± 21.7 (P = 0.44) respectively. The modified Clinical Pulmonary Infection Score was lower in the protective ventilation strategy at days 1 and 3. The percentage of patients in hospital at day 28 after surgery was not different between groups (7 vs. 15% respectively, P = 0.42). A protective ventilation strategy during abdominal surgery lasting more than 2 h improved respiratory function and reduced the modified Clinical Pulmonary Infection Score without affecting length of hospital stay.

  3. [Endogenous pyrogen formation by bone marrow cells].

    Science.gov (United States)

    Efremov, O M; Sorokin, A V; El'kina, O A

    1978-01-01

    The cells of the rabbit bone marrow produced endogenous pyrogen in response to stimulation with bacterial lipopolysaccharide. Incubation of the cells in medium No 199 containing a 15% homologous serum is optimal for the release of pyrogen. It is supposed that the cells of the bone marrow take part in the formation of endgenous pyrogen and in the mechanism of pyrexia in the organism.

  4. Protective effects and mechanisms of curcumin on podophyllotoxin toxicity in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Li, Juan; Dai, Cai-Xia; Sun, Hua [Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632 (China); Jin, Lu [Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632 (China); State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203 (China); Guo, Chong-Yi; Cao, Wei; Wu, Jie; Tian, Hai-Yan [Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632 (China); Luo, Cheng [State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203 (China); Ye, Wen-Cai [Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632 (China); Jiang, Ren-Wang, E-mail: trwjiang@jnu.edu.cn [Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632 (China)

    2012-12-01

    Podophyllotoxin (POD) is a naturally occurring lignan with pronounced antineoplastic and antiviral properties. POD binds to tubulin and prevents the formation of mitotic spindle. Although cases of overdose or accidental ingestion are quite often, no specific therapy is currently available to treat the POD intoxication. In the current investigation, the protective effects and mechanisms of curcumin (CUR) on podophyllotoxin toxicity were evaluated in vitro and in vivo. The results showed that CUR could protect POD-induced cytotoxicity by recovering the G2/M arrest and decrease the changes of membrane potential and microtubule structure in Vero cells. A significant decrease of mortality rates was observed in Swiss mice treated by intragastrical administration of POD + CUR as compared with POD alone. The POD + CUR group also exhibited decreases in plasma transaminases, alkaline phosphatase, lactate dehydrogenase, plasma urea, creatinine and malondialdehyde level but elevated superoxide dismutase and glutathione levels as compared to the POD group. Histological examination of the liver and kidney demonstrated less morphological changes in the treatment of POD + CUR as compared with POD alone. The mechanism of the protective effects might be due to the competitive binding of CUR with POD in the same colchicines binding site as revealed by the tubulin polymerization assay and the molecular docking analysis, and the antioxidant activity against the oxidative stress induced by POD. In summary, both in vitro and in vivo data indicated the promising role of CUR as a protective agent against the POD poisoning. Highlights: ► A potential antidote to treat the podophyllotoxin (POD) intoxication is found. ► Curcumin showed promising effects against POD poisoning in vitro and in vivo. ► The mechanisms lie in the antioxidant activity and competitive binding with tubulin.

  5. Exogenous vs. Endogenous Separation

    OpenAIRE

    Ramey, Garey

    2008-01-01

    This paper assesses how various approaches to modelling the separation margin a¤ect the ability of the Mortensen-Pissarides job matching model to explain key facts about the aggregate labor market. Allowing for realistic time variation in the separation rate, whether exogenous or endogenous, greatly in- creases the unemployment variability generated by the model. Speci…cations with exogenous separation rates, whether constant or time-varying, fail to pro- duce realistic volatility and prod...

  6. Hannay angle. Yet another symmetry-protected topological order parameter in classical mechanics

    International Nuclear Information System (INIS)

    Kariyado, Toshikaze; Hatsugai, Yasuhiro

    2016-01-01

    The topological way of thinking now goes beyond quantum solids, and topological characters of classical mechanical systems obeying Newton's law are attracting current interest. To provide a physical insight into the topological numbers in mechanics, we demonstrate the use of the Hannay angle, a “classical” Berry phase, as a symmetry-protected topological order parameter. The Hannay angle is derived using a canonical transformation that maps Newton's equation to a Schrödinger-type equation, and the condition for the quantization is discussed in connection with the symmetry in mechanics. Also, we demonstrate the use of the Hannay angle for a topological characterization of a spring-mass model focusing on the bulk-edge correspondence. (author)

  7. Evolutionarily Conserved Roles for Blood-Brain Barrier Xenobiotic Transporters in Endogenous Steroid Partitioning and Behavior

    Directory of Open Access Journals (Sweden)

    Samantha J. Hindle

    2017-10-01

    Full Text Available Summary: Central nervous system (CNS chemical protection depends upon discrete control of small-molecule access by the blood-brain barrier (BBB. Curiously, some drugs cause CNS side-effects despite negligible transit past the BBB. To investigate this phenomenon, we asked whether the highly BBB-enriched drug efflux transporter MDR1 has dual functions in controlling drug and endogenous molecule CNS homeostasis. If this is true, then brain-impermeable drugs could induce behavioral changes by affecting brain levels of endogenous molecules. Using computational, genetic, and pharmacologic approaches across diverse organisms, we demonstrate that BBB-localized efflux transporters are critical for regulating brain levels of endogenous steroids and steroid-regulated behaviors (sleep in Drosophila and anxiety in mice. Furthermore, we show that MDR1-interacting drugs are associated with anxiety-related behaviors in humans. We propose a general mechanism for common behavioral side effects of prescription drugs: pharmacologically challenging BBB efflux transporters disrupts brain levels of endogenous substrates and implicates the BBB in behavioral regulation. : Hindle et al. shed light on the curious finding that some drugs cause behavioral side-effects despite negligible access into the brain. These authors propose a unifying hypothesis that links blood-brain barrier drug transporter function and brain access of circulating steroids to common CNS adverse drug responses. Keywords: drug side effect mechanisms, central nervous system, blood brain barrier, behavior, toxicology, drug transporters, endobiotics, steroid hormones

  8. The microstructure, mechanical and friction properties of protective diamond like carbon films on magnesium alloy

    Science.gov (United States)

    Zou, Y. S.; Wu, Y. F.; Yang, H.; Cang, K.; Song, G. H.; Li, Z. X.; Zhou, K.

    2011-12-01

    Protective hard coatings deposited on magnesium alloys are believed to be effective for overcoming their poor wear properties. In this work, diamond-like carbon (DLC) films as hard protective films were deposited on AZ91 magnesium alloy by arc ion plating under negative pulse bias voltages ranging from 0 to -200 V. The microstructure, composition and mechanical properties of the DLC films were analyzed by scanning electron microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy and nanoindentation. The tribological behavior of uncoated and coated AZ91 magnesium alloy was investigated using a ball-on-disk tribotester. The results show that the negative pulse bias voltage used for film deposition has a significant effect on the sp3 carbon content and mechanical properties of the deposited DLC films. A maximum sp3 content of 33.3% was obtained at -100 V, resulting in a high hardness of 28.6 GPa and elastic modulus of 300.0 GPa. The DLC films showed very good adhesion to the AZ91 magnesium alloy with no observable cracks and delamination even during friction testing. Compared with the uncoated AZ91 magnesium alloy, the magnesium alloy coated with DLC films exhibits a low friction coefficient and a narrow, shallow wear track. The wear resistance and surface hardness of AZ91 magnesium alloy can be significantly improved by coating a layer of DLC protective film due to its high hardness and low friction coefficient.

  9. The microstructure, mechanical and friction properties of protective diamond like carbon films on magnesium alloy

    International Nuclear Information System (INIS)

    Zou, Y.S.; Wu, Y.F.; Yang, H.; Cang, K.; Song, G.H.; Li, Z.X.; Zhou, K.

    2011-01-01

    Protective hard coatings deposited on magnesium alloys are believed to be effective for overcoming their poor wear properties. In this work, diamond-like carbon (DLC) films as hard protective films were deposited on AZ91 magnesium alloy by arc ion plating under negative pulse bias voltages ranging from 0 to -200 V. The microstructure, composition and mechanical properties of the DLC films were analyzed by scanning electron microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy and nanoindentation. The tribological behavior of uncoated and coated AZ91 magnesium alloy was investigated using a ball-on-disk tribotester. The results show that the negative pulse bias voltage used for film deposition has a significant effect on the sp 3 carbon content and mechanical properties of the deposited DLC films. A maximum sp 3 content of 33.3% was obtained at -100 V, resulting in a high hardness of 28.6 GPa and elastic modulus of 300.0 GPa. The DLC films showed very good adhesion to the AZ91 magnesium alloy with no observable cracks and delamination even during friction testing. Compared with the uncoated AZ91 magnesium alloy, the magnesium alloy coated with DLC films exhibits a low friction coefficient and a narrow, shallow wear track. The wear resistance and surface hardness of AZ91 magnesium alloy can be significantly improved by coating a layer of DLC protective film due to its high hardness and low friction coefficient.

  10. The microstructure, mechanical and friction properties of protective diamond like carbon films on magnesium alloy

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Y.S., E-mail: yshzou75@gmail.com [School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu, 210094 (China); Wu, Y.F.; Yang, H.; Cang, K. [School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu, 210094 (China); Song, G.H. [School of Materials Science and Engineering, Shenyang University of Technology, Shenyang, Liaoning, 110178 (China); Li, Z.X.; Zhou, K. [School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu, 210094 (China)

    2011-12-01

    Protective hard coatings deposited on magnesium alloys are believed to be effective for overcoming their poor wear properties. In this work, diamond-like carbon (DLC) films as hard protective films were deposited on AZ91 magnesium alloy by arc ion plating under negative pulse bias voltages ranging from 0 to -200 V. The microstructure, composition and mechanical properties of the DLC films were analyzed by scanning electron microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy and nanoindentation. The tribological behavior of uncoated and coated AZ91 magnesium alloy was investigated using a ball-on-disk tribotester. The results show that the negative pulse bias voltage used for film deposition has a significant effect on the sp{sup 3} carbon content and mechanical properties of the deposited DLC films. A maximum sp{sup 3} content of 33.3% was obtained at -100 V, resulting in a high hardness of 28.6 GPa and elastic modulus of 300.0 GPa. The DLC films showed very good adhesion to the AZ91 magnesium alloy with no observable cracks and delamination even during friction testing. Compared with the uncoated AZ91 magnesium alloy, the magnesium alloy coated with DLC films exhibits a low friction coefficient and a narrow, shallow wear track. The wear resistance and surface hardness of AZ91 magnesium alloy can be significantly improved by coating a layer of DLC protective film due to its high hardness and low friction coefficient.

  11. Brain-lung crosstalk in critical care: how protective mechanical ventilation can affect the brain homeostasis.

    Science.gov (United States)

    Mazzeo, A T; Fanelli, V; Mascia, L

    2013-03-01

    The maintenance of brain homeostasis against multiple internal and external challenges occurring during the acute phase of acute brain injury may be influenced by critical care management, especially in its respiratory, hemodynamic and metabolic components. The occurrence of acute lung injury represents the most frequent extracranial complication after brain injury and deserves special attention in daily practice as optimal ventilatory strategy for patients with acute brain and lung injury are potentially in conflict. Protecting the lung while protecting the brain is thus a new target in the modern neurointensive care. This article discusses the essentials of brain-lung crosstalk and focuses on how mechanical ventilation may exert an active role in the process of maintaining or treatening brain homeostasis after acute brain injury, highlighting the following points: 1) the role of inflammation as common pathomechanism of both acute lung and brain injury; 2) the recognition of ventilatory induced lung injury as determinant of systemic inflammation affecting distal organs, included the brain; 3) the possible implication of protective mechanical ventilation strategy on the patient with an acute brain injury as an undiscovered area of research in both experimental and clinical settings.

  12. Failure Mechanisms of the Protective Coatings for the Hot Stamping Applications

    Science.gov (United States)

    Zhao, Chen

    In the present study, four different nitriding techniques were carried on the ductile irons NAAMS-D6510 and cast steels NAAMS-S0050A, which are widely used stamping die materials; duplex treatments (PVD CrN coating+nitriding) were carried on H13 steels, which are common inserts for the hot stamping dies. Inclined impact-sliding wear tests were performed on the nitriding cases under simulated stamping conditions. Surface profilometer, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) were used to investigate the wear and failure mechanisms of the protective coatings. It was found that the nitrided ductile iron samples performed better than the nitrided cast steel specimens. High temperature inclined impact-sliding wear tests were carried out on the CrN coatings. It was found that the coating performed better at elevated temperature. XPS analysis indicated the top surface layer (about 3-4nm) of the coating was oxidized at 400 °C and formed a Cr2O3 protective film. The in-situ formation of the thin Cr2O3 protective layer likely led to the change of wear mechanisms from severe adhesive failure to mild abrasive wear.

  13. Multi-targeted mechanisms underlying the endothelial protective effects of the diabetic-safe sweetener erythritol.

    Directory of Open Access Journals (Sweden)

    Daniëlle M P H J Boesten

    Full Text Available Diabetes is characterized by hyperglycemia and development of vascular pathology. Endothelial cell dysfunction is a starting point for pathogenesis of vascular complications in diabetes. We previously showed the polyol erythritol to be a hydroxyl radical scavenger preventing endothelial cell dysfunction onset in diabetic rats. To unravel mechanisms, other than scavenging of radicals, by which erythritol mediates this protective effect, we evaluated effects of erythritol in endothelial cells exposed to normal (7 mM and high glucose (30 mM or diabetic stressors (e.g. SIN-1 using targeted and transcriptomic approaches. This study demonstrates that erythritol (i.e. under non-diabetic conditions has minimal effects on endothelial cells. However, under hyperglycemic conditions erythritol protected endothelial cells against cell death induced by diabetic stressors (i.e. high glucose and peroxynitrite. Also a number of harmful effects caused by high glucose, e.g. increased nitric oxide release, are reversed. Additionally, total transcriptome analysis indicated that biological processes which are differentially regulated due to high glucose are corrected by erythritol. We conclude that erythritol protects endothelial cells during high glucose conditions via effects on multiple targets. Overall, these data indicate a therapeutically important endothelial protective effect of erythritol under hyperglycemic conditions.

  14. Formation mechanism of the graphite-rich protective layer in blast furnace hearths

    Science.gov (United States)

    Jiao, Ke-xin; Zhang, Jian-liang; Liu, Zheng-jian; Liu, Feng; Liang, Li-sheng

    2016-01-01

    A long campaign life of blast furnaces is heavily linked to the existence of a protective layer in their hearths. In this work, we conducted dissection studies and investigated damage in blast furnace hearths to estimate the formation mechanism of the protective layer. The results illustrate that a significant amount of graphite phase was trapped within the hearth protective layer. Furthermore, on the basis of the thermodynamic and kinetic calculations of the graphite precipitation process, a precipitation potential index related to the formation of the graphite-rich protective layer was proposed to characterize the formation ability of this layer. We determined that, under normal operating conditions, the precipitation of graphite phase from hot metal was thermodynamically possible. Among elements that exist in hot metal, C, Si, and P favor graphite precipitation, whereas Mn and Cr inhibit this process. Moreover, at the same hot-face temperature, an increase of carbon concentration in hot metal can shorten the precipitation time. Finally, the results suggest that measures such as reducing the hot-face temperature and increasing the degree of carbon saturation in hot metal are critically important to improve the precipitation potential index.

  15. Protective mechanism of agmatine pretreatment on RGC-5 cells injured by oxidative stress

    Directory of Open Access Journals (Sweden)

    Y. Iizuka

    2010-04-01

    Full Text Available Agmatine has neuroprotective effects on retinal ganglion cells (RGCs as well as cortical and spinal neurons. It protects RGCs from oxidative stress even when it is not present at the time of injury. As agmatine has high affinity for various cellular receptors, we assessed protective mechanisms of agmatine using transformed RGCs (RGC-5 cell line. Differentiated RGC-5 cells were pretreated with 100 μM agmatine and consecutively exposed to 1.0 mM hydrogen peroxide (H2O2. Cell viability was determined by measuring lactate dehydrogenase (LDH, and the effects of selective alpha 2-adrenergic receptor antagonist yohimbine (0-500 nM and N-methyl-D-aspartic acid (NMDA receptor agonist NMDA (0-100 µM were evaluated. Agmatine’s protective effect was compared to a selective NMDA receptor antagonist MK-801. After a 16-h exposure to H2O2, the LDH assay showed cell loss greater than 50%, which was reduced to about 30% when agmatine was pretreated before injury. Yohimbine almost completely inhibited agmatine’s protective effect, but NMDA did not. In addition, MK-801 (0-100 µM did not significantly attenuate the H2O2-induced cytotoxicity. Our results suggest that neuroprotective effects of agmatine on RGCs under oxidative stress may be mainly attributed to the alpha 2-adrenergic receptor signaling pathway.

  16. PROTECTIVE COATINGS OF FIBER BRAGG GRATING FOR MINIMIZING OF MECHANICAL IMPACT ON ITS WAVELENGTH CHARACTERISTICS

    Directory of Open Access Journals (Sweden)

    A. S. Munko

    2015-03-01

    Full Text Available The paper deals with the scheme for the study of the Bragg wavelength shift dependence on the applied tensile force. Samples of fiber Bragg gratings with different coatings have been studied: the restored acrylate coating, the heatshrinkable fusion splice protection sleeve without metal rod, the heat-shrinkable fusion splice protection sleeve with a metal rod, the metal capillary, polyvinylchloride tube. For different coatings of diffractive structure, dependences of wavelength shift for the Bragg grating resonance have been obtained on the tensile strength applied to the ends of an optical fiber. It was determined that the studied FBG coatings give the possibility to reduce the mechanical impact on the Bragg wavelength shift for 1.1-15 times as compared to an uncoated waveguide. The most effective version of coated fiber Bragg grating is the heatshrinkable fusion splice protection sleeve with a metal rod. When the force (equal to 6 N is applied to the 100 mm optical fiber area with the inscribed diffractive structure, the Bragg wavelength shift is 7.5 nm for the unprotected sample and 0.5 nm for the one coated with the heat-shrinkable fusion splice protection sleeve.

  17. Mechanism of Aloe Vera extract protection against UVA: shelter of lysosomal membrane avoids photodamage.

    Science.gov (United States)

    Rodrigues, Daniela; Viotto, Ana Cláudia; Checchia, Robert; Gomide, Andreza; Severino, Divinomar; Itri, Rosangela; Baptista, Maurício S; Martins, Waleska Kerllen

    2016-03-01

    The premature aging (photoaging) of skin characterized by wrinkles, a leathery texture and mottled pigmentation is a well-documented consequence of exposure to sunlight. UVA is an important risk factor for human cancer also associated with induction of inflammation, immunosuppression, photoaging and melanogenesis. Although herbal compounds are commonly used as photoprotectants against the harmful effects of UVA, the mechanisms involved in the photodamage are not precisely known. In this study, we investigated the effects of Aloe Vera (Aloe barbadensis mil) on the protection against UVA-modulated cell killing of HaCaT keratinocytes. Aloe Vera exhibited the remarkable ability of reducing both in vitro and in vivo photodamage, even though it does not have anti-radical properties. Interestingly, the protection conferred by Aloe Vera was associated with the maintenance of membrane integrity in both mimetic membranes and intracellular organelles. The increased lysosomal stability led to a decrease in lipofuscinogenesis and cell death. This study explains why Aloe Vera extracts offer protection against photodamage at a cellular level in both the UV and visible spectra, leading to its beneficial use as a supplement in protective dermatological formulations.

  18. Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

    International Nuclear Information System (INIS)

    Wang, Jun; Cao, Hui; Wang, Hongjie; Yin, Guoxiao; Du, Jiao; Xia, Fei; Lu, Jingli; Xiang, Ming

    2015-01-01

    Toll-like receptor 4 (TLR4) activation has been proposed to be important for islet cell inflammation and eventually β cell loss in the course of type 1 diabetes (T1D) development. However, according to the “hygiene hypothesis”, bacterial endotoxin lipopolysaccharide (LPS), an agonist on TLR4, inhibits T1D progression. Here we investigated possible mechanisms for the protective effect of LPS on T1D development in non-obese diabetic (NOD) mice. We found that LPS administration to NOD mice during the prediabetic state neither prevented nor reversed insulitis, but delayed the onset and decreased the incidence of diabetes, and that a multiple-injection protocol is more effective than a single LPS intervention. Further, LPS administration suppressed spleen T lymphocyte proliferation, increased the generation of CD4 + CD25 + Foxp3 + regulatory T cells (Tregs), reduced the synthesis of strong Th1 proinflammatory cytokines, and downregulated TLR4 and its downstream MyD88-dependent signaling pathway. Most importantly, multiple injections of LPS induced a potential tolerogenic dendritic cell (DC) subset with low TLR4 expression without influencing the DC phenotype. Explanting DCs from repeated LPS-treated NOD mice into NOD/SCID diabetic mice conferred sustained protective effects against the progression of diabetes in the recipients. Overall, these results suggest that multiple mechanisms are involved in the protective effects of LPS against the development of diabetes in NOD diabetic mice. These include Treg induction, down-regulation of TLR4 and its downstream MyD88-dependent signaling pathway, and the emergence of a potential tolerogenic DC subset. - Highlights: • Administration of lipopolysaccharide (LPS) prevented type 1 diabetes in NOD mice. • Downregulating TLR4 level and MyD88-dependent pathway contributed to protection of LPS. • LPS administration also hampered DC maturation and promoted Treg differentiation

  19. Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jun [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Department of Pharmacology, College of Medicine, Wuhan University of Science and Technology, Wuhan (China); Cao, Hui [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Wang, Hongjie [Section of Neurobiology, Torrey Pines Institute for Molecular Studies, Port Saint Lucie, FL (United States); Yin, Guoxiao; Du, Jiao; Xia, Fei; Lu, Jingli [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Xiang, Ming, E-mail: xiangming@mails.tjmu.edu.cn [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China)

    2015-06-15

    Toll-like receptor 4 (TLR4) activation has been proposed to be important for islet cell inflammation and eventually β cell loss in the course of type 1 diabetes (T1D) development. However, according to the “hygiene hypothesis”, bacterial endotoxin lipopolysaccharide (LPS), an agonist on TLR4, inhibits T1D progression. Here we investigated possible mechanisms for the protective effect of LPS on T1D development in non-obese diabetic (NOD) mice. We found that LPS administration to NOD mice during the prediabetic state neither prevented nor reversed insulitis, but delayed the onset and decreased the incidence of diabetes, and that a multiple-injection protocol is more effective than a single LPS intervention. Further, LPS administration suppressed spleen T lymphocyte proliferation, increased the generation of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells (Tregs), reduced the synthesis of strong Th1 proinflammatory cytokines, and downregulated TLR4 and its downstream MyD88-dependent signaling pathway. Most importantly, multiple injections of LPS induced a potential tolerogenic dendritic cell (DC) subset with low TLR4 expression without influencing the DC phenotype. Explanting DCs from repeated LPS-treated NOD mice into NOD/SCID diabetic mice conferred sustained protective effects against the progression of diabetes in the recipients. Overall, these results suggest that multiple mechanisms are involved in the protective effects of LPS against the development of diabetes in NOD diabetic mice. These include Treg induction, down-regulation of TLR4 and its downstream MyD88-dependent signaling pathway, and the emergence of a potential tolerogenic DC subset. - Highlights: • Administration of lipopolysaccharide (LPS) prevented type 1 diabetes in NOD mice. • Downregulating TLR4 level and MyD88-dependent pathway contributed to protection of LPS. • LPS administration also hampered DC maturation and promoted Treg differentiation.

  20. Molecular Mechanisms Responsible for Neuron-Derived Conditioned Medium (NCM-Mediated Protection of Ischemic Brain.

    Directory of Open Access Journals (Sweden)

    Chi-Hsin Lin

    Full Text Available The protective value of neuron-derived conditioned medium (NCM in cerebral ischemia and the underlying mechanism(s responsible for NCM-mediated brain protection against cerebral ischemia were investigated in the study. NCM was first collected from the neuronal culture growing under the in vitro ischemic condition (glucose-, oxygen- and serum-deprivation or GOSD for 2, 4 or 6 h. Through the focal cerebral ischemia (bilateral CCAO/unilateral MCAO animal model, we discovered that ischemia/reperfusion (I/R-induced brain infarction was significantly reduced by NCM, given directly into the cistern magna at the end of 90 min of CCAO/MCAO. Immunoblocking and chemical blocking strategies were applied in the in vitro ischemic studies to show that NCM supplement could protect microglia, astrocytes and neurons from GOSD-induced cell death, in a growth factor (TGFβ1, NT-3 and GDNF and p-ERK dependent manner. Brain injection with TGFβ1, NT3, GDNF and ERK agonist (DADS alone or in combination, therefore also significantly decreased the infarct volume of ischemic brain. Moreover, NCM could inhibit ROS but stimulate IL-1β release from GOSD-treated microglia and limit the infiltration of IL-β-positive microglia into the core area of ischemic brain, revealing the anti-oxidant and anti-inflammatory activities of NCM. In overall, NCM-mediated brain protection against cerebral ischemia has been demonstrated for the first time in S.D. rats, due to its anti-apoptotic, anti-oxidant and potentially anti-glutamate activities (NCM-induced IL-1β can inhibit the glutamate-mediated neurotoxicity and restriction upon the infiltration of inflammatory microglia into the core area of ischemic brain. The therapeutic potentials of NCM, TGFβ1, GDNF, NT-3 and DADS in the control of cerebral ischemia in human therefore have been suggested and require further investigation.

  1. [Protective effect and mechanism of compound Ginkgo biloba granules on oxidative stress injury of HUVEC].

    Science.gov (United States)

    Li, Qi; Chen, Xi; Kan, Xiao-Xi; Li, Yu-Jie; Yang, Qing; Wang, Ya-Jie; Chen, Ying; Weng, Xiao-Gang; Cai, Wei-Yan; Huang, He-Fei; Zhu, Xiao-Xin

    2016-02-01

    To reveal the protective and anti-apoptosis effect of compound Ginkgo biloba granules on oxidative stress injury of human umbilical vein endothelial cells (HUVEC). Negative control group, H2O2 model group and 4 drug pretreatment groups (80, 160, 320, 640 mg• L⁻¹) were established. The cell proliferation, morphological changes in each group after oxidative stress injury was detected by MTT assay and through microscope observation respectively. The content of LDH, MDA, SOD and NO and SOD activity in supernatant were detected to judge the protection effect of the drugs on endothelial cells. The protective effect on HUVEC apoptosis was analyzed by Caspase-3 activity test and Annexin V-FITC/PI staining. Western blot was used to observe the expression of apoptosis-related proteins Bcl-2 and Bax. Results showed that 1 200 μmol• L⁻¹ H2O2 can induce oxidative stress injury in endothelial cells and reduce the cell survival rate; cell proliferation inhibition degree is positively correlated with the effect time of H2O2. Besides, 80, 160, 320 640 mg•L⁻¹ compound Ginkgo biloba granules can protect HUVEC from oxidative stress injury, recover the normal proliferation level of cells, improve their state, prohibit cell apoptosis, and can up-regulate and down-regulate the expression level of Bcl-2 and Bax respectively. In conclusion, compound G. biloba granules can protect HUVEC from the oxidative stress injury induced by H2O2, its mechanism may be correlated with inhibition of the mitochondrial apoptotic pathway in HUVEC. Copyright© by the Chinese Pharmaceutical Association.

  2. A Protective Mechanism for the Access Control System in the Virtual Domain

    Institute of Scientific and Technical Information of China (English)

    Jinan Shen; Deqing Zou; Hai Jin; Kai Yang; Bin Yuan; Weiming Li

    2016-01-01

    In traditional framework,mandatory access control (MAC) system and malicious software are run in kernel mode.Malicious software can stop MAC systems to be started and make it do invalid.This problem cannot be solved under the traditional framework if the operating system (OS) is comprised since malwares are running in ring0 level.In this paper,we propose a novel way to use hypervisors to protect kernel integrity and the access control system in commodity operating systems.We separate the access control system into three parts:policy management (PM),security server (SS) and policy enforcement (PE).Policy management and the security server reside in the security domain to protect them against malware and the isolation feather of the hypervisor can protect them from attacks.We add an access vector cache (AVC) between SS and PE in the guest OS,in order to speed up communication between the guest OS and the security domain.The policy enforcement module is retained in the guest OS for performance.The security of AVC and PE can be ensured by using a memory protection mechanism.The goal of protecting the OS kemel is to ensure the security of the execution path.We implement the system by a modified Xen hypervisor.The result shows that we can secure the security of the access control system in the guest OS with no overhead compared with modules in the latter.Our system offers a centralized security policy for virtual domains in virtual machine environments.

  3. Skeletal muscle contraction in protecting joints and bones by absorbing mechanical impacts

    Science.gov (United States)

    Rudenko, O. V.; Tsyuryupa, S.; Sarvazyan, A.

    2016-09-01

    We have previously hypothesized that the dissipation of mechanical energy of external impact is a fundamental function of skeletal muscle in addition to its primary function to convert chemical energy into mechanical energy. In this paper, a mathematical justification of this hypothesis is presented. First, a simple mechanical model, in which the muscle is considered as a simple Hookean spring, is considered. This analysis serves as an introduction to the consideration of a biomechanical model taking into account the molecular mechanism of muscle contraction, kinetics of myosin bridges, sarcomere dynamics, and tension of muscle fibers. It is shown that a muscle behaves like a nonlinear and adaptive spring tempering the force of impact and increasing the duration of the collision. The temporal profiles of muscle reaction to the impact as functions of the levels of muscle contraction, durations of the impact front, and the time constants of myosin bridges closing, are obtained. The absorption of mechanical shock energy is achieved due to the increased viscoelasticity of the contracting skeletal muscle. Controlling the contraction level allows for the optimization of the stiffness and viscosity of the muscle necessary for the protection of the joints and bones.

  4. Mechanisms of PEDF-mediated protection against reactive oxygen species damage in diabetic retinopathy and neuropathy.

    Science.gov (United States)

    Elahy, Mina; Baindur-Hudson, Swati; Cruzat, Vinicius F; Newsholme, Philip; Dass, Crispin R

    2014-09-01

    Pigment epithelium-derived factor (PEDF) is a pluripotent glycoprotein belonging to the serpin family. PEDF can stimulate several physiological processes such as angiogenesis, cell proliferation, and survival. Oxidative stress plays an important role in the occurrence of diabetic retinopathy (DR), which is the major cause of blindness in young diabetic adults. PEDF plays a protective role in DR and there is accumulating evidence of the neuroprotective effect of PEDF. In this paper, we review the role of PEDF and the mechanisms involved in its antioxidative, anti-inflammatory, and neuroprotective properties. © 2014 Society for Endocrinology.

  5. The Endogenous Feedback Network

    DEFF Research Database (Denmark)

    Augustenborg, Claudia Carrara

    2010-01-01

    proposals, it will first be considered the extents of their reciprocal compatibility, tentatively shaping an integrated, theoretical profile of consciousness. A new theory, the Endogenous Feedback Network (EFN) will consequently be introduced which, beside being able to accommodate the main tenets...... of the reviewed theories, appears able to compensate for the explanatory gaps they leave behind. The EFN proposes consciousness as the phenomenon emerging from a distinct network of neural paths broadcasting the neural changes associated to any mental process. It additionally argues for the need to include a 5th...

  6. Hume and Endogenous Money

    OpenAIRE

    Maria Pia Paganelli

    2006-01-01

    David Hume’s monetary theory has three standard yet inconsistent readings. As a forefather of the quantity theory of money, Hume sees money as neutral. As an inflationist, Hume sees an active positive role for monetary policy. As a monetarist, Hume sees an active positive role for monetary policy only in the short run. This paper reads Hume consistently instead by showing that for Hume money is endogenous and demand-driven. Hume would read the money equation in terms of reverse causation and ...

  7. DNA Protection Protein, a Novel Mechanism of Radiation Tolerance: Lessons from Tardigrades.

    Science.gov (United States)

    Hashimoto, Takuma; Kunieda, Takekazu

    2017-06-15

    Genomic DNA stores all genetic information and is indispensable for maintenance of normal cellular activity and propagation. Radiation causes severe DNA lesions, including double-strand breaks, and leads to genome instability and even lethality. Regardless of the toxicity of radiation, some organisms exhibit extraordinary tolerance against radiation. These organisms are supposed to possess special mechanisms to mitigate radiation-induced DNA damages. Extensive study using radiotolerant bacteria suggested that effective protection of proteins and enhanced DNA repair system play important roles in tolerability against high-dose radiation. Recent studies using an extremotolerant animal, the tardigrade, provides new evidence that a tardigrade-unique DNA-associating protein, termed Dsup, suppresses the occurrence of DNA breaks by radiation in human-cultured cells. In this review, we provide a brief summary of the current knowledge on extremely radiotolerant animals, and present novel insights from the tardigrade research, which expand our understanding on molecular mechanism of exceptional radio-tolerability.

  8. Optimal loading and protection of multi-state systems considering performance sharing mechanism

    International Nuclear Information System (INIS)

    Xiao, Hui; Shi, Daimin; Ding, Yi; Peng, Rui

    2016-01-01

    Engineering systems are designed to carry the load. The performance of the system largely depends on how much load it carries. On the other hand, the failure rate of the system is strongly affected by its load. Besides internal failures, such as fatigue and aging process, systems may also fail due to external impacts such as nature disasters and terrorism. In this paper, we integrate the effect of loading and protection of external impacts on multi-state systems with performance sharing mechanism. The objective of this research is to determine how to balance the load and protection on system elements. An availability evaluation algorithm of the proposed system is suggested and the corresponding optimization problem is solved utilizing genetic algorithms. - Highlights: • Performance sharing of multi-state systems is considered. • The effect of load on system elements is analyzed. • Joint optimization model of element loading and protection is formulated. • Genetic Algorithms are adapted to solve the reliability optimization problem.

  9. Striatal increase of neurotrophic factors as a mechanism of nicotine protection in experimental parkinsonism.

    Science.gov (United States)

    Maggio, R; Riva, M; Vaglini, F; Fornai, F; Racagni, G; Corsini, G U

    1997-01-01

    The repeated finding of an apparent protective effect of cigarette smoking on the risk of Parkinson's disease is one of the few consistent results in the epidemiology of this disorder. Among the innumerous substances that originate from tobacco smoke, nicotine is by far the most widely studied, and the most likely candidate for a protective effect against neuronal degeneration in Parkinson's disease. Nicotine is a natural alkaloid that has considerable stimulatory effects on the central nervous system (CNS). Its effects on the CNS are mediated by the activation of neuronal heteromeric acetylcholine-gated ion channel receptors (nAChR, also termed nicotinic acetylcholine receptors). In the present study, we describe the neuroprotective effects of (-)nicotine in two animal models of parkinsonism: the diethyldithiocarbamate (DDC)-induced enhancement of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity in mice, and the methamphetamine-induced neurotoxicity in rats and mice. In parallel experiments, we found that (-)nicotine induces the basic fibroblast growth factor (FGF-2) and the brain-derived neurotrophic factor (BDNF) in rat striatum. As FGF-2 and BDNF have been reported to be neuroprotective for dopaminergic cells, our data indicate that the increase in neurotrophic factors is a possible mechanism by which (-)nicotine protects from experimental parkinsonisms. Moreover, they suggest that nAChR agonists could be of potential benefit in the progression of Parkinson's disease.

  10. Gaps in governance: protective mechanisms used by nurse leaders when policy and practice are misaligned.

    Science.gov (United States)

    Knight, Kaye M; Kenny, Amanda; Endacott, Ruth

    2015-04-09

    Due to large geographical distances, the telephone is central to enabling rural Australian communities to access care from their local health service. While there is a history of rural nurses providing care via the telephone, it has been a highly controversial practice that is not routinely documented and little is known about how the practice is governed. The lack of knowledge regarding governance extends to the role of Directors of Nursing as clinical leaders charged with the responsibility of ensuring practice safety, quality, regulation and risk management. The purpose of this study was to identify clinical governance processes related to managing telephone presentations, and to explore Directors of Nursing perceptions of processes and clinical practices related to the management of telephone presentations to health services in rural Victoria, Australia. Qualitative documentary analysis and semi structured interviews were used in the study to examine the content of health service policies and explore the perceptions of Directors of Nursing in eight rural health services regarding policy content and enactment when people telephone rural health services for care. Participants were purposively selected for their knowledge and leadership role in governance processes and clinical practice. Data from the interviews were analysed using framework analysis. The process of analysis resulted in the identification of five themes. The majority of policies reviewed provided little guidance for managing telephone presentations. The Directors of Nursing perceived policy content and enactment to be largely inadequate. When organisational structures failed to provide appropriate governance for the context, the Directors of Nursing engaged in protective mechanisms to support rural nurses who manage telephone presentations. Rural Directors of Nursing employed intuitive behaviours to protect rural nurses practicing within a clinical governance context that is inadequate for the

  11. Study on radiation protective effect of resveratrol and its molecular mechanism

    International Nuclear Information System (INIS)

    Lv Qiujun; Wen Liqing; Zhang Min; Guo Shaoming; Chen Yuanyuan; Wu Zuze

    2004-01-01

    Objective: To investigate radiation-protective effect of resveratrol and its molecular mechanism. Methods: Kunming mice were administered with resveratrol before 60 Co γ-irradiation. Thirty-day survival rate and the average life span of dead mice post-irradiation were observed. The apoptosis of spleen from irradiated mice was detected by FACS and in situ terminal labeling method. The effect of resveratrol on the activities of Caspase-3 and Caspase-8, and the expression levels of Bcl-2 and Fas were examined. Results: Administration with resveratrol resulted in increases of 30-day survival rate and prolongation of average life span of the dead mice. Apoptotic rate of spleen cells decreased, expression level of bcl-2 increased, the expression of Fas did not change, and the activities of Caspase-3 and Caspase-8 increased in spleen cells of irradiation groups. Conclusion: The results indicate that resveratrol has radiation-protective effect and its mechanism might be related with its suppression of apoptosis of radiation-sensitive cells

  12. Mechanisms of radiation interaction with DNA: Potential implications for radiation protection

    International Nuclear Information System (INIS)

    1988-01-01

    The Office of Health and Environmental Research (OHER) of the US Department of Energy conducts a broad multidisciplinary research program which includes basic biophysics, biophysical chemistry, molecular and cellular biology as well as experimental animal studies and opportunistic human studies. This research is directed at understanding how low levels of radiation of various qualities produce the spectrum of biological effects that are seen for such exposures. This workshop was entitled ''Mechanisms of Radiation Interaction with DNA: Potential Implications for Radiation Protection.'' It ws jointly sponsored by the Department of Energy and the Commission of European Communities. The aim of the workshop was to review the base of knowledge in the area of mechanisms of radiation action at the DNA level, and to explore ways in which this information can be applied to the development of scientifically sound concepts and procedures for use in the field of radiation protection. The overview of research provided by this multidisciplinary group will be helpful to the Office in program planning. This report includes a summary of the presentations, extended abstracts, the meeting agenda, research recommendations, and a list of participants. Individual papers are processed separately for the data base

  13. Mechanisms of radiation interaction with DNA: Potential implications for radiation protection

    Energy Technology Data Exchange (ETDEWEB)

    1988-01-01

    The Office of Health and Environmental Research (OHER) of the US Department of Energy conducts a broad multidisciplinary research program which includes basic biophysics, biophysical chemistry, molecular and cellular biology as well as experimental animal studies and opportunistic human studies. This research is directed at understanding how low levels of radiation of various qualities produce the spectrum of biological effects that are seen for such exposures. This workshop was entitled ''Mechanisms of Radiation Interaction with DNA: Potential Implications for Radiation Protection.'' It ws jointly sponsored by the Department of Energy and the Commission of European Communities. The aim of the workshop was to review the base of knowledge in the area of mechanisms of radiation action at the DNA level, and to explore ways in which this information can be applied to the development of scientifically sound concepts and procedures for use in the field of radiation protection. The overview of research provided by this multidisciplinary group will be helpful to the Office in program planning. This report includes a summary of the presentations, extended abstracts, the meeting agenda, research recommendations, and a list of participants. Individual papers are processed separately for the data base.

  14. Molecular mechanisms of green tea polyphenols with protective effects against skin photoaging.

    Science.gov (United States)

    Roh, Eunmiri; Kim, Jong-Eun; Kwon, Jung Yeon; Park, Jun Seong; Bode, Ann M; Dong, Zigang; Lee, Ki Won

    2017-05-24

    Whereas green tea has historically been consumed in high quantities in Northeast Asia, its popularity is also increasing in many Western countries. Green tea is an abundant source of plant polyphenols exhibiting numerous effects that are potentially beneficial for human health. Accumulating evidence suggests that green tea polyphenols confer protective effects on the skin against ultraviolet (UV) irradiation-induced acceleration of skin aging, involving antimelanogenic, antiwrinkle, antioxidant, and anti-inflammatory effects as well as prevention of immunosuppression. Melanin pigmentation in the skin is a major defense mechanism against UV irradiation, but pigmentation abnormalities such as melasma, freckles, senile lentigines, and other forms of melanin hyperpigmentation can also cause serious health and aesthetic issues. Furthermore, UV irradiation initiates the degradation of fibrillar collagen and elastic fibers, promoting the process of skin aging through deep wrinkle formation and loss of tissue elasticity. UV irradiation-induced formation of free radicals also contributes to accelerated photoaging. Additionally, immunosuppression caused by UV irradiation plays an important role in photoaging and skin carcinogenesis. In this review, we summarize the current literature regarding the antimelanogenic, antiwrinkle, antioxidant, and immunosuppression preventive mechanisms of green tea polyphenols that have been demonstrated to protect against UV irradiation-stimulated skin photoaging, and gauge the quality of evidence supporting the need for clinical studies using green tea polyphenols as anti-photoaging agents in novel cosmeceuticals.

  15. Oriented clay nanopaper from biobased components--mechanisms for superior fire protection properties.

    Science.gov (United States)

    Carosio, F; Kochumalayil, J; Cuttica, F; Camino, G; Berglund, L

    2015-03-18

    The toxicity of the most efficient fire retardant additives is a major problem for polymeric materials. Cellulose nanofiber (CNF)/clay nanocomposites, with unique brick-and-mortar structure and prepared by simple filtration, are characterized from the morphological point of view by scanning electron microscopy and X-ray diffraction. These nanocomposites have superior fire protection properties to other clay nanocomposites and fiber composites. The corresponding mechanisms are evaluated in terms of flammability (reaction to a flame) and cone calorimetry (exposure to heat flux). These two tests provide a wide spectrum characterization of fire protection properties in CNF/montmorrilonite (MTM) materials. The morphology of the collected residues after flammability testing is investigated. In addition, thermal and thermo-oxidative stability are evaluated by thermogravimetric analyses performed in inert (nitrogen) and oxidative (air) atmospheres. Physical and chemical mechanisms are identified and related to the unique nanostructure and its low thermal conductivity, high gas barrier properties and CNF/MTM interactions for char formation.

  16. Legal mechanisms in European Union and Serbia which aimed to protect women from domestic violence

    Directory of Open Access Journals (Sweden)

    Samardžić Sandra

    2012-01-01

    Full Text Available Violence against women is the most common form of domestic violence. This problem has long been ignored, because it is considered that family relations, e.g. relations between married and unmarried partners are a private matter and the state's obligation was to refrain from any interference. However, since the problem of domestic violence against women has become increasingly common, the attitude of the international community began to change, and it was increasingly emphasizes the need to create adequate legal mechanisms to provide protection to the victim. In this sense, in the United Nations, and the European Union a number of laws were enacted. In Serbia, there is also both, criminal and civil law regulation that seeks to prevent domestic violence and to punish perpetrators and protect victims. In addition to adequate legal mechanisms, which can always be improved, it is necessary to take certain initiatives by states that can lead to improved awareness among the people about the presence of violence, and the ways in which they can help.

  17. Protective immune mechanisms against pre-erythrocytic forms of Plasmodium berghei depend on the target antigen

    Directory of Open Access Journals (Sweden)

    Elke S. Bergmann-Leitner

    2014-01-01

    Full Text Available Pre-erythrocytic malaria vaccines are believed to either stop the injected sporozoites from reaching the liver or to direct cellular immune responses towards eliminating infected hepatocytes. The present study reveals for the first time the anatomical sites at which these immune mechanisms act against the malaria parasites. To determine the mechanisms leading to protection mediated by two previously characterized vaccines against either the circumsporozoite protein (CSP or the cell traversal protein for ookinetes and sporozoites (CelTOS, mice were immunized and subsequently challenged by subcutaneous injection of salivary gland sporozoites of luciferase-transgenic Plasmodium berghei parasites. The In Vivo Imaging System (IVIS was used to identify the anatomical site where the vaccine-induced immune response eliminates sporozoites after injection. The data demonstrate that CSP-based immunity acts at the site of infection (skin whereas CelTOS-based immunity is only partially efficient in the skin and allows reduced levels of liver infection that can be subsequently cleared. The results of this study challenge assumptions regarding CSP-mediated immune mechanisms and call into question the validity of some commonly used assays to evaluate anti-CSP immune responses. The knowledge of the mechanism and events leading to infection or immune defense will guide supportive treatment with drugs or combination therapies and thus accelerate the development of effective antimalarial strategies.

  18. Using hierarchical linear growth models to evaluate protective mechanisms that mediate science achievement

    Science.gov (United States)

    von Secker, Clare Elaine

    The study of students at risk is a major topic of science education policy and discussion. Much research has focused on describing conditions and problems associated with the statistical risk of low science achievement among individuals who are members of groups characterized by problems such as poverty and social disadvantage. But outcomes attributed to these factors do not explain the nature and extent of mechanisms that account for differences in performance among individuals at risk. There is ample theoretical and empirical evidence that demographic differences should be conceptualized as social contexts, or collections of variables, that alter the psychological significance and social demands of life events, and affect subsequent relationships between risk and resilience. The hierarchical linear growth models used in this dissertation provide greater specification of the role of social context and the protective effects of attitude, expectations, parenting practices, peer influences, and learning opportunities on science achievement. While the individual influences of these protective factors on science achievement were small, their cumulative effect was substantial. Meta-analysis conducted on the effects associated with psychological and environmental processes that mediate risk mechanisms in sixteen social contexts revealed twenty-two significant differences between groups of students. Positive attitudes, high expectations, and more intense science course-taking had positive effects on achievement of all students, although these factors were not equally protective in all social contexts. In general, effects associated with authoritative parenting and peer influences were negative, regardless of social context. An evaluation comparing the performance and stability of hierarchical linear growth models with traditional repeated measures models is included as well.

  19. Protection from Muscle Damage in the Absence of Changes in Muscle Mechanical Behavior.

    Science.gov (United States)

    Hoffman, Ben W; Cresswell, Andrew G; Carroll, Timothy J; Lichtwark, Glen A

    2016-08-01

    The repeated bout effect characterizes the protective adaptation after a single bout of unaccustomed eccentric exercise that induces muscle damage. Sarcomerogenesis and increased tendon compliance have been suggested as potential mechanisms for the repeated bout effect by preventing muscle fascicles from being stretched onto the descending limb of the length-tension curve (the region where sarcomere damage is thought to occur). In this study, evidence was sought for three possible mechanical changes that would support either the sarcomerogenesis or the increased tendon compliance hypotheses: a sustained rightward shift in the fascicle length-tension relationship, reduced fascicle strain amplitude, and reduced starting fascicle length. Subjects (n = 10) walked backward downhill (5 km·h, 20% incline) on a treadmill for 30 min on two occasions separated by 7 d. Kinematic data and medial gastrocnemius fascicle lengths (ultrasonography) were recorded at 10-min intervals to compare fascicle strains between bouts. Fascicle length-torque curves from supramaximal tibial nerve stimulation were constructed before, 2 h after, and 2 d after each exercise bout. Maximum torque decrement and elevated muscle soreness were present after the first, but not the second, backward downhill walking bout signifying a protective repeated bout effect. There was no sustained rightward shift in the length-torque relationship between exercise bouts, nor decreases in fascicle strain amplitude or shortening of the starting fascicle length. Protection from a repeated bout of eccentric exercise was conferred without changes in muscle fascicle strain behavior, indicating that sarcomerogenesis and increased tendon compliance were unlikely to be responsible. As fascicle strains are relatively small in humans, we suggest that changes to connective tissue structures, such as extracellular matrix remodeling, are better able to explain the repeated bout effect observed here.

  20. A review of protective factors and causal mechanisms that enhance the mental health of Indigenous Circumpolar youth

    OpenAIRE

    Petrasek MacDonald, Joanna; Ford, James D.; Cunsolo Willox, Ashlee; Ross, Nancy A.

    2013-01-01

    Objectives To review the protective factors and causal mechanisms which promote and enhance Indigenous youth mental health in the Circumpolar North. Study design A systematic literature review of peer-reviewed English-language research was conducted to systematically examine the protective factors and causal mechanisms which promote and enhance Indigenous youth mental health in the Circumpolar North. Methods This review followed the Preferred Reporting Items for Systematic Reviews and Meta-An...

  1. Unraveling the molecular mechanisms of nitrogenase conformational protection against oxygen in diazotrophic bacteria.

    Science.gov (United States)

    Lery, Letícia M S; Bitar, Mainá; Costa, Mauricio G S; Rössle, Shaila C S; Bisch, Paulo M

    2010-12-22

    G. diazotrophicus and A. vinelandii are aerobic nitrogen-fixing bacteria. Although oxygen is essential for the survival of these organisms, it irreversibly inhibits nitrogenase, the complex responsible for nitrogen fixation. Both microorganisms deal with this paradox through compensatory mechanisms. In A. vinelandii a conformational protection mechanism occurs through the interaction between the nitrogenase complex and the FeSII protein. Previous studies suggested the existence of a similar system in G. diazotrophicus, but the putative protein involved was not yet described. This study intends to identify the protein coding gene in the recently sequenced genome of G. diazotrophicus and also provide detailed structural information of nitrogenase conformational protection in both organisms. Genomic analysis of G. diazotrophicus sequences revealed a protein coding ORF (Gdia0615) enclosing a conserved "fer2" domain, typical of the ferredoxin family and found in A. vinelandii FeSII. Comparative models of both FeSII and Gdia0615 disclosed a conserved beta-grasp fold. Cysteine residues that coordinate the 2[Fe-S] cluster are in conserved positions towards the metallocluster. Analysis of solvent accessible residues and electrostatic surfaces unveiled an hydrophobic dimerization interface. Dimers assembled by molecular docking presented a stable behaviour and a proper accommodation of regions possibly involved in binding of FeSII to nitrogenase throughout molecular dynamics simulations in aqueous solution. Molecular modeling of the nitrogenase complex of G. diazotrophicus was performed and models were compared to the crystal structure of A. vinelandii nitrogenase. Docking experiments of FeSII and Gdia0615 with its corresponding nitrogenase complex pointed out in both systems a putative binding site presenting shape and charge complementarities at the Fe-protein/MoFe-protein complex interface. The identification of the putative FeSII coding gene in G. diazotrophicus genome

  2. Isolating Exogenous and Endogenous Modes of Temporal Attention

    Science.gov (United States)

    Lawrence, Michael A.; Klein, Raymond M.

    2013-01-01

    The differential allocation of information processing resources over time, here termed "temporal attention," may be achieved by relatively automatic "exogenous" or controlled "endogenous" mechanisms. Over 100 years of research has confounded these theoretically distinct dimensions of temporal attention. The current…

  3. Evolutionarily Conserved Roles for Blood-Brain Barrier Xenobiotic Transporters in Endogenous Steroid Partitioning and Behavior.

    Science.gov (United States)

    Hindle, Samantha J; Munji, Roeben N; Dolghih, Elena; Gaskins, Garrett; Orng, Souvinh; Ishimoto, Hiroshi; Soung, Allison; DeSalvo, Michael; Kitamoto, Toshihiro; Keiser, Michael J; Jacobson, Matthew P; Daneman, Richard; Bainton, Roland J

    2017-10-31

    Central nervous system (CNS) chemical protection depends upon discrete control of small-molecule access by the blood-brain barrier (BBB). Curiously, some drugs cause CNS side-effects despite negligible transit past the BBB. To investigate this phenomenon, we asked whether the highly BBB-enriched drug efflux transporter MDR1 has dual functions in controlling drug and endogenous molecule CNS homeostasis. If this is true, then brain-impermeable drugs could induce behavioral changes by affecting brain levels of endogenous molecules. Using computational, genetic, and pharmacologic approaches across diverse organisms, we demonstrate that BBB-localized efflux transporters are critical for regulating brain levels of endogenous steroids and steroid-regulated behaviors (sleep in Drosophila and anxiety in mice). Furthermore, we show that MDR1-interacting drugs are associated with anxiety-related behaviors in humans. We propose a general mechanism for common behavioral side effects of prescription drugs: pharmacologically challenging BBB efflux transporters disrupts brain levels of endogenous substrates and implicates the BBB in behavioral regulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. ENDOGENEITY OF INDONESIAN MONEY SUPPLY

    OpenAIRE

    Rachma, Meutia Safrina

    2011-01-01

    There has been a long debate about the endogeneity of money supply. The main objective of this article is to identify whether money supply in Indonesia is an exogenous or an endogenous variable. Using a Vector Autoregressive model and monthly data 1997(5)-2010(6), the estimation result shows that money supply in Indonesia is an endogenous variable. The movement of broad money supply does influence the movement of base money and Consumer Price Index. Consequently, the central bank does not hav...

  5. Endogeneity Of Indonesian Money Supply

    OpenAIRE

    Rachma, Meutia Safrina

    2010-01-01

    There has been a long debate about the endogeneity of money supply. The main objective of this article is to identify whether money supply in Indonesia is an exogenous or an endogenous variable. Using a Vector Autoregressive model and monthly data 1997(5)-2010(6), the estimation result shows that money supply in Indonesia is an endogenous variable. The movement of broad money supply does influence the movement of base money and Consumer Price Index. Consequently, the central bank does not hav...

  6. Habits, aspirations and endogenous fertility

    OpenAIRE

    Luciano Fanti

    2012-01-01

    Motivated by the increasing literature on endogenous preferences as well as on endogenous fertility, this paper investigates the implications of the interaction of the endogenous determination of the number of children with habit and aspiration formation in an OLG model. In contrast with the previous literature, we show that greater aspirations may lead to higher savings, and more interestingly, always increase the neoclassical economic growth.

  7. Endogenous Monetary Policy Regime Change

    OpenAIRE

    Troy Davig; Eric M. Leeper

    2006-01-01

    This paper makes changes in monetary policy rules (or regimes) endogenous. Changes are triggered when certain endogenous variables cross specified thresholds. Rational expectations equilibria are examined in three models of threshold switching to illustrate that (i) expectations formation effects generated by the possibility of regime change can be quantitatively important; (ii) symmetric shocks can have asymmetric effects; (iii) endogenous switching is a natural way to formally model preempt...

  8. PARTICULAR ASPECTS OF THE WTO MECHANISMS APPLICATION TO PROTECT THE NATIONAL ECONOMIC INTERESTS OF UKRAINE

    Directory of Open Access Journals (Sweden)

    Ivan Us

    2016-11-01

    Full Text Available The purpose of the paper is to analyze the issue of applying by Ukraine of mechanisms developed in the legal framework by the World Trade Organization to protect the internal market in order to prepare appropriate recommendations to state power authorities empowered to carry out trade policy. Methodology. The study is based on studying the experience of Ukraine to revise its commitments on tariff lines for the first three-year period after the accession to the WTO, as well as on the analysis of the most resonant steps to protect the internal market taken by Ukraine and the consequences of these steps. Result. The issue of applying by Ukraine of tools developed by the World Trade Organization to protect the interests of national producers has been described in this article. The situation of the use by Ukraine of a right to review the conditions of membership in the WTO has been reviewed step by step starting from the studying of this issue within the country and to the statements by the Government not to use this feature. All the stages of the process of using the possibility to revise the conditions of membership in the WTO have been analyzed as well as the mistakes that led to the absence of the desired result in the end. Also, the basic tools of protection of the domestic market in the WTO system, such as anti-dumping investigation and the investigation concerning the subsidized imports has been considered The dynamics of the use of such investigations by all WTO member countries since the establishment of the WTO, with particular emphasis on the period of the financial and economic crisis of 2008-2010 has been reviewed. The number of successful investigations led to the application of certain protective measures also has been determined. The risks that arise in the absence of the Government of Ukraine steps to improve the efficiency of representation of interests in the WTO have been analyzed. Recommendations improving the use of WTO

  9. Endogenous property rights

    NARCIS (Netherlands)

    Dari-Mattiacci, G.; Guerriero, C.

    2014-01-01

    Albeit the relevance of property rights is well known, their determinants are still poorly understood. When property is fully protected, some buyers with valuation higher than that of original owners are inefficiently excluded from trade due to transaction costs. When protection of property is weak,

  10. The protective effect of vein cuffed anastomoses is not mechanical in origin.

    Science.gov (United States)

    Norberto, J J; Sidawy, A N; Trad, K S; Jones, B A; Neville, R F; Najjar, S F; Sidawy, M K; DePalma, R G

    1995-04-01

    Intimal hyperplasia (IH) is a proliferative process of vascular smooth muscle cells that occurs after an arterial injury, particularly at outflow anastomoses of prosthetic bypass grafts. IH causes stenosis that leads ultimately to graft flow reduction and thrombosis. We have demonstrated previously that vein cuff interposition between an expanded polytetrafluoroethylene (e-PTFE) graft and artery at distal anastomoses diminished IH formation in the arterial outflow as compared with noncuffed anastomoses. Improved long-term patency rates associated with the placement of an interposition vein cuff at the distal anastomosis of e-PTFE grafts to infrageniculate arteries have also been demonstrated clinically. This study examined the mechanical factors that may contribute to the protective effect of cuffed anastomoses. These factors include the expansibility of the vein cuff as compared with e-PTFE, as well as the angle of the cuffed anastomosis. Compatible animals were selected by use of platelet aggregation studies. Nine dogs, group A, received a 4 mm e-PTFE graft plus a 1 cm long interposition vein cuff at the distal anastomosis in the left carotid artery. The same procedure was done on the right side, and in addition the vein cuff was encircled by an e-PTFE jacket incorporated into the anastomosis to prevent the expansion of the vein cuff with arterial pulsation. To study the effect of distal anastomotic angle and geometry on the formation of IH, five dogs, group B, received a 4 mm e-PTFE graft in both sides. On the left, the distal anastomosis was performed between the graft and the artery at an acute angle as it is commonly done when a bypass graft is placed. On the right side a 1 cm long, 6 mm diameter e-PTFE segment was interposed between the artery and the graft at a perpendicular angle. This geometry mimicked the right angle of a vein cuff-to-artery anastomosis. After 10 weeks the grafts were harvested, and the thickness of IH was measured with an ocular

  11. Endogenous Lunar Volatiles

    Science.gov (United States)

    McCubbin, F. M.; Liu, Y.; Barnes, J. J.; Boyce, J. W.; Day, J. M. D.; Elardo, S. M.; Hui, H.; Magna, T.; Ni, P.; Tartese, R.; hide

    2017-01-01

    The chapter will begin with an introduction that defines magmatic volatiles (e.g., H, F, Cl, S) versus geochemical volatiles (e.g., K, Rb, Zn). We will discuss our approach of understanding both types of volatiles in lunar samples and lay the ground work for how we will determine the overall volatile budget of the Moon. We will then discuss the importance of endogenous volatiles in shaping the "Newer Views of the Moon", specifically how endogenous volatiles feed forward into processes such as the origin of the Moon, magmatic differentiation, volcanism, and secondary processes during surface and crustal interactions. After the introduction, we will include a re-view/synthesis on the current state of 1) apatite compositions (volatile abundances and isotopic compositions); 2) nominally anhydrous mineral phases (moderately to highly volatile); 3) volatile (moderately to highly volatile) abundances in and isotopic compositions of lunar pyroclastic glass beads; 4) volatile (moderately to highly volatile) abundances in and isotopic compositions of lunar basalts; 5) volatile (moderately to highly volatile) abundances in and isotopic compositions of melt inclusions; and finally 6) experimental constraints on mineral-melt partitioning of moderately to highly volatile elements under lunar conditions. We anticipate that each section will summarize results since 2007 and focus on new results published since the 2015 Am Min review paper on lunar volatiles [9]. The next section will discuss how to use sample abundances of volatiles to understand the source region and potential caveats in estimating source abundances of volatiles. The following section will include our best estimates of volatile abundances and isotopic compositions (where permitted by available data) for each volatile element of interest in a number of important lunar reservoirs, including the crust, mantle, KREEP, and bulk Moon. The final section of the chapter will focus upon future work, outstanding questions

  12. Time course of lung inflammatory and fibrogenic responses during protective mechanical ventilation in healthy rats.

    Science.gov (United States)

    Krebs, Joerg; Pelosi, Paolo; Tsagogiorgas, Charalambos; Haas, Jenny; Yard, Benito; Rocco, Patricia R M; Luecke, Thomas

    2011-09-15

    This study aimed to assess pulmonary inflammatory and fibrogenic responses and their impact on lung mechanics and histology in healthy rats submitted to protective mechanical ventilation for different experimental periods. Eighteen Wistar rats were randomized to undergo open lung-mechanical ventilation (OL-MV) for 1, 6 or 12 h. Following a recruitment maneuver, a decremental PEEP trial was performed and PEEP set according to the minimal respiratory system static elastance. Respiratory system, lung, and chest-wall elastance and gas-exchange were maintained throughout the 12 h experimental period. Histological lung injury score remained low at 1 and 6 h, but was higher at 12 h due to overinflation. A moderate inflammatory response was observed with a distinct peak at 6h. Compared to unventilated controls, type I procollagen mRNA expression was decreased at 1 and 12h, while type III procollagen expression decreased throughout the 12h experimental period. In conclusion, OL-MV in healthy rats yielded overinflation after 6 h even though respiratory elastance and gas-exchange were preserved for up to 12 h. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Endogenous fertility and development traps with endogenous lifetime

    OpenAIRE

    Fanti, Luciano; Gori, Luca

    2010-01-01

    We extend the literature on endogenous lifetime and economic growth by Chakraborty (2004) and Bunzel and Qiao (2005) to endogenous fertility. We show that development traps due to underinvestments in health cannot appear when fertility is an economic decision variable and the costs of children are represented by a constant fraction of the parents' income used for their upbringing.

  14. Characterization of the corrosion protection mechanism of cerium-based conversion coatings on high strength aluminum alloys

    Science.gov (United States)

    Pinc, William Ross

    The aim of the work presented in this dissertation is to investigate the corrosion protection mechanism of cerium-based conversion coatings (CeCCs) used in the corrosion protection of high strength aluminum alloys. The corrosion resistance of CeCCs involves two general mechanisms; barrier and active. The barrier protection mechanism was influenced by processing parameters, specifically surface preparation, post-treatment, and the use of gelatin. Post-treatment and the addition of gelatin to the coating solution resulted in fewer cracks and transformation of the coating to CePO4, which increased the corrosion resistance by improving the barrier aspect of CeCCs. CeCCs were found to best act as barriers when crack size was limited and CePO4 was present in the coating. CeCCs were found to protect areas of the substrate that were exposed in the coating, indicating that the coatings were more than simple barriers. CeCCs contained large cracks, underneath which subsurface crevices were connected to the surface by the cracks. Despite the observation that no cerium was present in crevices, coatings with crevices exhibited significant corrosion protection. The impedance of post-treated coatings with crevices increased during salt spray exposure. The increase in impedance was associated with the formation of protective oxides / hydroxides; however, crevice-free coatings also exhibited active protection leading to the conclusion that the formation of interfacial layers between the CeCC and the substrate also contributed to the active protection. Based on the overall results of the study, the optimal corrosion protection of CeCCs occurred when processing conditions produced coatings with morphologies and compositions that facilitated both the barrier and active protection mechanisms.

  15. Monocular channels have a functional role in endogenous orienting.

    Science.gov (United States)

    Saban, William; Sekely, Liora; Klein, Raymond M; Gabay, Shai

    2018-03-01

    The literature has long emphasized the role of higher cortical structures in endogenous orienting. Based on evolutionary explanation and previous data, we explored the possibility that lower monocular channels may also have a functional role in endogenous orienting of attention. Sensitive behavioral manipulation was used to probe the contribution of monocularly segregated regions in a simple cue - target detection task. A central spatially informative cue, and its ensuing target, were presented to the same or different eyes at varying cue-target intervals. Results indicated that the onset of endogenous orienting was apparent earlier when the cue and target were presented to the same eye. The data provides converging evidence for the notion that endogenous facilitation is modulated by monocular portions of the visual stream. This, in turn, suggests that higher cortical mechanisms are not exclusively responsible for endogenous orienting, and that a dynamic interaction between higher and lower neural levels, might be involved. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Mitochondrial Protection and Anti-aging Activity of Astragalus Polysaccharides and Their Potential Mechanism

    Directory of Open Access Journals (Sweden)

    Xiao-Juan Xin

    2012-02-01

    Full Text Available The current study was performed to investigate mitochondrial protection and anti-aging activity of Astragalus polysaccharides (APS and the potential underlying mechanism. Lipid peroxidation of liver and brain mitochondria was induced by Fe2+–Vit C in vitro. Thiobarbituric acid (TBA colorimetry was used to measure the content of thiobarbituric acid reactive substances (TBARS. Mouse liver mitochondrial permeability transition (PT was induced by calcium overload in vitro and spectrophotometry was used to measure it. The scavenging activities of APS on superoxide anion (O2•- and hydroxyl radical (•OH, which were produced by reduced nicotinamide adenine dinucleotide (NADH—N-Methylphenazonium methyl sulfate (PMS and hydrogen peroxide (H2O2–Fe2+ system respectively, were measured by 4-nitrobluetetrazolium chloride (NBT reduction and Fenton reaction colorimetry respectively. The Na2S2O3 titration method was used to measure the scavenging activities of APS on H2O2. APS could inhibit TBARS production, protect mitochondria from PT, and scavenge O2•-, •OH and H2O2 significantly in a concentration-dependent manner respectively. The back of the neck of mice was injected subcutaneously with D-galactose to induce aging at a dose of 100 mg/kg/d for seven weeks. Moreover, the activities of catalase (CAT, surperoxide dismutase (SOD and glutathione peroxidase (GPx and anti-hydroxyl radical which were assayed by using commercial monitoring kits were increased significantly in vivo by APS. According to this research, APS protects mitochondria by scavenging reactive oxygen species (ROS, inhibiting mitochondrial PT and increasing the activities of antioxidases. Therefore, APS has the effect of promoting health.

  17. Possible mechanism of PNS protection against cisplatin-induced nephrotoxicity in rat models.

    Science.gov (United States)

    Liu, Xinwen; Huang, Zhenguang; Zou, Xiaoqin; Yang, Yufang; Qiu, Yue; Wen, Yan

    2015-01-01

    This study investigates the mechanism of the protective effect of Panax notoginsenosides (PNS) against cisplatin-induced nephrotoxicity via the hypoxia inducible factor 1 (HIF-1)/Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) pathway of autophagy. The rats underwent intraperitoneal injection with a single dose of cisplatin and a subset of rats were also intraperitoneally injected with 31.35 mg/kg PNS once a day. After 24 h exposure to cisplatin, the concentrations of urinary N-acetyl-β-D-glucosaminidase (NAG), blood urea nitrogen (BUN) and serum creatinine (Scr) were determined. The rat renal tissue was examined using H&E-staining, and the mitochondria of renal tubular epithelial cells were observed using transmission electron microscopy. The expressions of microtubule-associated protein-1 light chain (LC)3, autophagy-related gene (Atg)5, Beclin-1 and BNIP3 in rat renal tissue were detected using western blotting. The expression of HIF-1 was detected by immunohistochemistry. The results showed that PNS significantly protected against cisplatin-induced nephrotoxicity, as evidenced by decreasing the concentration of blood BUN and Scr, the attenuation of renal histopathological changes and the mitochondrial damages of renal cells, and the increase of mitochondria autophagosome in renal tubular epithelial cells. Additionally, PNS significantly increased the expression of LC3 and the ratio of LC3II/LC3I in rat renal tissue. Moreover, PNS significantly increased the expression of HIF-1α, BNIP3, Atg5 and Beclin-1 in rat renal tissue. In conclusion, the protective effect of PNS on cisplatin-induced nephrotoxicity was mainly due to its ability to enhancing the mitochondrial autophagy of renal tissue via the HIF-1α/BNIP3 pathway, and here is the first demonstration about it.

  18. Quantifying causal mechanisms to determine how protected areas affect poverty through changes in ecosystem services and infrastructure

    Science.gov (United States)

    Ferraro, Paul J.; Hanauer, Merlin M.

    2014-01-01

    To develop effective environmental policies, we must understand the mechanisms through which the policies affect social and environmental outcomes. Unfortunately, empirical evidence about these mechanisms is limited, and little guidance for quantifying them exists. We develop an approach to quantifying the mechanisms through which protected areas affect poverty. We focus on three mechanisms: changes in tourism and recreational services; changes in infrastructure in the form of road networks, health clinics, and schools; and changes in regulating and provisioning ecosystem services and foregone production activities that arise from land-use restrictions. The contributions of ecotourism and other ecosystem services to poverty alleviation in the context of a real environmental program have not yet been empirically estimated. Nearly two-thirds of the poverty reduction associated with the establishment of Costa Rican protected areas is causally attributable to opportunities afforded by tourism. Although protected areas reduced deforestation and increased regrowth, these land cover changes neither reduced nor exacerbated poverty, on average. Protected areas did not, on average, affect our measures of infrastructure and thus did not contribute to poverty reduction through this mechanism. We attribute the remaining poverty reduction to unobserved dimensions of our mechanisms or to other mechanisms. Our study empirically estimates previously unidentified contributions of ecotourism and other ecosystem services to poverty alleviation in the context of a real environmental program. We demonstrate that, with existing data and appropriate empirical methods, conservation scientists and policymakers can begin to elucidate the mechanisms through which ecosystem conservation programs affect human welfare. PMID:24567397

  19. Maintenance, endogeneous, respiration, lysis, decay and predation

    DEFF Research Database (Denmark)

    loosdrecht, Marc C. M. Van; Henze, Mogens

    1999-01-01

    mechanism is microbiologically correct. The lysis/decay model mechanism is a strongly simplified representation of reality. This paper tries to review the processes grouped under endogenous respiration in activated sludge models. Mechanisms and processes such as maintenance, lysis, internal and external...... decay, predation and death-regeneration are discussed. From recent microbial research it has become evident that cells do not die by themselves. Bacteria are however subject to predation by protozoa. Bacteria store reserve polymers that in absence of external substrate are used for growth...

  20. Fire protection in nuclear power plants. Pt. 3. Fire protection for mechanical and electrotechnical equipment and components

    International Nuclear Information System (INIS)

    1994-01-01

    The KTA rule applies to LWRs and defines requirements to be met for fire protection of equipment and installations of the safety system, and all safety-relevant systems, and of those operating systems that under the effect of fire, may cause improper functioning of safety system components. (orig./HP) [de

  1. Protective effect of astrocyte-conditioned medium on neurons following hypoxia and mechanical injury

    Directory of Open Access Journals (Sweden)

    YAN Ji-wen

    2013-02-01

    Full Text Available 【Abstract】Objective: To investigate the protec-tive effect of mouse astrocyte-conditioned medium (ACM on hypoxic and mechanically injured neurons by a cell model in vitro, and to explore the possible mechanism. Methods: The model of hypoxic neuronal injury was caused by 3% O 2 in three-gas incubator. Neurons were cul-tured with ordinary medium or 20% ACM respectively and randomly divided into hypoxic group (hypoxia for 4, 8, 24 h and marked as H4R0, H8R0, H24R0 and hypoxia reoxygenation group (H4R24, H8R24, H24R24. Mechanical injury model was developed by scratching neurons cultured in 20% ACM or ordinary medium to different degrees. Neu-rons in both medium were divided into normal control group, mild, moderate and severe injury groups. The 20% ACM was added 24 h before hypoxia/reoxygenation or mechanical injury. The morphology and survival of neurons were observed and counted by trypan blue staining. The concentration of NO, lactic dehydrogenase (LDH and membrane ATPase activity were detected by corresponding kits. Results: It was showed that 20% ACM can obviously promote the survival rate of hypoxia/reoxygenated neurons and scratched neurons as well. The morphology and num-ber of neurons exposed to hypoxia or scratch injury showed great difference between groups with or without ACM treatment. Compared with control group, the concentration of NO and LDH was much lower in hypoxic/reoxygenated neurons treated with 20% ACM, and the ATPase activity was higher. For the mechanical injury model, neurons with moderate injury also revealed a lower NO and LDH concen-tration than the control group. All the differences were sta-tistically significant (P<0.05. Conclusion: ACM can promote the survival and func-tional recovery of neurons following hypoxia or scratching to a certain degree. The mechanism may be associated with reducing the synthesis and release of NO and LDH as well as increasing the activity of membrane ATPase. Key words: Glial cell line

  2. Priming by Rhizobacterium Protects Tomato Plants from Biotrophic and Necrotrophic Pathogen Infections through Multiple Defense Mechanisms

    Science.gov (United States)

    Ahn, Il-Pyung; Lee, Sang-Woo; Kim, Min Gab; Park, Sang-Ryeol; Hwang, Duk-Ju; Bae, Shin-Chul

    2011-01-01

    A selected strain of rhizobacterium, Pseudomonas putida strain LSW17S (LSW17S), protects tomato plants (Lycopersicon esculentum L. cv. Seokwang) from bacterial speck by biotrophic Pseudomonas syringae pv. tomato strain DC3000 (DC3000) and bacterial wilt by necrotrophic Ralstonia solanacearum KACC 10703 (Rs10703). To investigate defense mechanisms induced by LSW17S in tomato plants, transcription patterns of pathogenesis-related (PR) genes and H2O2 production were analyzed in plants treated with LSW17S and subsequent pathogen inoculation. LSW17S alone did not induce transcriptions of employed PR genes in leaves and roots. DC3000 challenge following LSW17S triggered rapid transcriptions of PR genes and H2O2 production in leaves and roots. Catalase infiltration with DC3000 attenuated defense-related responses and resistance against DC3000 infection. Despite depriving H2O2 production and PR1b transcription by the same treatment, resistance against Rs10703 infection was not deterred significantly. H2O2 is indispensable for defense signaling and/or mechanisms primed by LSW17S and inhibition of bacterial speck, however, it is not involved in resistance against bacterial wilt. PMID:21710203

  3. Propagation prevention: a complementary mechanism for "lung protective" ventilation in acute respiratory distress syndrome.

    Science.gov (United States)

    Marini, John J; Gattinoni, Luciano

    2008-12-01

    To describe the clinical implications of an often neglected mechanism through which localized acute lung injury may be propagated and intensified. Experimental and clinical evidence from the medical literature relevant to the airway propagation hypothesis and its consequences. The diffuse injury that characterizes acute respiratory distress syndrome is often considered a process that begins synchronously throughout the lung, mediated by inhaled or blood-borne noxious agents. Relatively little attention has been paid to possibility that inflammatory lung injury may also begin focally and propagate sequentially via the airway network, proceeding mouth-ward from distal to proximal. Were this true, modifications of ventilatory pattern and position aimed at geographic containment of the injury process could help prevent its generalization and limit disease severity. The purposes of this communication are to call attention to this seldom considered mechanism for extending lung injury that might further justify implementation of low tidal volume/high positive end-expiratory pressure ventilatory strategies for lung protection and to suggest additional therapeutic measures implied by this broadened conceptual paradigm.

  4. Investigation and exploitation of the radiation in peaceful uses and its juridical protection mechanism

    International Nuclear Information System (INIS)

    Solorzano R, S.A.

    1991-10-01

    In is included in a brief way the radioisotopes and ionizing radiations application in Guatemala; the risk an the radioactive damage from the juridical point of view; the nuclear energy's juridical nature, without any doubt, has its place in the law's world causing several effects which we have to determine the civil responsabilities; we expose the Guatemala's civil order the objective responsability of the nuclear law and its foundation. We had to mention the different international organisms that have relationship between each other in this area, for example: International Atomic Energy Agency (IAEA): Its objetives and functions; its services and attendance; juridical activities, etc. and as a national institution the general Directorate for the Nuclear Energy that belong to the energy and Mines Ministry, it is the charge of the sutdy, promotion, control, supervision, thechnical vigilance and investigate the use of the nuclear energy In the juridical mechanisms of the radiation applications, we find in Guatemala the ''protection an environment improvement law'' decree 68-86 of the Republic Congress; ''the control, use and application of radioisotopes and ionizing radiation law (nuclear law) law decree 11-86 which is transcribed because it is related with the nuclear energy subject. The rules also emphasize because of the technical aspects requirement concurrence that develop the law's precepts. As a viable juridical mechanism to guarantee the nuclear damage indemnity it is considered in others contracts determined the necessary constitution of the civil responsability insurance of the nuclear damages to guarantee the right indemnity of it. (Author)

  5. Mechanism of protection induced by group A Streptococcus vaccine candidate J8-DT: contribution of B and T-cells towards protection.

    Directory of Open Access Journals (Sweden)

    Manisha Pandey

    Full Text Available Vaccination with J8-DT, a leading GAS vaccine candidate, results in protective immunity in mice. Analysis of immunologic correlates of protection indicated a role of J8-specific antibodies that were induced post-immunization. In the present study, several independent experimental approaches were employed to investigate the protective immunological mechanisms involved in J8-DT-mediated immunity. These approaches included the passive transfer of mouse or rabbit immune serum/antibodies in addition to selective depletion of T-cell subsets prior to bacterial challenge. Passive transfer of J8-DT antiserum/antibodies from mice and rabbits conferred significant resistance against challenge to mice. To exclude the possibility of involvement of other host immune factors, the studies were repeated in SCID mice, which highlighted the need for an ongoing immune response for long-lived protection. Depletion of CD4(+ and CD8(+ T-cell subsets confirmed that an active de novo immune response, involving CD4(+ T-helper cells, is required for continued synthesis of antibodies resulting in protection against GAS infection. Taken together these results indicate an involvement of CD4(+ T-cells in J8-DT-mediated protection possibly via an ability to maintain antibody levels. These results have considerable relevance to the development of a broad spectrum passive immunotherapy for GAS disease.

  6. Comparison between conventional protective mechanical ventilation and high-frequency oscillatory ventilation associated with the prone position.

    Science.gov (United States)

    Fioretto, José Roberto; Klefens, Susiane Oliveira; Pires, Rafaelle Fernandes; Kurokawa, Cilmery Suemi; Carpi, Mario Ferreira; Bonatto, Rossano César; Moraes, Marcos Aurélio; Ronchi, Carlos Fernando

    2017-01-01

    To compare the effects of high-frequency oscillatory ventilation and conventional protective mechanical ventilation associated with the prone position on oxygenation, histology and pulmonary oxidative damage in an experimental model of acute lung injury. Forty-five rabbits with tracheostomy and vascular access were underwent mechanical ventilation. Acute lung injury was induced by tracheal infusion of warm saline. Three experimental groups were formed: healthy animals + conventional protective mechanical ventilation, supine position (Control Group; n = 15); animals with acute lung injury + conventional protective mechanical ventilation, prone position (CMVG; n = 15); and animals with acute lung injury + high-frequency oscillatory ventilation, prone position (HFOG; n = 15). Ten minutes after the beginning of the specific ventilation of each group, arterial gasometry was collected, with this timepoint being called time zero, after which the animal was placed in prone position and remained in this position for 4 hours. Oxidative stress was evaluated by the total antioxidant performance assay. Pulmonary tissue injury was determined by histopathological score. The level of significance was 5%. Both groups with acute lung injury showed worsening of oxygenation after induction of injury compared with the Control Group. After 4 hours, there was a significant improvement in oxygenation in the HFOG group compared with CMVG. Analysis of total antioxidant performance in plasma showed greater protection in HFOG. HFOG had a lower histopathological lesion score in lung tissue than CMVG. High-frequency oscillatory ventilation, associated with prone position, improves oxygenation and attenuates oxidative damage and histopathological lung injury compared with conventional protective mechanical ventilation.

  7. Insight into PreImplantation Factor (PIF* mechanism for embryo protection and development: target oxidative stress and protein misfolding (PDI and HSP through essential RIKP [corrected] binding site.

    Directory of Open Access Journals (Sweden)

    Eytan R Barnea

    Full Text Available Endogenous PIF, upon which embryo development is dependent, is secreted only by viable mammalian embryos, and absent in non-viable ones. Synthetic PIF (sPIF administration promotes singly cultured embryos development and protects against their demise caused by embryo-toxic serum. To identify and characterize critical sPIF-embryo protein interactions novel biochemical and bio-analytical methods were specifically devised.FITC-PIF uptake/binding by cultured murine and equine embryos was examined and compared with scrambled FITC-PIF (control. Murine embryo (d10 lysates were fractionated by reversed-phase HPLC, fractions printed onto microarray slides and probed with Biotin-PIF, IDE and Kv1.3 antibodies, using fluorescence detection. sPIF-based affinity column was developed to extract and identify PIF-protein interactions from lysates using peptide mass spectrometry (LC/MS/MS. In silico evaluation examined binding of PIF to critical targets, using mutation analysis.PIF directly targets viable cultured embryos as compared with control peptide, which failed to bind. Multistep Biotin-PIF targets were confirmed by single-step PIF-affinity column based isolation. PIF binds protein disulfide isomerases a prolyl-4-hydroxylase β-subunit, (PDI, PDIA4, PDIA6-like containing the antioxidant thioredoxin domain. PIF also binds protective heat shock proteins (70&90, co-chaperone, BAG-3. Remarkably, PIF targets a common RIKP [corrected] site in PDI and HSP proteins. Further, single PIF amino acid mutation significantly reduced peptide-protein target bonding. PIF binds promiscuous tubulins, neuron backbones and ACTA-1,2 visceral proteins. Significant anti-IDE, while limited anti-Kv1.3b antibody-binding to Biotin-PIF positive lysates HPLC fractions were documented.Collectively, data identifies PIF shared targets on PDI and HSP in the embryo. Such are known to play a critical role in protecting against oxidative stress and protein misfolding. PIF-affinity-column is a

  8. Mechanisms involved in reproductive damage caused by gossypol in rats and protective effects of vitamin E

    Directory of Open Access Journals (Sweden)

    Andréia T Santana

    2015-01-01

    Full Text Available BACKGROUND: Gossypol is a chemical present in the seeds of cotton plants (Gossypium sp. that reduces fertility in farm animals. Vitamin E is an antioxidant and may help to protect cells and tissues against the deleterious effects of free radicals. The aim of this study was to evaluate the mechanisms of reproductive toxicity of gossypol in rats and the protective effects of vitamin E. Forty Wistar rats were used, divided into four experimental groups (n = 10: DMSO/ saline + corn oil; DMSO/saline + vitamin E; gossypol + corn oil; and gossypol + vitamin E. RESULTS: Fertility was significantly reduced in male rats treated with gossypol in that a significant decrease in epididy-mal sperm count was observed (P 0.05. The levels of reduced glutathione and pyridine nucleotides in testis homogen-ate were significantly reduced by gossypol (P < 0.05 and P < 0.01, respectively and this reduction was accompanied by increased levels of oxidized glutathione (P < 0.05. Vitamin E showed a preventive effect on the changes in the levels of these substances. Gossypol significantly increased the levels of malondialdehyde (P < 0.01, a lipid peroxida-tion indicator, whereas treatment with vitamin E inhibited the action of the gossypol. Vitamin E prevented a decrease in mitochondrial ATP induced by gossypol (P < 0.05. CONCLUSIONS: This study suggests that the reproductive dysfunction caused by gossypol may be related to oxidative stress and mitochondrial bioenergetic damage and that treatment with vitamin E can prevent the infertility caused by the toxin.

  9. Mechanism of protection of moderately diet restricted rats against doxorubicin-induced acute cardiotoxicity

    International Nuclear Information System (INIS)

    Mitra, Mayurranjan S.; Donthamsetty, Shashikiran; White, Brent; Latendresse, John R.; Mehendale, Harihara M.

    2007-01-01

    Clinical use of doxorubicin (Adriamycin (registered) ), an antitumor agent, is limited by its oxyradical-mediated cardiotoxicity. We tested the hypothesis that moderate diet restriction protects against doxorubicin-induced cardiotoxicity by decreasing oxidative stress and inducing cardioprotective mechanisms. Male Sprague-Dawley rats (250-275 g) were maintained on diet restriction [35% less food than ad libitum]. Cardiotoxicity was estimated by measuring biomarkers of cardiotoxicity, cardiac function, lipid peroxidation, and histopathology. A LD 100 dose of doxorubicin (12 mg/kg, ip) administered on day 43 led to 100% mortality in ad libitum rats between 7 and 13 days due to higher cardiotoxicity and cardiac dysfunction, whereas all the diet restricted rats exhibited normal cardiac function and survived. Toxicokinetic analysis revealed equal accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the ad libitum and diet restricted hearts. Mechanistic studies revealed that diet restricted rats were protected due to (1) lower oxyradical stress from increased cardiac antioxidants leading to downregulation of uncoupling proteins 2 and 3, (2) induction of cardiac peroxisome proliferators activated receptor-α and plasma adiponectin increased cardiac fatty acid oxidation (666.9 ±14.0 nmol/min/g heart in ad libitum versus 1035.6 ± 32.3 nmol/min/g heart in diet restriction) and mitochondrial AMPα2 protein kinase. The changes led to 51% higher cardiac ATP levels (17.7 ± 2.1 μmol/g heart in ad libitum versus 26.7 ± 1.9 μmol/g heart in diet restriction), higher ATP/ADP ratio, and (3) increased cardiac erythropoietin and decreased suppressor of cytokine signaling 3, which upregulates cardioprotective JAK/STAT3 pathway. These findings collectively show that moderate diet restriction renders resiliency against doxorubicin cardiotoxicity by lowering oxidative stress, enhancing ATP synthesis, and inducing the JAK/STAT3 pathway

  10. Forest Protection and Reforestation in Costa Rica: Evaluation of a Clean Development Mechanism Prototype.

    Science.gov (United States)

    Subak

    2000-09-01

    / Costa Rica has recently established a program that provides funds for reforestation and forest protection on private lands, partly through the sale of carbon certificates to industrialized countries. Countries purchasing these carbon offsets hope one day to receive credit against their own commitments to limit emissions of greenhouse gases. Costa Rica has used the proceeds of the sale of carbon offsets to Norway to help finance this forest incentive program, called the Private Forestry Project, which pays thousands of participants to reforest or protect forest on their lands. The Private Forestry Project is accompanied by a monitoring program conducted by Costa Rican forest engineers that seeks to determine net carbon storage accomplished on these lands each year. The Private Forestry Project, which is officially registered as an Activity Implemented Jointly, is a possible model for bundled projects funded by the Clean Development Mechanism (CDM) established by the 1997 Kyoto Protocol to the UN Framework Convention on Climate Change. It also serves as an interesting example for the CDM because it was designed by a developing country host-not by an industrialized country investor. Accordingly, it reflects the particular "sustainable development" objectives of the host country or at least the host planners. Early experience in implementing the Private Forestry Project is evaluated in light of the main objectives of the CDM and its precursor-Activities Implemented Jointly. It is concluded that the project appears to meet the criteria of global cost-effectiveness and financing from non-ODA sources. The sustainable development implications of the project are specific to the region and would not necessarily match the ideals of all investing and developing countries. The project may be seen to achieve additional greenhouse gas abatement when compared against some (although not all) baselines.

  11. Pollution and Sun Exposure: a Deleterious Synergy. Mechanisms and Opportunities for Skin Protection.

    Science.gov (United States)

    Marrot, Laurent

    2017-09-18

    Pollutants are highly diverse chemical entities, including gases such as ozone or nitrogen and sulphur oxides and particulate matter of different sizes and with different chemical constituents. PM2.5 is composed of particles that are sometimes about ten nanometres or so in size (ultrafine particles) which can be deposited in lung alveoli, translocated into capillaries and then distributed to all organs through blood circulation. PM2.5 is often associated with toxic chemicals such as heavy metals or polycyclic aromatic hydrocarbons (PAHs) and some photo-reactive PAHs can induce strong oxidative stress under UVA exposure. Skin may thus be impacted by external influences through oxidation of some of its surface components. Moreover, internal contamination is highly probable since some pollutants present in plasma could be delivered by the circulation of the blood. In fact, aggravation of skin diseases such as atopy or eczema during peaks in pollution suggests that skin surface is not the only one to be impacted. Moreover, epidemiological data pointed to a significant correlation between exposure to pollution or cigarette smoke and early occurrence of aging markers. Oxidative stress, inflammation and metabolic impairments are among the most probable mechanisms of pollution-derived dermatological hazards which might be amplified by the deleterious synergy of pollution and sun, particularly UVA. Protection strategies should thus combine surface protection (sunscreens with high UVA absorption, antioxidants preventing lipid peroxidation) and enhanced deeper skin tissue resistance to oxidative stress and inflammation, with antioxidants targeting mitochondria or the induction of natural antioxidation and detoxification such as the Nrf2 pathway. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Mycobacterium tuberculosis has diminished capacity to counteract redox stress induced by elevated levels of endogenous superoxide.

    Science.gov (United States)

    Tyagi, Priyanka; Dharmaraja, Allimuthu T; Bhaskar, Ashima; Chakrapani, Harinath; Singh, Amit

    2015-07-01

    Mycobacterium tuberculosis (Mtb) has evolved protective and detoxification mechanisms to maintain cytoplasmic redox balance in response to exogenous oxidative stress encountered inside host phagocytes. In contrast, little is known about the dynamic response of this pathogen to endogenous oxidative stress generated within Mtb. Using a noninvasive and specific biosensor of cytoplasmic redox state of Mtb, we for first time discovered a surprisingly high sensitivity of this pathogen to perturbation in redox homeostasis induced by elevated endogenous reactive oxygen species (ROS). We synthesized a series of hydroquinone-based small molecule ROS generators and found that ATD-3169 permeated mycobacteria to reliably enhance endogenous ROS including superoxide radicals. When Mtb strains including multidrug-resistant (MDR) and extensively drug-resistant (XDR) patient isolates were exposed to this compound, a dose-dependent, long-lasting, and irreversible oxidative shift in intramycobacterial redox potential was detected. Dynamic redox potential measurements revealed that Mtb had diminished capacity to restore cytoplasmic redox balance in comparison with Mycobacterium smegmatis (Msm), a fast growing nonpathogenic mycobacterial species. Accordingly, Mtb strains were extremely susceptible to inhibition by ATD-3169 but not Msm, suggesting a functional linkage between dynamic redox changes and survival. Microarray analysis showed major realignment of pathways involved in redox homeostasis, central metabolism, DNA repair, and cell wall lipid biosynthesis in response to ATD-3169, all consistent with enhanced endogenous ROS contributing to lethality induced by this compound. This work provides empirical evidence that the cytoplasmic redox poise of Mtb is uniquely sensitive to manipulation in steady-state endogenous ROS levels, thus revealing the importance of targeting intramycobacterial redox metabolism for controlling TB infection. Copyright © 2015 The Authors. Published by

  13. CIVIL PROTECTION MECHANISM OF THE ASSIGNEE RIGHTS BASED ON THE PATENT CLAIM

    Directory of Open Access Journals (Sweden)

    N. V. Marchenko

    2014-04-01

    Full Text Available Purpose. Statistical analysis of inventive activity in Ukraine shows that the largest number of applications is submitted by employees of universities and research institutions – almost 60% of all inventions. Practice of inventions execution proves that for researchers, especially for students, the most difficult part of the application and author documents is the claim. The purpose of research is a synthesis and supplying the general principles of quality drafting the patent claim, providing further legal protection of the patent. Methodology. Monitoring and analysis of the world documentary informational flow through the civil protection mechanism of the assignee rights on the basis of the patent claim allows us to compare the world systems of formulas development and summarize some key moments concerning the point in question. The example analysis of the correct patent claim drafting and its interpretation in court cases on intellectual property was made. Findings. The specific properties of the patent claim were described. They are conciseness, latitude, completeness and certainty, compliance with unity requirements and novelty of the invention. On the basis of the research it is established that there is a great difference between Ukrainian and American patent claims. A number of common mistakes and shortcomings during the claim drafting were identified. The need to restore the various forms of the invention training in universities of Ukraine was emphasized, since on this basis one should train a number of specialists who are able to carry out the commercialization of intellectual property results into productive findings. Originality. A number of issues and techniques was investigated and summarized. They can be applied by the courts in interpreting of the patent claim in the processing of intellectual property cases. Especially it concerns determining the correct drafting of the patent claim. Practical value. This work may be used

  14. Wallerian degeneration slow mouse neurons are protected against cell death caused by mechanisms involving mitochondrial electron transport dysfunction.

    Science.gov (United States)

    Tokunaga, Shinji; Araki, Toshiyuki

    2012-03-01

    Ischemia elicits a variety of stress responses in neuronal cells, which result in cell death. wld(S) Mice bear a mutation that significantly delays Wallerian degeneration. This mutation also protects all neuronal cells against other types of stresses resulting in cell death, including ischemia. To clarify the types of stresses that neuronal cell bodies derived from wld(S) mice are protected from, we exposed primary cultured neurons derived from wld(S) mice to various components of hypoxic stress. We found that wld(S) mouse neurons are protected against cellular injury induced by reoxygenation following hypoxic stress. Furthermore, we found that wld(S) mouse neurons are protected against functional impairment of the mitochondrial electron transport chain. These data suggest that Wld(S) protein expression may provide protection against neuronal cell death caused by mechanisms involving mitochondrial electron transport dysfunction. Copyright © 2011 Wiley Periodicals, Inc.

  15. Protective

    Directory of Open Access Journals (Sweden)

    Wessam M. Abdel-Wahab

    2013-10-01

    Full Text Available Many active ingredients extracted from herbal and medicinal plants are extensively studied for their beneficial effects. Antioxidant activity and free radical scavenging properties of thymoquinone (TQ have been reported. The present study evaluated the possible protective effects of TQ against the toxicity and oxidative stress of sodium fluoride (NaF in the liver of rats. Rats were divided into four groups, the first group served as the control group and was administered distilled water whereas the NaF group received NaF orally at a dose of 10 mg/kg for 4 weeks, TQ group was administered TQ orally at a dose of 10 mg/kg for 5 weeks, and the NaF-TQ group was first given TQ for 1 week and was secondly administered 10 mg/kg/day NaF in association with 10 mg/kg TQ for 4 weeks. Rats intoxicated with NaF showed a significant increase in lipid peroxidation whereas the level of reduced glutathione (GSH and the activity of superoxide dismutase (SOD, catalase (CAT, glutathione S-transferase (GST and glutathione peroxidase (GPx were reduced in hepatic tissues. The proper functioning of the liver was also disrupted as indicated by alterations in the measured liver function indices and biochemical parameters. TQ supplementation counteracted the NaF-induced hepatotoxicity probably due to its strong antioxidant activity. In conclusion, the results obtained clearly indicated the role of oxidative stress in the induction of NaF toxicity and suggested hepatoprotective effects of TQ against the toxicity of fluoride compounds.

  16. Lung protective mechanical ventilation and two year survival in patients with acute lung injury: prospective cohort study.

    Science.gov (United States)

    Needham, Dale M; Colantuoni, Elizabeth; Mendez-Tellez, Pedro A; Dinglas, Victor D; Sevransky, Jonathan E; Dennison Himmelfarb, Cheryl R; Desai, Sanjay V; Shanholtz, Carl; Brower, Roy G; Pronovost, Peter J

    2012-04-05

    To evaluate the association of volume limited and pressure limited (lung protective) mechanical ventilation with two year survival in patients with acute lung injury. Prospective cohort study. 13 intensive care units at four hospitals in Baltimore, Maryland, USA. 485 consecutive mechanically ventilated patients with acute lung injury. Two year survival after onset of acute lung injury. 485 patients contributed data for 6240 eligible ventilator settings, as measured twice daily (median of eight eligible ventilator settings per patient; 41% of which adhered to lung protective ventilation). Of these patients, 311 (64%) died within two years. After adjusting for the total duration of ventilation and other relevant covariates, each additional ventilator setting adherent to lung protective ventilation was associated with a 3% decrease in the risk of mortality over two years (hazard ratio 0.97, 95% confidence interval 0.95 to 0.99, P=0.002). Compared with no adherence, the estimated absolute risk reduction in two year mortality for a prototypical patient with 50% adherence to lung protective ventilation was 4.0% (0.8% to 7.2%, P=0.012) and with 100% adherence was 7.8% (1.6% to 14.0%, P=0.011). Lung protective mechanical ventilation was associated with a substantial long term survival benefit for patients with acute lung injury. Greater use of lung protective ventilation in routine clinical practice could reduce long term mortality in patients with acute lung injury. Clinicaltrials.gov NCT00300248.

  17. Tumor-Protective Mechanism Identified from Premature Aging Disease | Center for Cancer Research

    Science.gov (United States)

    Hutchinson-Gilford Progeria Syndrome (HGPS) is an extraordinarily rare genetic disorder caused by a mutation in the LMNA gene, which encodes architectural proteins of the human cell nucleus. The mutation causes the production of a mutant protein called progerin. Patients with HGPS display signs of premature aging, such as hair loss, slowed growth, weakening of bone and joint integrity, and cardiovascular disease. Most die in their mid-teens of heart disease or stroke. Intriguingly, these patients do not develop another aging-related disease, cancer, despite having dramatically elevated levels of DNA damage. Tom Misteli, Ph.D., of CCR’s Laboratory of Receptor Biology and Gene Expression, and his colleagues hypothesized that, rather than patients not living long enough to develop cancer, a resistance mechanism was operating in HGPS cells to prevent cancer formation. To begin testing this idea, the researchers transformed fibroblasts from HGPS patients or age-matched, healthy controls with telomerase, constitutively-activated HRAS, and SV40 large and small T antigens. Transformed HGPS cells displayed morphological changes and increased proliferation similar to transformed controls but formed fewer colonies in soft agar and fewer tumors when injected into mice. When the investigators examined global gene expression in the two populations of cells, they found that transformed HGPS cells failed to activate many of the genes that are induced in response to transformation in controls, including oncogenic and proliferation pathways. In addition the transformed HGPS cells were unable to undergo oncogenic de-differentiation. Importantly, the tumor resistance in HGPS cells was due to the presence of the progerin protein, which was both necessary and sufficient to protect cells from oncogenic transformation. Together these results suggested that HGPS cells resist cancer-inducing stimuli by not undergoing the genetic reprogramming necessary for tumor initiation. The scientists

  18. Endogenous Natural Complement Inhibitor Regulates Cardiac Development

    DEFF Research Database (Denmark)

    Mortensen, Simon A; Skov, Louise L; Kjaer-Sorensen, Kasper

    2017-01-01

    mechanisms during fetal development and adult homeostasis. In this article, we describe the function of an endogenous complement inhibitor, mannan-binding lectin (MBL)-associated protein (MAp)44, in regulating the composition of a serine protease-pattern recognition receptor complex, MBL-associated serine...... of MAp44 caused impaired cardiogenesis, lowered heart rate, and decreased cardiac output. These defects were associated with aberrant neural crest cell behavior. We found that MAp44 competed with MASP-3 for pattern recognition molecule interaction, and knockdown of endogenous MAp44 expression could...... be rescued by overexpression of wild-type MAp44. Our observations provide evidence that immune molecules are centrally involved in the orchestration of cardiac tissue development....

  19. Lung-protective mechanical ventilation does not protect against acute kidney injury in patients without lung injury at onset of mechanical ventilation

    NARCIS (Netherlands)

    Cortjens, Bart; Royakkers, Annick A. N. M.; Determann, Rogier M.; van Suijlen, Jeroen D. E.; Kamphuis, Stephan S.; Foppen, Jannetje; de Boer, Anita; Wieland, Cathrien W.; Spronk, Peter E.; Schultz, Marcus J.; Bouman, Catherine S. C.

    2012-01-01

    Introduction: Preclinical and clinical studies suggest that mechanical ventilation contributes to the development of acute kidney injury (AKI), particularly in the setting of lung-injurious ventilator strategies. Objective: To determine whether ventilator settings in critically ill patients without

  20. Lung protective mechanical ventilation strategies in cardiothoracic critical care: a retrospective study

    Directory of Open Access Journals (Sweden)

    Zochios V

    2016-11-01

    Full Text Available Vasileios Zochios,1–3 Matthew Hague,3,4 Kimberly Giraud,5 Nicola Jones3 1Department of Intensive Care Medicine, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, 2Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, 3Department of Anesthesia and Intensive Care Medicine, Papworth Hospital NHS Foundation Trust, Papworth Everard, Cambridge, 4Department of Medicine, Colchester Hospital University NHS Foundation Trust, Colchester General Hospital, Colchester, 5Research and Development Department, Papworth Hospital NHS Foundation Trust, Papworth Everard, Cambridge, UK Abstract: A body of evidence supports the use of low tidal volumes in ventilated patients without lung pathology to slow progress to acute respiratory distress syndrome (ARDS due to ventilator associated lung injury. We undertook a retrospective chart review and tested the hypothesis that tidal volume is a predictor of mortality in cardiothoracic (medical and surgical critical care patients receiving invasive mechanical ventilation. Independent predictors of mortality in our study included: type of surgery, albumin, H+, bilirubin, and fluid balance. In particular, it is important to note that cardiac, thoracic, and transplant surgical patients were associated with lower mortality. However, our study did not sample equally from The Berlin Definition of ARDS severity categories (mild, moderate, and severe hypoxemia. Although our study was not adequately powered to detect a difference in mortality between these groups, it will inform the development of a large prospective cohort study exploring the role of low tidal volume ventilation in cardiothoracic critically ill patients. Keywords: lung protective ventilation, cardiothoracic critical care, acute respiratory distress syndrome, invasive mechanical ventilation

  1. Taurine protects methamphetamine-induced developmental angiogenesis defect through antioxidant mechanism

    International Nuclear Information System (INIS)

    Shao, Xue; Hu, Zhengtao; Hu, Chunyan; Bu, Qian; Yan, Guangyan; Deng, Pengchi; Lv, Lei; Wu, Dan; Deng, Yi; Zhao, Jinxuan; Zhu, Ruiming; Li, Yan; Li, Hongyu; Xu, Youzhi; Yang, Hanshuo; Zhao, Yinglan; Cen, Xiaobo

    2012-01-01

    Investigations have characterized addictive drug-induced developmental cardiovascular malformation in human, non-human primate and rodent. However, the underlying mechanism of malformation caused by drugs during pregnancy is still largely unknown, and preventive and therapeutic measures have been lacking. Using 1 H NMR spectroscopy, we profiled the metabolites from human embryo endothelial cells exposed to methamphetamine (METH) and quantified a total of 226 peaks. We identified 11 metabolites modified robustly and found that taurine markedly increased. We then validated the hypothesis that this dramatic increase in taurine could attribute to its effect in inhibiting METH-induced developmental angiogenesis defect. Taurine supplement showed a more significant potential than other metabolites in protecting against METH-induced injury in endothelial cells. Taurine strongly attenuated METH-induced inhibition of proliferation and migration in endothelial cells. Furthermore, death rate and vessel abnormality of zebrafish embryos treated with METH were greatly reversed by taurine. In addition, taurine supplement caused a rapid decrease in reactive oxygen species generation and strongly attenuated the excitable arise of antioxidase activities in the beginning of METH exposure prophase. Dysregulations of NF-κB, p-ERK as well as Bax, which reflect apoptosis, cell cycle arrest and oxidative stress in vascular endothelium, were blocked by taurine. Our results provide the first evidence that taurine prevents METH-caused developmental angiogenesis defect through antioxidant mechanism. Taurine could serve as a potential therapeutic or preventive intervention of developmental vascular malformation for the pregnant women with drug use. Highlights: ► Metabonomics findings. ► Abnormal development. ► Dysregulations of key proteins.

  2. Taurine protects methamphetamine-induced developmental angiogenesis defect through antioxidant mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Shao, Xue; Hu, Zhengtao; Hu, Chunyan; Bu, Qian; Yan, Guangyan [National Chengdu Center for Safety Evaluation of Drugs, State Key Lab of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041 (China); Deng, Pengchi [Analytical and Testing Center, Sichuan University, Chengdu 610041 (China); Lv, Lei [National Chengdu Center for Safety Evaluation of Drugs, State Key Lab of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041 (China); Wu, Dan [College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041 (China); Deng, Yi; Zhao, Jinxuan; Zhu, Ruiming; Li, Yan; Li, Hongyu; Xu, Youzhi; Yang, Hanshuo; Zhao, Yinglan [National Chengdu Center for Safety Evaluation of Drugs, State Key Lab of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041 (China); Cen, Xiaobo, E-mail: xbcenalan@vip.sina.com [National Chengdu Center for Safety Evaluation of Drugs, State Key Lab of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041 (China)

    2012-05-01

    Investigations have characterized addictive drug-induced developmental cardiovascular malformation in human, non-human primate and rodent. However, the underlying mechanism of malformation caused by drugs during pregnancy is still largely unknown, and preventive and therapeutic measures have been lacking. Using {sup 1}H NMR spectroscopy, we profiled the metabolites from human embryo endothelial cells exposed to methamphetamine (METH) and quantified a total of 226 peaks. We identified 11 metabolites modified robustly and found that taurine markedly increased. We then validated the hypothesis that this dramatic increase in taurine could attribute to its effect in inhibiting METH-induced developmental angiogenesis defect. Taurine supplement showed a more significant potential than other metabolites in protecting against METH-induced injury in endothelial cells. Taurine strongly attenuated METH-induced inhibition of proliferation and migration in endothelial cells. Furthermore, death rate and vessel abnormality of zebrafish embryos treated with METH were greatly reversed by taurine. In addition, taurine supplement caused a rapid decrease in reactive oxygen species generation and strongly attenuated the excitable arise of antioxidase activities in the beginning of METH exposure prophase. Dysregulations of NF-κB, p-ERK as well as Bax, which reflect apoptosis, cell cycle arrest and oxidative stress in vascular endothelium, were blocked by taurine. Our results provide the first evidence that taurine prevents METH-caused developmental angiogenesis defect through antioxidant mechanism. Taurine could serve as a potential therapeutic or preventive intervention of developmental vascular malformation for the pregnant women with drug use. Highlights: ► Metabonomics findings. ► Abnormal development. ► Dysregulations of key proteins.

  3. Oxidative stress protection and stomatal patterning as components of salinity tolerance mechanism in quinoa (Chenopodium quinoa).

    Science.gov (United States)

    Shabala, Lana; Mackay, Alex; Tian, Yu; Jacobsen, Sven-Erik; Zhou, Daowei; Shabala, Sergey

    2012-09-01

    Two components of salinity stress are a reduction in water availability to plants and the formation of reactive oxygen species. In this work, we have used quinoa (Chenopodium quinoa), a dicotyledonous C3 halophyte species displaying optimal growth at approximately 150 mM NaCl, to study mechanisms by which halophytes cope with the afore-mentioned components of salt stress. The relative contribution of organic and inorganic osmolytes in leaves of different physiological ages (e.g. positions on the stem) was quantified and linked with the osmoprotective function of organic osmolytes. We show that the extent of the oxidative stress (UV-B irradiation) damage to photosynthetic machinery in young leaves is much less when compared with old leaves, and attribute this difference to the difference in the size of the organic osmolyte pool (1.5-fold difference under control conditions; sixfold difference in plants grown at 400 mM NaCl). Consistent with this, salt-grown plants showed higher Fv/Fm values compared with control plants after UV-B exposure. Exogenous application of physiologically relevant concentrations of glycine betaine substantially mitigated oxidative stress damage to PSII, in a dose-dependent manner. We also show that salt-grown plants showed a significant (approximately 30%) reduction in stomatal density observed in all leaves. It is concluded that accumulation of organic osmolytes plays a dual role providing, in addition to osmotic adjustment, protection of photosynthetic machinery against oxidative stress in developing leaves. It is also suggested that salinity-induced reduction in stomatal density represents a fundamental mechanism by which plants optimize water use efficiency under saline conditions. Copyright © Physiologia Plantarum 2012.

  4. Endogenous 5-methylcytosine protects neighboring guanines from N7 and O6-methylation and O6-pyridyloxobutylation by the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

    Science.gov (United States)

    Ziegel, Rebecca; Shallop, Anthony; Upadhyaya, Pramod; Jones, Roger; Tretyakova, Natalia

    2004-01-20

    All CG dinucleotides along exons 5-8 of the p53 tumor suppressor gene contain endogenous 5-methylcytosine (MeC). These same sites (e.g., codons 157, 158, 245, 248, and 273) are mutational hot spots in smoking-induced lung cancer. Several groups used the UvrABC endonuclease incision assay to demonstrate that methylated CG dinucleotides of the p53 gene are the preferred binding sites for the diol epoxides of bay region polycyclic aromatic hydrocarbons (PAH). In contrast, effects of endogenous cytosine methylation on the distribution of DNA lesions induced by tobacco-specific nitrosamines, e.g., 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), have not been elucidated. In the work presented here, a stable isotope labeling HPLC-ESI-MS/MS approach was employed to analyze the reactivity of the N7 and O6 positions of guanines within hemimethylated and fully methylated CG dinucleotides toward NNK-derived methylating and pyridyloxobutylating species. 15N3-labeled guanine bases were placed within synthetic DNA sequences representing endogenously methylated p53 codons 154, 157, and 248, followed by treatment with acetylated precursors to NNK diazohydroxides. HPLC-ESI-MS/MS analysis was used to determine the relative yields of N7- and O6-guanine adducts at the 15N3-labeled position. In all cases, the presence of MeC inhibited the formation of N7-methylguanine, O6-methylguanine, and O6-pyridyloxobutylguanine at a neighboring G, with the greatest decrease observed in fully methylated dinucleotides and at guanines preceded by MeC. Furthermore, the O6-Me-dG/N7-Me-G molar ratios were decreased in the presence of the 5'-neighboring MeC, suggesting that the observed decline in O6-alkylguanine adduct yields is, at least partially, a result of an altered reactivity pattern in methylated CG dinucleotides. These results indicate that, unlike N2-guanine adducts of PAH diol epoxides, NNK-induced N7- and O6-alkylguanine adducts are not preferentially formed at the endogenously

  5. In Vitro Protective Effect and Antioxidant Mechanism of Resveratrol Induced by Dapsone Hydroxylamine in Human Cells.

    Directory of Open Access Journals (Sweden)

    Rosyana V Albuquerque

    Full Text Available Dapsone (DDS hydroxylamine metabolites cause oxidative stress- linked adverse effects in patients, such as methemoglobin formation and DNA damage. This study evaluated the ameliorating effect of the antioxidant resveratrol (RSV on DDS hydroxylamine (DDS-NHOH mediated toxicity in vitro using human erythrocytes and lymphocytes. The antioxidant mechanism was also studied using in-silico methods. In addition, RSV provided intracellular protection by inhibiting DNA damage in human lymphocytes induced by DDS-NHOH. However, whilst pretreatment with RSV (10-1000 μM significantly attenuated DDS-NHOH-induced methemoglobinemia, but it was not only significantly less effective than methylene blue (MET, but also post-treatment with RSV did not reverse methemoglobin formation, contrarily to that observed with MET. DDS-NHOH inhibited catalase (CAT activity and reactive oxygen species (ROS generation, but did not alter superoxide dismutase (SOD activity in erythrocytes. Pretreatment with RSV did not alter these antioxidant enzymes activities in erythrocytes treated with DDS-NHOH. Theoretical calculations using density functional theory methods showed that DDS-NHOH has a pro-oxidant effect, whereas RSV and MET have antioxidant effect on ROS. The effect on methemoglobinemia reversion for MET was significantly higher than that of RSV. These data suggest that the pretreatment with resveratrol may decrease heme-iron oxidation and DNA damage through reduction of ROS generated in cells during DDS therapy.

  6. Protective mechanical ventilation in United Kingdom critical care units: A multicentre audit.

    Science.gov (United States)

    Newell, Christopher P; Martin, Matthew J; Richardson, Neil; Bourdeaux, Christopher P

    2017-05-01

    Lung protective ventilation is becoming increasingly used for all critically ill patients being mechanically ventilated on a mandatory ventilator mode. Compliance with the universal application of this ventilation strategy in intensive care units in the United Kingdom is unknown. This 24-h audit of ventilation practice took place in 16 intensive care units in two regions of the United Kingdom. The mean tidal volume for all patients being ventilated on a mandatory ventilator mode was 7.2(±1.4) ml kg -1 predicted body weight and overall compliance with low tidal volume ventilation (≤6.5 ml kg -1 predicted body weight) was 34%. The mean tidal volume for patients ventilated with volume-controlled ventilation was 7.0(±1.2) ml kg -1 predicted body weight and 7.9(±1.8) ml kg -1 predicted body weight for pressure-controlled ventilation ( P  < 0.0001). Overall compliance with recommended levels of positive end-expiratory pressure was 72%. Significant variation in practice existed both at a regional and individual unit level.

  7. Protective effect of oestradiol in the coeliac ganglion against ovarian apoptotic mechanism on dioestrus.

    Science.gov (United States)

    Cynthia, Bronzi; Cristina, Daneri Becerra; Adriana, Vega Orozco; Belén, Delsouc María; María, Rastrilla Ana; Marilina, Casais; Zulema, Sosa

    2013-05-01

    The aims of this work were to investigate if oestradiol 10(-8)M in the incubation media of either the ovary alone (OV) or the ganglion compartment of an ex vivo coeliac ganglion-superior ovarian nerve-ovary system (a) modifies the release of ovarian progesterone (P4) and oestradiol (E2) on dioestrus II, and (b) modifies the ovarian gene expression of 3β-HSD and 20α-HSD enzymes and markers of apoptosis. The concentration of ovarian P4 release was measured in both experimental schemes, and ovarian P4 and E2 in the ex vivo system by RIA at different times. The expression of 3β-hydroxysteroid dehydrogenase, 20α-hydroxysteroid dehydrogenase and antiapoptotic bcl-2 and proapoptotic bax by RT-PCR were determined. E2 added in the coeliac ganglion caused an increase in the ovarian release of the P4, E2 and 3β-HSD, while in the ovary incubation alone it decreased P4 and 3β-HSD but increased and 20α-HSD and bax/bcl-2 ratio. It is concluded that through a direct effect on the ovary, E2 promotes luteal regression in DII rats, but the addition of E2 in the coeliac ganglion does not have the same effect. The peripheral nervous system, through the superior ovarian nerve, has a protective effect against the apoptotic mechanism on DII. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. An alternative mechanism for international health aid: evaluating a Global Social Protection Fund.

    Science.gov (United States)

    Basu, Sanjay; Stuckler, David; McKee, Martin

    2014-01-01

    Several public health groups have called for the creation of a global fund for 'social protection'-a fund that produces the international equivalent of domestic tax collection and safety net systems to finance care for the ill and disabled and related health costs. All participating countries would pay into a global fund based on a metric of their ability to pay and withdraw from the common pool based on a metric of their need for funds. We assessed how alternative strategies and metrics by which to operate such a fund would affect its size and impact on health system financing. Using a mathematical model, we found that common targets for health funding in low-income countries require higher levels of aid expenditures than presently distributed. Some mechanisms exist that may incentivize reduction of domestic health inequalities, and direct most funds towards the poorest populations. Payments from high-income countries are also likely to decrease over time as middle-income countries' economies grow.

  9. Forest conservation and the clean development mechanism. Lessons from the Costa Rican protected areas project

    International Nuclear Information System (INIS)

    Voehringer, F.

    2004-01-01

    Deforestation is currently the source of about 20% of anthropogenic CO2 emissions. Avoided deforestation has, nonetheless, been ruled out as a Clean Development Mechanism (CDM) category in the Kyoto Protocol's first commitment period, because several methodological issues were considered too difficult to resolve. This paper explores whether CDM issues such as (1) carbon quantification, (2) additionality and baseline setting, (3) leakage risks, (4) non-permanence risks, and (5) sustainable development can be adequately dealt with in large, diversified forest conservation projects. To this aim, it studies the case of the Costa Rican Protected Areas Project (PAP), an Activities Implemented Jointly (AIJ) project which was meant to consolidate the national park system to avoid deforestation, promote the growth of secondary forests and regenerate pastures on an area that, in total, covers 10% of the national territory. The case study examines how the issues mentioned above have been addressed in the project design and in the certification process. It is found that baseline uncertainties are the major problem in this case. Nonetheless, the case suggests the possibility to address CDM issues by specific requirements for project design and very conservative and temporary crediting. Provided that other case studies support this conclusion, eligibility of well-designed forest conservation projects under the CDM in the second commitment period may be worth considering, given the secondary benefits of avoided deforestation

  10. Mechanism of the Protective Effect of Yulangsan Flavonoid on Myocardial Ischemia/Reperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Xudong Zhang

    2014-09-01

    Full Text Available Aims: Effect and mechanism of Yulangsan flavonoid (YLSF on rat myocardial ischemia/reperfusion injury (MI/RI has been investigated. Methods: Sprague-Dawley (SD rats were randomly divided into seven groups (sham group, model group and NS group: 2 mL of normal saline/kg body weight was administered; diltiazem group: 5 mg of diltiazem hydrochloride/kg body weight was administered; YLSFL, YLSFM and YLSFH groups: 20, 40 and 80 mg of YLSF/kg body weight was administered and the MI/RI model was established. Myocardial infarct area, levels of myocardial enzymes and nitric oxide synthase (NOS were measured. Caspase-3 and adenine nucleotide translocator-1 (ANT1 mRNA expression were evaluated by reverse transcription polymerase chain reaction (RT-PCR. Pathological structure and cardiocyte ultrastructure were also analysed. Results: Compared with the MI/RI group, pretreatment with YLSF or diltiazem hydrochloride decreased the infarct area, levels of inducible nitric oxide synthase (iNOS, caspase-3 as well as the leakage of myocardial enzyme and increased activities of total nitric oxide synthase (tNOS as well as constitutive nitric oxide synthase (cNOS. Cellular edema and the infiltration of inflammatory cells were alleviated. Conclusions: The experiment showed that YLSF protected the heart against MI/RI, possibly by reducing lipid peroxidation damage, regulating NOS activity and modulating the apoptosis genes expression.

  11. Architecture and material properties of diatom shells provide effective mechanical protection

    Science.gov (United States)

    Hamm, Christian E.; Merkel, Rudolf; Springer, Olaf; Jurkojc, Piotr; Maier, Christian; Prechtel, Kathrin; Smetacek, Victor

    2003-02-01

    Diatoms are the major contributors to phytoplankton blooms in lakes and in the sea and hence are central in aquatic ecosystems and the global carbon cycle. All free-living diatoms differ from other phytoplankton groups in having silicified cell walls in the form of two `shells' (the frustule) of manifold shape and intricate architecture whose function and role, if any, in contributing to the evolutionary success of diatoms is under debate. We explored the defence potential of the frustules as armour against predators by measuring their strength. Real and virtual loading tests (using calibrated glass microneedles and finite element analysis) were performed on centric and pennate diatom cells. Here we show that the frustules are remarkably strong by virtue of their architecture and the material properties of the diatom silica. We conclude that diatom frustules have evolved as mechanical protection for the cells because exceptional force is required to break them. The evolutionary arms race between diatoms and their specialized predators will have had considerable influence in structuring pelagic food webs and biogeochemical cycles.

  12. ENDOGENEITY OF INDONESIAN MONEY SUPPLY

    Directory of Open Access Journals (Sweden)

    Meutia Safrina Rachma

    2011-09-01

    Full Text Available There has been a long debate about the endogeneity of money supply. The main objective of this article is to identify whether money supply in Indonesia is an exogenous or an endogenous variable. Using a Vector Autoregressive model and monthly data 1997(5-2010(6, the estimation result shows that money supply in Indonesia is an endogenous variable. The movement of broad money supply does influence the movement of base money and Consumer Price Index. Consequently, the central bank does not have control power on money supply. The bank is only able to maintain the stability and control the movement of broad money supply. Keywords: Endogenous variable, money supply, vector autoregressionJEL classification numbers: E51, E52, E58

  13. Lung-protective mechanical ventilation does not protect against acute kidney injury in patients without lung injury at onset of mechanical ventilation.

    Science.gov (United States)

    Cortjens, Bart; Royakkers, Annick A N M; Determann, Rogier M; van Suijlen, Jeroen D E; Kamphuis, Stephan S; Foppen, Jannetje; de Boer, Anita; Wieland, Cathrien W; Spronk, Peter E; Schultz, Marcus J; Bouman, Catherine S C

    2012-06-01

    Preclinical and clinical studies suggest that mechanical ventilation contributes to the development of acute kidney injury (AKI), particularly in the setting of lung-injurious ventilator strategies. To determine whether ventilator settings in critically ill patients without acute lung injury (ALI) at onset of mechanical ventilation affect the development of AKI. Secondary analysis of a randomized controlled trial (N = 150), comparing conventional tidal volume (V(T), 10 mL/kg) with low tidal volume (V(T), 6 mL/kg) mechanical ventilation in critically ill patients without ALI at randomization. During the first 5 days of mechanical ventilation, the RIFLE class was determined daily, whereas neutrophil gelatinase-associated lipocalin and cystatin C levels were measured in plasma collected on days 0, 2, and 4. Eighty-six patients had no AKI at inclusion, and 18 patients (21%) subsequently developed AKI, but without significant difference between ventilation strategies. (Cumulative hazard, 0.26 vs 0.23; P = .88.) The courses of neutrophil gelatinase-associated lipocalin and cystatin C plasma levels did not differ significantly between randomization groups. In the present study in critically patients without ALI at onset of mechanical ventilation, lower tidal volume ventilation did not reduce the development or worsening of AKI compared with conventional tidal volume ventilation. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. 59 eyes with endogenous endophthalmitis

    DEFF Research Database (Denmark)

    Bjerrum, Søren Solborg; la Cour, Morten

    2017-01-01

    BACKGROUND: To study the epidemiology of patients with endogenous endophthalmitis in Denmark. MATERIAL AND METHODS: Retrospective and prospective case series of 59 eyes in patients with endogenous endophthalmitis in Denmark between 2000 and 2016. RESULTS: The age of the patients ranged from 28 to......, the visual outcome and the mortality of the patients. The epidemiology of the disease is very different in Scandinavia compared to Asia. The visual prognosis remains grave and the majority of the eyes lose useful vision....

  15. Inhibition of HMGCoA reductase by simvastatin protects mice from injurious mechanical ventilation.

    Science.gov (United States)

    Manitsopoulos, Nikolaos; Orfanos, Stylianos E; Kotanidou, Anastasia; Nikitopoulou, Ioanna; Siempos, Ilias; Magkou, Christina; Dimopoulou, Ioanna; Zakynthinos, Spyros G; Armaganidis, Apostolos; Maniatis, Nikolaos A

    2015-02-14

    Mortality from severe acute respiratory distress syndrome exceeds 40% and there is no available pharmacologic treatment. Mechanical ventilation contributes to lung dysfunction and mortality by causing ventilator-induced lung injury. We explored the utility of simvastatin in a mouse model of severe ventilator-induced lung injury. Male C57BL6 mice (n = 7/group) were pretreated with simvastatin or saline and received protective (8 mL/kg) or injurious (25 mL/kg) ventilation for four hours. Three doses of simvastatin (20 mg/kg) or saline were injected intraperitoneally on days -2, -1 and 0 of the experiment. Lung mechanics, (respiratory system elastance, tissue damping and airway resistance), were evaluated by forced oscillation technique, while respiratory system compliance was measured with quasi-static pressure-volume curves. A pathologist blinded to treatment allocation scored hematoxylin-eosin-stained lung sections for the presence of lung injury. Pulmonary endothelial dysfunction was ascertained by bronchoalveolar lavage protein content and lung tissue expression of endothelial junctional protein Vascular Endothelial cadherin by immunoblotting. To assess the inflammatory response in the lung, we determined bronchoalveolar lavage fluid total cell content and neutrophil fraction by microscopy and staining in addition to Matrix-Metalloprotease-9 by ELISA. For the systemic response, we obtained plasma levels of Tumor Necrosis Factor-α, Interleukin-6 and Matrix-Metalloprotease-9 by ELISA. Statistical hypothesis testing was undertaken using one-way analysis of variance and Tukey's post hoc tests. Ventilation with high tidal volume (HVt) resulted in significantly increased lung elastance by 3-fold and decreased lung compliance by 45% compared to low tidal volume (LVt) but simvastatin abrogated lung mechanical alterations of HVt. Histologic lung injury score increased four-fold by HVt but not in simvastatin-pretreated mice. Lavage pleocytosis and neutrophilia were

  16. A fracture mechanics assessment of surface cracks existing in protective layers of multi-layer composite pipes

    Czech Academy of Sciences Publication Activity Database

    Hutař, Pavel; Náhlík, Luboš; Šestáková, Lucie; Ševčík, Martin; Knésl, Zdeněk; Nezbedová, E.

    2010-01-01

    Roč. 92, č. 5 (2010), s. 1120-1125 ISSN 0263-8223 R&D Projects: GA ČR GA106/09/0279 Institutional research plan: CEZ:AV0Z20410507 Keywords : Protective layers * Multi-layer pipes damage * Fracture mechanics * Bi-material interface * Generalized stress intensity factor Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 2.028, year: 2010

  17. Mechanisms of alteration of the immune system by ionizing radiations: a basis for radiation protection

    International Nuclear Information System (INIS)

    Bourguignon, M.; Perez, M.; Dubner, D.; Michelin, S.; Carosella, E.

    2006-01-01

    Full text of publication follows: Alterations of the immune system appear in relationship with exposure to ionizing radiation (IR) in different situations, e.g., accidents, radiation therapy of cancer, prenatal irradiation, some human diseases with hypersensitivity to IR and aging. Thus, the comprehension of the mechanisms of the alterations of the immune system by IR is necessary to elaborate strategies of protection and to pave the way for future possible therapies. At least 9 mechanisms of alterations can be identified: 1- Apoptosis. Apoptosis is a key mechanism of the natural regulation of the immune system and plays also a key role in the response to IR: lymphocytes die rapidly by apoptosis after exposure. Different pathways of induction of apoptosis have been identified, and include p53 dependent and mitochondria mediated pathways, as well as CD95 and ROS initiation; 2- TCR mutations. The T cell antigen receptor is responsible to discriminate between self and non self. Mutations of the TCR may result from exposure to IR; 3- Modification of the Th1-Th2 balance. T helper cells may express 2 distinct secretion patterns: Th1 cytokines promote cell-mediated immunity while Th2 cytokines favor humoral immunity. Although the effects of IR on the Th1/Th2 balance remains controversial, an imbalance towards a Th2 profile is likely and patients with cancer and systemic auto-immune disease often present a switch from Th1 to Th2; 4- Bystander effects and genetic instability. Stimulatory effect or genomic instability have been observed in haematopoietic cells exposed to IR and related to a bystander mechanism. 5- Shift toward an inflammatory profile. Ionizing radiation may induce a persistent inflammatory profile as a result of dis-regulation of cytokine production; such a status of persistent inflammation has been observed in Hiroshima and Nagasaki survivors. 6- Modification of antigen presentation. Antigen presentation by dendritic cells is an essential function preceding

  18. Mechanisms of alteration of the immune system by ionizing radiations: a basis for radiation protection

    Energy Technology Data Exchange (ETDEWEB)

    Bourguignon, M. [Direction Generale de la Surete Nucleaire et de la Radioprotection, 75 - Paris (France); Perez, M.; Dubner, D.; Michelin, S. [Autoridad Regulatoria Nuclear, Buenos Aires (Argentina); Carosella, E. [CEA, Service de Recherches en Hemato -Immunologie, 75 - Paris (France)

    2006-07-01

    Full text of publication follows: Alterations of the immune system appear in relationship with exposure to ionizing radiation (IR) in different situations, e.g., accidents, radiation therapy of cancer, prenatal irradiation, some human diseases with hypersensitivity to IR and aging. Thus, the comprehension of the mechanisms of the alterations of the immune system by IR is necessary to elaborate strategies of protection and to pave the way for future possible therapies. At least 9 mechanisms of alterations can be identified: 1- Apoptosis. Apoptosis is a key mechanism of the natural regulation of the immune system and plays also a key role in the response to IR: lymphocytes die rapidly by apoptosis after exposure. Different pathways of induction of apoptosis have been identified, and include p53 dependent and mitochondria mediated pathways, as well as CD95 and ROS initiation; 2- TCR mutations. The T cell antigen receptor is responsible to discriminate between self and non self. Mutations of the TCR may result from exposure to IR; 3- Modification of the Th1-Th2 balance. T helper cells may express 2 distinct secretion patterns: Th1 cytokines promote cell-mediated immunity while Th2 cytokines favor humoral immunity. Although the effects of IR on the Th1/Th2 balance remains controversial, an imbalance towards a Th2 profile is likely and patients with cancer and systemic auto-immune disease often present a switch from Th1 to Th2; 4- Bystander effects and genetic instability. Stimulatory effect or genomic instability have been observed in haematopoietic cells exposed to IR and related to a bystander mechanism. 5- Shift toward an inflammatory profile. Ionizing radiation may induce a persistent inflammatory profile as a result of dis-regulation of cytokine production; such a status of persistent inflammation has been observed in Hiroshima and Nagasaki survivors. 6- Modification of antigen presentation. Antigen presentation by dendritic cells is an essential function preceding

  19. ECONOMIC MECHANISMS OF POPULATION PROTECTION AGAINST PENSION RISKS AS A TOOL FOR SOCIO-ECONOMIC DEVELOPMENT OF THE REGION

    Directory of Open Access Journals (Sweden)

    Lyubov V. Grigoryeva

    2017-06-01

    Full Text Available The problem of finding effective economic instruments for socio-economic development of the regions has recently become of increasing relevance. Strengthening the regional differentiation, highlighting the leading and lagging regions, the lack of own resources in the regions has forced regional authorities to use new instruments of territorial development, in particular, economic mechanisms of protection against pension risks. The use of these mechanisms has a dual effect (economic and social, due to the attraction of the regions with additional financial resources in the form of “long money” and increasing the protection of citizens against pension risks (the increase in the level of pension payments. The analysis of the current use of economic mechanisms of protection against pension risks in the regions of the Southern Federal District helped to articulate key issues of their use, in particular, low pension literacy of the population, distrust towards specialized financial institutions, the investment policy of the regions does not take into account the possibility of attracting private pension funds into regional projects, and there is no mechanism to support regional National Pension Fund. Territorial analysis revealed the potential application of economic mechanisms to protect against pension risks in the regions of the Southern Federal District as a tool for socio-economic development, which is based on the existence of regional pension funds and insurance companies (providing services for pension insurance, as well as participation in private pension provision. The Krasnodar, Rostov and Volgograd regions have the highest potential among the regions of the Southern Federal District, as there already exist regional National Pension Fund, and the participation in private pension insurance is confirmed by the statistics of the contributions paid. The study of existing economic mechanisms to protect against pension risks will provide the

  20. An epigenetic signal encoded protection mechanism is activated by graphene oxide to inhibit its induced reproductive toxicity in Caenorhabditis elegans.

    Science.gov (United States)

    Zhao, Yunli; Wu, Qiuli; Wang, Dayong

    2016-02-01

    Although many studies have suggested the adverse effects of engineered nanomaterials (ENMs), the self-protection mechanisms for organisms against ENMs toxicity are still largely unclear. Using Caenorhabditis elegans as an in vivo assay system, our results suggest the toxicity of graphene oxide in reducing reproductive capacity by inducing damage on gonad development. The observed reproductive toxicity of GO on gonad development was due to the combinational effect of germline apoptosis and cell cycle arrest, and DNA damage activation might act as an inducer for this combinational effect. For the underlying molecular mechanism of reproductive toxicity of GO, we raised a signaling cascade of HUS-1/CLK-2-CEP-1-EGL-1-CED-4-CED-3 to explain the roles of core apoptosis signaling pathway and DNA damage checkpoints. Moreover, we identified a miRNA regulation mechanism activated by GO to suppress its induced reproductive toxicity. A mir-360 regulation mechanism was activated by GO to suppress its induced DNA damage-apoptosis signaling cascade through affecting component of CEP-1. Our identified epigenetic signal encoded protection mechanism activated by GO suggests a novel self-protection mechanism for organisms against the ENMs toxicity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Mechanical stress analysis during a quench in CLIQ protected 16 T dipole magnets designed for the future circular collider

    Science.gov (United States)

    Zhao, Junjie; Prioli, Marco; Stenvall, Antti; Salmi, Tiina; Gao, Yuanwen; Caiffi, Barbara; Lorin, Clement; Marinozzi, Vittorio; Farinon, Stefania; Sorbi, Massimo

    2018-07-01

    Protecting the magnets in case of a quench is a challenge for the 16 T superconducting dipole magnets presently designed for the 100 TeV: Future Circular Collider (FCC). These magnets are driven to the foreseen technological limits in terms of critical current, mechanical strength and quench protection. The magnets are protected with CLIQ (Coupling-Loss Induced Quench) system, which is a recently developed quench protection method based on discharging a capacitor bank across part of the winding. The oscillation of the magnet currents and the dissipation of the high stored energy into the windings cause electrodynamic forces and thermal stresses, which may need to be considered in the magnet mechanical design. This paper focuses on mechanical stress analysis during a quench of the 16 T cos-θ and block type dipole magnets. A finite element model allowed studying the stress due to the non-uniform temperature and current distribution in the superconducting coils. Two different CLIQ configurations were considered for the cos-θ design and one for the block type magnet. The analyses of the mechanical behavior of two magnets during a quench without or with hot spot turn were separately carried out. The simulation results show that the stress related to a quench should be considered when designing a high field magnet.

  2. Research on Protective Effect and Mechanism of Idazoxan on lps Attacked Acute Hepatic Injury

    Science.gov (United States)

    Zhu, Junyu; Ying, Shangqi; Kang, Wenyuan; Huang, Wenjuan; Liang, Huaping

    2018-01-01

    Objective: To observe the protection effect of Idazoxan (IDA) on LPS induced acute hepatic injury, and to explore its action mechanism. Methods: 60 adult C57BL/6 mice were divided into a control group (20 mice, intraperitoneal injection of phosphate buffer), a model group (20 mice, intraperitoneal injection of LPS 10 mg/kg) and a agmatine group (20 mice, intraperitoneal injection of LPS 10 mg/kg and agmatine 200 mg/kg) according to random number table method. Blood and liver tissue were collected for preparation of tissue homogenate. Enzyme-linked immunosorbent assay (ELISA) was adopted for detecting tumor necrosis factor-α (TNF-α) and interleukin (IL- 1β and IL - 6) contents in the serum and liver tissue at 24h after molding. Automatic biochemical analyzer is used for determining alanine transaminase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) level at 24h after molding; The liver tissue pathology changes were observed at 24h after molding. Macrophage RAW264.7 cells were stimulated by 10 μg/mL LPS and with or without IDA (100 μmol/L). 2’, 7’-dichlorofluoresce in diacetate (DCFH-DA) was used as a fluorescent probe for detection of intracellular reactive oxygen species (ROS) level; qRT - PCR method was used for detecting antioxidant enzymes HO-1 and NQO-1 mRNA expression level at 2h, 4h and 8 h. Results: mice in the model group suffered from depression, curling and food water forbidding at 6h after molding. Mice in the Idazoxan group have obviously better spirit and activity than that of model group. The serum ALT, AST and LDH level of LPS attacked acute hepatic injury mice can be effectively alleviated after Idazoxan treatment. The expression of proinflammatory factor TNF-α and IL-6 in the liver can be reduced. The liver showed obvious pathological changes at 24 h after injection, such as liver cell swelling, necrosis, congestion, inflammatory cell infiltration, etc.; The liver cell injury was prominently alleviated in IDA

  3. Exogenous and endogenous spatial attention effects on visuospatial working memory.

    Science.gov (United States)

    Botta, Fabiano; Santangelo, Valerio; Raffone, Antonino; Lupiáñez, Juan; Belardinelli, Marta Olivetti

    2010-08-01

    In this study, we investigate how exogenous and endogenous orienting of spatial attention affect visuospatial working memory (VSWM). Specifically, we focused on two attentional effects and their consequences on storage in VSWM, when exogenous (Experiment 1) or endogenous (Experiment 2) orienting cues were used. The first effect, known as the meridian effect, is given by a decrement in behavioural performance when spatial cues and targets are presented in locations separated by vertical and/or horizontal meridians. The second effect, known as the distance effect, is given by a decrement in the orienting effects as a function of the spatial distance between cues and targets. Our results revealed a dissociation between exogenous and endogenous orienting mechanisms in terms of both meridian and distance effects. We found that meridian crossing affects performance only when endogenous cues were used. Specifically, VSWM performance with endogenous cueing depended more on the number of meridian crossings than on distance between cue and target. By contrast, a U-shaped distance dependency was observed using exogenous cues. Our findings therefore suggest that exogenous and endogenous orienting mechanisms lead to different forms of attentional bias for storage in VSWM.

  4. Structural drivers and social protection: mechanisms of HIV risk and HIV prevention for South African adolescents.

    Science.gov (United States)

    Cluver, Lucie Dale; Orkin, Frederick Mark; Meinck, Franziska; Boyes, Mark Edward; Sherr, Lorraine

    2016-01-01

    Social protection is high on the HIV-prevention agenda for youth in sub-Saharan Africa. However, questions remain: How do unconditional cash transfers work? What is the effect of augmenting cash provision with social care? And can "cash plus care" social protection reduce risks for adolescents most vulnerable to infection? This study tackles these questions by first identifying mediated pathways to adolescent HIV risks and then examining potential main and moderating effects of social protection in South Africa. This study was a prospective observational study of 3515 10-to-17-year-olds (56.7% female; 96.8% one-year retention). Within randomly selected census areas in four rural and urban districts in two South African provinces, all homes with a resident adolescent were sampled between 2009/2010 and 2011/2012. Measures included 1) potential structural drivers of HIV infection such as poverty and community violence; 2) HIV risk behaviours; 3) hypothesized psychosocial mediating factors; and 4) types of social protection involving cash and care. Using gender-disaggregated analyses, longitudinal mediation models were tested for potential main and moderating effects of social protection. Structural drivers were associated with increased onset of adolescent HIV risk behaviour (psocial protection were associated with reductions in HIV risk behaviour and psychosocial deprivations. In addition, cash social protection moderated risk pathways: for adolescent girls and boys experiencing more acute structural deprivation, social protection had the greatest associations with HIV risk prevention (e.g. moderation effects for girls: B=-0.08, psocial protection has the greatest prevention effects for the most vulnerable. Social protection comprising unconditional cash plus care was associated with reduced risk pathways through moderation and main effects, respectively. Our findings suggest the importance of social protection within a combination package of HIV

  5. Vulnerability to glutamate toxicity of dopaminergic neurons is dependent on endogenous dopamine and MAPK activation.

    Science.gov (United States)

    Izumi, Yasuhiko; Yamamoto, Noriyuki; Matsuo, Takaaki; Wakita, Seiko; Takeuchi, Hiroki; Kume, Toshiaki; Katsuki, Hiroshi; Sawada, Hideyuki; Akaike, Akinori

    2009-07-01

    Dopaminergic neurons are more vulnerable than other types of neurons in cases of Parkinson disease and ischemic brain disease. An increasing amount of evidence suggests that endogenous dopamine plays a role in the vulnerability of dopaminergic neurons. Although glutamate toxicity contributes to the pathogenesis of these disorders, the sensitivity of dopaminergic neurons to glutamate toxicity has not been clarified. In this study, we demonstrated that dopaminergic neurons were preferentially affected by glutamate toxicity in rat mesencephalic cultures. Glutamate toxicity in dopaminergic neurons was blocked by inhibiting extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase, and p38 MAPK. Furthermore, depletion of dopamine by alpha-methyl-dl-p-tyrosine methyl ester (alpha-MT), an inhibitor of tyrosine hydroxylase (TH), protected dopaminergic neurons from the neurotoxicity. Exposure to glutamate facilitated phosphoryration of TH at Ser31 by ERK, which contributes to the increased TH activity. Inhibition of ERK had no additive effect on the protection offered by alpha-MT, whereas alpha-MT and c-jun N-terminal kinase or p38 MAPK inhibitors had additive effects and yielded full protection. These data suggest that endogenous dopamine is responsible for the vulnerability to glutamate toxicity of dopaminergic neurons and one of the mechanisms may be an enhancement of dopamine synthesis mediated by ERK.

  6. Further comparisons of endogenous pyrogens and leukocytic endogenous mediators.

    Science.gov (United States)

    Kampschmidt, R F; Upchurch, H F; Worthington, M L

    1983-07-01

    It was recently shown (Murphy et al., Infect. Immun. 34:177-183), that rabbit macrophages produce two biochemically and immunologically distinct endogenous pyrogens. One of these has or copurifies with substances having a molecular weight of 13,000 and a pI of 7.3. This protein was produced by blood monocytes or inflammatory cells elicited in 16-h rabbit peritoneal exudates. These acute peritoneal exudates were produced by the intraperitoneal injection of large volumes of saline containing shellfish glycogen. When the leukocytes in these exudates were washed and incubated at 37 degrees C in saline, they released an endogenous pyrogen. The injection of this pyrogen into rabbits, rats, or mice caused the biological manifestations which have been attributed to leukocytic endogenous mediator. These effects were increases in blood neutrophils, the lowering of plasma iron and zinc levels, and the increased synthesis of the acute-phase proteins. The other rabbit endogenous pyrogen seems to be a family of proteins with isoelectric points between 4.5 and 5.0. These proteins are produced by macrophages in the lung, liver, or in chronic peritoneal exudates. In these experiments, the lower-isoelectric-point endogenous pyrogens were produced by macrophages from the peritoneal cavity of rabbits that had been injected 4 days earlier with 50 ml of light mineral oil. These rabbit pyrogens were found to have leukocytic endogenous mediator activity in mice but to be completely inactive in rats. When injected into rabbits, these proteins produced fever, lowered plasma iron, increased blood neutrophils, but failed to elevate plasma fibrinogen.

  7. The endogenous hallucinogen and trace amine N,N-dimethyltryptamine (DMT displays potent protective effects against hypoxia via sigma-1 receptor activation in human primary iPSC-derived cortical neurons and microglia-like immune cells

    Directory of Open Access Journals (Sweden)

    Attila Szabo

    2016-09-01

    Full Text Available N,N-dimethyltryptamine (DMT is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R, an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins. Due to this function, the activation of Sig-1R can mitigate the outcome of hypoxia or oxidative stress. In this paper we aimed to test the hypothesis that DMT plays a neuroprotective role in the brain by activating the Sig-1R. We tested whether DMT can mitigate hypoxic stress in in vitro cultured human cortical neurons (derived from induced pluripotent stem cells, and in monocyte-derived macrophages and dendritic cells. Here we report that DMT robustly increases the survival of these cell types in severe hypoxia (0.5% O2 through the Sig-1R. Furthermore, this phenomenon is associated with the decreased expression and function of the alpha subunit of the hypoxia-inducible factor 1 (HIF-1 suggesting that DMT-mediated Sig-1R activation may alleviate hypoxia-induced cellular stress and increase survival in a HIF-1-independent manner. Our results reveal a novel and important role of DMT in human cellular physiology. We postulate that this compound may be endogenously generated in situations of stress, ameliorating the adverse effects of hypoxic/ischemic insult to the brain.

  8. The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells.

    Science.gov (United States)

    Szabo, Attila; Kovacs, Attila; Riba, Jordi; Djurovic, Srdjan; Rajnavolgyi, Eva; Frecska, Ede

    2016-01-01

    N,N-dimethyltryptamine (DMT) is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R), an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER) and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins. Due to this function, the activation of Sig-1R can mitigate the outcome of hypoxia or oxidative stress. In this paper, we aimed to test the hypothesis that DMT plays a neuroprotective role in the brain by activating the Sig-1R. We tested whether DMT can mitigate hypoxic stress in in vitro cultured human cortical neurons (derived from induced pluripotent stem cells, iPSCs), monocyte-derived macrophages (moMACs), and dendritic cells (moDCs). Results showed that DMT robustly increases the survival of these cell types in severe hypoxia (0.5% O2) through the Sig-1R. Furthermore, this phenomenon is associated with the decreased expression and function of the alpha subunit of the hypoxia-inducible factor 1 (HIF-1) suggesting that DMT-mediated Sig-1R activation may alleviate hypoxia-induced cellular stress and increase survival in a HIF-1-independent manner. Our results reveal a novel and important role of DMT in human cellular physiology. We postulate that this compound may be endogenously generated in situations of stress, ameliorating the adverse effects of hypoxic/ischemic insult to the brain.

  9. Psychological rehabilitation of patients with endogenous disease

    Directory of Open Access Journals (Sweden)

    Tamara Kryvonis

    2013-07-01

    Full Text Available The rationale for early psychotherapeutic intervention in combination with psychopharmatherapy in patients with endogenous disorders is provided. The mechanisms of psychological defenses to deal with traumatic experience, used by personalities functioning on a psychotic level, are also described here. Characteristic behavior patterns of extended family members in terms of emotional codependence are provided. Individual pathopsychology is considered as a symptom of abnormal functioning of the family. Emphasis is placed on the importance of inclusion of family members in psychotherapeutic interaction in order to correct interpersonal relations.

  10. Gravity effects on endogenous movements

    Science.gov (United States)

    Johnsson, Anders; Antonsen, Frank

    Gravity effects on endogenous movements A. Johnsson * and F. Antonsen *+ * Department of Physics, Norwegian University of Science and Technology,NO-7491, Trond-heim, Norway, E-mail: anders.johnsson@ntnu.no + Present address: Statoil Research Center Trondheim, NO-7005, Trondheim, Norway Circumnutations in stems/shoots exist in many plants and often consists of more or less regular helical movements around the plumb line under Earth conditions. Recent results on circumnu-tations of Arabidopsis in space (Johnsson et al. 2009) showed that minute amplitude oscilla-tions exist in weightlessness, but that centripetal acceleration (mimicking the gravity) amplified and/or created large amplitude oscillations. Fundamental mechanisms underlying these results will be discussed by modeling the plant tissue as a cylinder of cells coupled together. As a starting point we have modeled (Antonsen 1998) standing waves on a ring of biological cells, as first discussed in a classical paper (Turing 1952). If the coupled cells can change their water content, an `extension' wave could move around the ring. We have studied several, stacked rings of cells coupled into a cylinder that together represent a cylindrical plant tissue. Waves of extensions travelling around the cylinder could then represent the observable circumnutations. The coupling between cells can be due to cell-to-cell diffusion, or to transport via channels, and the coupling can be modeled to vary in both longitudinal and transversal direction of the cylinder. The results from ISS experiments indicate that this cylindrical model of coupled cells should be able to 1) show self-sustained oscillations without the impact of gravity (being en-dogenous) and 2) show how an environmental factor like gravity can amplify or generate the oscillatory movements. Gravity has been introduced in the model by a negative, time-delayed feed-back transport across the cylinder. This represents the physiological reactions to acceler

  11. IFN-Gamma-Dependent and Independent Mechanisms of CD4+ Memory T Cell-Mediated Protection from Listeria Infection

    Directory of Open Access Journals (Sweden)

    Stephanie M. Meek

    2018-02-01

    Full Text Available While CD8+ memory T cells can promote long-lived protection from secondary exposure to intracellular pathogens, less is known regarding the direct protective mechanisms of CD4+ T cells. We utilized a prime/boost model in which mice are initially exposed to an acutely infecting strain of lymphocytic choriomeningitis virus (LCMV, followed by a heterologous rechallenge with Listeria monocytogenes recombinantly expressing the MHC Class II-restricted LCMV epitope, GP61–80 (Lm-gp61. We found that heterologous Lm-gp61 rechallenge resulted in robust activation of CD4+ memory T cells and that they were required for rapid bacterial clearance. We further assessed the relative roles of TNF and IFNγ in the direct anti-bacterial function of CD4+ memory T cells. We found that disruption of TNF resulted in a complete loss of protection mediated by CD4+ memory T cells, whereas disruption of IFNγ signaling to macrophages results in only a partial loss of protection. The protective effect mediated by CD4+ T cells corresponded to the rapid accumulation of pro-inflammatory macrophages in the spleen and an altered inflammatory environment in vivo. Overall, we conclude that protection mediated by CD4+ memory T cells from heterologous Listeria challenge is most directly dependent on TNF, whereas IFNγ only plays a minor role.

  12. Immunogenicity, protective efficacy and mechanism of novel CCS adjuvanted influenza vaccine.

    Science.gov (United States)

    Even-Or, Orli; Samira, Sarit; Rochlin, Eli; Balasingam, Shobana; Mann, Alex J; Lambkin-Williams, Rob; Spira, Jack; Goldwaser, Itzhak; Ellis, Ronald; Barenholz, Yechezkel

    2010-09-07

    We optimized the immunogenicity of adjuvanted seasonal influenza vaccine based on commercial split influenza virus as an antigen (hemagglutinin = HA) and on a novel polycationic liposome as a potent adjuvant and efficient antigen carrier (CCS/C-HA vaccine). The vaccine was characterized physicochemically, and the mechanism of action of CCS/C as antigen carrier and adjuvant was studied. The optimized CCS/C-HA split virus vaccine, when administered intramuscularly (i.m.), is significantly more immunogenic in mice, rats and ferrets than split virus HA vaccine alone, and it provides for protective immunity in ferrets and mice against live virus challenge that exceeds the degree of efficacy of the split virus vaccine. Similar adjuvant effects of optimized CCS/C are also observed in mice for H1N1 swine influenza antigen. The CCS/C-HA vaccine enhances immune responses via the Th1 and Th2 pathways, and it increases both the humoral responses and the production of IL-2 and IFN-γ but not of the pro-inflammatory factor TNFα. In mice, levels of CD4(+) and CD8(+) T-cells and of MHC II and CD40 co-stimulatory molecules are also elevated. Structure-function relationship studies of the CCS molecule as an adjuvant/carrier show that replacing the saturated palmitoyl acyl chain with the mono-unsaturated oleoyl (C18:1) chain affects neither size distribution and zeta potential nor immune responses in mice. However, replacing the polyalkylamine head group spermine (having two secondary amines) with spermidine (having only one secondary amine) reduces the enhancement of the immune response by ∼ 50%, while polyalkylamines by themselves are ineffective in improving the immunogenicity over the commercial HA vaccine. This highlights the importance of the particulate nature of the carrier and the polyalkylamine secondary amines in the enhancement of the immune responses against seasonal influenza. Altogether, our results suggest that the CCS/C polycationic liposomes combine the

  13. Different immunization routes induce protection against Aeromonas salmonicida through different immune mechanisms in rainbow trout

    DEFF Research Database (Denmark)

    Villumsen, Kasper Rømer; Raida, Martin Kristian

    in fish immunology and vaccinology, resulting in the development of both oral, immersion and injectable vaccine strategies over time. Applying mineral oil adjuvants, injectable vaccines inducing high levels of protection in salmon (Salmo salar) rose to prominence in the 1990’s. In general injectable......, adjuvanted vaccines have been shown to induce long-lasting increases in specific antibody levels. In general the majority of the published work concerning vaccination against A. salmonicida has been conducted on salmon. Using injectable oil-adjuvanted vaccines, we have previously shown that the induced level...... against A. salmonicida. The effect of immersion vaccination against A. salmonicida has been questioned over time. While some have presented excellent protection as a result of immersion vaccines, others have reported limited or absent protective effects. We have performed experiments on the protection...

  14. Mechanisms of injury and protection in cells and tissues at low temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Mazur, P.

    1976-06-01

    The survival of frozen-thawed cells is importantly influenced by the cooling rate. In general, cells exhibit maximum survival at an intermediate cooling rate, the numerical value of which depends on the type of cell, the additive present, and the warming rate. Theory and experiment now strongly indicate that death at supraoptimal cooling rates is the result of the formation of intracellular ice crystals during cooling and their growth to damaging size during warming. The causes of death in cells cooled at suboptimal rates, on the other hand, are more complex and more uncertain. Although additives like glycerol and dimethyl sulfoxide do not protect against injury at supraoptimal rates, they are generally essential for the survival of slowly frozen mammalian cells. The two major theories of slow freezing injury predict that protection is chiefly a colligative effect and that it requires the presence of additive inside the cell as well as outside. The evidence of the colligative aspects of protection is conflicting. The evidence on the requirement for permeation is increasingly negative, a fact which suggests that to protect the whole cell it may be sufficient to protect the cell surface. Slow freezing injury appears due to a number of sequential events. The first may well be high electrolyte concentrations. Additives protect against these, but may themselves introduce other forms of injury, the most likely of which is osmotic shock.

  15. Innate heart regeneration: endogenous cellular sources and exogenous therapeutic amplification.

    Science.gov (United States)

    Malliaras, Konstantinos; Vakrou, Styliani; Kapelios, Chris J; Nanas, John N

    2016-11-01

    The -once viewed as heretical- concept of the adult mammalian heart as a dynamic organ capable of endogenous regeneration has recently gained traction. However, estimated rates of myocyte turnover vary wildly and the underlying mechanisms of cardiac plasticity remain controversial. It is still unclear whether the adult mammalian heart gives birth to new myocytes through proliferation of resident myocytes, through cardiomyogenic differentiation of endogenous progenitors or through both mechanisms. In this review, the authors discuss the cellular origins of postnatal mammalian cardiomyogenesis and touch upon therapeutic strategies that could potentially amplify innate cardiac regeneration. The adult mammalian heart harbors a limited but detectable capacity for spontaneous endogenous regeneration. During normal aging, proliferation of pre-existing cardiomyocytes is the dominant mechanism for generation of new cardiomyocytes. Following myocardial injury, myocyte proliferation increases modestly, but differentiation of endogenous progenitor cells appears to also contribute to cardiomyogenesis (although agreement on the latter point is not universal). Since cardiomyocyte deficiency underlies almost all types of heart disease, development of therapeutic strategies that amplify endogenous regeneration to a clinically-meaningful degree is of utmost importance.

  16. Therapeutic targeting strategies using endogenous cells and proteins.

    Science.gov (United States)

    Parayath, Neha N; Amiji, Mansoor M

    2017-07-28

    Targeted drug delivery has become extremely important in enhancing efficacy and reducing the toxicity of therapeutics in the treatment of various disease conditions. Current approaches include passive targeting, which relies on naturally occurring differences between healthy and diseased tissues, and active targeting, which utilizes various ligands that can recognize targets expressed preferentially at the diseased site. Clinical translation of these mechanisms faces many challenges including the immunogenic and toxic effects of these non-natural systems. Thus, use of endogenous targeting systems is increasingly gaining momentum. This review is focused on strategies for employing endogenous moieties, which could serve as safe and efficient carriers for targeted drug delivery. The first part of the review involves cells and cellular components as endogenous carriers for therapeutics in multiple disease states, while the second part discusses the use of endogenous plasma components as endogenous carriers. Further understanding of the biological tropism with cells and proteins and the newer generation of delivery strategies that exploits these endogenous approaches promises to provide better solutions for site-specific delivery and could further facilitate clinical translations. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Controlled hydrostatic pressure stress downregulates the expression of ribosomal genes in preimplantation embryos: a possible protection mechanism?

    Science.gov (United States)

    Bock, I; Raveh-Amit, H; Losonczi, E; Carstea, A C; Feher, A; Mashayekhi, K; Matyas, S; Dinnyes, A; Pribenszky, C

    2016-04-01

    The efficiency of various assisted reproductive techniques can be improved by preconditioning the gametes and embryos with sublethal hydrostatic pressure treatment. However, the underlying molecular mechanism responsible for this protective effect remains unknown and requires further investigation. Here, we studied the effect of optimised hydrostatic pressure treatment on the global gene expression of mouse oocytes after embryonic genome activation. Based on a gene expression microarray analysis, a significant effect of treatment was observed in 4-cell embryos derived from treated oocytes, revealing a transcriptional footprint of hydrostatic pressure-affected genes. Functional analysis identified numerous genes involved in protein synthesis that were downregulated in 4-cell embryos in response to hydrostatic pressure treatment, suggesting that regulation of translation has a major role in optimised hydrostatic pressure-induced stress tolerance. We present a comprehensive microarray analysis and further delineate a potential mechanism responsible for the protective effect of hydrostatic pressure treatment.

  18. Monopoly Insurance and Endogenous Information

    DEFF Research Database (Denmark)

    Lagerlöf, Johan N. M.; Schottmüller, Christoph

    2018-01-01

    We study a monopoly insurance model with endogenous information acquisi- tion. Through a continuous effort choice, consumers can determine the precision of a privately observed signal that is informative about their accident risk. The equilibrium effort is, depending on parameter values, either...

  19. Endogeneously arising network allocation rules

    NARCIS (Netherlands)

    Slikker, M.

    2006-01-01

    In this paper we study endogenously arising network allocation rules. We focus on three allocation rules: the Myerson value, the position value and the component-wise egalitarian solution. For any of these three rules we provide a characterization based on component efficiency and some balanced

  20. Endogenizing Prospect Theory's Reference Point

    OpenAIRE

    Ulrich Schmidt; Horst Zank

    2010-01-01

    In previous models of (cumulative) prospect theory reference-dependence of preferences is imposed beforehand and the location of the reference point is exogenously determined. This note provides a foundation of prospect theory, where reference-dependence is derived from preference conditions and a unique reference point arises endogenously.

  1. Human endogenous retroviruses in neurologic disease.

    Science.gov (United States)

    Christensen, Tove

    2016-01-01

    Endogenous retroviruses are pathogenic - in other species than the human. Disease associations for Human Endogenous RetroViruses (HERVs) are emerging, but so far an unequivocal pathogenetic cause-effect relationship has not been established. A role for HERVs has been proposed in neurological and neuropsychiatric diseases as diverse as multiple sclerosis (MS) and schizophrenia (SCZ). Particularly for MS, many aspects of the activation and involvement of specific HERV families (HERV-H/F and HERV-W/MSRV) have been reported, both for cells in the circulation and in the central nervous system. Notably envelope genes and their gene products (Envs) appear strongly associated with the disease. For SCZ, for ALS, and for HIV-associated dementia (HAD), indications are accumulating for involvement of the HERV-K family, and also HERV-H/F and/or HERV-W. Activation is reasonably a prerequisite for causality as most HERV sequences remain quiescent in non-pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, derepression, and also involvement of retroviral restriction factors, is emerging. HERV-directed antiretrovirals have potential as novel therapeutic paradigms in neurologic disease, particularly in MS. The possible protective or ameliorative effects of antiretroviral therapy in MS are substantiated by reports that treatment of HIV infection may be associated with a significantly decreased risk of MS. Further studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are essential. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  2. Variable versus conventional lung protective mechanical ventilation during open abdominal surgery: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Spieth, Peter M; Güldner, Andreas; Uhlig, Christopher; Bluth, Thomas; Kiss, Thomas; Schultz, Marcus J; Pelosi, Paolo; Koch, Thea; Gama de Abreu, Marcelo

    2014-05-02

    General anesthesia usually requires mechanical ventilation, which is traditionally accomplished with constant tidal volumes in volume- or pressure-controlled modes. Experimental studies suggest that the use of variable tidal volumes (variable ventilation) recruits lung tissue, improves pulmonary function and reduces systemic inflammatory response. However, it is currently not known whether patients undergoing open abdominal surgery might benefit from intraoperative variable ventilation. The PROtective VARiable ventilation trial ('PROVAR') is a single center, randomized controlled trial enrolling 50 patients who are planning for open abdominal surgery expected to last longer than 3 hours. PROVAR compares conventional (non-variable) lung protective ventilation (CV) with variable lung protective ventilation (VV) regarding pulmonary function and inflammatory response. The primary endpoint of the study is the forced vital capacity on the first postoperative day. Secondary endpoints include further lung function tests, plasma cytokine levels, spatial distribution of ventilation assessed by means of electrical impedance tomography and postoperative pulmonary complications. We hypothesize that VV improves lung function and reduces systemic inflammatory response compared to CV in patients receiving mechanical ventilation during general anesthesia for open abdominal surgery longer than 3 hours. PROVAR is the first randomized controlled trial aiming at intra- and postoperative effects of VV on lung function. This study may help to define the role of VV during general anesthesia requiring mechanical ventilation. Clinicaltrials.gov NCT01683578 (registered on September 3 3012).

  3. Endogenous fibrinolysis facilitates clot retraction in vivo.

    Science.gov (United States)

    Samson, Andre L; Alwis, Imala; Maclean, Jessica A A; Priyananda, Pramith; Hawkett, Brian; Schoenwaelder, Simone M; Jackson, Shaun P

    2017-12-07

    Clot retraction refers to the process whereby activated platelets transduce contractile forces onto the fibrin network of a thrombus, which over time increases clot density and decreases clot size. This process is considered important for promoting clot stability and maintaining blood vessel patency. Insights into the mechanisms regulating clot retraction at sites of vascular injury have been hampered by a paucity of in vivo experimental models. By pairing localized vascular injury with thrombin microinjection in the mesenteric circulation of mice, we have demonstrated that the fibrin network of thrombi progressively compacts over a 2-hour period. This was a genuine retraction process, as treating thrombi with blebbistatin to inhibit myosin IIa-mediated platelet contractility prevented shrinkage of the fibrin network. Real-time confocal analysis of fibrinolysis after recombinant tissue-type plasminogen activator (tPA) administration revealed that incomplete proteolysis of fibrin polymers markedly facilitated clot retraction. Similarly, inhibiting endogenous fibrinolysis with tranexamic acid reduced retraction of fibrin polymers in vivo. In vitro clot retraction experiments indicated that subthreshold doses of tPA facilitated clot retraction through a plasmin-dependent mechanism. These effects correlated with changes in the elastic modulus of fibrin clots. These findings define the endogenous fibrinolytic system as an important regulator of clot retraction, and show that promoting clot retraction is a novel and complementary means by which fibrinolytic enzymes can reduce thrombus size. © 2017 by The American Society of Hematology.

  4. Mechanical evaluation of hip pads to protect against fracture of elderly femurs in falls.

    Science.gov (United States)

    Tadano, Shigeru; Nakatsuchi, Hiroki; Goto, Naoko; Fujisaki, Kazuhiro; Nakatsuchi, Yukio

    2011-01-01

    Hip fracture in the aged easily occurs by falls and may cause these persons to become bedridden. Hip pads are effective in protecting hip fracture as they directly deflect and absorb the impact forces by falls. It is necessary for the material and the structure of hip pads to be designed to realize both high impact absorption and compliance (comfort during wearing). In this report, an impact testing system was developed to test the impact absorbing performance of hip pad with air cushions designed by the research group. The impact absorbing performance was evaluated by the impact load, collision time, and maximum load. To confirm the effectiveness in protecting against hip fracture, an impact force was applied to the greater trochanter of the human femur and the degree of fracture was measured by X-ray examination. As a result, the hip pad with air cushions had a high impact absorbing performance and was sufficiently effective to protect against hip fracture.

  5. Downregulation of Endogenous Hydrogen Sulfide Pathway Is Involved in Mitochondrion-Related Endothelial Cell Apoptosis Induced by High Salt

    Directory of Open Access Journals (Sweden)

    Yanfang Zong

    2015-01-01

    Full Text Available Background. The study aimed to investigate whether endogenous H2S pathway was involved in high-salt-stimulated mitochondria-related vascular endothelial cell (VEC apoptosis. Methods. Cultured human umbilical vein endothelial cells (HUVECs were used in the study. H2S content in the supernatant was detected. Western blot was used to detect expression of cystathionine gamma-lyase (CSE, cleaved-caspase-3, and mitochondrial and cytosolic cytochrome c (cytc. Fluorescent probes were used to quantitatively detect superoxide anion generation and measure the in situ superoxide anion generation in HUVEC. Mitochondrial membrane pore opening, mitochondrial membrane potential, and caspase-9 activities were measured. The cell apoptosis was detected by cell death ELISA and TdT-mediated dUTP nick end labeling (TUNEL methods. Results. High-salt treatment downregulated the endogenous VEC H2S/CSE pathway, in association with increased generation of oxygen free radicals, decreased mitochondrial membrane potential, enhanced the opening of mitochondrial membrane permeability transition pore and leakage of mitochondrial cytc, activated cytoplasmic caspase-9 and caspase-3 and subsequently induced VEC apoptosis. However, supplementation of H2S donor markedly inhibited VEC oxidative stress and mitochondria-related VEC apoptosis induced by high salt. Conclusion. H2S/CSE pathway is an important endogenous defensive system in endothelial cells antagonizing high-salt insult. The protective mechanisms for VEC damage might involve inhibiting oxidative stress and protecting mitochondrial injury.

  6. Mechanisms of radioprotection - a review

    International Nuclear Information System (INIS)

    Copeland, E.S.

    1978-01-01

    Theories of radiation protection can be considered at both the molecular and biochemical-physiological levels. Four molecular level protection hypotheses, radical scavenging, hydrogen transfer reactions, the mixed disulfide hypothesis and the endogenous non-protein sulfhydryl hypothesis, probably describe different aspects of the actual protection mechanism, although each has inconsistencies. At the biochemical-physiological level, hypothermia induction and biochemical shock may be involved in protection of the organism against radiation induced damage and death. It is most likely that no single mechanism can account for the protection offered by a radioprotective drug. Certain compounds may operate primarily by means of physiological effects resulting in hypoxia or hypothermia in critical tissues. Others may operate primarily by influencing the intrinsic radiosensitivity of target molecules by causing localized radical scavenging or by donating a hydrogen atom. Metabolic effects such as biochemical shock, release of endogenous non-protein sulfhydryls, induction of structural changes in target molecules or delay in DNA synthesis and cell division are also possible mechanisms for radioprotection. (author)

  7. Mechanism of pitting corrosion protection of metals and alloys in new-generation water treatment plants

    Directory of Open Access Journals (Sweden)

    Grachev Vladimir

    2017-01-01

    Full Text Available In this article authors set out a principle of pitting corrosion protection, suggested a new class of multilayer materials with high corrosion resistance. They substantiated the choice of the layers for the multilayer material designed for exploitation in oxidizing and non-oxidizing environment. The sphere of application of the multilyer materials was defined.

  8. L-Citrulline Protects Skeletal Muscle Cells from Cachectic Stimuli through an iNOS-Dependent Mechanism.

    Directory of Open Access Journals (Sweden)

    Daniel J Ham

    Full Text Available Dietary L-citrulline is thought to modulate muscle protein turnover by increasing L-arginine availability. To date, the direct effects of increased L-citrulline concentrations in muscle have been completely neglected. Therefore, we determined the role of L-citrulline in regulating cell size during catabolic conditions by depriving mature C2C12 myotubes of growth factors (serum free; SF or growth factors and nutrients (HEPES buffered saline; HBS. Cells were treated with L-citrulline or equimolar concentrations of L-arginine (positive control or L-alanine (negative control and changes in cell size and protein turnover were assessed. In myotubes incubated in HBS or SF media, L-citrulline improved rates of protein synthesis (HBS: +63%, SF: +37% and myotube diameter (HBS: +18%, SF: +29%. L-citrulline treatment substantially increased iNOS mRNA expression (SF: 350%, HBS: 750%. The general NOS inhibitor L-NAME and the iNOS specific inhibitor aminoguanidine prevented these effects in both models. Depriving myotubes in SF media of L-arginine or L-leucine, exacerbated wasting which was not attenuated by L-citrulline. The increased iNOS mRNA expression was temporally associated with increases in mRNA of the endogenous antioxidants SOD1, SOD3 and catalase. Furthermore, L-citrulline prevented inflammation (LPS and oxidative stress (H2O2 induced muscle cell wasting. In conclusion, we demonstrate a novel direct protective effect of L-citrulline on skeletal muscle cell size independent of L-arginine that is mediated through induction of the inducible NOS (iNOS isoform. This discovery of a nutritional modulator of iNOS mRNA expression in skeletal muscle cells could have substantial implications for the treatment of muscle wasting conditions.

  9. Cellular and Molecular Mechanisms in Perioperative Hepatic Protection: A Review of Current Interventions

    Directory of Open Access Journals (Sweden)

    Zahra Talebi

    2017-05-01

    Full Text Available Liver is one of the most important organs needing great concern during the perioperative period. There are a number of different mechanisms that interact with liver cells and might affect their integrity and cell live. Though these mechanisms are not all the same, there is a great common point: all affect the metabolic pathways of the liver. Ischemia, anesthetic drug effects and other perioperative insults may affect the liver. Disturbance in an organ’s blood flow is an inherent part of diverse surgical procedures, which leads to lack of oxygen and nutrient supply. These ischemic periods can be particularly long in case of liver surgeries, such as resection of large hepatic tumors, management of hepatic trauma and liver transplant. Once the blood flow and oxygen supply are restored, the interruption of blood flow affects the oxygen dependent cells in liver, which require mitochondrial oxidative phosphorylation for their metabolism. Molecular mechanisms such as Redox status, ionic interchange disturbances as well as different mediators and cells like KC, SEC, dendritic cells, leukocytes, and lymphocytes, are involved in the process ultimately leading to cell death by apoptosis and necrosis. This review provides an overview on the cellular and molecular mechanisms involved in liver injuries, categorizing these mechanisms in 3 different classes: preoperative mechanisms, intraoperative mechanisms and postoperative mechanisms. Each of them are discussed in a different part of the manuscript

  10. Endogenous opiates and behavior: 2014.

    Science.gov (United States)

    Bodnar, Richard J

    2016-01-01

    This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (endogenous opioids and receptors), and the roles of these opioid peptides and receptors in pain and analgesia (pain and analgesia); stress and social status (human studies); tolerance and dependence (opioid mediation of other analgesic responses); learning and memory (stress and social status); eating and drinking (stress-induced analgesia); alcohol and drugs of abuse (emotional responses in opioid-mediated behaviors); sexual activity and hormones, pregnancy, development and endocrinology (opioid involvement in stress response regulation); mental illness and mood (tolerance and dependence); seizures and neurologic disorders (learning and memory); electrical-related activity and neurophysiology (opiates and conditioned place preferences (CPP)); general activity and locomotion (eating and drinking); gastrointestinal, renal and hepatic functions (alcohol and drugs of abuse); cardiovascular responses (opiates and ethanol); respiration and thermoregulation (opiates and THC); and immunological responses (opiates and stimulants). This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular

  11. Preparation of UV-protective kefiran/nano-ZnO nanocomposites: physical and mechanical properties.

    Science.gov (United States)

    Shahabi-Ghahfarrokhi, Iman; Khodaiyan, Faramarz; Mousavi, Mohammad; Yousefi, Hossein

    2015-01-01

    In this study, we investigated the effect of ZnO nanoparticles (ZN) as a UV-protective agent of kefiran biopolymers. Our results showed that with increasing ZN content, the tensile strength, elongation at break, and tensile energy to break the kefiran film and nanocomposites also increased. Kefiran nanocomposites with a ZN content higher than 2% produced a UV-protective film with good visual properties, low sensibility to water, and low water-vapor permeability. The thermal properties of all specimens, analyzed by DSC, showed that the ZN content had a negative effect on Tg and a positive effect on nanocomposites' melting point. TEM, SEM micrography and XRD spectrum analysis confirmed the hypothesis that ZNs act like a ball bearing, making movement of kefiran chains easier and increasing elongation at break, while simultaneously decreasing the Tg of kefiran nanocomposites. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Ticuna traditional knowledge on chagra agriculture and innovative mechanisms for its protection

    Directory of Open Access Journals (Sweden)

    Luis Eduardo Acosta Muñoz

    2012-08-01

    Full Text Available The relationship of indigenous peoples to the global market is a reality and it sets strategies of appropriation of traditional knowledge, without any rule mediating the restitution of rights that knowledge holders have, while indigenous people are asking a sui generis system for protection and equitable participation in these markets. The paper presents the results of a participatory research carried out with Ticuna communities of the south of the Colombian Amazon, in the border with Brazil and Peru, in the upper part of the Amazon River. From the knowledge about the use and management of chagra agriculture, the research analyzes how the productive chain of manioc (Manihot esculenta Crantz is structured. It also explains how indigenous people discuss the intellectual property rights they have on it, and how the geographical indications and the collective trademarks can help to protect traditional knowledge associated to biodiversity.

  13. Investigation of a Potential Protective Mechanism Against Heparin-Induced Thrombocytopenia in Patients on Chronic Intermittent Hemodialysis

    Science.gov (United States)

    Tanhehco, Yvette C.; Cuker, Adam; Rudnick, Michael; Sachais, Bruce S.

    2015-01-01

    BACKGROUND Heparin-induced thrombocytopenia (HIT) develops as a result of platelet (PLT) activation by anti-platelet factor 4 (PF4)/heparin complex antibodies. Despite repeated exposure to heparin, patients undergoing chronic intermittent hemodialysis (HD) rarely develop HIT. We investigated the possibility that HD decreases/removes PF4 from PLT surfaces and/or plasma, thereby disfavoring immune complex formation as a mechanism of protection against HIT. MATERIALS AND METHODS We enrolled 20 patients undergoing chronic HD at the Penn Presbyterian Medical Center. Blood samples were drawn before, during and after treatment in the presence and absence of heparin. PF4, PF4/heparin antibody, heparin, and P-selectin levels were measured. RESULTS No patients demonstrated clinical symptoms of HIT. PLT surface PF4 levels decreased and plasma PF4 levels increased concurrently with increase in plasma heparin concentration. In the absence of heparin, PLT surface and plasma PF4 levels were unchanged. Anti-PF4/heparin antibodies, which were non-functional by the serotonin release assay, were detectable in 8 patients. PLT surface P-selectin levels did not change during treatment. CONCLUSIONS Removal of PLT surface and/or plasma PF4 as a mechanism of protection against HIT in patients undergoing HD is not supported by the results of our study, although the transient decrease in PLT surface PF4 in the presence of large amounts of heparin remains a candidate mechanism. The small sample size, single type of dialyzer membrane, and early sampling time points may have led to the inability to detect changes in PF4 levels. Future studies should explore other potential protective mechanisms. PMID:23305841

  14. Protection mechanisms and services for young workers in Central Asia and the European Union

    OpenAIRE

    Kulakhmetova, Anel

    2010-01-01

    The UN Convention on the rights of the child speaks not only about needs but about the rights of children from the moment of a birth. The Convention covers a wide scale of the rights consolidated in three basic categories: - The right to life, - The right for survival and development, - The right for protection and participation. The Convention provisions assume that children should live in the environment providing for realization of their rights starting from the right for a nam...

  15. Protection of cortical cells by equine estrogens against glutamate-induced excitotoxicity is mediated through a calcium independent mechanism

    Directory of Open Access Journals (Sweden)

    Perrella Joel

    2005-05-01

    Full Text Available Abstract Background High concentrations of glutamate can accumulate in the brain and may be involved in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease. This form of neurotoxicity involves changes in the regulation of cellular calcium (Ca2+ and generation of free radicals such as peroxynitrite (ONOO-. Estrogen may protect against glutamate-induced cell death by reducing the excitotoxic Ca2+ influx associated with glutamate excitotoxicity. In this study, the inhibition of N-methyl-D-aspartate (NMDA receptor and nitric oxide synthase (NOS along with the effect of 17β-estradiol (17β-E2 and a more potent antioxidant Δ8, 17β-estradiol (Δ8, 17β-E2 on cell viability and intracellular Ca2+ ([Ca2+]i, following treatment of rat cortical cells with glutamate, was investigated. Results Primary rat cortical cells were cultured for 7–12 days in Neurobasal medium containing B27 supplements. Addition of glutamate (200 μM decreased cell viability to 51.3 ± 0.7% compared to control. Treatment with the noncompetitive NMDAR antagonist, MK-801, and the NOS inhibitor, L-NAME, completely prevented cell death. Pretreatment (24 hrs with 17β-E2 and Δ8, 17β-E2 (0.01 to 10 μM significantly reduced cell death. 17β-E2 was more potent than Δ8, 17β-E2. Glutamate caused a rapid 2.5 fold increase in [Ca2+]i. Treatment with 0.001 to 10 μM MK-801 reduced the initial Ca2+ influx by 14–41% and increased cell viability significantly. Pretreatment with 17β-E2 and Δ8, 17β-E2 had no effect on Ca2+ influx but protected the cortical cells against glutamate-induced cell death. Conclusion Glutamate-induced cell death in cortical cultures can occur through NMDAR and NOS-linked mechanisms by increasing nitric oxide and ONOO-. Equine estrogens: 17β-E2 and Δ8, 17β-E2, significantly protected cortical cells against glutamate-induced excitotoxicity by a mechanism that appears to be independent of Ca2+ influx. To our knowledge, this is a first

  16. Engineered chitosan based nanomaterials: Bioactivities, mechanisms and perspectives in plant protection and growth.

    Science.gov (United States)

    Kumaraswamy, R V; Kumari, Sarita; Choudhary, Ram Chandra; Pal, Ajay; Raliya, Ramesh; Biswas, Pratim; Saharan, Vinod

    2018-07-01

    Excessive use of agrochemicals for enhancing crop production and its protection posed environmental and health concern. Integration of advanced technology is required to realize the concept of precision agriculture by minimizing the input of pesticides and fertilizers per unit while improving the crop productivity. Notably, chitosan based biodegradable nanomaterials (NMs) including nanoparticles, nanogels and nanocomposites have eventually proceeded as a key choice in agriculture due to their inimitable properties like antimicrobial and plant growth promoting activities. The foreseeable role of chitosan based NMs in plants might be in achieving sustainable plant growth through boosting the intrinsic potential of plants. In-spite of the fact that chitosan based NMs abode immense biological activities in plants, these materials have not yet been widely adopted in agriculture due to poor understanding of their bioactivity and modes of action towards pathogenic microbes and in plant protection and growth. To expedite the anticipated claims of chitosan based NMs, it is imperative to line up all the possible bioactivities which denote for sustainable agriculture. Herein, we have highlighted, in-depth, various chitosan based NMs which have been used in plant growth and protection mainly against fungi, bacteria and viruses and have also explained their modes of action. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Apoptosis induction by sennoside laxatives in man; escape from a protective mechanism during chronic sennoside use?

    NARCIS (Netherlands)

    van Gorkom, B A; Karrenbeld, A; van der Sluis, T; Zwart, N; de Vries, E G; Kleibeuker, J H

    Chronic sennoside use induces melanosis coli (MC) and possibly increases colorectal cancer risk. Sennosides alter colonic crypt length, proliferative activity, and bcl-2 expression 18 h after administration. To investigate possible mechanisms for carcinogenesis, the effects of acute sennoside use

  18. Details about Mechanism of Identification of Viruses by Microsoft Security Essentials (Microsoft Forefront Endpoint Protection

    Directory of Open Access Journals (Sweden)

    D. S. Silnov

    2012-12-01

    Full Text Available A special mechanism of signature method while detecting virus signatures in binary files is detected and researched. It has been found that antivirus Microsoft Secutiry Essentials does not detect viruses in digitally signed binary files.

  19. Understanding Key Mechanisms of Exercise-Induced Cardiac Protection to Mitigate Disease: Current Knowledge and Emerging Concepts.

    Science.gov (United States)

    Bernardo, Bianca C; Ooi, Jenny Y Y; Weeks, Kate L; Patterson, Natalie L; McMullen, Julie R

    2018-01-01

    The benefits of exercise on the heart are well recognized, and clinical studies have demonstrated that exercise is an intervention that can improve cardiac function in heart failure patients. This has led to significant research into understanding the key mechanisms responsible for exercise-induced cardiac protection. Here, we summarize molecular mechanisms that regulate exercise-induced cardiac myocyte growth and proliferation. We discuss in detail the effects of exercise on other cardiac cells, organelles, and systems that have received less or little attention and require further investigation. This includes cardiac excitation and contraction, mitochondrial adaptations, cellular stress responses to promote survival (heat shock response, ubiquitin-proteasome system, autophagy-lysosomal system, endoplasmic reticulum unfolded protein response, DNA damage response), extracellular matrix, inflammatory response, and organ-to-organ crosstalk. We summarize therapeutic strategies targeting known regulators of exercise-induced protection and the challenges translating findings from bench to bedside. We conclude that technological advancements that allow for in-depth profiling of the genome, transcriptome, proteome and metabolome, combined with animal and human studies, provide new opportunities for comprehensively defining the signaling and regulatory aspects of cell/organelle functions that underpin the protective properties of exercise. This is likely to lead to the identification of novel biomarkers and therapeutic targets for heart disease.

  20. Study of the mechanical properties of single- layer and multi-layer metallic coatings with protective-decorative applications

    Directory of Open Access Journals (Sweden)

    Cherneva Sabina

    2018-01-01

    Full Text Available Single thin coating of matt nickel (Nimat, a mirror bright copper (Cubright, a mirror bright nickel (Nibright and their combinations were electrochemically deposited on brass substrate with thickness 500 μm. The basic aim was electrodeposition of two-layer Cubright/Nimat and Nibright/Cubright systems, and three-layer Nibright Cubrigh/Nimat system, which are among the most widely applied protective and decorative systems in light and medium operating conditions of corrosion. The thicknesses of the obtained films varied from 1 μm to 3.25 μm. They were investigated via nanoindentation experiments, in order to characterize their basic physical and mechanical characteristics, related with their good adhesion and corrosion protective ability, as well as ensuring the integrity of the system “protective coating/substrate” to possible mechanical, dynamic and/or thermal stresses. As a result, load-displacement curves were obtained and indentation hardness and indentation modulus were calculated using the Oliver & Pharr approximation method. The dependence of the indentation modulus and the indentation hardness on the depth of the indentation, surface morphology and structure of the obtained coatings, their texture and surface roughness were investigated too. The obtained results showed that the three-layer Nibright/Cubright /Niimat/CuZn37 system has highest indentation modulus and indentation hardness, following by two-layer Nibright/Cubright system and single layer coatings.

  1. Endogenous scheduling preferences and congestion

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Small, Kenneth

    2017-01-01

    We consider the timing of activities through a dynamic model of commuting with congestion, in which workers care solely about leisure and consumption. Implicit preferences for the timing of the commute form endogenously due to temporal agglomeration economies. Equilibrium exists uniquely and is i......We consider the timing of activities through a dynamic model of commuting with congestion, in which workers care solely about leisure and consumption. Implicit preferences for the timing of the commute form endogenously due to temporal agglomeration economies. Equilibrium exists uniquely...... and is indistinguishable from that of a generalized version of the classical Vickrey bottleneck model, based on exogenous trip-timing preferences, but optimal policies differ: the Vickrey model will misstate the benefits of a capacity increase, it will underpredict the benefits of congestion pricing, and pricing may make...

  2. Exogenic and endogenic Europa minerals

    Science.gov (United States)

    Maynard-Casely, H. E.; Brand, H. E. A.; Wilson, S. A.

    2016-12-01

    The Galileo Near Infrared Mapping Spectrometer (NIMS) identified a significant `non-ice' component upon the surface of Jupiter's moon Europa. Current explanations invoke both endogenic and exogenic origins for this material. It has long been suggested that magnesium and sodium sulfate minerals could have leached from the rock below a putative ocean (endogenic) 1 and that sulfuric acid hydrate minerals could have been radiologically produced from ionised sulfur originally from Io's volcanoes (exogenic) 2. However, a more recent theory proposes that the `non-ice' component could be radiation damaged NaCl leached from Europa's speculative ocean 3. What if the minerals are actually from combination of both endogenic and exogenic sources? To investigate this possibility we have focused on discovering new minerals that might form in the combination of the latter two cases, that is a mixture of leached sulfates hydrates with radiologically produced sulfuric acid. To this end we have explored a number of solutions in the MgSO4-H2SO4-H2O and Na2SO4-H2SO4-H2O systems, between 80 and 280 K with synchrotron x-ray powder diffraction. We report a number of new materials formed in this these ternary systems. This suggests that it should be considered that the `non-ice' component of the Europa's surface could be a material derived from endogenic and exogenic components. 1 Kargel, J. S. Brine volcanism and the interior structures of asteroids and icy satellites. Icarus 94, 368-390 (1991). 2 Carlson, R. W., Anderson, M. S., Mehlman, R. & Johnson, R. E. Distribution of hydrate on Europa: Further evidence for sulfuric acid hydrate. Icarus 177, 461-471, doi:10.1016/j.icarus.2005.03.026 (2005). 3 Hand, K. P. & Carlson, R. W. Europa's surface color suggests an ocean rich with sodium chloride. Geophysical Research Letters, 2015GL063559, doi:10.1002/2015gl063559 (2015).

  3. Money, banks and endogenous volatility

    OpenAIRE

    Pere Gomis-Porqueras

    2000-01-01

    In this paper I consider a monetary growth model in which banks provide liquidity, and the government fixes a constant rate of money creation. There are two underlying assets in the economy, money and capital. Money is dominated in rate of return. In contrast to other papers with a larger set of government liabilities, I find a unique equilibrium when agents' risk aversion is moderate. However, indeterminacies and endogenous volatility can be observed when agents are relatively risk averse.

  4. Protective role of Nrf2 against mechanical-stretch-induced apoptosis in mouse fibroblasts: a potential therapeutic target of mechanical-trauma-induced stress urinary incontinence.

    Science.gov (United States)

    Li, Qiannan; Li, Bingshu; Liu, Cheng; Wang, Linlin; Tang, Jianming; Hong, Li

    2018-01-10

    We investigated the protective effect and underlying molecular mechanism of nuclear factor-E2-related factor 2 (Nrf2) against mechanical-stretch-induced apoptosis in mouse fibroblasts. Normal cells, Nrf2 silencing cells, and Nrf2 overexpressing cells were respectively divided into two groups-nonintervention and cyclic mechanical strain (CMS)-subjected to CMS of 5333 μ (1.0 Hz for 4 h), six groups in total (control, CMS, shNfe212, shNfe212 + CMS, LV-shNfe212, and LV-shNfe212 + CMS). After treatment, cell apoptosis; cell-cycle distribution; expressions of Nrf2, Bax, Bcl-2, Cyt-C, caspase-3, caspase-9, cleaved-caspase-3, and cleaved-caspase-9; mitochondrial membrane potential (ΔΨm); reactive oxygen species (ROS); and malondialdehyde (MDA) levels were measured. Thirty virgin female C57BL/6 mice were divided into two groups: control (without intervention) and vaginal distension (VD) groups, which underwent VD for 1 h with an 8-mm dilator (0.3 ml saline). Leak-point pressure (LPP) was tested on day 7 after VD; Nrf2 expression, apoptosis, and MDA levels were then measured in urethra and anterior vaginal wall. Mechanical stretch decreased Nrf2 messenger RNA (mRNA) and protein expressions. Overexpression of Nrf2 alleviated mechanical-stretch-induced cell apoptosis; S-phase arrest of cell cycle; up-regulation of Bax, cytochrome C (Cyt-C), ROS, MDA, ratio of cleaved-caspase-3/caspase-3 and cleaved-caspase-9/caspase-9; and exacerbated the decrease of Bcl2 and ΔΨm in L929 cells. On the contrary, silencing of Nrf2 showed opposite effects. Besides, VD reduced LPP levels and Nrf2 expression and increased cell apoptosis and MDA generation in the urethra and anterior vaginal wall. Nrf2 exhibits a protective role against mechanical-stretch -induced apoptosis on mouse fibroblasts, which might indicate a potential therapeutic target of mechanical-trauma-induced stress urinary incontinence (SUI).

  5. REFERENCE MODELS OF ENDOGENOUS ECONOMIC GROWTH

    OpenAIRE

    GEAMĂNU MARINELA

    2012-01-01

    The new endogenous growth theories are a very important research area for shaping the most effective policies and long term sustainable development strategies. Endogenous growth theory has emerged as a reaction to the imperfections of neoclassical theory, by the fact that the economic growth is the endogenous product of an economical system.

  6. Endogenous Cortical Oscillations Constrain Neuromodulation by Weak Electric Fields

    Science.gov (United States)

    Schmidt, Stephen L.; Iyengar, Apoorva K.; Foulser, A. Alban; Boyle, Michael R.; Fröhlich, Flavio

    2014-01-01

    Background Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation modality that may modulate cognition by enhancing endogenous neocortical oscillations with the application of sine-wave electric fields. Yet, the role of endogenous network activity in enabling and shaping the effects of tACS has remained unclear. Objective We combined optogenetic stimulation and multichannel slice electrophysiology to elucidate how the effect of weak sine-wave electric field depends on the ongoing cortical oscillatory activity. We hypothesized that the structure of the response to stimulation depended on matching the stimulation frequency to the endogenous cortical oscillation. Methods We studied the effect of weak sine-wave electric fields on oscillatory activity in mouse neocortical slices. Optogenetic control of the network activity enabled the generation of in vivo like cortical oscillations for studying the temporal relationship between network activity and sine-wave electric field stimulation. Results Weak electric fields enhanced endogenous oscillations but failed to induce a frequency shift of the ongoing oscillation for stimulation frequencies that were not matched to the endogenous oscillation. This constraint on the effect of electric field stimulation imposed by endogenous network dynamics was limited to the case of weak electric fields targeting in vivo-like network dynamics. Together, these results suggest that the key mechanism of tACS may be enhancing but not overriding of intrinsic network dynamics. Conclusion Our results contribute to understanding the inconsistent tACS results from human studies and propose that stimulation precisely adjusted in frequency to the endogenous oscillations is key to rational design of non-invasive brain stimulation paradigms. PMID:25129402

  7. Multi-spectral endogenous fluorescence imaging for bacterial differentiation

    Science.gov (United States)

    Chernomyrdin, Nikita V.; Babayants, Margarita V.; Korotkov, Oleg V.; Kudrin, Konstantin G.; Rimskaya, Elena N.; Shikunova, Irina A.; Kurlov, Vladimir N.; Cherkasova, Olga P.; Komandin, Gennady A.; Reshetov, Igor V.; Zaytsev, Kirill I.

    2017-07-01

    In this paper, the multi-spectral endogenous fluorescence imaging was implemented for bacterial differentiation. The fluorescence imaging was performed using a digital camera equipped with a set of visual bandpass filters. Narrowband 365 nm ultraviolet radiation passed through a beam homogenizer was used to excite the sample fluorescence. In order to increase a signal-to-noise ratio and suppress a non-fluorescence background in images, the intensity of the UV excitation was modulated using a mechanical chopper. The principal components were introduced for differentiating the samples of bacteria based on the multi-spectral endogenous fluorescence images.

  8. Endogenous opioids regulate moment-to-moment neuronal communication and excitability

    Science.gov (United States)

    Winters, Bryony L.; Gregoriou, Gabrielle C.; Kissiwaa, Sarah A.; Wells, Oliver A.; Medagoda, Danashi I.; Hermes, Sam M.; Burford, Neil T.; Alt, Andrew; Aicher, Sue A.; Bagley, Elena E.

    2017-01-01

    Fear and emotional learning are modulated by endogenous opioids but the cellular basis for this is unknown. The intercalated cells (ITCs) gate amygdala output and thus regulate the fear response. Here we find endogenous opioids are released by synaptic stimulation to act via two distinct mechanisms within the main ITC cluster. Endogenously released opioids inhibit glutamate release through the δ-opioid receptor (DOR), an effect potentiated by a DOR-positive allosteric modulator. Postsynaptically, the opioids activate a potassium conductance through the μ-opioid receptor (MOR), suggesting for the first time that endogenously released opioids directly regulate neuronal excitability. Ultrastructural localization of endogenous ligands support these functional findings. This study demonstrates a new role for endogenously released opioids as neuromodulators engaged by synaptic activity to regulate moment-to-moment neuronal communication and excitability. These distinct actions through MOR and DOR may underlie the opposing effect of these receptor systems on anxiety and fear. PMID:28327612

  9. Do high sound pressure levels of crowing in roosters necessitate passive mechanisms for protection against self-vocalization?

    Science.gov (United States)

    Claes, Raf; Muyshondt, Pieter G G; Dirckx, Joris J J; Aerts, Peter

    2018-02-01

    High sound pressure levels (>120dB) cause damage or death of the hair cells of the inner ear, hence causing hearing loss. Vocalization differences are present between hens and roosters. Crowing in roosters is reported to produce sound pressure levels of 100dB measured at a distance of 1m. In this study we measured the sound pressure levels that exist at the entrance of the outer ear canal. We hypothesize that roosters may benefit from a passive protective mechanism while hens do not require such a mechanism. Audio recordings at the level of the entrance of the outer ear canal of crowing roosters, made in this study, indeed show that a protective mechanism is needed as sound pressure levels can reach amplitudes of 142.3dB. Audio recordings made at varying distances from the crowing rooster show that at a distance of 0.5m sound pressure levels already drop to 102dB. Micro-CT scans of a rooster and chicken head show that in roosters the auditory canal closes when the beak is opened. In hens the diameter of the auditory canal only narrows but does not close completely. A morphological difference between the sexes in shape of a bursa-like slit which occurs in the outer ear canal causes the outer ear canal to close in roosters but not in hens. Copyright © 2017 Elsevier GmbH. All rights reserved.

  10. Comparison of usual and alternative methods to measure height in mechanically ventilated patients: potential impact on protective ventilation.

    Science.gov (United States)

    Bojmehrani, Azadeh; Bergeron-Duchesne, Maude; Bouchard, Carmelle; Simard, Serge; Bouchard, Pierre-Alexandre; Vanderschuren, Abel; L'Her, Erwan; Lellouche, François

    2014-07-01

    Protective ventilation implementation requires the calculation of predicted body weight (PBW), determined by a formula based on gender and height. Consequently, height inaccuracy may be a limiting factor to correctly set tidal volumes. The objective of this study was to evaluate the accuracy of different methods in measuring heights in mechanically ventilated patients. Before cardiac surgery, actual height was measured with a height gauge while subjects were standing upright (reference method); the height was also estimated by alternative methods based on lower leg and forearm measurements. After cardiac surgery, upon ICU admission, a subject's height was visually estimated by a clinician and then measured with a tape measure while the subject was supine and undergoing mechanical ventilation. One hundred subjects (75 men, 25 women) were prospectively included. Mean PBW was 61.0 ± 9.7 kg, and mean actual weight was 30.3% higher. In comparison with the reference method, estimating the height visually and using the tape measure were less accurate than both lower leg and forearm measurements. Errors above 10% in calculating the PBW were present in 25 and 40 subjects when the tape measure or visual estimation of height was used in the formula, respectively. With lower leg and forearm measurements, 15 subjects had errors above 10% (P bedridden patients on mechanical ventilation. Alternative methods based on lower leg and forearm measurements are potentially interesting solutions to facilitate the accurate application of protective ventilation. Copyright © 2014 by Daedalus Enterprises.

  11. Fat or lean: adjustment of endogenous energy stores to predictable and unpredictable changes in allostatic load

    Science.gov (United States)

    Schultner, Jannik; Kitaysky, Alexander S.; Welcker, Jorg; Hatch, Scott

    2013-01-01

    1. The ability to store energy endogenously is an important ecological mechanism that allows animals to buffer predictable and unpredictable variation in allostatic load. The secretion of glucocorticoids, which reflects changes in allostatic load, is suggested to play a major role in the adjustment of endogenous stores to these varying conditions.

  12. Melatonin in Children with Autism Spectrum Disorders: Endogenous and Pharmacokinetic Profiles in Relation to Sleep

    Science.gov (United States)

    Goldman, Suzanne E.; Adkins, Karen W.; Calcutt, M. Wade; Carter, Melissa D.; Goodpaster, Robert L.; Wang, Lily; Shi, Yaping; Burgess, Helen J.; Hachey, David L.; Malow, Beth A.

    2014-01-01

    Supplemental melatonin has been used to treat sleep onset insomnia in children with autism spectrum disorders (ASD), although the mechanism of action is uncertain. We assessed endogenous and supplemental melatonin profiles in relation to sleep in nine children with ASD. In endogenous samples, maximal melatonin concentration (C[subscript max]) and…

  13. Corrosion protection of metals by phosphate coatings and ecologically beneficial alternatives. Properties and mechanisms

    International Nuclear Information System (INIS)

    Weng Duan.

    1995-01-01

    The corrosion and protection characteristics of inorganic zinc and manganese phosphate coatings in aqueous solution have been examined by physical methods, accelerated corrosion tests and electrochemical polarization and impedance measurements. Some water-soluble organic films have been evaluated for the temporary protection of metal parts as the ecologically beneficial alternatives to phosphate coatings. The results show that zinc phosphate is a better insulator than manganese phosphate, but the porosity of the former is inferior to that of the latter. In neutral and alkaline solutions the anodic current of both zinc and manganese phosphates decreases and their open potential moves in a positive direction. In acidic medium both the polarization current and the open potential are close to those of the substrate. Confirmed by the impedance measurements, the corrosion of phosphated steel in acidic solution is controlled by a dissolution reaction, in neutral medium is first reaction controlled then diffusion controlled, and in alkaline environment only diffusion controlled. The insulation of acrylate+copolymer, epoxy and inhibitor+bonding materials is superior to that of zinc or manganese phosphates. In general, most of the alternatives can afford a better temporary protection for metal parts compared to inorganic phosphate coatings. The corrosion failure of inorganic phosphate coatings is mainly induced by the electrochemical dissolution of the substrate. This electrochemical process initiates at the bottom of the pores within the coating. In neutral solution, the hydrolysis of corrosion products decrease the pH value of the solution in the anodic zone, resulting in an acidic dissolution of phosphate coatings. At the same time, the depolarization of oxygen increases the pH value in the cathodic zone, causing an alkaline hydrolysis of phosphates. (author) figs., tabs., 149 refs

  14. Effect of N-protecting compound ammonium bicarbonate and its mechanism

    International Nuclear Information System (INIS)

    Guo Zhifen; Zeng Hanting; Huang Min; Tu Shuxin; Wen Xianfang

    2004-01-01

    A kind of N-protecting compound ammonium bicarbonate fertilizer was created. Compared with common ammonium bicarbonate, the fertilizer can raise nitrogen use efficiency by 5.2%-15% and reduce ammonia loss due to volatilization by 5%-12%. Yields of rice and cotton were raised by 5%-10% and 6%-20%, respectively. And it also has the following characteristics, such as hard lump not be formed, easy to use, less bad smell caused by ammonia, reducing of production cost, etc. Demonstration of applying this fertilizer to cotton and rice in more than 13.3 hm 2 showed good effect on increasing crop yield

  15. Protecting DNA from errors and damage: an overview of DNA repair mechanisms in plants compared to mammals.

    Science.gov (United States)

    Spampinato, Claudia P

    2017-05-01

    The genome integrity of all organisms is constantly threatened by replication errors and DNA damage arising from endogenous and exogenous sources. Such base pair anomalies must be accurately repaired to prevent mutagenesis and/or lethality. Thus, it is not surprising that cells have evolved multiple and partially overlapping DNA repair pathways to correct specific types of DNA errors and lesions. Great progress in unraveling these repair mechanisms at the molecular level has been made by several talented researchers, among them Tomas Lindahl, Aziz Sancar, and Paul Modrich, all three Nobel laureates in Chemistry for 2015. Much of this knowledge comes from studies performed in bacteria, yeast, and mammals and has impacted research in plant systems. Two plant features should be mentioned. Plants differ from higher eukaryotes in that they lack a reserve germline and cannot avoid environmental stresses. Therefore, plants have evolved different strategies to sustain genome fidelity through generations and continuous exposure to genotoxic stresses. These strategies include the presence of unique or multiple paralogous genes with partially overlapping DNA repair activities. Yet, in spite (or because) of these differences, plants, especially Arabidopsis thaliana, can be used as a model organism for functional studies. Some advantages of this model system are worth mentioning: short life cycle, availability of both homozygous and heterozygous lines for many genes, plant transformation techniques, tissue culture methods and reporter systems for gene expression and function studies. Here, I provide a current understanding of DNA repair genes in plants, with a special focus on A. thaliana. It is expected that this review will be a valuable resource for future functional studies in the DNA repair field, both in plants and animals.

  16. A review of protective factors and causal mechanisms that enhance the mental health of Indigenous Circumpolar youth.

    Science.gov (United States)

    MacDonald, Joanna Petrasek; Ford, James D; Willox, Ashlee Cunsolo; Ross, Nancy A

    2013-12-09

    To review the protective factors and causal mechanisms which promote and enhance Indigenous youth mental health in the Circumpolar North. A systematic literature review of peer-reviewed English-language research was conducted to systematically examine the protective factors and causal mechanisms which promote and enhance Indigenous youth mental health in the Circumpolar North. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with elements of a realist review. From 160 records identified in the initial search of 3 databases, 15 met the inclusion criteria and were retained for full review. Data were extracted using a codebook to organize and synthesize relevant information from the articles. More than 40 protective factors at the individual, family, and community levels were identified as enhancing Indigenous youth mental health. These included practicing and holding traditional knowledge and skills, the desire to be useful and to contribute meaningfully to one's community, having positive role models, and believing in one's self. Broadly, protective factors at the family and community levels were identified as positively creating and impacting one's social environment, which interacts with factors at the individual level to enhance resilience. An emphasis on the roles of cultural and land-based activities, history, and language, as well as on the importance of social and family supports, also emerged throughout the literature. More than 40 protective factors at the individual, family, and community levels were identified as enhancing Indigenous youth mental health. These included practicing and holding traditional knowledge and skills, the desire to be useful and to contribute meaningfully to one's community, having positive role models, and believing in one's self. Broadly, protective factors at the family and community levels were identified as positively creating and impacting one's social

  17. Mechanism of protection of transepithelial barrier function by Lactobacillus salivarius: strain dependence and attenuation by bacteriocin production.

    Science.gov (United States)

    Miyauchi, Eiji; O'Callaghan, John; Buttó, Ludovica F; Hurley, Gráinne; Melgar, Silvia; Tanabe, Soichi; Shanahan, Fergus; Nally, Kenneth; O'Toole, Paul W

    2012-11-01

    Enhanced barrier function is one mechanism whereby commensals and probiotic bacteria limit translocation of foreign antigens or pathogens in the gut. However, barrier protection is not exhibited by all probiotic or commensals and the strain-specific molecules involved remain to be clarified. We evaluated the effects of 33 individual Lactobacillus salivarius strains on the hydrogen peroxide (H(2)O(2))-induced barrier impairment in human epithelial Caco-2 cells. These strains showed markedly different effects on H(2)O(2)-induced reduction in transepithelial resistance (TER). The effective strains such as UCC118 and CCUG38008 attenuated H(2)O(2)-induced disassembly and relocalization of tight junction proteins, but the ineffective strain AH43324 did not. Strains UCC118 and CCUG38008 induced phosphorylation of extracellular signal-regulated kinase (ERK) in Caco-2 cells, and the ERK inhibitor U0126 attenuated the barrier-protecting effect of these strains. In contrast, the AH43324 strain induced phosphorylation of Akt and p38, which was associated with an absence of a protective effect. Global transcriptome analysis of UCC118 and AH43324 revealed that some genes in a bacteriocin gene cluster were upregulated in AH43324 under TER assay conditions. A bacteriocin-negative UCC118 mutant displayed significantly greater suppressive effect on H(2)O(2)-induced reduction in TER compared with wild-type UCC118. The wild-type strain augmented H(2)O(2)-induced phosphorylation of Akt and p38, whereas a bacteriocin-negative UCC118 mutant did not. These observations indicate that L. salivarius strains are widely divergent in their capacity for barrier protection, and this is underpinned by differences in the activation of intracellular signaling pathways. Furthermore, bacteriocin production appears to have an attenuating influence on lactobacillus-mediated barrier protection.

  18. Physics basis and mechanical design of the actively cooled duct scraper protection for the JET neutral beam enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, D.J. [UKAEA Fusion/Euratom Association, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom)], E-mail: dwilson@jet.uk; Ciric, D.; Cox, S.J.; Jones, T.T.C.; Kovari, M. [UKAEA Fusion/Euratom Association, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom); Li Puma, A. [Association EURATOM-CEA, CEA-Cadarache, 13108 St. Paul-Lez-Durance (France); Martin, D.; Milnes, J.; Shannon, M.; Surrey, E. [UKAEA Fusion/Euratom Association, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom)

    2007-10-15

    The objectives of the JET neutral beam enhancement (NBE) include raising the delivered power from the present 25 MW to more than 34 MW and increasing the pulse length from 10 to 20 s. The additional power will be obtained partly by increasing the fractional energy components of the beam, resulting from acceleration of molecular ions, hence increasing the total particle flux. These changes place extreme demands on the design of the upgraded protection to the torus entry duct. The present inertial duct protection already reaches its thermomechanical limit in 10 s pulses, and active cooling of the upgraded duct protection is therefore essential. Extensive analysis of the pressure and temperature evolution in the present un-cooled duct established the relationship between gas re-emission and surface temperature for copper in this operating environment. This information was used in an integrated physics and engineering approach to the design of the actively cooled duct protection, taking into account the power loads from direct beam interception and re-ionisation. Surface temperature determines power density through the gas re-emission and consequential beam re-ionisation. These considerations define the normal operating point for the chosen enhanced hypervapotron element technology. This approach demonstrated that supplementary in situ duct cryopumping would not be needed, provided that the required heat-transfer performance could be met without any encroachment of the elements beyond the space envelope of the existing inertial duct protection plates. This requirement posed severe constraints on the mechanical design of the hypervapotron element array and its manifolding; the adopted engineering design solutions are presented.

  19. Piperine Enhances the Protective Effect of Curcumin Against 3-NP Induced Neurotoxicity: Possible Neurotransmitters Modulation Mechanism.

    Science.gov (United States)

    Singh, Shamsher; Jamwal, Sumit; Kumar, Puneet

    2015-08-01

    3-Nitropropionic acid (3-NP) is a fungal toxin well established model used for inducing symptoms of Huntington's disease. Curcumin a natural polyphenol has been reported to possess neuroprotective activity by decreasing oxidative stress. The aim of present study was to investigate neuroprotective effect of curcumin with piperine (bioavailability enhancer) against 3-NP induced neurotoxicity in rats. Administration of 3-NP (10 mg/kg for 21 days) showed loss in body weight, declined motor function and changes in biochemical (LPO, nitrite and glutathione level), neuroinflammatory (TNF-α and IL-1β level) and neurochemical (DA, NE, 5-HT, DOPAC, 5-HIAA and HVA). Chronic treatment with curcumin (25 and 50 mg/kg) and curcumin (25 mg/kg) with piperine (2.5 mg/kg) once daily for 21 days prior to 3-NP administration. All the behavioral parameters were studied at 1st, 7th, 14th, and 21st day. On 22nd day all the animals was scarified and striatum was separated. Curcumin alone and combination (25 mg/kg) with piperine (2.5 mg/kg) showed beneficial effect against 3-NP induced motor deficit, biochemical and neurochemical abnormalities in rats. Piperine (2.5 mg/kg) with curcumin (25 mg/kg) significantly enhances its protective effect as compared with curcumin alone treated group. The results of the present study indicate that protective effect of curcumin potentiated in the presence of piperine (bioavailability enhancer) against 3-NP-induced behavioral and molecular alteration.

  20. Legal Statement on Investment Protection and Investor-State Dispute Settlement Mechanisms in TTIP and CETA

    DEFF Research Database (Denmark)

    Savin, Andrej; Trzaskowski, Jan

    2016-01-01

    the fundamental legal issues within these mechanisms and explains how they pose grave threats to public interest, democratic principles and state budgets. Authors: Prof. Anneli Albi, University of Kent Prof. Diamond Ashiagbor, University of London Prof. Dr. Antoine Bailleux, Université Saint-Louis – Bruxelles Dr...

  1. Insulator-protected mechanically controlled break junctions for measuring single-molecule conductance in aqueous environments

    NARCIS (Netherlands)

    Muthusubramanian, N.; Galan, E.; Maity, C.; Eelkema, R.; Grozema, F.C.; van der Zant, H.S.J.

    2016-01-01

    We present a method to fabricate insulated gold mechanically controlled break junctions (MCBJ) by coating the metal with a thin layer of aluminum oxide using plasma enhanced atomic layer deposition. The Al2O3 thickness deposited on the MCBJ devices was varied from 2 to 15 nm

  2. Endogenous versus Exogenous Growth Factor Regulation of Articular Chondrocytes

    Science.gov (United States)

    Shi, Shuiliang; Chan, Albert G.; Mercer, Scott; Eckert, George J.; Trippel, Stephen B.

    2014-01-01

    Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-ß1 stimulated these reparative functions, while endogenous TGF-ß1 had little effect. Endogenous TGF-ß1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-ß1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. PMID:24105960

  3. Endogenous Cartilage Repair by Recruitment of Stem Cells.

    Science.gov (United States)

    Im, Gun-Il

    2016-04-01

    Articular cartilage has a very limited capacity for repair after injury. The adult body has a pool of stem cells that are mobilized during injury or disease. These cells exist inside niches in bone marrow, muscle, adipose tissue, synovium, and other connective tissues. A method that mobilizes this endogenous pool of stem cells will provide a less costly and less invasive alternative if these cells successfully regenerate defective cartilage. Traditional microfracture procedures employ the concept of bone marrow stimulation to regenerate cartilage. However, the regenerated tissue usually is fibrous cartilage, which has very poor mechanical properties compared to those of normal hyaline cartilage. A method that directs the migration of a large number of autologous mesenchymal stem cells toward injury sites, retains these cells around the defects, and induces chondrogenic differentiation that would enhance success of endogenous cartilage repair. This review briefly summarizes chemokines and growth factors that induce recruitment, proliferation, and differentiation of endogenous progenitor cells, endogenous cell sources for regenerating cartilage, scaffolds for delivery of bioactive factors, and bioadhesive materials that are necessary to bring about endogenous cartilage repair.

  4. Endogenous versus exogenous growth factor regulation of articular chondrocytes.

    Science.gov (United States)

    Shi, Shuiliang; Chan, Albert G; Mercer, Scott; Eckert, George J; Trippel, Stephen B

    2014-01-01

    Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-β1 stimulated these reparative functions, while endogenous TGF-β1 had little effect. Endogenous TGF-β1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-β1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. Published 2013 by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. This article is a U.S. Government work and is in the public domain in the USA.

  5. On the origins of endogenous thoughts.

    Science.gov (United States)

    Tillas, Alexandros

    2017-05-01

    Endogenous thoughts are thoughts that we activate in a top-down manner or in the absence of the appropriate stimuli. We use endogenous thoughts to plan or recall past events. In this sense, endogenous thinking is one of the hallmarks of our cognitive lives. In this paper, I investigate how it is that we come to possess endogenous control over our thoughts. Starting from the close relation between language and thinking, I look into speech production-a process motorically controlled by the inferior frontal gyrus (IFG). Interestingly, IFG is also closely related to silent talking, as well as volition. The connection between IFG and volition is important given that endogenous thoughts are or at least greatly resemble voluntary actions. Against this background, I argue that IFG is key to understanding the origins of conscious endogenous thoughts. Furthermore, I look into goal-directed thinking and show that IFG plays a key role also in unconscious endogenous thinking.

  6. Protection of type 316 austenitic stainless steel from intergranular stress corrosion cracking by thermo-mechanical treatment

    International Nuclear Information System (INIS)

    Kiuchi, Kiyoshi; Tsuji, Hirokazu; Kondo, Tatsuo

    1980-03-01

    Thermomechanical treatment that causes carbide stabilizing aging of cold worked material followed by recrystallization heating made standard stainless steels highly resistant to intergranular corrosion and stress corrosion cracking in different test environments. After a typical thermal history of simulated welding, several IGSCC susceptibility tests were made. The results showed that the treatment was successful in type 316 steel in wide range of conditions, while type 304 was protected only to a small extent even by closely controlled treatment. Response of the materials to the sensitizing heating in terms of impurity segregation at grain boundaries was also examined by means of microchemical analysis. Advantage of method is that no special care is required in selecting heats of material, so that conventional type 316 is usable by improving the mechanical properties substantially through the treatment. In some optimized cases the mechanical property improvement was typically recognized by the yield strength by about 20% higher at room temperature, compared with the material mill annealed. (author)

  7. Adaptive mechanisms of insect pests against plant protease inhibitors and future prospects related to crop protection: a review.

    Science.gov (United States)

    Macedo, Maria L R; de Oliveira, Caio F R; Costa, Poliene M; Castelhano, Elaine C; Silva-Filho, Marcio C

    2015-01-01

    The overwhelming demand for food requires the application of technology on field. An important issue that limits the productivity of crops is related to insect attacks. Hence, several studies have evaluated the application of different compounds to reduce the field losses, especially insecticide compounds from plant sources. Among them, plant protease inhibitors (PIs) have been studied in both basic and applied researches, displaying positive results in control of some insects. However, certain species are able to bypass the insecticide effects exerted by PIs. In this review, we disclosed the adaptive mechanisms showed by lepidopteran and coleopteran insects, the most expressive insect orders related to crop predation. The structural aspects involved in adaptation mechanisms are presented as well as the newest alternatives for pest control. The application of biotechnological tools in crop protection will be mandatory in agriculture, and it will be up to researchers to find the best candidates for effective control in long-term.

  8. Resveratrol plays important role in protective mechanisms in renal disease - mini-review

    Directory of Open Access Journals (Sweden)

    Guilherme Albertoni

    2015-03-01

    Full Text Available Resveratrol (RESV is a polyphenolic compound found in various plants, including grapes, berries and peanuts, and its processed foods as red wine. RESV possesses a variety of bioactivities, including antioxidant, anti-inflammatory, cardioprotective, antidiabetic, anticancer, chemopreventive, neuroprotective, renal lipotoxicity preventative, and renal protective effects. Numerous studies have demonstrated that polyphenols promote cardiovascular health. Furthermore, RESV can ameliorate several types of renal injury in animal models, including diabetic nephropathy, hyperuricemic, drug-induced injury, aldosterone-induced injury, ischemia-reperfusion injury, sepsis-related injury, and endothelial dysfunction. In addition, RESV can prevent the increase in vasoconstrictors, such as angiotensin II (AII and endothelin-1 (ET-1, as well as intracellular calcium, in mesangial cells. Together, these findings suggest a potential role for RESV as a supplemental therapy for the prevention of renal injury.

  9. Regular tobacco use among American Indian and Alaska native adolescents: an examination of protective mechanisms.

    Science.gov (United States)

    Osilla, Karen Chan; Lonczak, Heather S; Mail, Patricia D; Larimer, Mary E; Marlatt, G Alan

    2007-01-01

    American Indian and Alaska Native (AIAN) adolescents use tobacco at earlier ages and in larger quantities compared to non-AIAN peers. Regular tobacco use was examined against five protective factors (peer networks supportive of not using drugs, college aspirations, team sports, playing music, and volunteerism). Participants consisted of 112 adolescents between the ages of 13 and 19 who participated in a study testing the efficacy of a life-skills program aimed at reducing substance-related consequences. Findings indicated that, with the exception of prosocial peer networks and volunteerism, each of the above factors was significantly associated with a reduced probability of being a regular tobacco user. Gender differences were notable. These results hold important treatment implications regarding the reduction and prevention of tobacco use among AIAN youth.

  10. Fundamental roles of reactive oxygen species and protective mechanisms in the female reproductive system

    Directory of Open Access Journals (Sweden)

    Okada Futoshi

    2005-09-01

    Full Text Available Abstract Controlled oxidation, such as disulfide bond formation in sperm nuclei and during ovulation, plays a fundamental role in mammalian reproduction. Excess oxidation, however, causes oxidative stress, resulting in the dysfunction of the reproductive process. Antioxidation reactions that reduce the levels of reactive oxygen species are of prime importance in reproductive systems in maintaining the quality of gametes and support reproduction. While anti-oxidative enzymes, such as superoxide dismutase and peroxidase, play a central role in eliminating oxidative stress, reduction-oxidation (redox systems, comprised of mainly glutathione and thioredoxin, function to reduce the levels of oxidized molecules. Aldo-keto reductase, using NADPH as an electron donor, detoxifies carbonyl compounds resulting from the oxidation of lipids and proteins. Thus, many antioxidative and redox enzyme genes are expressed and aggressively protect gametes and embryos in reproductive systems.

  11. Cortex proliferation in the root is a protective mechanism against abiotic stress.

    Science.gov (United States)

    Cui, Hongchang

    2015-01-01

    Although as an organ the root plays a pivotal role in nutrient and water uptake as well anchorage, individual cell types function distinctly. Cortex is regarded as the least differentiated cell type in the root, but little is known about its role in plant growth and physiology. In recent studies, we found that cortex proliferation can be induced by oxidative stress. Since all types of abiotic stress lead to oxidative stress, this finding suggests a role for cortex in coping with abiotic stress. This hypothesis was tested in this study using the spy mutant, which has an extra layer of cortex in the root. Interestingly, the spy mutant was shown to be hypersensitive to salt and oxidizing reagent applied to the leaves, but it was as tolerant as the wild type to these compounds in the soil. This result lends support to the notion that cortex has a protective role against abiotic stress arising from the soil.

  12. Resveratrol influences platinum pharmacokinetics: A novel mechanism in protection against cisplatin-induced nephrotoxicity.

    Science.gov (United States)

    Darwish, Mostafa A; Abo-Youssef, Amira M; Khalaf, Marwa M; Abo-Saif, Ali A; Saleh, Ibrahim G; Abdelghany, Tamer M

    2018-06-15

    Cisplatin (CP) is a widely used drug in treatment of solid tumors. However, the use of CP was hampered by its serious side effects especially nephrotoxicity. This study aims to investigate the effect of resveratrol (RES) on CP-induced nephrotoxicity, particularly, the effect of RES on CP pharmacokinetics (PKs). Male white albino rats were divided to four group's six rats each. The first group received (1%) tween 80 in normal saline and served as control. The second group received RES (30 mg kg -1 ) per day for 14 consecutive day's i.p. The third and fourth groups were given a single i.p. injection of CP (6 mg kg -1 ) with or without pre-treatment of RES (30 mg kg -1 per day for 14 consecutive days), respectively. Following administration of CP, plasma, urine and kidney platinum concentration were monitored to study PKs of CP. Five days after the CP injection, rats were killed; blood samples were collected; kidneys were dissected; and biochemical, immunohistochemical, and histological examinations were performed. Our results revealed that CP treatment significantly deteriorated kidney functions with subsequent alteration in redox balance of the kidney. On the other hand, RES successfully ameliorated CP-induced kidney injury and recovered normal kidney tissue redox status. Importantly, while RES pre-treatment did not significantly alter the plasma CP level, it dramatically decreased the urine concentration of CP and lowered its accumulation into the kidneys. Moreover, it increased CP plasma half-life (t 1/2 ) with subsequent decrease in its elimination rate constant, indicating an important role of PKs modulation in RES protection against CP-induced renal damage. Taken together, RES may protect the kidney tissue from the deleterious effects of CP through constringe of CP renal accumulation and enhancement of CP-induced oxidative stress. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Protective Mechanism of STAT3-siRNA on Cerebral Ischemia Injury

    Science.gov (United States)

    He, Jinting; Yang, Le; Liang, Wenzhao

    2018-01-01

    Nerve cells in ischemic brain injury will occur a series of complex signal transduction pathway changes and produce the corresponding biological function, thus affecting the central nervous system functionally different cells in the ischemic brain injury metabolism, division, Differentiation and death process, while changes in signal pathways also play an important role in the repair process of the post-ischemic nervous system. JAK/STAT pathway and vascular lesions have some relevance, but its exact mechanism after cerebral ischemia is not yet fully understood. This study is intended to further explore the JAK / STAT pathway in the functional site of STAT3 in neuronal ischemia Hypoxic injury and related molecular mechanisms, targeting these targets design intervention strategies to block the signal pathway, in order to provide a theoretical basis for the treatment of ischemic brain damage in this pathway.

  14. Brown algae overproduce cell wall polysaccharides as a protection mechanism against the heavy metal toxicity

    International Nuclear Information System (INIS)

    Andrade, Leonardo R.; Leal, Raquel N.; Noseda, Miguel; Duarte, Maria Eugenia R.; Pereira, Mariana S.; Mourao, Paulo A.S.; Farina, Marcos; Amado Filho, Gilberto M.

    2010-01-01

    Brown algae are often used as heavy metal biomonitors and biosorbents because they can accumulate high concentrations of metals. Cation-exchange performed by cell wall polysaccharides is pointed out as the main chemical mechanism for the metal sequestration. Here, we biochemically investigated if the brown alga Padina gymnospora living in a heavy metal contaminated area would modify their polysaccharidic content. We exposed non-living biomass to Cd and Pb and studied the metals adsorption and localization. We found that raw dried polysaccharides, sulfate groups, uronic acids, fucose, mannose, and galactose were significantly higher in contaminated algae compared with the control ones. Metal concentrations adsorbed by non-living biomass were rising comparatively to the tested concentrations. Electron microscopy showed numerous granules in the cell walls and X-ray microanalysis revealed Cd as the main element. We concluded that P. gymnospora overproduces cell wall polysaccharides when exposed to high metal concentrations as a defense mechanism.

  15. Mechanisms of resistance to quinolones: target alterations, decreased accumulation and DNA gyrase protection.

    Science.gov (United States)

    Ruiz, Joaquim

    2003-05-01

    Quinolones are broad-spectrum antibacterial agents, commonly used in both clinical and veterinary medicine. Their extensive use has resulted in bacteria rapidly developing resistance to these agents. Two mechanisms of quinolone resistance have been established to date: alterations in the targets of quinolones, and decreased accumulation due to impermeability of the membrane and/or an overexpression of efflux pump systems. Recently, mobile elements have also been described, carrying the qnr gene, which confers resistance to quinolones.

  16. Insulator-protected mechanically controlled break junctions for measuring single-molecule conductance in aqueous environments

    OpenAIRE

    Muthusubramanian, N.; Galan, E.; Maity, C.; Eelkema, R.; Grozema, F.C.; van der Zant, H.S.J.

    2016-01-01

    We present a method to fabricate insulated gold mechanically controlled break junctions (MCBJ) by coating the metal with a thin layer of aluminum oxide using plasma enhanced atomic layer deposition. The Al2O3 thickness deposited on the MCBJ devices was varied from 2 to 15 nm to test the suppression of leakage currents in deionized water and phosphate buffered saline. Junctions coated with a 15 nm thick oxide layer yielded atomically sharp electrodes and negligible conductance counts in the ra...

  17. Public Procurement of Innovation as Endogenous

    DEFF Research Database (Denmark)

    Rolfstam, Max

    Public procurement used as an innovation policy instrument has attracted attention the last decade. It has been argued that public procurement can be used to stimulate innovation from the demand-side. This paper problematizes ‘demand’ understood as a problem defined by a public procurer given...... to potential suppliers to solve. By drawing on a cross-case analysis of two similar projects the paper attempts to explicate an understanding of the role of public procurement of innovation not primarily as a ‘demand-side innovation instrument’, as such thinking might run the risk of ignoring important...... underlying mechanisms critical for success. Instead the paper views public procurement of innovation as an instrument of endogenous- exogenous knowledge conversion....

  18. Transfer of endogenous pyrogens across artificial membranes?

    Science.gov (United States)

    Lonnemann, G; Linnenweber, S; Burg, M; Koch, K M

    1998-05-01

    Synthetic high-flux dialyzer membranes used in continuous veno-venous hemofiltration are permeable to middle molecular size endogenous pyrogens, the pro-inflammatory cytokines IL-1 beta and TNF-alpha. The quantities removed by sieving are, however, negligible in vitro as well as in vivo. Adsorption of cytokines to the membrane polymer is the major mechanism of pyrogen removal. Adsorption seems to be semispecific for pro-inflammatory cytokines because levels of anti-inflammatory mediators were not changed or even increased during CVVH. Thus, CVVH may change cytokine profiles in septic patients supporting the predominance of anti-inflammatory over pro-inflammatory activity in plasma. It remains to be demonstrated whether modifications of extracorporeal blood purification systems (high-volume CVVH, plasma separation + adsorption) are able to amplify the change in cytokine profiles and whether this change influences outcome of septic patients.

  19. Synergy of multi-scale toughening and protective mechanisms at hierarchical branch-stem interfaces

    Science.gov (United States)

    Müller, Ulrich; Gindl-Altmutter, Wolfgang; Konnerth, Johannes; Maier, Günther A.; Keckes, Jozef

    2015-09-01

    Biological materials possess a variety of artful interfaces whose size and properties are adapted to their hierarchical levels and functional requirements. Bone, nacre, and wood exhibit an impressive fracture resistance based mainly on small crystallite size, interface organic adhesives and hierarchical microstructure. Currently, little is known about mechanical concepts in macroscopic biological interfaces like the branch-stem junction with estimated 1014 instances on earth and sizes up to few meters. Here we demonstrate that the crack growth in the upper region of the branch-stem interface of conifer trees proceeds along a narrow predefined region of transversally loaded tracheids, denoted as sacrificial tissue, which fail upon critical bending moments on the branch. The specific arrangement of the tracheids allows disconnecting the overloaded branch from the stem in a controlled way by maintaining the stem integrity. The interface microstructure based on the sharply adjusted cell orientation and cell helical angle secures a zig-zag crack propagation path, mechanical interlock closing after the bending moment is removed, crack gap bridging and self-repairing by resin deposition. The multi-scale synergetic concepts allows for a controllable crack growth between stiff stem and flexible branch, as well as mechanical tree integrity, intact physiological functions and recovery after the cracking.

  20. Ni-P/Zn-Ni compositionally modulated multilayer coatings - Part 2: Corrosion and protection mechanisms

    Science.gov (United States)

    Bahadormanesh, Behrouz; Ghorbani, Mohammad

    2018-06-01

    The Ni-P/Zn-Ni compositionally modulated multilayer coatings CMMCs were electrodeposited from a single bath by switching the deposition current density. The corrosion resistance of the deposits was studied and compared with that of monolayers of Ni-P and Zn-Ni alloys via Tafel polarization, EIS and salt spray tests. Characterization of corrosion products by means of EDS and XRD revealed more details from the corrosion mechanism of the monolayers and multilayers. The corrosion current density of Ni-P/Zn-Ni CMMCs were around one tenth of Zn-Ni monolayer. The CMMC with incomplete layers performed lower polarization resistance and higher corrosion current density compared to the CMMC with complete layers. The electrical circuit that was proposed for modeling the corrosion process based on the EIS spectrum, proved that layering reduces the porosity and consequently improves the barrier properties. Although, layering of Zn-Ni layers with Ni-P deposits increased the time to red rust in salt spray test, the time for white rust formation decreased. The corrosion mechanism of both Zn-Ni and Ni-P (containing small amount of Zn) was preferential dissolution of Zn and the corrosion products were comprised of mainly Zn hydroxychloride and Zn hydroxycarbonate. Also, Ni and P did not take part in the corrosion products. Based on the electrochemical character of the layers and the morphology of the corroded surface, the corrosion mechanism of multilayers was discussed.

  1. A novel mechanical design of broken rope protection device for enhancing the safety performances of overhead manned equipment in coal mine

    Directory of Open Access Journals (Sweden)

    Xiaoguang Zhang

    2015-08-01

    Full Text Available A novel mechanical design of the broken rope protection device is proposed to enhance the safety performances of the overhead manned equipment. According to the operating characteristics and functional requirements of the overhead manned equipment, a three-dimensional mechanical model of the broken rope protection device was redesigned. Based on the known parameters of the mechanical model, the stress and strength of the main components are readjusted using the statics characteristics of finite element analysis. To ensure the reliability of the control system of the broken rope protection device, the process of people’s falling, the response performance of the tension sensor, and the signal extraction of the broken rope are analyzed under different loading and unloading speeds. The working principle of the broken rope protection device is expounded in detail. The experimental results showed that better effect is obtained by the new broken rope protection device, which is characterized by good durability, low investment, and high reliability.

  2. Cognitive and Neuroplasticity Mechanisms by Which Congenital or Early Blindness May Confer a Protective Effect Against Schizophrenia

    Science.gov (United States)

    Silverstein, Steven M.; Wang, Yushi; Keane, Brian P.

    2013-01-01

    Several authors have noted that there are no reported cases of people with schizophrenia who were born blind or who developed blindness shortly after birth, suggesting that congenital or early (C/E) blindness may serve as a protective factor against schizophrenia. By what mechanisms might this effect operate? Here, we hypothesize that C/E blindness offers protection by strengthening cognitive functions whose impairment characterizes schizophrenia, and by constraining cognitive processes that exhibit excessive flexibility in schizophrenia. After briefly summarizing evidence that schizophrenia is fundamentally a cognitive disorder, we review areas of perceptual and cognitive function that are both impaired in the illness and augmented in C/E blindness, as compared to healthy sighted individuals. We next discuss: (1) the role of neuroplasticity in driving these cognitive changes in C/E blindness; (2) evidence that C/E blindness does not confer protective effects against other mental disorders; and (3) evidence that other forms of C/E sensory loss (e.g., deafness) do not reduce the risk of schizophrenia. We conclude by discussing implications of these data for designing cognitive training interventions to reduce schizophrenia-related cognitive impairment, and perhaps to reduce the likelihood of the development of the disorder itself. PMID:23349646

  3. Cognitive and Neuroplasticity Mechanisms By Which Congenital or Early Blindness May Confer a Protective Effect Against Schizophrenia

    Directory of Open Access Journals (Sweden)

    Steven eSilverstein

    2013-01-01

    Full Text Available Several authors have noted that there are no reported cases of people with schizophrenia who were born blind or who developed blindness shortly after birth, suggesting that congenital or early (C/E blindness may serve as a protective factor against schizophrenia. By what mechanisms might this effect operate? Here, we hypothesize that C/E blindness offers protection by strengthening cognitive functions whose impairment characterizes schizophrenia, and by constraining cognitive processes that exhibit excessive flexibility in schizophrenia. After briefly summarizing evidence that schizophrenia is fundamentally a cognitive disorder, we review areas of perceptual and cognitive function that are both impaired in the illness and augmented in C/E blindness, as compared to healthy sighted individuals. We next discuss: 1 the role of neuroplasticity in driving these cognitive changes in C/E blindness; 2 evidence that C/E blindness does not confer protective effects against other mental disorders; and 3 evidence that other forms of C/E sensory loss (e.g., deafness do not reduce the risk of schizophrenia. We conclude by discussing implications of these data for designing cognitive training interventions to reduce schizophrenia-related cognitive impairment, and perhaps to reduce the likelihood of the development of the disorder itself.

  4. Endogenous scheduling preferences and congestion

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Small, Kenneth

    2010-01-01

    and leisure, but agglomeration economies at home and at work lead to scheduling preferences forming endogenously. Using bottleneck congestion technology, we obtain an equilibrium queuing pattern consistent with a general version of the Vickrey bottleneck model. However, the policy implications are different....... Compared to the predictions of an analyst observing untolled equilibrium and taking scheduling preferences as exogenous, we find that both the optimal capacity and the marginal external cost of congestion have changed. The benefits of tolling are greater, and the optimal time varying toll is different....

  5. Endogenous money, circuits and financialization

    OpenAIRE

    Malcolm Sawyer

    2013-01-01

    This paper locates the endogenous money approach in a circuitist framework. It argues for the significance of the credit creation process for the evolution of the economy and the absence of any notion of ‘neutrality of money’. Clearing banks are distinguished from other financial institutions as the providers of initial finance in a circuit whereas other financial institutions operate in a final finance circuit. Financialization is here viewed in terms of the growth of financial assets an...

  6. In Vivo Sub-chronic Treatment with Dichlorvos in Young Rats Promotes Synaptic Plasticity and Learning by a Mechanism that Involves Acylpeptide Hydrolase Instead of Acetylcholinesterase Inhibition. Correlation with Endogenous β-Amyloid Levels

    Directory of Open Access Journals (Sweden)

    Gonzalo García-Rojo

    2017-07-01

    Full Text Available Acylpeptide hydrolase (APEH is a serine hydrolase that displays two catalytic activities, acting both as an exopeptidase toward short N-acylated peptides and as an endopeptidase toward oxidized peptides or proteins. It has been demonstrated that this enzyme can degrade monomers, dimers, and trimers of the Aβ1-40 peptide in the conditioned media of neuroblastoma cells. In a previous report, we showed that the specific inhibition of this enzyme by the organophosphate molecule dichlorvos (DDVP triggers an enhancement of long-term potentiation in rat hippocampal slices. In this study, we demonstrate that the same effect can be accomplished in vivo by sub-chronic treatment of young rats with a low dose of DDVP (0.1 mg/kg. Besides exhibiting a significant enhancement of LTP, the treated animals also showed improvements in parameters of spatial learning and memory. Interestingly, higher doses of DDVP such as 2 mg/kg did not prove to be beneficial for synaptic plasticity or behavior. Due to the fact that at 2 mg/kg we observed inhibition of both APEH and acetylcholinesterase, we interpret that in order to achieve positive effects on the measured parameters only APEH inhibition should be obtained. The treatment with both DDVP doses produced an increase in the endogenous concentration of Aβ1-40, although this was statistically significant only at the dose of 0.1 mg/kg. We propose that APEH represents an interesting pharmacological target for cognitive enhancement, acting through the modulation of the endogenous concentration of Aβ1-40.

  7. Protective effect of ciliary neurotrophic factor (CNTF) in a model of endotoxic shock: action mechanisms and role of CNTF receptor alpha.

    Science.gov (United States)

    Demitri, M T; Benigni, F; Meazza, C; Zinetti, M; Fratelli, M; Villa, P; Acheson, A; Panayotatos, N; Ghezzi, P

    1998-01-01

    Ciliary neurotrophic factor (CNTF) inhibits the production of tumor necrosis factor (TNF) in lipopolysaccharide (LPS)-treated mice and protects against LPS lethality when coadministered with its soluble receptor (sCNTFR alpha). Both of these activities are abolished in adrenalectomized (ADX) mice. LPS-induced pulmonary polymorphonuclear neutrophil (PMN) infiltration and nitric oxide (NO) production were also inhibited by CNTF + sCNTFR alpha but not by CNTF alone. sCNTFR alpha did not alter the clearance or tissue distribution of CNTF. Furthermore, CNTF variants coadministered with sCNTFR alpha protected against LPS toxicity in a manner related to their affinity for the beta components of CNTFR. Thus, inhibition of TNF production and protection against LPS lethality by CNTF/sCNTFR alpha require an intact hypothalamus-pituitary-adrenal axis (HPAA) and may be mediated by endogenous glucocorticoids. This protective effect is, at least in part, due to the inhibition of PMN infiltration and NO production, and appears to be mediated by cells displaying only beta-receptor subtypes.

  8. Intraoperative Protective Mechanical Ventilation for Prevention of Postoperative Pulmonary Complications A Comprehensive Review of the Role of Tidal Volume, Positive End-expiratory Pressure, and Lung Recruitment Maneuvers

    NARCIS (Netherlands)

    Güldner, Andreas; Kiss, Thomas; Serpa Neto, Ary; Hemmes, Sabrine N. T.; Canet, Jaume; Spieth, Peter M.; Rocco, Patricia R. M.; Schultz, Marcus J.; Pelosi, Paolo; Gama de Abreu, Marcelo

    2015-01-01

    Postoperative pulmonary complications are associated with increased morbidity, length of hospital stay, and mortality after major surgery. Intraoperative lung-protective mechanical ventilation has the potential to reduce the incidence of postoperative pulmonary complications. This review discusses

  9. Intra-operative protective mechanical ventilation in lung transplantation: a randomised, controlled trial.

    Science.gov (United States)

    Verbeek, G L; Myles, P S; Westall, G P; Lin, E; Hastings, S L; Marasco, S F; Jaffar, J; Meehan, A C

    2017-08-01

    Primary graft dysfunction occurs in up to 25% of patients after lung transplantation. Contributing factors include ventilator-induced lung injury, cardiopulmonary bypass, ischaemia-reperfusion injury and excessive fluid administration. We evaluated the feasibility, safety and efficacy of an open-lung protective ventilation strategy aimed at reducing ventilator-induced lung injury. We enrolled adult patients scheduled to undergo bilateral sequential lung transplantation, and randomly assigned them to either a control group (volume-controlled ventilation with 5 cmH 2 O, positive end-expiratory pressure, low tidal volumes (two-lung ventilation 6 ml.kg -1 , one-lung ventilation 4 ml.kg -1 )) or an alveolar recruitment group (regular step-wise positive end-expiratory pressure-based alveolar recruitment manoeuvres, pressure-controlled ventilation set at 16 cmH 2 O with 10 cmH 2 O positive end-expiratory pressure). Ventilation strategies were commenced from reperfusion of the first lung allograft and continued for the duration of surgery. Regular PaO 2 /F I O 2 ratios were calculated and venous blood samples collected for inflammatory marker evaluation during the procedure and for the first 24 h of intensive care stay. The primary end-point was the PaO 2 /F I O 2 ratio at 24 h after first lung reperfusion. Thirty adult patients were studied. The primary outcome was not different between groups (mean (SD) PaO 2 /F I O 2 ratio control group 340 (111) vs. alveolar recruitment group 404 (153); adjusted p = 0.26). Patients in the control group had poorer mean (SD) PaO 2 /F I O 2 ratios at the end of the surgical procedure and a longer median (IQR [range]) time to tracheal extubation compared with the alveolar recruitment group (308 (144) vs. 402 (154) (p = 0.03) and 18 (10-27 [5-468]) h vs. 15 (11-36 [5-115]) h (p = 0.01), respectively). An open-lung protective ventilation strategy during surgery for lung transplantation is feasible, safe and achieves favourable

  10. Protective effect of total flavones of Abelmoschus manihot L. Medic against poststroke depression injury in mice and its action mechanism.

    Science.gov (United States)

    Liu, Mei; Jiang, Qiu-Hong; Hao, Ji-Li; Zhou, Lan-Lan

    2009-03-01

    Total flavones of Abelmoschus manihot L. Medic (TFA) is the major active component isolated from the traditional Chinese herb Abelmoschus manihot L. Medic. We investigated the protective effect of TFA against poststroke depression (PSD) injury in mice and its action mechanism. A mouse model of PSD was induced by middle cerebral artery occlusion (MACO) 30 min/reperfusion, followed by isolation feeding and chronic unpredictable mild stress for 2 weeks. Treatment groups received TFA at three different doses (160, 80, and 40 mg/kg, p.o.) or fluoxetine (Flu, 2.5 mg/kg, p.o.) daily for 24 days. Change in behavior, brain tissue malondialdehyde (MDA) levels, and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured. The expression of brain-derived neurotrophic factor (BDNF) was detected by immunohistochemistry, and mRNA expression of BDNF and cAMP response element-binding protein (CREB) analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Treatment with TFA (160, 80, and 40 mg/kg) significantly ameliorated mice escape-directed behavioral impairment induced by PSD, markedly reduced MDA levels, and increased the activity of SOD, GSH-Px close to normal levels. TFA administration also attenuated PSD-induced neuronal death/losses, upregulated expression of BDNF both at mRNA and protein levels, as well as CREB mRNA levels. TFA had a protective effect against PSD injury in mice. Cardioprotection involves the inhibition of lipid peroxidation and upregulation of BDNF-CREB levels in the hippocampus, which may also be important mechanism of its antidepressants. This potential protection makes TFA a promising therapeutic agent for the PSD. (c) 2009 Wiley-Liss, Inc.

  11. The Current State of the System of Mechanisms of Realisation and Protection of the Rights of the Child: Conceptual and Legal Aspects

    Science.gov (United States)

    Drozdova, Alexandra Michailowna; Gulakova, Violetta Yurevna; Ivanchenko, Elena Anatolevna; Lesnichenko, Inna Pavlovna; Tereshchenko, Elena Anatolevna

    2016-01-01

    The article is devoted to the analytical understanding of the problems in the field of realisation and protection of the rights of children in Russia to identify and highlight existing problems in order to try to remove shortcomings and embark on further development and improvement of the legal and social mechanisms for the protection of…

  12. Cisplatin and doxorubicin induce distinct mechanisms of ovarian follicle loss; imatinib provides selective protection only against cisplatin.

    Directory of Open Access Journals (Sweden)

    Stephanie Morgan

    Full Text Available Chemotherapy treatment in premenopausal women has been linked to ovarian follicle loss and premature ovarian failure; the exact mechanism by which this occurs is uncertain. Here, two commonly used chemotherapeutic agents (cisplatin and doxorubicin were added to a mouse ovary culture system, to compare the sequence of events that leads to germ cell loss. The ability of imatinib mesylate to protect the ovary against cisplatin or doxorubicin-induced ovarian damage was also examined.Newborn mouse ovaries were cultured for a total of six days, exposed to a chemotherapeutic agent on the second day: this allowed for the examination of the earliest stages of follicle development. Cleaved PARP and TUNEL were used to assess apoptosis following drug treatment. Imatinib was added to cultures with cisplatin and doxorubicin to determine any protective effect.Histological analysis of ovaries treated with cisplatin showed oocyte-specific damage; in comparison doxorubicin preferentially caused damage to the granulosa cells. Cleaved PARP expression significantly increased for cisplatin (16 fold, p<0.001 and doxorubicin (3 fold, p<0.01. TUNEL staining gave little evidence of primordial follicle damage with either drug. Imatinib had a significant protective effect against cisplatin-induced follicle damage (p<0.01 but not against doxorubicin treatment.Cisplatin and doxorubicin both induced ovarian damage, but in a markedly different pattern, with imatinib protecting the ovary against damage by cisplatin but not doxorubicin. Any treatment designed to block the effects of chemotherapeutic agents on the ovary may need to be specific to the drug(s the patient is exposed to.

  13. Protective mechanisms against oxidative stress and angiopathy in young patients with diabetes type 1 (DM1).

    Science.gov (United States)

    Koutroumani, Nikolitsa; Partsalaki, Ioanna; Lamari, Fotini; Dettoraki, Athina; Gil, Andrea Paola Rojas; Karvela, Alexia; Kostopoulou, Eirini; Spiliotis, Bessie E

    2013-01-01

    Advanced glycation end-products (AGEs) via their receptor, RAGE, are involved in diabetic angiopathy. Soluble RAGE, an inhibitor of this axis, is formed by enzymatic catalysis (sRAGE) or alternative splicing (esRAGE). Malondialdehyde (MDA) is an oxidative stress marker, and ferric reducing ability of plasma (FRAP) is an anti-oxidant capacity marker. In isolated mononuclear blood cells from 110 DM1-patients (P) and 124 controls (C) (4-29 years) RAGE mRNA (g) and protein expression (pe) were measured by RT-PCR and Western immunoblotting, respectively. Plasma levels of CML (AGEs) and sRAGE were measured by ELISA, MDA by flurometry and FRAP according to 'Benzie and Strain'. P showed: (i) higher g of RAGE, especially in p>13 years of age and >5 years DM1, (ii) increased pe of esRAGE in DM1>5 years and (iii) increased FRAP and MDA. The increased esRAGE and FRAP with increased levels of CML and MDA possibly reflects a protective response against the formation of diabetic complications in these young diabetic patients.

  14. Magnetization pinning in modulated nanowires: from topological protection to the "corkscrew" mechanism.

    Science.gov (United States)

    Fernandez-Roldan, Jose Angel; Perez Del Real, Rafael; Bran, Cristina; Vazquez, Manuel; Chubykalo-Fesenko, Oksana

    2018-03-29

    Diameter-modulated nanowires offer an important paradigm to design the magnetization response of 3D magnetic nanostructures by engineering the domain wall pinning. With the aim to understand its nature and to control the process, we analyze the magnetization response in FeCo periodically modulated polycrystalline nanowires varying the minor segment diameter. Our modelling indicates a very complex behavior with a strong dependence on the disorder distribution and an important role of topologically non-trivial magnetization structures. We demonstrate that modulated nanowires with a small diameter difference are characterized by an increased coercive field in comparison to the straight ones, which is explained by a formation of topologically protected walls formed by two 3D skyrmions with opposite chiralities. For a large diameter difference we report the occurrence of a novel pinning type called here the "corkscrew": the magnetization of the large diameter segment forms a skyrmion tube with a core position in a helical modulation along the nanowire. This structure is pinned at the constriction and in order to penetrate the narrow segments the vortex/skyrmion core size should be reduced.

  15. Effects and mechanisms of cavidine protecting mice against LPS-induced endotoxic shock

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Zhang, Hailin; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn; Wang, Xiumei; Wang, Yu; He, Zehong; Yao, Huan

    2016-08-15

    LPS sensitized mice are usually considered as an experimental model of endotoxin shock. The present study aims to evaluate effects of cavidine on LPS-induced endotoxin shock. Mice were intraperitoneally administrated with cavidine (1, 3 and 10 mg/kg) or DEX (5 mg/kg) at 1 and 12 h before injecting LPS (30 mg/kg) intraperitoneally. Blood samples, liver, lung and kidney tissues were harvested after LPS injection. The study demonstrated that pretreatment with cavidine reduced the mortality of mice during 72 h after endotoxin injection. In addition, cavidine administration significantly attenuated histological pathophysiology features of LPS-induced injury in lung, liver and kidney. Furthermore, cavidine administration inhibited endotoxin-induced production of pro-inflammatory cytokines including TNF-α, IL-6 and HMGB1. Moreover, cavidine pretreatment attenuated the phosphorylation of mitogen-activated protein kinase primed by LPS. In summary, cavidine protects mice against LPS-induced endotoxic shock via inhibiting early pro-inflammatory cytokine TNF-α, IL-6 and late-phase cytokine HMGB1, and the modulation of HMGB1 may be related with MAPK signal pathway. - Highlights: • Cavidine significantly reduced mortality in mice during 72 h after LPS injection. • Cavidine attenuated histopathological changes in lung, liver and kidney. • Cavidine decreased the level of early inflammatory cytokine TNF-α, IL-6 in LPS- stimulated mice. • Cavidine inhibited late inflammatory cytokine HMGB1 through MAPK pathway.

  16. Pharmacological inhibition of NADPH oxidase protects against cisplatin induced nephrotoxicity in mice by two step mechanism.

    Science.gov (United States)

    Wang, Yimin; Luo, Xiao; Pan, Hao; Huang, Wei; Wang, Xueping; Wen, Huali; Shen, Kezhen; Jin, Baiye

    2015-09-01

    Cisplatin induced nephrotoxicity is primarily caused by ROS (Reactive Oxygen Species) induced proximal tubular cell death. NADPH oxidase is major source of ROS production by cisplatin. Here, we reported that pharmacological inhibition of NADPH oxidase by acetovanillone (obtained from medicinal herb Picrorhiza kurroa) led to reduced cisplatin nephrotoxicity in mice. In this study we used various molecular biology and biochemistry methods a clinically relevant model of nephropathy, induced by an important chemotherapeutic drug cisplatin. Cisplatin-induced nephrotoxicity was evident by histological damage from loss of the tubular structure. The damage was also marked by the increase in blood urea nitrogen, creatinine, protein nitration as well as cell death markers such as caspase 3/7 activity and DNA fragmentation. Tubular cell death by cisplatin led to pro-inflammatory response by production of TNFα and IL1β followed by leukocyte/neutrophil infiltration which resulted in new wave of ROS involving more NADPH oxidases. Cisplatin-induced markers of kidney damage such as oxidative stress, cell death, inflammatory cytokine production and nephrotoxicity were attenuated by acetovanillone. In addition to that, acetovanillone enhanced cancer cell killing efficacy of cisplatin. Thus, pharmacological inhibition of NADPH oxidase can be protective for cisplatin-induced nephrotoxicity in mice. Copyright © 2015. Published by Elsevier Ltd.

  17. Transglutaminase inhibition: possible therapeutic mechanisms to protect cells from death in neurological disorders

    Directory of Open Access Journals (Sweden)

    Nicola Gaetano Gatta

    2017-10-01

    Full Text Available Transglutaminases are a family of Ca2+-dependent enzymes which catalyze post-translational modifications of proteins. The main activity of these enzymes is the cross-linking of glutaminyl residues of a protein/peptide substrate to lysyl residues of a protein/peptide co-substrate. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono- or bi-substituted/crosslinked adducts or −OH groups (to form ester linkages. In absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl residue. Transglutaminase activity has been suggested to be involved in molecular mechanisms responsible for both physiological or pathological processes. In particular, transglutaminase activity has been shown to be responsible for human autoimmune diseases, and Celiac Disease is just one of them. Interestingly, neurodegenerative diseases, such as Alzheimer’s Disease, Parkinson’s Disease, supranuclear palsy, Huntington’s Disease and other polyglutamine diseases, are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. Here we describe the possible molecular mechanisms by which these enzymes could be responsible for such diseases and the possible use of transglutaminase inhibitors for patients with diseases characterized by aberrant transglutaminase activity.

  18. Enhanced prefrontal-amygdala connectivity following childhood adversity as a protective mechanism against internalizing in adolescence.

    Science.gov (United States)

    Herringa, Ryan J; Burghy, Cory A; Stodola, Diane E; Fox, Michelle E; Davidson, Richard J; Essex, Marilyn J

    2016-07-01

    Much research has focused on the deleterious neurobiological effects of childhood adversity that may underlie internalizing disorders. While most youth show emotional adaptation following adversity, the corresponding neural mechanisms remain poorly understood. In this longitudinal community study, we examined the associations among childhood family adversity, adolescent internalizing symptoms, and their interaction on regional brain activation and amygdala/hippocampus functional connectivity during emotion processing in 132 adolescents. Consistent with prior work, childhood adversity predicted heightened amygdala reactivity to negative, but not positive, images in adolescence. However, amygdala reactivity was not related to internalizing symptoms. Furthermore, childhood adversity predicted increased fronto-amygdala connectivity to negative, but not positive, images, yet only in lower internalizing adolescents. Childhood adversity also predicted increased fronto-hippocampal connectivity to negative images, but was not moderated by internalizing. These findings were unrelated to adolescence adversity or externalizing symptoms, suggesting specificity to childhood adversity and adolescent internalizing. Together, these findings suggest that adaptation to childhood adversity is associated with augmentation of fronto-subcortical circuits specifically for negative emotional stimuli. Conversely, insufficient enhancement of fronto-amygdala connectivity, with increasing amygdala reactivity, may represent a neural signature of vulnerability for internalizing by late adolescence. These findings implicate early childhood as a critical period in determining the brain's adaptation to adversity, and suggest that even normative adverse experiences can have significant impact on neurodevelopment and functioning. These results offer potential neural mechanisms of adaptation and vulnerability which could be used in the prediction of risk for psychopathology following childhood

  19. Protective role of Arapaima gigas fish scales: structure and mechanical behavior.

    Science.gov (United States)

    Yang, Wen; Sherman, Vincent R; Gludovatz, Bernd; Mackey, Mason; Zimmermann, Elizabeth A; Chang, Edwin H; Schaible, Eric; Qin, Zhao; Buehler, Markus J; Ritchie, Robert O; Meyers, Marc A

    2014-08-01

    The scales of the arapaima (Arapaima gigas), one of the largest freshwater fish in the world, can serve as inspiration for the design of flexible dermal armor. Each scale is composed of two layers: a laminate composite of parallel collagen fibrils and a hard, highly mineralized surface layer. We review the structure of the arapaima scales and examine the functions of the different layers, focusing on the mechanical behavior, including tension and penetration of the scales, with and without the highly mineralized outer layer. We show that the fracture of the mineral and the stretching, rotation and delamination of collagen fibrils dissipate a significant amount of energy prior to catastrophic failure, providing high toughness and resistance to penetration by predator teeth. We show that the arapaima's scale has evolved to minimize damage from penetration by predator teeth through a Bouligand-like arrangement of successive layers, each consisting of parallel collagen fibrils with different orientations. This inhibits crack propagation and restricts damage to an area adjoining the penetration. The flexibility of the lamellae is instrumental to the redistribution of the compressive stresses in the underlying tissue, decreasing the severity of the concentrated load produced by the action of a tooth. The experimental results, combined with small-angle X-ray scattering characterization and molecular dynamics simulations, provide a complete picture of the mechanisms of deformation, delamination and rotation of the lamellae during tensile extension of the scale. Copyright © 2014 Acta Materialia Inc. All rights reserved.

  20. Human endogenous retroviruses and cancer prevention: evidence and prospects

    Directory of Open Access Journals (Sweden)

    Cegolon Luca

    2013-01-01

    Full Text Available Abstract Background Cancer is a significant and growing problem worldwide. While this increase may, in part, be attributed to increasing longevity, improved case notifications and risk-enhancing lifestyle (such as smoking, diet and obesity, hygiene-related factors resulting in immuno-regulatory failure may also play a major role and call for a revision of vaccination strategies to protect against a range of cancers in addition to infections. Discussion Human endogenous retroviruses (HERVs are a significant component of a wider family of retroelements that constitutes part of the human genome. They were originated by the integration of exogenous retroviruses into the human genome millions of years ago. HERVs are estimated to comprise about 8% of human DNA and are ubiquitous in somatic and germinal tissues. Physiologic and pathologic processes are influenced by some biologically active HERV families. HERV antigens are only expressed at low levels by the host, but in circumstances of inappropriate control their genes may initiate or maintain pathological processes. Although the precise mechanism leading to abnormal HERVs gene expression has yet to be clearly elucidated, environmental factors seem to be involved by influencing the human immune system. HERV-K expression has been detected in different types of tumors. Among the various human endogenous retroviral families, the K series was the latest acquired by the human species. Probably because of its relatively recent origin, the HERV-K is the most complete and biologically active family. The abnormal expression of HERV-K seemingly triggers pathological processes leading to melanoma onset, but also contributes to the morphological and functional cellular modifications implicated in melanoma maintenance and progression. The HERV-K-MEL antigen is encoded by a pseudo-gene incorporated in the HERV-K env-gene. HERV-K-MEL is significantly expressed in the majority of dysplastic and normal naevi, as well

  1. Human endogenous retroviruses and cancer prevention: evidence and prospects.

    Science.gov (United States)

    Cegolon, Luca; Salata, Cristiano; Weiderpass, Elisabete; Vineis, Paolo; Palù, Giorgio; Mastrangelo, Giuseppe

    2013-01-03

    Cancer is a significant and growing problem worldwide. While this increase may, in part, be attributed to increasing longevity, improved case notifications and risk-enhancing lifestyle (such as smoking, diet and obesity), hygiene-related factors resulting in immuno-regulatory failure may also play a major role and call for a revision of vaccination strategies to protect against a range of cancers in addition to infections. Human endogenous retroviruses (HERVs) are a significant component of a wider family of retroelements that constitutes part of the human genome. They were originated by the integration of exogenous retroviruses into the human genome millions of years ago. HERVs are estimated to comprise about 8% of human DNA and are ubiquitous in somatic and germinal tissues.Physiologic and pathologic processes are influenced by some biologically active HERV families. HERV antigens are only expressed at low levels by the host, but in circumstances of inappropriate control their genes may initiate or maintain pathological processes. Although the precise mechanism leading to abnormal HERVs gene expression has yet to be clearly elucidated, environmental factors seem to be involved by influencing the human immune system.HERV-K expression has been detected in different types of tumors.Among the various human endogenous retroviral families, the K series was the latest acquired by the human species. Probably because of its relatively recent origin, the HERV-K is the most complete and biologically active family.The abnormal expression of HERV-K seemingly triggers pathological processes leading to melanoma onset, but also contributes to the morphological and functional cellular modifications implicated in melanoma maintenance and progression.The HERV-K-MEL antigen is encoded by a pseudo-gene incorporated in the HERV-K env-gene. HERV-K-MEL is significantly expressed in the majority of dysplastic and normal naevi, as well as other tumors like sarcoma, lymphoma, bladder and

  2. Human endogenous retroviruses and cancer prevention: evidence and prospects

    International Nuclear Information System (INIS)

    Cegolon, Luca; Salata, Cristiano; Weiderpass, Elisabete; Vineis, Paolo; Palù, Giorgio; Mastrangelo, Giuseppe

    2013-01-01

    Cancer is a significant and growing problem worldwide. While this increase may, in part, be attributed to increasing longevity, improved case notifications and risk-enhancing lifestyle (such as smoking, diet and obesity), hygiene-related factors resulting in immuno-regulatory failure may also play a major role and call for a revision of vaccination strategies to protect against a range of cancers in addition to infections. Human endogenous retroviruses (HERVs) are a significant component of a wider family of retroelements that constitutes part of the human genome. They were originated by the integration of exogenous retroviruses into the human genome millions of years ago. HERVs are estimated to comprise about 8% of human DNA and are ubiquitous in somatic and germinal tissues. Physiologic and pathologic processes are influenced by some biologically active HERV families. HERV antigens are only expressed at low levels by the host, but in circumstances of inappropriate control their genes may initiate or maintain pathological processes. Although the precise mechanism leading to abnormal HERVs gene expression has yet to be clearly elucidated, environmental factors seem to be involved by influencing the human immune system. HERV-K expression has been detected in different types of tumors. Among the various human endogenous retroviral families, the K series was the latest acquired by the human species. Probably because of its relatively recent origin, the HERV-K is the most complete and biologically active family. The abnormal expression of HERV-K seemingly triggers pathological processes leading to melanoma onset, but also contributes to the morphological and functional cellular modifications implicated in melanoma maintenance and progression. The HERV-K-MEL antigen is encoded by a pseudo-gene incorporated in the HERV-K env-gene. HERV-K-MEL is significantly expressed in the majority of dysplastic and normal naevi, as well as other tumors like sarcoma, lymphoma, bladder

  3. Human-Specific Endogenous Retroviruses

    Directory of Open Access Journals (Sweden)

    Anton Buzdin

    2007-01-01

    Full Text Available This review focuses on a small family of human-specific genomic repetitive elements, presented by 134 members that shaped ~330 kb of the human DNA. Although modest in terms of its copy number, this group appeared to modify the human genome activity by endogenizing ~50 functional copies of viral genes that may have important implications in the immune response, cancer progression, and antiretroviral host defense. A total of 134 potential promoters and enhancers have been added to the human DNA, about 50% of them in the close gene vicinity and 22% in gene introns. For 60 such human-specific promoters, their activity was confirmed by in vivo assays, with the transcriptional level varying ~1000-fold from hardly detectable to as high as ~3% of β-actin transcript level. New polyadenylation signals have been provided to four human RNAs, and a number of potential antisense regulators of known human genes appeared due to human-specific retroviral insertional activity. This information is given here in the context of other major genomic changes underlining differences between human and chimpanzee DNAs. Finally, a comprehensive database, is available for download, of human-specific and polymorphic endogenous retroviruses is presented, which encompasses the data on their genomic localization, primary structure, encoded viral genes, human gene neighborhood, transcriptional activity, and methylation status.

  4. Endogenous Opiates and Behavior: 2006

    Science.gov (United States)

    Bodnar, Richard J.

    2009-01-01

    This paper is the twenty-ninth consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning thirty years of research. It summarizes papers published during 2006 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurological disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). PMID:17949854

  5. Endogenous opiates and behavior: 2012.

    Science.gov (United States)

    Bodnar, Richard J

    2013-12-01

    This paper is the thirty-fifth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2012 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Endogenous Receptor Agonists: Resolving Inflammation

    Directory of Open Access Journals (Sweden)

    Gerhard Bannenberg

    2007-01-01

    Full Text Available Controlled resolution or the physiologic resolution of a well-orchestrated inflammatory response at the tissue level is essential to return to homeostasis. A comprehensive understanding of the cellular and molecular events that control the termination of acute inflammation is needed in molecular terms given the widely held view that aberrant inflammation underlies many common diseases. This review focuses on recent advances in the understanding of the role of arachidonic acid and ω-3 polyunsaturated fatty acids (PUFA–derived lipid mediators in regulating the resolution of inflammation. Using a functional lipidomic approach employing LC-MS-MS–based informatics, recent studies, reviewed herein, uncovered new families of local-acting chemical mediators actively biosynthesized during the resolution phase from the essential fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. These new families of local chemical mediators are generated endogenously in exudates collected during the resolution phase, and were coined resolvins and protectins because specific members of these novel chemical families control both the duration and magnitude of inflammation in animal models of complex diseases. Recent advances on the biosynthesis, receptors, and actions of these novel anti-inflammatory and proresolving lipid mediators are reviewed with the aim to bring to attention the important role of specific lipid mediators as endogenous agonists in inflammation resolution.

  7. Mechanisms Underpinning Degradation of Protective Oxides and Thermal Barrier Coatings in High Hydrogen Content (HHC) - Fueled Turbines

    Energy Technology Data Exchange (ETDEWEB)

    Mumm, Daniel

    2013-08-31

    The overarching goal of this research program has been to evaluate the potential impacts of coal-derived syngas and high-hydrogen content fuels on the degradation of turbine hot-section components through attack of protective oxides and thermal barrier coatings. The primary focus of this research program has been to explore mechanisms underpinning the observed degradation processes, and connections to the combustion environments and characteristic non-combustible constituents. Based on the mechanistic understanding of how these emerging fuel streams affect materials degradation, the ultimate goal of the program is to advance the goals of the Advanced Turbine Program by developing materials design protocols leading to turbine hot-section components with improved resistance to service lifetime degradation under advanced fuels exposures. This research program has been focused on studying how: (1) differing combustion environments – relative to traditional natural gas fired systems – affect both the growth rate of thermally grown oxide (TGO) layers and the stability of these oxides and of protective thermal barrier coatings (TBCs); and (2) how low levels of fuel impurities and characteristic non-combustibles interact with surface oxides, for instance through the development of molten deposits that lead to hot corrosion of protective TBC coatings. The overall program has been comprised of six inter-related themes, each comprising a research thrust over the program period, including: (i) evaluating the role of syngas and high hydrogen content (HHC) combustion environments in modifying component surface temperatures, heat transfer to the TBC coatings, and thermal gradients within these coatings; (ii) understanding the instability of TBC coatings in the syngas and high hydrogen environment with regards to decomposition, phase changes and sintering; (iii) characterizing ash deposition, molten phase development and infiltration, and associated corrosive

  8. Experimental intra-abdominal hypertension influences airway pressure limits for lung protective mechanical ventilation.

    Science.gov (United States)

    Cortes-Puentes, Gustavo A; Cortes-Puentes, Luis A; Adams, Alexander B; Anderson, Christopher P; Marini, John J; Dries, David J

    2013-06-01

    Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) may complicate monitoring of pulmonary mechanics owing to their impact on the respiratory system. However, recommendations for mechanical ventilation of patients with IAH/ACS and the interpretation of thoracoabdominal interactions remain unclear. Our study aimed to characterize the influence of elevated intra-abdominal pressure (IAP) and positive end-expiratory pressure (PEEP) on airway plateau pressure (PPLAT) and bladder pressure (PBLAD). Nine deeply anesthetized swine were mechanically ventilated via tracheostomy: volume-controlled mode at tidal volume (VT) of 10 mL/kg, frequency of 15, inspiratory-expiratory ratio of 1:2, and PEEP of 1 and 10 cm H2O (PEEP1 and PEEP10, respectively). A tracheostomy tube was placed in the peritoneal cavity, and IAP levels of 5, 10, 15, 20, and 25 mm Hg were applied, using a continuous positive airway pressure system. At each IAP level, PBLAD and airway pressure measurements were performed during both PEEP1 and PEEP10. PBLAD increased as experimental IAP rose (y = 0.83x + 0.5; R = 0.98; p < 0.001 at PEEP1). Minimal underestimation of IAP by PBLAD was observed (-2.5 ± 0.8 mm Hg at an IAP of 10-25 mm Hg). Applying PEEP10 did not significantly affect the correlation between experimental IAP and PBLAD. Approximately 50% of the PBLAD (in cm H2O) was reflected by changes in PPLAT, regardless of the PEEP level applied. Increasing IAP did not influence hemodynamics at any level of IAP generated. With minimal underestimation, PBLAD measurements closely correlated with experimentally regulated IAP, independent of the PEEP level applied. For each PEEP level applied, a constant proportion (approximately 50%) of measured PBLAD (in cm H2O) was reflected in PPLAT. A higher safety threshold for PPLAT should be considered in the setting of IAH/ACS as the clinician considers changes in VT. A strategy of reducing VT to cap PPLAT at widely recommended values may not be

  9. The Endogenous Origins of Experience, Routines and Organizational Capabilities

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul; Felin, Teppo

    2011-01-01

    In this paper we discuss the origins and emergence of organizational routines and capabilities. We first argue that there are theoretical and endogeneity-related concerns associated with the key antecedents and mechanisms specified by the extant routines and capabilities literature. Specifically,...... or rationalist, choice-based approach can provide a more fruitful (though preliminary) foundation for understanding organizational behavior and capabilities.......In this paper we discuss the origins and emergence of organizational routines and capabilities. We first argue that there are theoretical and endogeneity-related concerns associated with the key antecedents and mechanisms specified by the extant routines and capabilities literature. Specifically......, we explicate the behaviorist and empiricist foundations of the organizational routines and capabilities literature and the extant emphasis placed on experience, repetition, and observation as the key antecedents and mechanisms of routines and capabilities. Based on this discussion we highlight...

  10. Variability in usual care mechanical ventilation for pediatric acute lung injury: the potential benefit of a lung protective computer protocol.

    Science.gov (United States)

    Khemani, Robinder G; Sward, Katherine; Morris, Alan; Dean, J Michael; Newth, Christopher J L

    2011-11-01

    Although pediatric intensivists claim to embrace lung protective ventilation for acute lung injury (ALI), ventilator management is variable. We describe ventilator changes clinicians made for children with hypoxemic respiratory failure, and evaluate the potential acceptability of a pediatric ventilation protocol. This was a retrospective cohort study performed in a tertiary care pediatric intensive care unit (PICU). The study period was from January 2000 to July 2007. We included mechanically ventilated children with PaO(2)/FiO(2) (P/F) ratio less than 300. We assessed variability in ventilator management by evaluating actual changes to ventilator settings after an arterial blood gas (ABG). We evaluated the potential acceptability of a pediatric mechanical ventilation protocol we adapted from National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) Acute Respiratory Distress Syndrome (ARDS) Network protocols by comparing actual practice changes in ventilator settings to changes that would have been recommended by the protocol. A total of 2,719 ABGs from 402 patients were associated with 6,017 ventilator settings. Clinicians infrequently decreased FiO(2), even when the PaO(2) was high (>68 mmHg). The protocol would have recommended more positive end expiratory pressure (PEEP) than was used in actual practice 42% of the time in the mid PaO(2) range (55-68 mmHg) and 67% of the time in the low PaO(2) range (ventilator rate (VR) when the protocol would have recommended a change, even when the pH was greater than 7.45 with PIP at least 35 cmH(2)O. There may be lost opportunities to minimize potentially injurious ventilator settings for children with ALI. A reproducible pediatric mechanical ventilation protocol could prompt clinicians to make ventilator changes that are consistent with lung protective ventilation.

  11. Mild hypothermia increases pulmonary anti-inflammatory response during protective mechanical ventilation in a piglet model of acute lung injury.

    Science.gov (United States)

    Cruces, Pablo; Erranz, Benjamín; Donoso, Alejandro; Carvajal, Cristóbal; Salomón, Tatiana; Torres, María Fernanda; Díaz, Franco

    2013-11-01

    The effects of mild hypothermia (HT) on acute lung injury (ALI) are unknown in species with metabolic rate similar to that of humans, receiving protective mechanical ventilation (MV). We hypothesized that mild hypothermia would attenuate pulmonary and systemic inflammatory responses in piglets with ALI managed with a protective MV. Acute lung injury (ALI) was induced with surfactant deactivation in 38 piglets. The animals were then ventilated with low tidal volume, moderate positive end-expiratory pressure (PEEP), and permissive hypercapnia throughout the experiment. Subjects were randomized to HT (33.5°C) or normothermia (37°C) groups over 4 h. Plasma and tissue cytokines, tissue apoptosis, lung mechanics, pulmonary vascular permeability, hemodynamic, and coagulation were evaluated. Lung interleukin-10 concentrations were higher in subjects that underwent HT after ALI induction than in those that maintained normothermia. No difference was found in other systemic and tissue cytokines. HT did not induce lung or kidney tissue apoptosis or influence lung mechanics or markers of pulmonary vascular permeability. Heart rate, cardiac output, oxygen uptake, and delivery were significantly lower in subjects that underwent HT, but no difference in arterial lactate, central venous oxygen saturation, and coagulation test was observed. Mild hypothermia induced a local anti-inflammatory response in the lungs, without affecting lung function or coagulation, in this piglet model of ALI. The HT group had lower cardiac output without signs of global dysoxia, suggesting an adaptation to the decrease in oxygen uptake and delivery. Studies are needed to determine the therapeutic role of HT in ALI. © 2013 John Wiley & Sons Ltd.

  12. Mechanisms of Protection from Interest Rate Risk with Reference to the Life Insurance Market in Montenegro

    Directory of Open Access Journals (Sweden)

    Burić Milijana Novović

    2018-01-01

    Full Text Available Insurance companies are facing major challenges that point to the need for control process and risk management. Risk management in insurance has a direct impact on solvency, economic security, and overall financial stability of insurance companies. It is very important for insurance companies to adequately calculate risks to which they are exposed. Asset liability management (ALM, as an integrated approach to financial management, requires simultaneous decision-making about categories and values of assets and liabilities in order to establish the optimum volume and the ratio of assets and liabilities, with the understanding of complexity of the financial market in which financial institutions operate. ALM focuses on a significant number of risks, whereby the emphasis in this paper will be on interest rate risk which indicates potential losses that may reflect in a lower interest margin, a lower value of assets or both, in terms of changes in interest rates. In the above context, the aim of this paper is to show how to protect from interest rate changes and how these changes influence the insurance market in Montenegro, both from the theoretical and the practical point of view. The authors consider this to be an interesting and very important topic, especially because the life insurance market in Montenegro is underdeveloped and subject to fluctuations. Also, taking into account the fact that Montenegro is a country that has been making serious efforts to join the EU, it is expected that insurance companies in Montenegro will strengthen their financial position in the market even using the ALM traditional techniques, which is shown in this paper.

  13. Insulator-protected mechanically controlled break junctions for measuring single-molecule conductance in aqueous environments

    Energy Technology Data Exchange (ETDEWEB)

    Muthusubramanian, N.; Zant, H. S. J. van der [Kavli Institute of Nanoscience, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft (Netherlands); Galan, E.; Maity, C.; Eelkema, R.; Grozema, F. C. [Department of Chemical Engineering, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft (Netherlands)

    2016-07-04

    We present a method to fabricate insulated gold mechanically controlled break junctions (MCBJ) by coating the metal with a thin layer of aluminum oxide using plasma enhanced atomic layer deposition. The Al{sub 2}O{sub 3} thickness deposited on the MCBJ devices was varied from 2 to 15 nm to test the suppression of leakage currents in deionized water and phosphate buffered saline. Junctions coated with a 15 nm thick oxide layer yielded atomically sharp electrodes and negligible conductance counts in the range of 1 to 10{sup −4} G{sub 0} (1 G{sub 0} = 77 μS), where single-molecule conductances are commonly observed. The insulated devices were used to measure the conductance of an amphiphilic oligophenylene ethynylene derivative in deionized water.

  14. Lung protective mechanical ventilation strategies in cardiothoracic critical care: a retrospective study.

    Science.gov (United States)

    Zochios, Vasileios; Hague, Matthew; Giraud, Kimberly; Jones, Nicola

    2016-01-01

    A body of evidence supports the use of low tidal volumes in ventilated patients without lung pathology to slow progress to acute respiratory distress syndrome (ARDS) due to ventilator associated lung injury. We undertook a retrospective chart review and tested the hypothesis that tidal volume is a predictor of mortality in cardiothoracic (medical and surgical) critical care patients receiving invasive mechanical ventilation. Independent predictors of mortality in our study included: type of surgery, albumin, H + , bilirubin, and fluid balance. In particular, it is important to note that cardiac, thoracic, and transplant surgical patients were associated with lower mortality. However, our study did not sample equally from The Berlin Definition of ARDS severity categories (mild, moderate, and severe hypoxemia). Although our study was not adequately powered to detect a difference in mortality between these groups, it will inform the development of a large prospective cohort study exploring the role of low tidal volume ventilation in cardiothoracic critically ill patients.

  15. Antioxidant and protective mechanisms against hypoxia and hypoglycaemia in cortical neurons in vitro.

    Science.gov (United States)

    Merino, José Joaquín; Roncero, César; Oset-Gasque, María Jesús; Naddaf, Ahmad; González, María Pilar

    2014-02-12

    In the present work, we have studied whether cell death could be induced in cortical neurons from rats subjected to different period of O2 deprivation and low glucose (ODLG). This "in vitro" model is designed to emulate the penumbra area under ischemia. In these conditions, cortical neurons displayed loss of mitochondrial respiratory ability however, nor necrosis neither apoptosis occurred despite ROS production. The absence of cellular death could be a consequence of increased antioxidant responses such as superoxide dismutase-1 (SOD1) and GPX3. In addition, the levels of reduced glutathione were augmented and HIF-1/3α overexpressed. After long periods of ODLG (12-24 h) cortical neurons showed cellular and mitochondrial membrane alterations and did not recuperate cellular viability during reperfusion. This could mean that therapies directed toward prevention of cellular and mitochondrial membrane imbalance or cell death through mechanisms other than necrosis or apoptosis, like authophagy, may be a way to prevent ODLG damage.

  16. Protective molecular mechanisms of resveratrol in UVR-induced Skin carcinogenesis.

    Science.gov (United States)

    Aziz, Saba W; Aziz, Moammir H

    2018-01-01

    Skin cancer is a major health problem worldwide. It is the most common cancer in the United States and poses a significant healthcare burden. Excessive UVR exposure is the most common cause of skin cancer. Despite various precautionary measures to avoid direct UVR exposure, the incidence of skin cancer and mortality related to it remains high. Furthermore, the current treatment options are expensive and have side effects including toxicity to normal cells. Thus, a safe and effective approach is needed to prevent and treat skin cancer. Chemopreventive strategy using naturally occurring compounds, such as resveratrol, is a promising approach to reduce the incidence of UVR-induced skin cancer and delay its progression. This review highlights the current body of evidence related to chemopreventive role of resveratrol and its molecular mechanisms in UVR-induced skin carcinogenesis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Insulator-protected mechanically controlled break junctions for measuring single-molecule conductance in aqueous environments

    Science.gov (United States)

    Muthusubramanian, N.; Galan, E.; Maity, C.; Eelkema, R.; Grozema, F. C.; van der Zant, H. S. J.

    2016-07-01

    We present a method to fabricate insulated gold mechanically controlled break junctions (MCBJ) by coating the metal with a thin layer of aluminum oxide using plasma enhanced atomic layer deposition. The Al2O3 thickness deposited on the MCBJ devices was varied from 2 to 15 nm to test the suppression of leakage currents in deionized water and phosphate buffered saline. Junctions coated with a 15 nm thick oxide layer yielded atomically sharp electrodes and negligible conductance counts in the range of 1 to 10-4 G0 (1 G0 = 77 μS), where single-molecule conductances are commonly observed. The insulated devices were used to measure the conductance of an amphiphilic oligophenylene ethynylene derivative in deionized water.

  18. Ultrananocrystalline diamond film as a wear resistant and protective coating for mechanical seal applications

    International Nuclear Information System (INIS)

    Sumant, A.V.; Krauss, A.R.; Gruen, D.M.; Auciello, O.; Erdemir, A.; Williams, M.; Artiles, A.F.; Adams, W.

    2005-01-01

    Mechanical shaft seals used in pumps are critically important to the safe operation of the paper, pulp, and chemical process industry, as well as petroleum and nuclear power plants. Specifically, these seals prevent the leakage of toxic gases and hazardous chemicals to the environment and final products from the rotating equipment used in manufacturing processes. Diamond coatings have the potential to provide negligible wear, ultralow friction, and high corrosion resistance for the sliding surfaces of mechanical seals, because diamond exhibits outstanding tribological, physical, and chemical properties. However, diamond coatings produced by conventional chemical vapor deposition (CVD) exhibit high surface roughness (R a ≥ 1 μm), which results in high wear of the seal counterface, leading to premature seal failure. To avoid this problem, we have developed an ultrananocrystalline diamond (UNCD) film formed by a unique CH 4 /Ar microwave plasma CVD method. This method yields extremely smooth diamond coatings with surface roughness R a = 20-30 nm and an average grain size of 2-5 nm. We report the results of a systematic test program involving uncoated and UNCD-coated SiC shaft seals. Results confirmed that the UNCD-coated seals exhibited neither measurable wear nor any leakage during long-duration tests that took 21 days to complete. In addition, the UNCD coatings reduced the frictional torque for seal rotation by five to six times compared with the uncoated seals. This work promises to lead to rotating shaft seals with much improved service life, reduced maintenance cost, reduced leakage of environmentally hazardous materials, and increased energy savings. This technology may also have many other tribological applications involving rolling or sliding contacts.

  19. A review of protective factors and causal mechanisms that enhance the mental health of Indigenous Circumpolar youth

    Directory of Open Access Journals (Sweden)

    Joanna Petrasek MacDonald

    2013-12-01

    Full Text Available Objectives . To review the protective factors and causal mechanisms which promote and enhance Indigenous youth mental health in the Circumpolar North. Study design . A systematic literature review of peer-reviewed English-language research was conducted to systematically examine the protective factors and causal mechanisms which promote and enhance Indigenous youth mental health in the Circumpolar North. Methods . This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA guidelines, with elements of a realist review. From 160 records identified in the initial search of 3 databases, 15 met the inclusion criteria and were retained for full review. Data were extracted using a codebook to organize and synthesize relevant information from the articles. Results . More than 40 protective factors at the individual, family, and community levels were identified as enhancing Indigenous youth mental health. These included practicing and holding traditional knowledge and skills, the desire to be useful and to contribute meaningfully to one's community, having positive role models, and believing in one's self. Broadly, protective factors at the family and community levels were identified as positively creating and impacting one's social environment, which interacts with factors at the individual level to enhance resilience. An emphasis on the roles of cultural and land-based activities, history, and language, as well as on the importance of social and family supports, also emerged throughout the literature. Conclusions . Healthy communities and families foster and support youth who are resilient to mental health challenges and able to adapt and cope with multiple stressors, be they social, economic, or environmental. Creating opportunities and environments where youth can successfully navigate challenges and enhance their resilience can in turn contribute to fostering healthy Circumpolar communities. Looking at the

  20. Endogenous retroviral promoter exaptation in human cancer

    Directory of Open Access Journals (Sweden)

    Artem Babaian

    2016-12-01

    Full Text Available Abstract Cancer arises from a series of genetic and epigenetic changes, which result in abnormal expression or mutational activation of oncogenes, as well as suppression/inactivation of tumor suppressor genes. Aberrant expression of coding genes or long non-coding RNAs (lncRNAs with oncogenic properties can be caused by translocations, gene amplifications, point mutations or other less characterized mechanisms. One such mechanism is the inappropriate usage of normally dormant, tissue-restricted or cryptic enhancers or promoters that serve to drive oncogenic gene expression. Dispersed across the human genome, endogenous retroviruses (ERVs provide an enormous reservoir of autonomous gene regulatory modules, some of which have been co-opted by the host during evolution to play important roles in normal regulation of genes and gene networks. This review focuses on the “dark side” of such ERV regulatory capacity. Specifically, we discuss a growing number of examples of normally dormant or epigenetically repressed ERVs that have been harnessed to drive oncogenes in human cancer, a process we term onco-exaptation, and we propose potential mechanisms that may underlie this phenomenon.

  1. Intraoperative protective mechanical ventilation for prevention of postoperative pulmonary complications: a comprehensive review of the role of tidal volume, positive end-expiratory pressure, and lung recruitment maneuvers.

    Science.gov (United States)

    Güldner, Andreas; Kiss, Thomas; Serpa Neto, Ary; Hemmes, Sabrine N T; Canet, Jaume; Spieth, Peter M; Rocco, Patricia R M; Schultz, Marcus J; Pelosi, Paolo; Gama de Abreu, Marcelo

    2015-09-01

    Postoperative pulmonary complications are associated with increased morbidity, length of hospital stay, and mortality after major surgery. Intraoperative lung-protective mechanical ventilation has the potential to reduce the incidence of postoperative pulmonary complications. This review discusses the relevant literature on definition and methods to predict the occurrence of postoperative pulmonary complication, the pathophysiology of ventilator-induced lung injury with emphasis on the noninjured lung, and protective ventilation strategies, including the respective roles of tidal volumes, positive end-expiratory pressure, and recruitment maneuvers. The authors propose an algorithm for protective intraoperative mechanical ventilation based on evidence from recent randomized controlled trials.

  2. Mechanical Stress and Antioxidant Protection in the Retina of Hindlimb Suspended Rats

    Science.gov (United States)

    Glass, Aziza; Theriot, Corey A.; Alway, Stephen E.; Zanello, Susana B.

    2012-01-01

    It has been postulated that hindlimb suspension (HS) causes a cephalad fluid shift in quadrupeds similar to that occurring to humans in microgravity. Therefore, HS may provide a suitable animal model in which to recapitulate the ocular changes observed in the human Visual Impairment and Intracranial Pressure (VIIP) syndrome. This work reports preliminary results from a tissue sharing project using 34 week-old Brown Norway rats. Two different experiments compared normal posture controls and HS rats for 2 weeks and rats exposed to HS for 2 weeks but allowed to recover in normal posture for 2 additional weeks. The effects of two nutritional countermeasures, green tea extract (GT) and plant polyphenol resveratrol (Rv), were also evaluated. Green tea contains the antioxidant epigallocatechin gallate (EGCG). qPCR gene expression analysis of selected targets was performed on RNA from isolated retinas, and histologic analysis was done on one fixed eye per rat. The transcription factor early growth response protein 1 (Egr1) was upregulated almost 2-fold in HS retinas relative to controls (P = 0.059), and its expression returned to control levels after 2 weeks of recovery in normal posture (P = 0.023). HS-induced upregulation of Egr1 was attenuated (but not significantly) in retinas from rats fed an antioxidant rich (GT extract) diet. In rats fed the GT-enriched diet, antioxidant enzymes were induced, evidenced by the upregulation of the gene heme oxygenase 1 (Hmox1) (P = 0.042) and the gene superoxide dismutase 2 (Sod2) (P = 0.0001). Egr1 is a stretch-activated transcription factor, and the Egr1 mechanosensitive response to HS may have been caused by a change in the translaminal pressure and/or mechanical deformation of the eye globe. The observed histologic measurements of the various retinal layers in the HS rats were lower in value than those of the control animal (n = 1), however insufficient data were available for statistical analysis. Aquaporin 4, a water

  3. Endogenous ω-3 polyunsaturated fatty acid production confers resistance to obesity, dyslipidemia, and diabetes in mice.

    Science.gov (United States)

    Li, Jie; Li, Fanghong R; Wei, Dong; Jia, Wei; Kang, Jing X; Stefanovic-Racic, Maja; Dai, Yifan; Zhao, Allan Z

    2014-08-01

    Despite the well-documented health benefits of ω-3 polyunsaturated fatty acids (PUFAs), their use in clinical management of hyperglycemia and obesity has shown little success. To better define the mechanisms of ω-3 PUFAs in regulating energy balance and insulin sensitivity, we deployed a transgenic mouse model capable of endogenously producing ω-3 PUFAs while reducing ω-6 PUFAs owing to the expression of a Caenorhabditis elegans fat-1 gene encoding an ω-3 fatty acid desaturase. When challenged with high-fat diets, fat-1 mice strongly resisted obesity, diabetes, hypercholesterolemia, and hepatic steatosis. Endogenous elevation of ω-3 PUFAs and reduction of ω-6 PUFAs did not alter the amount of food intake but led to increased energy expenditure in the fat-1 mice. The requirements for the levels of ω-3 PUFAs as well as the ω-6/ω-3 ratios in controlling blood glucose and obesity are much more stringent than those in lipid metabolism. These metabolic phenotypes were accompanied by attenuation of the inflammatory state because tissue levels of prostaglandin E2, leukotriene B4, monocyte chemoattractant protein-1, and TNF-α were significantly decreased. TNF-α-induced nuclear factor-κB signaling was almost completely abolished. Consistent with the reduction in chronic inflammation and a significant increase in peroxisome proliferator-activated receptor-γ activity in the fat-1 liver tissue, hepatic insulin signaling was sharply elevated. The activities of prolipogenic regulators, such as liver X receptor, stearoyl-CoA desaturase-1, and sterol regulatory element binding protein-1 were sharply decreased, whereas the activity of peroxisome proliferator-activated receptor-α, a nuclear receptor that facilitates lipid β-oxidation, was markedly increased. Thus, endogenous conversion of ω-6 to ω-3 PUFAs via fat-1 strongly protects against obesity, diabetes, inflammation, and dyslipidemia and may represent a novel therapeutic modality to treat these prevalent

  4. Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats: therapeutic time window and its mechanism.

    Science.gov (United States)

    Jia, Jie; Zhang, Xi; Hu, Yong-Shan; Wu, Yi; Wang, Qing-Zhi; Li, Na-Na; Wu, Cai-Qin; Yu, Hui-Xian; Guo, Qing-Chuan

    2009-03-01

    Tetramethyl pyrazine has been considered an effective agent in treating neurons ischemia/reperfusion injury, but the mechanism of its therapeutic effect remains unclear. This study was to explore the therapeutic time window and mechanism of tetramethyl pyrazine on temporary focal cerebral ischemia/reperfusion injury. Middle cerebral artery occlusion was conducted in male Sprague-Dawley rats and 20 mg/kg of tetramethyl pyrazine was intraperitoneally injected at different time points. At 72 h after reperfusion, all animals' neurologic deficit scores were evaluated. Cerebrums were removed and cerebral infarction volume was measured. The expression of thioredoxin and thioredoxin reductase mRNA was determined at 6 and 24 h after reperfusion. Cerebral infarction volume and neurological deficit scores were significantly decreased in the group with tetramethyl pyrazine treatment. The expression of thioredoxin-1/thioredoxin-2 and thioredoxin reductase-1/thioredoxin reductase-2 was significantly decreased in rats with ischemia/reperfusion injury, while it was increased by tetramethyl pyrazine administration. Treatment with tetramethyl pyrazine, within 4 h after reperfusion, protects the brain from ischemic reperfusion injury in rats. The neuroprotective mechanism of tetramethyl pyrazine treatment is, in part, mediated through the upregulation of thioredoxin transcription.

  5. An integrative view of cisplatin-induced renal and cardiac toxicities: molecular mechanisms, current treatment challenges and potential protective measures

    Science.gov (United States)

    Dugbartey, George J.; Peppone, Luke J.; de Graaf, Inge A.M.

    2017-01-01

    Cisplatin is currently one of the most widely-used chemotherapeutic agents against various malignancies. Its clinical application is limited, however, by inherent renal and cardiac toxicities and other side effects, of which the underlying mechanisms are only partly understood. Experimental studies show cisplatin generates reactive oxygen species, which impair the cell’s antioxidant defense system, causing oxidative stress and potentiating injury, thereby culminating in kidney and heart failure. Understanding the molecular mechanisms of cisplatin-induced renal and cardiac toxicities may allow clinicians to prevent or treat this problem better and may also provide a model for investigating drug-induced organ toxicity in general. This review discusses some of the major molecular mechanisms of cisplatin-induced renal and cardiac toxicities including disruption of ionic homeostasis and energy status of the cell leading to cell injury and cell death. We highlight clinical manifestations of both toxicities as well as (novel)biomarkers such as kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We also present some current treatment challenges and propose potential protective strategies with novel pharmacological compounds that might mitigate or prevent these toxicities, which include the use of hydrogen sulfide. PMID:27717837

  6. Antioxidant and Protective Mechanisms against Hypoxia and Hypoglycaemia in Cortical Neurons in Vitro

    Directory of Open Access Journals (Sweden)

    José Joaquín Merino

    2014-02-01

    Full Text Available In the present work, we have studied whether cell death could be induced in cortical neurons from rats subjected to different period of O2 deprivation and low glucose (ODLG. This “in vitro” model is designed to emulate the penumbra area under ischemia. In these conditions, cortical neurons displayed loss of mitochondrial respiratory ability however, nor necrosis neither apoptosis occurred despite ROS production. The absence of cellular death could be a consequence of increased antioxidant responses such as superoxide dismutase-1 (SOD1 and GPX3. In addition, the levels of reduced glutathione were augmented and HIF-1/3α overexpressed. After long periods of ODLG (12–24 h cortical neurons showed cellular and mitochondrial membrane alterations and did not recuperate cellular viability during reperfusion. This could mean that therapies directed toward prevention of cellular and mitochondrial membrane imbalance or cell death through mechanisms other than necrosis or apoptosis, like authophagy, may be a way to prevent ODLG damage.

  7. A Novel Visual Interface to Foster Innovation in Mechanical Engineering and Protect from Patent Infringement

    Science.gov (United States)

    Sorce, Salvatore; Malizia, Alessio; Jiang, Pingfei; Atherton, Mark; Harrison, David

    2018-04-01

    One of the main time and money consuming tasks in the design of industrial devices and parts is the checking of possible patent infringements. Indeed, the great number of documents to be mined and the wide variety of technical language used to describe inventions are reasons why considerable amounts of time may be needed. On the other hand, the early detection of a possible patent conflict, in addition to reducing the risk of legal disputes, could stimulate a designers’ creativity to overcome similarities in overlapping patents. For this reason, there are a lot of existing patent analysis systems, each with its own features and access modes. We have designed a visual interface providing an intuitive access to such systems, freeing the designers from the specific knowledge of querying languages and providing them with visual clues. We tested the interface on a framework aimed at representing mechanical engineering patents; the framework is based on a semantic database and provides patent conflict analysis for early-stage designs. The interface supports a visual query composition to obtain a list of potentially overlapping designs.

  8. Defence mechanisms: the role of physiology in current and future environmental protection paradigms

    Science.gov (United States)

    Glover, Chris N

    2018-01-01

    Abstract Ecological risk assessments principally rely on simplified metrics of organismal sensitivity that do not consider mechanism or biological traits. As such, they are unable to adequately extrapolate from standard laboratory tests to real-world settings, and largely fail to account for the diversity of organisms and environmental variables that occur in natural environments. However, an understanding of how stressors influence organism health can compensate for these limitations. Mechanistic knowledge can be used to account for species differences in basal biological function and variability in environmental factors, including spatial and temporal changes in the chemical, physical and biological milieu. Consequently, physiological understanding of biological function, and how this is altered by stressor exposure, can facilitate proactive, predictive risk assessment. In this perspective article, existing frameworks that utilize physiological knowledge (e.g. biotic ligand models, adverse outcomes pathways and mechanistic effect models), are outlined, and specific examples of how mechanistic understanding has been used to predict risk are highlighted. Future research approaches and data needs for extending the incorporation of physiological information into ecological risk assessments are discussed. Although the review focuses on chemical toxicants in aquatic systems, physical and biological stressors and terrestrial environments are also briefly considered. PMID:29564135

  9. Tetracycline compounds with non-antimicrobial organ protective properties: possible mechanisms of action

    Science.gov (United States)

    Griffin, Michael O.; Ceballos, Guillermo; Villarreal, Francisco

    2010-01-01

    Tetracyclines were developed as a result of the screening of soil samples for antibiotics. The firstt of these compounds, chlortetracycline, was introduced in 1947. Tetracyclines were found to be highly effective against various pathogens including rickettsiae, as well as both gram-positive and gram-negative bacteria, thus becoming the first class of broad spectrum antibiotics. Many other interesting properties, unrelated to their antibiotic activity, have been identified for tetracyclines which have led to widely divergent experimental and clinical uses. For example, tetracyclines are also an effective anti-malarial drug. Minocycline, which can readily cross cell membranes, is known to be a potent anti-apoptotic agent. Another tetracycline, doxycycline is known to exert anti-protease activities. Doxycycline can inhibit matrix metalloproteinases which contribute to tissue destruction activities in diseases such as periodontitis. A large body of literature has provided additional evidence for the “beneficial” actions of tetracyclines, including their ability to act as reactive oxygen species scavengers and anti-inflammatory agents. This review provides a summary of tetracycline’s multiple mechanisms of action as a means to understand their beneficial effects. PMID:20951211

  10. Endogenous money: the evolutionary versus revolutionary views

    OpenAIRE

    Louis-Philippe Rochon; Sergio Rossi

    2013-01-01

    The purpose of this paper is to shed light on the endogenous nature of money. Contrary to the established post-Keynesian, or evolutionary, view, this paper argues that money has always been endogenous, irrespective of the historical period. Instead of the evolutionary theory of money and banking that can be traced back to Chick (1986), this paper puts forward a revolutionary definition of endogenous money consistent with many aspects of post-Keynesian economics as well as with the monetary ci...

  11. Endogenous price flexibility and optimal monetary policy

    OpenAIRE

    Ozge Senay; Alan Sutherland

    2014-01-01

    Much of the literature on optimal monetary policy uses models in which the degree of nominal price flexibility is exogenous. There are, however, good reasons to suppose that the degree of price flexibility adjusts endogenously to changes in monetary conditions. This article extends the standard new Keynesian model to incorporate an endogenous degree of price flexibility. The model shows that endogenizing the degree of price flexibility tends to shift optimal monetary policy towards complete i...

  12. Ezetimibe Increases Endogenous Cholesterol Excretion in Humans.

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Ostlund, Richard E

    2017-05-01

    Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers low-density lipoprotein cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly mixing endogenous cholesterol pool into the stool. In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with low-density lipoprotein cholesterol 100 to 200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/d or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 in a lipid emulsion and dietary cholesterol with cholesterol-d 5 and sitostanol-d 4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30±4.3% (SE, P <0.0001) and low-density lipoprotein cholesterol 19.8±1.9% ( P =0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6±12.2% ( P <0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7±14.3% ( P <0.0001), whereas plasma cholesterol turnover rose 26.2±3.6% ( P =0.0096). Fecal bile acids were unchanged. Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603758. © 2017 American Heart Association, Inc.

  13. Endogenous, Imperfectly Competitive Business Cycles

    DEFF Research Database (Denmark)

    Whitta-Jacobsen, Hans Jørgen

    We investigate how imperfect competition affects the occurrence and the properties of endogenous, rational expectations business cycles in an overlapping generations model with constant returns to scale in production. The model has explicit product and labor markets all characterized...... by monopolistic competition. An implicit assumption of barriers to entry justifies that the number of firms is fixed even when positive profits occur. It turns out that both market power of firms on the product markets and market power of unions on the labor markets make the occurrence of cycles more likely....... In particular, imperfect competition on the product markets and the positive profits associated with it may have the effect that there is a cycle even if the labor supply curve is increasing in the real-wage rate. For competitive cycles is required not only a decreasing labor supply curve, but a wage elasticity...

  14. Heme oxygenase-1 enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Chenglong [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China); Zheng, Haining [Department of Hyperbaric Oxygen, Nanjing General Hospital of Nanjing Military Command, Nanjing (China); Huang, Shanshan; You, Na; Xu, Jiarong; Ye, Xiaolong; Zhu, Qun; Feng, Yamin; You, Qiang; Miao, Heng [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China); Ding, Dafa, E-mail: dingdafa2004@aliyun.com [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China); Lu, Yibing, E-mail: luyibing2004@126.com [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China)

    2015-10-01

    Injury and loss of podocytes play vital roles in diabetic nephropathy progression. Emerging evidence suggests autophagy, which is induced by multiple stressors including hyperglycemia, plays a protective role. Meanwhile, heme oxygenase-1 (HO-1) possesses powerful anti-apoptotic properties. Therefore, we investigated the impact of autophagy on podocyte apoptosis under diabetic conditions and its association with HO-1. Mouse podocytes were cultured in vitro; apoptosis was detected by flow cytometry. Transmission electron microscopy and biochemical autophagic flux assays were used to measure the autophagy markers microtubule-associated protein 1 light chain 3-II (LC3-II) and beclin-1. LC3-II and beclin-1 expression peaked 12–24 h after exposing podocytes to high glucose. Inhibition of autophagy with 3-methyladenine or Beclin-1 siRNAs or Atg 5 siRNAs sensitized cells to apoptosis, suggesting autophagy is a survival mechanism. HO-1 inactivation inhibited autophagy, which aggravated podocyte injury in vitro. Hemin-induced autophagy also protected podocytes from hyperglycemia in vitro and was abrogated by HO-1 siRNA. Adenosine monophosphate-activated protein kinase phosphorylation was higher in hemin-treated and lower in HO-1 siRNA-treated podocytes. Suppression of AMPK activity reversed HO-1-mediated Beclin-1 upregulation and autophagy, indicating HO-1-mediated autophagy is AMPK dependent. These findings suggest HO-1 induction and regulation of autophagy are potential therapeutic targets for diabetic nephropathy. - Highlights: • High glucose leads to increased autophagy in podocytes at an early stage. • The early autophagic response protects against high glucose-induced apoptosis. • Heme oxygenase-1 enhances autophagy and decreases high glucose -mediated apoptosis. • Heme oxygenase-1 induces autophagy through the activation of AMPK.

  15. Heme oxygenase-1 enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis

    International Nuclear Information System (INIS)

    Dong, Chenglong; Zheng, Haining; Huang, Shanshan; You, Na; Xu, Jiarong; Ye, Xiaolong; Zhu, Qun; Feng, Yamin; You, Qiang; Miao, Heng; Ding, Dafa; Lu, Yibing

    2015-01-01

    Injury and loss of podocytes play vital roles in diabetic nephropathy progression. Emerging evidence suggests autophagy, which is induced by multiple stressors including hyperglycemia, plays a protective role. Meanwhile, heme oxygenase-1 (HO-1) possesses powerful anti-apoptotic properties. Therefore, we investigated the impact of autophagy on podocyte apoptosis under diabetic conditions and its association with HO-1. Mouse podocytes were cultured in vitro; apoptosis was detected by flow cytometry. Transmission electron microscopy and biochemical autophagic flux assays were used to measure the autophagy markers microtubule-associated protein 1 light chain 3-II (LC3-II) and beclin-1. LC3-II and beclin-1 expression peaked 12–24 h after exposing podocytes to high glucose. Inhibition of autophagy with 3-methyladenine or Beclin-1 siRNAs or Atg 5 siRNAs sensitized cells to apoptosis, suggesting autophagy is a survival mechanism. HO-1 inactivation inhibited autophagy, which aggravated podocyte injury in vitro. Hemin-induced autophagy also protected podocytes from hyperglycemia in vitro and was abrogated by HO-1 siRNA. Adenosine monophosphate-activated protein kinase phosphorylation was higher in hemin-treated and lower in HO-1 siRNA-treated podocytes. Suppression of AMPK activity reversed HO-1-mediated Beclin-1 upregulation and autophagy, indicating HO-1-mediated autophagy is AMPK dependent. These findings suggest HO-1 induction and regulation of autophagy are potential therapeutic targets for diabetic nephropathy. - Highlights: • High glucose leads to increased autophagy in podocytes at an early stage. • The early autophagic response protects against high glucose-induced apoptosis. • Heme oxygenase-1 enhances autophagy and decreases high glucose -mediated apoptosis. • Heme oxygenase-1 induces autophagy through the activation of AMPK

  16. Electrical stimulation of the vagus nerve protects against cerebral ischemic injury through an anti-infammatory mechanism

    Directory of Open Access Journals (Sweden)

    Yao-xian Xiang

    2015-01-01

    Full Text Available Vagus nerve stimulation exerts protective effects against ischemic brain injury; however, the underlying mechanisms remain unclear. In this study, a rat model of focal cerebral ischemia was established using the occlusion method, and the right vagus nerve was given electrical stimulation (constant current of 0.5 mA; pulse width, 0.5 ms; frequency, 20 Hz; duration, 30 seconds; every 5 minutes for a total of 60 minutes 30 minutes, 12 hours, and 1, 2, 3, 7 and 14 days after surgery. Electrical stimulation of the vagus nerve substantially reduced infarct volume, improved neurological function, and decreased the expression levels of tumor necrosis factor-and interleukin- 6 in rats with focal cerebral ischemia. The experimental findings indicate that the neuroprotective effect of vagus nerve stimulation following cerebral ischemia may be associated with the inhibition of tumor necrosis factor- and interleukin-6 expression.

  17. Mechanism of Human Influenza Virus RNA Persistence and Virion Survival in Feces: Mucus Protects Virions From Acid and Digestive Juices.

    Science.gov (United States)

    Hirose, Ryohei; Nakaya, Takaaki; Naito, Yuji; Daidoji, Tomo; Watanabe, Yohei; Yasuda, Hiroaki; Konishi, Hideyuki; Itoh, Yoshito

    2017-07-01

    Although viral RNA or infectious virions have been detected in the feces of individuals infected with human influenza A and B viruses (IAV/IBV), the mechanism of viral survival in the gastrointestinal tract remains unclear. We developed a model that attempts to recapitulate the conditions encountered by a swallowed virus. While IAV/IBV are vulnerable to simulated digestive juices (gastric acid and bile/pancreatic juice), highly viscous mucus protects viral RNA and virions, allowing the virus to retain its infectivity. Our results suggest that virions and RNA present in swallowed mucus are not inactivated or degraded by the gastrointestinal environment, allowing their detection in feces. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  18. Poor Adherence to Lung-Protective Mechanical Ventilation in Pediatric Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Ward, Shan L; Quinn, Carson M; Valentine, Stacey L; Sapru, Anil; Curley, Martha A Q; Willson, Douglas F; Liu, Kathleen D; Matthay, Michael A; Flori, Heidi R

    2016-10-01

    To determine the frequency of low-tidal volume ventilation in pediatric acute respiratory distress syndrome and assess if any demographic or clinical factors improve low-tidal volume ventilation adherence. Descriptive post hoc analysis of four multicenter pediatric acute respiratory distress syndrome studies. Twenty-six academic PICU. Three hundred fifteen pediatric acute respiratory distress syndrome patients. All patients who received conventional mechanical ventilation at hours 0 and 24 of pediatric acute respiratory distress syndrome who had data to calculate ideal body weight were included. Two cutoff points for low-tidal volume ventilation were assessed: less than or equal to 6.5 mL/kg of ideal body weight and less than or equal to 8 mL/kg of ideal body weight. Of 555 patients, we excluded 240 for other respiratory support modes or missing data. The remaining 315 patients had a median PaO2-to-FIO2 ratio of 140 (interquartile range, 90-201), and there were no differences in demographics between those who did and did not receive low-tidal volume ventilation. With tidal volume cutoff of less than or equal to 6.5 mL/kg of ideal body weight, the adherence rate was 32% at hour 0 and 33% at hour 24. A low-tidal volume ventilation cutoff of tidal volume less than or equal to 8 mL/kg of ideal body weight resulted in an adherence rate of 58% at hour 0 and 60% at hour 24. Low-tidal volume ventilation use was no different by severity of pediatric acute respiratory distress syndrome nor did adherence improve over time. At hour 0, overweight children were less likely to receive low-tidal volume ventilation less than or equal to 6.5 mL/kg ideal body weight (11% overweight vs 38% nonoverweight; p = 0.02); no difference was noted by hour 24. Furthermore, in the overweight group, using admission weight instead of ideal body weight resulted in misclassification of up to 14% of patients as receiving low-tidal volume ventilation when they actually were not. Low

  19. Molecular and cellular mechanisms of vitamin D3 protection in experimental prednisolone-induced osteoporosis

    Directory of Open Access Journals (Sweden)

    I.O. Shymanskyi

    2017-08-01

    Full Text Available Background. Osteoporosis is the most common side effect of glucocorticoid (GC therapy. Vitamin D is known to play a crucial role in bone remodeling, but the precise molecular mechanisms of its action on GC-induced impairments of cytokine systems, in particular RANK (receptor activator of nuclear factor kappa-B/RANKL (RANK ligand/OPG (osteoprotegerin, are still controversial. Thus, the purpose of the study was to evaluate GC-induced changes in the RANK/RANKL/OPG system and osteocalcin synthesis in rat bone depending on vitamin D bioavailability and vitamin D receptor (VDR expression. Materials and methods. Female Wistar rats received prednisolone (5 mg/kg b.w. with or without 100 IU of vitamin D3 (for 30 days. The levels of VDR, osteocalcin, RANK, RANKL and OPG in bone tissue were determined by western blotting. Blood serum 25OHD was assayed by enzyme-linked immunosorbent assay. The levels of Ca2+, Pi, activity of alkaline phosphatase (AP and its bone isoenzyme were determined using spectrophotometry. Results. Prednisolone significantly lowered 25OHD content in the blood serum and VDR level in bone tissue that has been accompanied by an elevation of the AP bone isoenzyme activity in the blood serum, hypocalcemia and hypophosphatemia. A significant decrease in the expression of osteocalcin, a well-known marker of bone formation, was also observed. GC-induced disturbances in vitamin D status led to a reduction of the RANK and OPG level, while RANKL level was unaffected. Vitamin D3 administration restored 25OHD and VDR levels that resulted in amelioration of GC-induced changes in bone tissue and normalization of mineral metabolism through elevation of RANK, OPG and osteocalcin levels. Conclusions. Prednisolone-induced imbalance in the RANK/RANKL/OPG and osteocalcin systems is related to the reduction of vitamin D bioavailability and impairments in VDR signaling. Thus, normalization of vitamin D bioavailability might be perspective in reducing the

  20. Protective effects of ulinastatin on cardiac dysfunction in mice with heat stroke and its mechanism

    Directory of Open Access Journals (Sweden)

    Jing-jing JI

    2017-06-01

    Full Text Available Objective To examine the effects of ulinastatin (UTI on cardiac dysfunction in mice with heat stroke and its possible mechanism. Methods 20 mice were divided into four groups randomly: room temperature plus normal saline (Sham+NS, room temperature plus UTI (Sham+UTI, heat stress plus normal saline (HS+NS, heat stress plus UTI (HS+UTI, 5 each. 105U/kg UTI was delivered by intraperitoneal injection before the onset of the heat stress. Room temperature groups were housed at room temperature (23.0±0.5℃, while heat stress groups were kept in an incubator at 36.5±0.5℃ and humidity of 65.0%±2.0%. The rectal temperature (Tr reaching 42℃ was taken as severe heat stroke, and the time in two heat stress groups was recorded. The mice were transferred to the room temperature (23.0±0.5℃ for natural cooling after the heat stroke onset. 6 hours after the treatment, cardiac output (CO was ultrasonographically detected, the myocardium was separated for histopathological examination and the expression of total p38 and phosphorylated p38 (p-p38 was determined by Western blotting. Results The time to reach 42℃ in HS+UTI group was significantly prolonged (P=0.044. Compared with the Sham+NS group, the CO in HS+NS and HS+UTI group decreased significantly (P=0.017, and the score of myocardial inflammation (P<0.001 and p-p38/p38 ratio (P<0.001 increased. The CO was significantly higher in HS+UTI group than in HS+NS group (P=0.030, and the score of myocardial inflammation (P<0.001 and p-p38/p38 ratio (P=0.001 were significantly lower. Conclusion Ulinastatin might improve the cardiac function in mice with heat stroke by decreasing the p-p38 and alleviating the inflammation response. DOI: 10.11855/j.issn.0577-7402.2017.04.04

  1. Mechanical properties of superelastic Cu–Al–Be wires at cold temperatures for the seismic protection of bridges

    International Nuclear Information System (INIS)

    Zhang Yunfeng; Zhu Songye; Camilleri, Joseph A

    2008-01-01

    This paper examines the suitability of superelastic copper–aluminum–beryllium (Cu–Al–Be) alloy wires for the seismic protection of bridges in cold regions. Experimental results for the mechanical properties of superelastic Cu–Al–Be alloy wires at a variety of temperatures and loading rates are presented. This research is motivated by the recent use of shape memory alloys for bridge restrainers subject to harsh winter conditions, especially in cold regions. Bridge restrainers made of superelastic Cu–Al–Be wire strands are expected to be used for protecting bridge decks from excessive displacement when subjected to strong earthquakes. Using a temperature chamber, superelastic Cu–Al–Be wires with a diameter of 1.4 mm were tested under uniaxial cyclic loading at various loading rates and cold temperatures. The test results from 23 to −50 °C demonstrate that Cu–Al–Be exhibits superelastic behavior at cold temperatures down to −85 °C. It is also found that with decreasing temperature the transformation plateau stress is reduced while its fatigue life increases under cyclic testing

  2. Acute Responses of Microorganisms from Membrane Bioreactors in the Presence of NaOCl: Protective Mechanisms of Extracellular Polymeric Substances.

    Science.gov (United States)

    Han, Xiaomeng; Wang, Zhiwei; Chen, Mei; Zhang, Xingran; Tang, Chuyang Y; Wu, Zhichao

    2017-03-21

    Extracellular polymeric substances (EPS) are key foulants in membrane bioreactors (MBRs). However, their positive functions of protecting microorganisms from environmental stresses, e.g., during in situ hypochlorite chemical cleaning of membranes, have not been adequately elucidated. In this work, we investigated the response of microorganisms in an MBR to various dosages of NaOCl, with a particular emphasis on the mechanistic roles of EPS. Results showed that functional groups in EPS such as the hydroxyl and amino groups were attacked by NaOCl, causing the oxidation of polysaccharides, denaturation of amino acids, damage to protein secondary structure, and transformation of tryptophan protein-like substances to condensed aromatic ring substances. The presence of EPS alleviated the negative impacts on catalase and superoxide dismutase, which in turn reduced the concentration of reactive oxygen species (ROS) in microbial cells. The direct extracellular reaction and the mitigated intracellular oxidative responses facilitated the maintenance of microbial metabolism, as indicated by the quantity of adenosine triphosphate and the activity of dehydrogenase. The reaction with NaOCl also led to the changes of cell integrity and adhesion properties of EPS, which promoted the release of organic matter into bulk solution. Our results systematically demonstrate the protective roles of EPS and the underlying mechanisms in resisting the environmental stress caused by NaOCl, which provides important implications for in situ chemical cleaning in MBRs.

  3. Mechanism of Mitochondrial Connexin43′s Protection of the Neurovascular Unit under Acute Cerebral Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Shuai Hou

    2016-05-01

    Full Text Available We observed mitochondrial connexin43 (mtCx43 expression under cerebral ischemia-reperfusion (I/R injury, analyzed its regulation, and explored its protective mechanisms. Wistar rats were divided into groups based on injections received before middle cerebral artery occlusion (MCAO. Cerebral infarction volume was detected by 2,3,5-triphenyltetrazolim chloride staining, and cell apoptosis was observed by transferase dUTP nick end labeling. We used transmission electron microscopy to observe mitochondrial morphology and determined superoxide dismutase (SOD activity and malondialdehyde (MDA content. MtCx43, p-mtCx43, protein kinase C (PKC, and p-PKC expression were detected by Western blot. Compared with those in the IR group, cerebral infarction volumes in the carbenoxolone (CBX and diazoxide (DZX groups were obviously smaller, and the apoptosis indices were down-regulated. Mitochondrial morphology was damaged after I/R, especially in the IR and 5-hydroxydecanoic acid (5-HD groups. Similarly, decreased SOD activity and increased MDA were observed after MCAO; CBX, DZX, and phorbol-12-myristate-13-acetate (PMA reduced mitochondrial functional injury. Expression of mtCx43 and p-mtCx43 and the p-Cx43/Cx43 ratio were significantly lower in the IR group than in the sham group. These abnormalities were ameliorated by CBX, DZX, and PMA. MtCx43 may protect the neurovascular unit from acute cerebral IR injury via PKC activation induced by mitoKATP channel agonists.

  4. Hydraulic testing of intravascular axial flow blood pump designs with a protective cage of filaments for mechanical cavopulmonary assist.

    Science.gov (United States)

    Kapadia, Jugal Y; Pierce, Kathryn C; Poupore, Amy K; Throckmorton, Amy L

    2010-01-01

    To provide hemodynamic support to patients with a failing single ventricle, we are developing a percutaneously inserted, magnetically levitated axial flow blood pump designed to augment pressure in the cavopulmonary circulation. The device is designed to serve as a bridge-to-transplant, bridge-to-recovery, bridge-to-hemodynamic stability, or bridge-to-surgical reconstruction. This study evaluated the hydraulic performance of three blood pump prototypes (a four-bladed impeller, a three-bladed impeller, and a three-bladed impeller with a four-bladed diffuser) whose designs evolved from previous design optimization phases. Each prototype included the same geometric protective cage of filaments, which stabilize the rotor within the housing and protect the housing wall from the rotating blades. All prototypes delivered pressure rises over a range of flow rates and rotational speeds that would be sufficient to augment hemodynamic conditions in the cavopulmonary circulation. The four-bladed impeller outperformed the two remaining prototypes by >40%; this design was able to generate a pressure rise of 4-28 mm Hg for flow rates of 0.5-10 L/min at rotational speeds of 4,000-7,000 RPM. Successful development of this blood pump will provide clinicians with a feasible therapeutic option for mechanically supporting the failing Fontan.

  5. Cellular and Molecular Mechanisms in Vascular Smooth Muscle Cells by which Total Saponin Extracted from Tribulus Terrestris Protects Against Artherosclerosis

    Directory of Open Access Journals (Sweden)

    Mengquan Li

    2013-11-01

    Full Text Available Background/Aims: Total saponin extracted from Tribulus terrestris (TSETT has been reported to protect against atherosclerosis. We here investigate the cellular and molecular mechanisms of TSETT underlying protection against atherosclerosis. Methods: Cell proliferation was measured with Methyl thiazolyl tetrazolium (MTT; Intracellular H2O2 was measured with DCFH-DA, a fluorescent dye; Intracellular free Ca2+ was measured with a confocal laser scanning microscopy; Genes expression was measured with gene array and real-time quantitative polymerase chain reaction (RT-PCR; Phosphorylation of extracellular signal-regulated kinase 1/2 (phospho-ERK1/2 was measured with cell-based enzyme-linked immunosorbent assay (ELISA and western blotting. Results: TSETT significantly suppressed the increase in cells proliferation induced by angiotensin II, significantly suppressed the increase in the intracellular production of H2O2 induced by angiotensin II, significantly inhibited the increase in intracellular free Ca2+ induced by H2O2, significantly inhibited the increase in phospho-ERK1/2 induced by angiotensin II; significantly inhibited the increase in mRNA expression of c-fos, c-jun and pkc-α induced by angiotensin II. Conclusion: These findings provide a new insight into the antiatherosclerotic properties of TSETT and provide a pharmacological basis for the clinical application of TSETT in anti-atherosclerosis.

  6. Cellular and molecular mechanisms in vascular smooth muscle cells by which total saponin extracted from Tribulus terrestris protects against artherosclerosis.

    Science.gov (United States)

    Li, Mengquan; Guan, Yue; Liu, Jiaqi; Zhai, Fengguo; Zhang, Xiuping; Guan, Lixin

    2013-01-01

    Total saponin extracted from Tribulus terrestris (TSETT) has been reported to protect against atherosclerosis. We here investigate the cellular and molecular mechanisms of TSETT underlying protection against atherosclerosis. Cell proliferation was measured with Methyl thiazolyl tetrazolium (MTT); Intracellular H2O2 was measured with DCFH-DA, a fluorescent dye; Intracellular free Ca(2+) was measured with a confocal laser scanning microscopy; Genes expression was measured with gene array and real-time quantitative polymerase chain reaction (RT-PCR); Phosphorylation of extracellular signal-regulated kinase 1/2 (phospho-ERK1/2) was measured with cell-based enzyme-linked immunosorbent assay (ELISA) and western blotting. TSETT significantly suppressed the increase in cells proliferation induced by angiotensin II, significantly suppressed the increase in the intracellular production of H2O2 induced by angiotensin II, significantly inhibited the increase in intracellular free Ca(2+) induced by H2O2, significantly inhibited the increase in phospho-ERK1/2 induced by angiotensin II; significantly inhibited the increase in mRNA expression of c-fos, c-jun and pkc-α induced by angiotensin II. These findings provide a new insight into the antiatherosclerotic properties of TSETT and provide a pharmacological basis for the clinical application of TSETT in anti-atherosclerosis. © 2013 S. Karger AG, Basel.

  7. Protective effects of melittin on transforming growth factor-β1 injury to hepatocytes via anti-apoptotic mechanism

    International Nuclear Information System (INIS)

    Lee, Woo-Ram; Park, Ji-Hyun; Kim, Kyung-Hyun; Park, Yoon-Yub; Han, Sang-Mi; Park, Kwan-kyu

    2011-01-01

    Melittin is a cationic, hemolytic peptide that is the main toxic component in the venom of the honey bee (Apis mellifera). Melittin has multiple effects, including anti-bacterial, anti-viral and anti-inflammatory, in various cell types. However, the anti-apoptotic mechanisms of melittin have not been fully elucidated in hepatocytes. Apoptosis contributes to liver inflammation and fibrosis. Knowledge of the apoptotic mechanisms is important to develop new and effective therapies for treatment of cirrhosis, portal hypertension, liver cancer, and other liver diseases. In the present study, we investigated the anti-apoptotic effect of melittin on transforming growth factor (TGF)-β1-induced apoptosis in hepatocytes. TGF-β1-treated hepatocytes were exposed to low doses (0.5 and 1 μg/mL) and high dose (2 μg/mL) of melittin. The low doses significantly protected these cells from DNA damage in TGF-β1-induced apoptosis compared to the high dose. Also, melittin suppressed TGF-β1-induced apoptotic activation of the Bcl-2 family and caspase family of proteins, which resulted in the inhibition of poly-ADP-ribose polymerase (PARP) cleavage. These results demonstrate that TGF-β1 induces hepatocyte apoptosis and that an optimal dose of melittin exerts anti-apoptotic effects against TGF-β1-induced injury to hepatocytes via the mitochondrial pathway. These results suggest that an optimal dose of melittin can serve to protect cells against TGF-β1-mediated injury. - Highlights: → We investigated the anti-apoptotic effect of melittin on TGF-β1-induced hepatocyte. → TGF-β1 induces hepatocyte apoptosis. → TGF-β1-treated hepatocytes were exposed to low doses and high dose of melittin. → Optimal dose of melittin exerts anti-apoptotic effects to hepatocytes.

  8. Variable lung protective mechanical ventilation decreases incidence of postoperative delirium and cognitive dysfunction during open abdominal surgery.

    Science.gov (United States)

    Wang, Ruichun; Chen, Junping; Wu, Guorong

    2015-01-01

    Postoperative cognitive dysfunction (POCD) is a subtle impairment of cognitive abilities and can manifest on different neuropsychological features in the early postoperative period. It has been proved that the use of mechanical ventilation (MV) increased the development of delirium and POCD. However, the impact of variable and conventional lung protective mechanical ventilation on the incidence of POCD still remains unknown, which was the aim of this study. 162 patients scheduled to undergo elective gastrointestinal tumor resection via laparotomy in Ningbo No. 2 hospital with expected duration >2 h from June, 2013 to June, 2015 were enrolled in this study. Patients included were divided into two groups according to the scheme of lung protective MV, variable ventilation group (VV group, n=79) and conventional ventilation group (CV group, n=83) by randomization performed by random block randomization. The plasma levels of inflammatory cytokines, characteristics of the surgical procedure, incidence of delirium and POCD were collected and compared. Postoperative delirium was detected in 36 of 162 patients (22.2%) and 12 patients of these (16.5%) belonged to the VV group while 24 patients (28.9%) were in the CV group (P=0.036). POCD on the seventh postoperative day in CV group (26/83, 31.3%) was increased in comparison with the VV group (14/79, 17.7%) with significant statistical difference (P=0.045). The levels of inflammatory cytokines were all significantly higher in CV group than those in VV group on the 1st postoperative day (Pprotective MV decreased the incidence of postoperative delirium and POCD by reducing the systemic proinflammatory response.

  9. Solar radiation induced skin damage: review of protective and preventive options.

    Science.gov (United States)

    Svobodová, Alena; Vostálová, Jitka

    2010-12-01

    Solar energy has a number of short- and long-term detrimental effects on skin that can result in several skin disorders. The aim of this review is to summarise current knowledge on endogenous systems within the skin for protection from solar radiation and present research findings to date, on the exogenous options for such skin photoprotection. Endogenous systems for protection from solar radiation include melanin synthesis, epidermal thickening and an antioxidant network. Existing lesions are eliminated via repair mechanisms. Cells with irreparable damage undergo apoptosis. Excessive and chronic sun exposure however can overwhelm these mechanisms leading to photoaging and the development of cutaneous malignancies. Therefore exogenous means are a necessity. Exogenous protection includes sun avoidance, use of photoprotective clothing and sufficient application of broad-spectrum sunscreens as presently the best way to protect the skin. However other strategies that may enhance currently used means of protection are being investigated. These are often based on the endogenous protective response to solar light such as compounds that stimulate pigmentation, antioxidant enzymes, DNA repair enzymes, non-enzymatic antioxidants. More research is needed to confirm the effectiveness of new alternatives to photoprotection such as use of DNA repair and antioxidant enzymes and plant polyphenols and to find an efficient way for their delivery to the skin. New approaches to the prevention of skin damage are important especially for specific groups of people such as (young) children, photosensitive people and patients on immunosuppressive therapy. Changes in public awareness on the subject too must be made.

  10. The epigenetic alterations of endogenous retroelements in aging.

    Science.gov (United States)

    Cardelli, Maurizio

    2018-02-16

    Endogenous retroelements, transposons that mobilize through RNA intermediates, include some of the most abundant repetitive sequences of the human genome, such as Alu and LINE-1 sequences, and human endogenous retroviruses. Recent discoveries demonstrate that these mobile genetic elements not only act as intragenomic parasites, but also exert regulatory roles in living cells. The risk of genomic instability represented by endogenous retroelements is normally counteracted by a series of epigenetic control mechanisms which include, among the most important, CpG DNA methylation. Indeed, most of the genomic CpG sites subjected to DNA methylation in the nuclear DNA are carried by these repetitive elements. As other parts of the genome, endogenous retroelements and other transposable elements are subjected to deep epigenetic alterations during aging, repeatedly observed in the context of organismal and cellular senescence, in human and other species. This review summarizes the current status of knowledge about the epigenetic alterations occurring in this large, non-genic portion of the genome in aging and age-related conditions, with a focus on the causes and the possible functional consequences of these alterations. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Cinnamaldehyde promotes root branching by regulating endogenous hydrogen sulfide.

    Science.gov (United States)

    Xue, Yan-Feng; Zhang, Meng; Qi, Zhong-Qiang; Li, You-Qin; Shi, Zhiqi; Chen, Jian

    2016-02-01

    Cinnamaldehyde (CA) has been widely applied in medicine and food preservation. However, whether and how CA regulates plant physiology is largely unknown. To address these gaps, the present study investigated the beneficial effect of CA on root branching and its possible biochemical mechanism. The lateral root (LR) formation of pepper seedlings could be markedly induced by CA at specific concentrations without any inhibitory effect on primary root (PR) growth. CA could induce the generation of endogenous hydrogen sulfide (H2S) by increasing the activity of L-cysteine desulfhydrase in roots. By fluorescently tracking endogenous H2S in situ, it could be clearly observed that H2S accumulated in the outer layer cells of the PR where LRs emerge. Sodium hydrosulfide (H2S donor) treatment induced LR formation, while hypotaurine (H2S scavenger) showed an adverse effect. The addition of hypotaurine mitigated the CA-induced increase in endogenous H2S level, which in turn counteracted the inducible effect of CA on LR formation. CA showed great potential in promoting LR formation, which was mediated by endogenous H2S. These results not only shed new light on the application of CA in agriculture but also extend the knowledge of H2S signaling in the regulation of root branching. © 2015 Society of Chemical Industry.

  12. Endogenous mitigation of H2S inside of the landfills.

    Science.gov (United States)

    Fang, Yuan; Zhong, Zhong; Shen, Dongsheng; Du, Yao; Xu, Jing; Long, Yuyang

    2016-02-01

    Vast quantities of hydrogen sulfide (H2S) emitted from landfill sites require urgent disposal. The current study focused on source control and examined the migration and conversion behavior of sulfur compounds in two lab-scale simulated landfills with different operation modes. It aimed to explore the possible strategies and mechanisms for H2S endogenous mitigation inside of landfills during decomposition. It was found that the strength of H2S emissions from the landfill sites was dependent on the municipal solid waste (MSW) degradation speed and vertical distribution of sulfide. Leachate recirculation can shorten both the H2S influence period and pollution risk to the surrounding environment. H2S endogenous mitigation may be achieved by chemical oxidation, biological oxidation, adsorption, and/or precipitation in different stages. Migration and conversion mainly affected H2S release behavior during the initial stabilization phase in the landfill. Microbial activities related to sulfur, nitrogen, and iron can further promote H2S endogenous mitigation during the high reducing phase. Thus, H2S endogenous mitigation can be effectively enhanced via control of the aforementioned processes.

  13. Protecting knowledge

    DEFF Research Database (Denmark)

    Sofka, Wolfgang; de Faria, Pedro; Shehu, Edlira

    2018-01-01

    Most firms use secrecy to protect their knowledge from potential imitators. However, the theoretical foundations for secrecy have not been well explored. We extend knowledge protection literature and propose theoretical mechanisms explaining how information visibility influences the importance...... of secrecy as a knowledge protection instrument. Building on mechanisms from information economics and signaling theory, we postulate that secrecy is more important for protecting knowledge for firms that have legal requirements to reveal information to shareholders. Furthermore, we argue that this effect...... and a firm's investment in fixed assets. Our findings inform both academics and managers on how firms balance information disclosure requirements with the use of secrecy as a knowledge protection instrument....

  14. Eye retraction in the giant guitarfish, Rhynchobatus djiddensis (Elasmobranchii: Batoidea): a novel mechanism for eye protection in batoid fishes.

    Science.gov (United States)

    Tomita, Taketeru; Murakumo, Kiyomi; Miyamoto, Kei; Sato, Keiichi; Oka, Shin-ichiro; Kamisako, Haruka; Toda, Minoru

    2016-02-01

    Eye retraction behavior has evolved independently in some vertebrate linages such as mudskippers (fish), frogs and salamanders (amphibians), and cetaceans (mammals). In this paper, we report the eye retraction behavior of the giant guitarfish (Rhynchobatus djiddensis) for the first time, and discuss its mechanism and function. The eye retraction distance was nearly the same as the diameter of the eyeball itself, indicating that eye retraction in the giant guitarfish is probably one of the largest among vertebrates. Eye retraction is achieved by unique arrangement of the eye muscle: one of the anterior eye muscles (the obliquus inferior) is directed ventrally from the eyeball and attaches to the ventral surface of the neurocranium. Due to such muscle arrangement, the obliquus inferior can pull the eyeball ventrally. This mechanism was also confirmed by electrical stimulation of the obliquus inferior. The eye retraction ability of the giant guitarfish likely represents a novel eye protection behavior of elasmobranch fishes. Copyright © 2015 Elsevier GmbH. All rights reserved.

  15. Mechanism study of endothelial protection and inhibits platelet activation of low molecular weight fucoidan from Laminaria japonica

    Science.gov (United States)

    Chen, Anjin; Zhang, Fang; Shi, Jie; Zhao, Xue; Yan, Meixing

    2016-10-01

    Several studies have indicated that fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica could inhibit the activation of platelets directly by reducing the platelet aggregation. To explore the direct effect of LMW fucoidan on the platelet system furthermore and examine the possible mechanism, the endothelial protection and inhibits platelet activation effects of two LMW fucoidan were investigated. In the present study, Endothelial injury model of rats was made by injection of adrenaline (0.4 mg kg-1) and human umbilical vein endothelial cells were cultured. vWF level was be investigated in vivo and in vitro as an important index of endothelial injury. LMW fucoidan could significantly reduce vWF level in vascular endothelial injury rats and also significantly reduce vWF level in vitro. The number of EMPs was be detected as another important index of endothelial injury. The results showed that LMW fucoidan reduced EMPs stimulated by tumor necrosis factor. In this study, it was found that by inhibiting platelet adhesion, LMW fucoidan played a role in anti-thrombosis and the specific mechanism of action is to inhibit the flow of extracellular Ca2+. All in a word, LMW fucoidan could inhibit the activation of platelets indirectly by reducing the concentration of EMPs and vWF, at the same time; LMW fucoidan inhibited the activation of platelets directly by inhibiting the flow of extracellular Ca2+.

  16. Interplay between endogenous and exogenous fluctuations in financial markets

    OpenAIRE

    Gontis, Vygintas

    2016-01-01

    We address microscopic, agent based, and macroscopic, stochastic, modeling of the financial markets combining it with the exogenous noise. The interplay between the endogenous dynamics of agents and the exogenous noise is the primary mechanism responsible for the observed long-range dependence and statistical properties of high volatility return intervals. By exogenous noise we mean information flow or/and order flow fluctuations. Numerical results based on the proposed model reveal that the ...

  17. Human neuromelanin: an endogenous microglial activator for dopaminergic neuron death

    OpenAIRE

    Zhang, Wei; Zecca, Luigi; Wilson, Belinda; Ren, RW; Wang, Yong-jun; Wang, Xiao-min; Hong, Jau-Shyong

    2013-01-01

    Substantial evidence indicates that neuroinflammation caused by over-activation of microglial in the substantia nigra is critical in the pathogenesis of dopaminergic neurodegeneration in Parkinson’s disease (PD). Increasing data demonstrates that environmental factors such as rotenone, paraquat play pivotal roles in the death of dopaminergic neurons. Here, potential role and mechanism of neuromelanin (NM), a major endogenous component in dopaminergic neurons of the substantia nigra, on microg...

  18. Applying Endogenous Knowledge in the African Context ...

    African Journals Online (AJOL)

    The question presented in this article is how to improve the dispute resolution competence of practitioners in Africa. The response offered involves enhancing the endogenous knowledge of a dispute and how to resolve it. This requires not only an understanding of what endogenous knowledge is, but also an alignment of ...

  19. Endogenous Peer Effects: Fact or Fiction?

    Science.gov (United States)

    Yeung, Ryan; Nguyen-Hoang, Phuong

    2016-01-01

    The authors examine endogenous peer effects, which occur when a student's behavior or outcome is a function of the behavior or outcome of his or her peer group. Endogenous peer effects have important implications for educational policies such as busing, school choice and tracking. In this study, the authors quantitatively review the literature on…

  20. Human endogenous retroviruses and ADHD.

    Science.gov (United States)

    Balestrieri, Emanuela; Pitzianti, Mariabernarda; Matteucci, Claudia; D'Agati, Elisa; Sorrentino, Roberta; Baratta, Antonia; Caterina, Rosa; Zenobi, Rossella; Curatolo, Paolo; Garaci, Enrico; Sinibaldi-Vallebona, Paola; Pasini, Augusto

    2014-08-01

    Several lines of evidences suggest that human endogenous retroviruses (HERVs) are implicated in the development of many complex diseases with a multifactorial aetiology and a strong heritability, such as neurological and psychiatric diseases. Attention deficit hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that results from a complex interaction of environmental, biological and genetic factors. Our aim was to analyse the expression levels of three HERV families (HERV-H, K and W) in patients with ADHD. The expression of retroviral mRNAs from the three HERV families was evaluated in peripheral blood mononuclear cells (PBMCs) from 30 patients with ADHD and 30 healthy controls by quantitative RT-PCR. The expression levels of HERV-H are significantly higher in patients with ADHD compared to healthy controls, while there are no differences in the expression levels of HERV-K and W. Since the ADHD aetiology is due to a complex interaction of environmental, biological and genetic factors, HERVs may represent one link among these factors and clinical phenotype of ADHD. A future confirmation of HERV-H overexpression in a larger number of ADHD patients will make possible to identify it as a new parameter for this clinical condition, also contributing to deepen the study on the role of HERVs in the neurodevelopment diseases.

  1. Molecular mechanisms underlying the protective effects of hydrogen-saturated saline on noise-induced hearing loss.

    Science.gov (United States)

    Chen, Liwei; Han, Mingkun; Lu, Yan; Chen, Daishi; Sun, Xuejun; Yang, Shiming; Sun, Wei; Yu, Ning; Zhai, Suoqiang

    2017-10-01

    This study aimed to explore the molecular mechanism of the protective effects of hydrogen-saturated saline on NIHL. Guinea pigs were divided into three groups: hydrogen-saturated saline; normal saline; and control. For saline administration, the guinea pigs were given daily abdominal injections 3 d before and 1 h before noise exposure. ABR were tested to examine cochlear physiology changes. The changes of 8-hydroxy-desoxyguanosine (8-HOdG), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), intercellular cell adhesion molecule-1 (ICAM-1) and high mobility group box-1 protein (HMGB1) in the cochlea were also examined. The results showed that pre-treatment with hydrogen-saturated saline could significantly attenuate noise-induced hearing loss. The concentration of 8-HOdG was also significantly decreased in the hydrogen-saturated saline group compared with the normal saline group. After noise exposure, the concentrations of IL-1, IL-6, TNF-α, and ICAM-1 in the cochlea of guinea pigs in the hydrogen-saturated saline group were dramatically reduced compared to those in the normal saline group. The concentrations of HMGB-1 and IL-10 in the hydrogen-saturated saline group were significantly higher than in those in the normal saline group immediately and at 7 d after noise exposure. This study revealed for the first time the protective effects of hydrogen-saturated saline on noise-induced hearing loss (NIHL) are related to both the anti-oxidative activity and anti-inflammatory activity.

  2. [The study of the protective effect and its mechanism of Edaravone to neurons with hydrogen peroxide stimulated].

    Science.gov (United States)

    Long, Hao; Zhang, Ning; Fan, Jin; Li, Qing-qing; Li, Yi-ming; Tang, Jian; Cheng, Gang; Yin, Guo-yong; Cai, Wei-hua

    2013-03-01

    To prove the protective effect of Edaravone to neurons and to study the particular mechanism. Neurons were collected from 18-day fetal rat brains and a culture of almost pure neurons was obtained after 14-day culture, then the cells were randomly assigned to one of the three groups: control group, hydrogen peroxide (H₂O₂)-treated group, and Edaravone-treated group. In H₂O₂-treated group, 300 µmol/L H₂O₂ was added to the medium, followed by returning to the normal culture for the presupposition of time. In Edaravone-treated group, 500 µmol/L Edaravone was prophylactically added to the medium for 30 minutes before the insult. Morphology of mitochondria was visualized by transmission electron microscopy. The rate of apoptotic cells was detected by flow cytometry analysis. The relationships between the proteins and the key proteins expressions were observed by immunoprecipitation and immunoblotting. Compared to the Edaravone-treated group, mitochondria in H₂O₂-treated group displayed more vesicular matrix compartments at the same time. Percentage of apoptotic cells in H₂O₂-treated group after 0.5, 2, 6 and 12 h were 14.40% ± 1.23%, 45.50% ± 2.81%, 56.40% ± 3.53%, 62.50% ± 4.23%, which were higher than control group (F = 274.8, P Edaravone-treated group were 0.90% ± 0.07%, 1.10% ± 0.08%, 3.50% ± 1.90%, 12.60% ± 1.10%, which were lower than H₂O₂-treated group (F = 362.7, P Edaravone-treated group. As a free radical scavenger, the Edaravone could protect neurons by inhibiting the activity of JNK, the disassociation of BAD from 14-3-3 and the translocation of BAX from the cytosol to mitochondria.

  3. Protective effects of total glucosides of paeony and the underlying mechanisms in carbon tetrachloride-induced experimental liver injury

    Science.gov (United States)

    Qin, Ying; Tian, Ya-ping

    2011-01-01

    Introduction We explored the protective effects of total glucosides of paeony (TGP) and the underlying mechanisms in carbon tetrachloride (CCl4)-induced experimental liver injury in mice. Material and methods Chronic liver damage was induced by intraperitoneal injection of CCl4 (0.5 µl/g) three times per week for 8 weeks. Mice also received 25, 50 or 100 mg/kg TGP. Liver sections were stained with haematoxylin/eosin. Serum amino transferases, lipid peroxidation and tumour necrosis factor-α (TNF-α) levels were determined using commercial assays. Quantitative real-time polymerase chain reaction was used to determine the changes in hepatic TNF-α, COX-2, iNOS and HO-1 expression. Protein levels of nitric oxide synthase, cyclooxygenase-2, haem oxygenase-1 and cytochrome P450 2E1 were determined by western blotting. Results Histological results showed that TGP improved the CCl4-induced changes in liver structure and alleviated lobular necrosis. The increases in serum protein and hepatic mRNA expression of TNF-α induced by CCl4 treatment were suppressed by TGP. Total glucosides of paeony also attenuated the increase the expression in iNOS and CYP2E1 but augmented the increase in HO-1.The mRNA and protein expression levels of inducible HO-1 increased significantly after CCl4 treatment. Conclusions Total glucosides of paeony protects hepatocytes from oxidative damage induced by CCl4. Total glucosides of paeony may achieve these effects by enhancing HO-1 expression and inhibiting the expression of proinflammatory mediators. PMID:22291795

  4. ANTI-DISCRIMINATION LAW AND COURT PRACTICE IN CROATIA-INDIVIDUAL AND ASSOCIATIONAL ANTI-DISCRIMINATION CLAIM AS (IN)EFFICIENT MECHANISMS FOR LEGAL PROTECTION

    OpenAIRE

    Paula Poretti

    2015-01-01

    In the paper basic legal sources of European and Croatian anti-discrimination law are presented. Special attention is given to Anti-discrimination Act from 2009 which was enacted with the aim to provide anti-discrimination legal framework as a guarantee of a high level of legal protection from different forms of discrimination in Croatian legal system. Individual and associational anti—discrimination claim as legal mechanisms for efficient legal protection are questioned. Also, along with the...

  5. CD4 T cell-mediated protection from lethal influenza: perforin and antibody-mediated mechanisms give a one-two punch.

    Science.gov (United States)

    Brown, Deborah M; Dilzer, Allison M; Meents, Dana L; Swain, Susan L

    2006-09-01

    The mechanisms whereby CD4 T cells contribute to the protective response against lethal influenza infection remain poorly characterized. To define the role of CD4 cells in protection against a highly pathogenic strain of influenza, virus-specific TCR transgenic CD4 effectors were generated in vitro and transferred into mice given lethal influenza infection. Primed CD4 effectors conferred protection against lethal infection over a broad range of viral dose. The protection mediated by CD4 effectors did not require IFN-gamma or host T cells, but did result in increased anti-influenza Ab titers compared with untreated controls. Further studies indicated that CD4-mediated protection at high doses of influenza required B cells, and that passive transfer of anti-influenza immune serum was therapeutic in B cell-deficient mice, but only when CD4 effectors were present. Primed CD4 cells also acquired perforin (Pfn)-mediated cytolytic activity during effector generation, suggesting a second mechanism used by CD4 cells to confer protection. Pfn-deficient CD4 effectors were less able to promote survival in intact BALB/c mice and were unable to provide protection in B cell-deficient mice, indicating that Ab-independent protection by CD4 effectors requires Pfn. Therefore, CD4 effectors mediate protection to lethal influenza through at least two mechanisms: Pfn-mediated cytotoxicity early in the response promoted survival independently of Ab production, whereas CD4-driven B cell responses resulted in high titer Abs that neutralized remaining virus.

  6. Microbial endogenous response to acute inhibitory impact of antibiotics.

    Science.gov (United States)

    Pala-Ozkok, I; Kor-Bicakci, G; Çokgör, E U; Jonas, D; Orhon, D

    2017-06-13

    Enhanced endogenous respiration was observed as the significant/main response of the aerobic microbial culture under pulse exposure to antibiotics: sulfamethoxazole, tetracycline and erythromycin. Peptone mixture and acetate were selected as organic substrates to compare the effect of complex and simple substrates. Experiments were conducted with microbial cultures acclimated to different sludge ages of 10 and 2 days, to visualize the effect of culture history. Evaluation relied on modeling of oxygen uptake rate profiles, reflecting the effect of all biochemical reactions associated with substrate utilization. Model calibration exhibited significant increase in values of endogenous respiration rate coefficient with all antibiotic doses. Enhancement of endogenous respiration was different with antibiotic type and initial dose. Results showed that both peptone mixture and acetate cultures harbored resistance genes against the tested antibiotics, which suggests that biomass spends cellular maintenance energy for activating the required antibiotic resistance mechanisms to survive, supporting higher endogenous decay rates. [Formula: see text]: maximum growth rate for X H (day -1 ); K S : half saturation constant for growth of X H (mg COD/L); b H : endogenous decay rate for X H (day -1 ); k h : maximum hydrolysis rate for S H1 (day -1 ); K X : hydrolysis half saturation constant for S H1 (mg COD/L); k hx : maximum hydrolysis rate for X S1 (day -1 ); K XX : hydrolysis half saturation constant for X S1 (mg COD/L); k STO : maximum storage rate of PHA by X H (day -1 ); [Formula: see text]: maximum growth rate on PHA for X H (day -1 ); K STO : half saturation constant for storage of PHA by X H (mg COD/L); X H1 : initial active biomass (mg COD/L).

  7. Rescue therapeutic strategy combining ultra-protective mechanical ventilation with extracorporeal CO2 removal membrane in near-fatal asthma with severe pulmonary barotraumas: A case report.

    Science.gov (United States)

    Pavot, Arthur; Mallat, Jihad; Vangrunderbeeck, Nicolas; Thevenin, Didier; Lemyze, Malcolm

    2017-10-01

    Mechanical ventilation of severe acute asthma is still considered a challenging issue, mainly because of the gas trapping phenomenon with the potential for life-threatening barotraumatic pulmonary complications. Herein, we describe 2 consecutive cases of near-fatal asthma for whom the recommended protective mechanical ventilation approach using low tidal volume of 6 mL/kg and small levels of PEEP was rapidly compromised by giant pneumomediastinum with extensive subcutaneousemphysema. Near fatal asthma. A rescue therapeutic strategy combining extracorporeal CO2 removal membrane with ultra-protective extremely low tidal volume (3 mL/kg) ventilation was applied. Both patients survived hospital discharge. These 2 cases indicate that ECCO2R associated with ultra-protective ventilation could be an alternative to surgery in case of life-threatening barotrauma occurring under mechanical ventilation.

  8. Protective Effects and Mechanism of Puerarin on Learning-Memory Disorder after Global Cerebral Ischemia-Reperfusion Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    WU Hai-qin; GUO He-na; WANG Hu-qing; CHANG Ming-ze; ZHANG Gui-lian; ZHAO Ying-xian

    2009-01-01

    Objective: To observe the effect of puerarin on the learning-memory disorder after global cerebral ischemia-reperfusion injury in rats, and to explore its mechanism of action. Methods: The global cerebral ischemia-reperfusion injury model was established using the modified Pulsinelli four-vessel occlusion in Sprague-Dawley rats. Rats were intraperitoneally injected with puerarin (100 mg/kg) 1 h before ischemia and once every 6 h afterwards. The learning-memory ability was evaluated by the passive avoidance test. The dynamic changes of the cell counts of apoptosis and positive expression of Bcl-2 in the hippocampus CA1 region were determined by the TUNEL and immunohistochemical methods, respectively. Results: (1) Compared with the reperfusion group, the step through latency (STL) in the passive avoidance test in the puerarin group was prolonged significantly (P<0.01). (2) The apoptotic neurons were injured most severely on the 3rd day in the hippocampal CA1 region after global ischemia and reperfusion. In the pueradn group, the number of apoptotic cells decreased at respective time points after ischemia-reperfusion (P<0.01). (3) The level of positive expression of Bcl-2 varied according to the duration of reperfusion and the peak level occurred on day 1 in the hippocampal CA1 region after global cerebral ischemia. Compared with the reperfusion group, the expression of Bcl-2 in the pueradn group was up-regulated at the respective time points after ischemia raperfusion (P<0.01), reaching the peak on day 1. Conclusions: Puerarin could improve the learning-memory ability after global cerebral ischemia and reperfusion in rats. The protective mechanism might be related to the effect of inhibiting or delaying the cell apoptosis through up-regulating the expression of Bcl-2 after ischemia and reperfusion.

  9. The protective potential and possible mechanism of Phyllanthus amarus Schum. & Thonn. aqueous extract on paracetamol-induced hepatotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Apichat Muso

    2006-05-01

    Full Text Available The hepatoprotective potential of Phyllanthus amarus Schum. & Thonn. was studied on paracetamolinduced hepatotoxicity in rats by measuring the levels of serum transaminase (SGOT and SGPT, alkaline phosphatase (ALP and bilirubin, as well as by histopathological examination of the liver. Furthermore, the hepatoprotective mechanisms were investigated by determining the amount of paracetamol and its metabolites (glucuronide, sulfate, cysteine and mercapturic acid conjugates in urine and pentobarbital-induced sleeping time to indicate the inhibition on cytochrome P450. The involvement of glutathione was evaluated by determining hepatic reduced glutathione. Its radical scavenging activity, iron chelating activity and total phenolic content were also determined. P. amarus aqueous extracts (0.8, 1.6 or 3.2 g/kg were orally administered twice daily for 7 days prior, for 2 days after, or for 7 days prior and followed by 2 days after a single oral dose of paracetamol (3 g/kg. The results showed that the extract at the doses of 1.6 and 3.2 g/kg decreased the paracetamol-induced hepatotoxicity as indicated by the decrease in SGOT, SGPT, bilirubin and histopathological score while the ALP did not change. Moreover, it is suggested that the hepatoprotective mechanism of this plant was related neither to the inhibition on cytochrome P450, nor to the induction on sulfate and/or glucuronide conjugation pathways of paracetamol, but partly due to the protective effect on the depletion of hepatic reduced glutathione and also its antioxidant activity, especially the radical scavenging and iron chelating activity, which might be related to the high polyphenolic contents. These results support the value of P. amarus, which has been used in Thai folk medicine for the treatment of liver diseases.

  10. Genotoxic consequences of endogenous aldehydes on mouse haematopoietic stem cell function.

    Science.gov (United States)

    Garaycoechea, Juan I; Crossan, Gerry P; Langevin, Frederic; Daly, Maria; Arends, Mark J; Patel, Ketan J

    2012-09-27

    Haematopoietic stem cells (HSCs) regenerate blood cells throughout the lifespan of an organism. With age, the functional quality of HSCs declines, partly owing to the accumulation of damaged DNA. However, the factors that damage DNA and the protective mechanisms that operate in these cells are poorly understood. We have recently shown that the Fanconi anaemia DNA-repair pathway counteracts the genotoxic effects of reactive aldehydes. Mice with combined inactivation of aldehyde catabolism (through Aldh2 knockout) and the Fanconi anaemia DNA-repair pathway (Fancd2 knockout) display developmental defects, a predisposition to leukaemia, and are susceptible to the toxic effects of ethanol-an exogenous source of acetaldehyde. Here we report that aged Aldh2(-/-) Fancd2(-/-) mutant mice that do not develop leukaemia spontaneously develop aplastic anaemia, with the concomitant accumulation of damaged DNA within the haematopoietic stem and progenitor cell (HSPC) pool. Unexpectedly, we find that only HSPCs, and not more mature blood precursors, require Aldh2 for protection against acetaldehyde toxicity. Additionally, the aldehyde-oxidizing activity of HSPCs, as measured by Aldefluor stain, is due to Aldh2 and correlates with this protection. Finally, there is more than a 600-fold reduction in the HSC pool of mice deficient in both Fanconi anaemia pathway-mediated DNA repair and acetaldehyde detoxification. Therefore, the emergence of bone marrow failure in Fanconi anaemia is probably due to aldehyde-mediated genotoxicity restricted to the HSPC pool. These findings identify a new link between endogenous reactive metabolites and DNA damage in HSCs, and define the protective mechanisms that counteract this threat.

  11. Endogenous Retroviruses: With Us and Against Us

    Science.gov (United States)

    Meyer, Thomas J.; Rosenkrantz, Jimi L.; Carbone, Lucia; Chavez, Shawn L.

    2017-04-01

    Mammalian genomes are scattered with thousands of copies of endogenous retroviruses (ERVs), mobile genetic elements that are relics of ancient retroviral infections. After inserting copies into the germ line of a host, most ERVs accumulate mutations that prevent the normal assembly of infectious viral particles, becoming trapped in host genomes and unable to leave to infect other cells. While most copies of ERVs are inactive, some are transcribed and encode the proteins needed to generate new insertions at novel loci. In some cases, old copies are removed via recombination and other mechanisms. This creates a shifting landscape of ERV copies within host genomes. New insertions can disrupt normal expression of nearby genes via directly inserting into key regulatory elements or by containing regulatory motifs within their sequences. Further, the transcriptional silencing of ERVs via epigenetic modification may result in changes to the epigenetic regulation of adjacent genes. In these ways, ERVs can be potent sources of regulatory disruption as well as genetic innovation. Here, we provide a brief review of the association between ERVs and gene expression, especially as observed in pre-implantation development and placentation. Moreover, we will describe the roles ERVs may play in somatic tissues, mostly in the context of human disease, including cancer, neurodegenerative disorders, and schizophrenia. Lastly, we discuss the recent discovery that some ERVs may have been pressed into the service of their host genomes to aid in the innate immune response to exogenous viral infections.

  12. Gaseous Mediators Nitric Oxide and Hydrogen Sulfide in the Mechanism of Gastrointestinal Integrity, Protection and Ulcer Healing

    Directory of Open Access Journals (Sweden)

    Marcin Magierowski

    2015-05-01

    Full Text Available Nitric oxide (NO and hydrogen sulfide (H2S are known as biological messengers; they play an important role in human organism and contribute to many physiological and pathophysiological processes. NO is produced from l-arginine by constitutive NO synthase (NOS and inducible NOS enzymatic pathways. This gaseous mediator inhibits platelet aggregation, leukocyte adhesion and contributes to the vessel homeostasis. NO is known as a vasodilatory molecule involved in control of the gastric blood flow (GBF and the maintenance of gastric mucosal barrier integrity in either healthy gastric mucosa or that damaged by strong irritants. Biosynthesis of H2S in mammals depends upon two enzymes cystathionine-β-synthase and cystathionine γ-lyase. This gaseous mediator, similarly to NO and carbon monoxide, is involved in neuromodulation, vascular contractility and anti-inflammatory activities. For decades, H2S has been known to inhibit cytochrome c oxidase and reduce cell energy production. Nowadays it is generally considered to act through vascular smooth muscle ATP-dependent K+ channels, interacting with intracellular transcription factors and promote sulfhydration of protein cysteine moieties within the cell, but the mechanism of potential gastroprotective and ulcer healing properties of H2S has not been fully explained. The aim of this review is to compare current results of the studies concerning the role of H2S and NO in gastric mucosa protection and outline areas that may pose new opportunities for further development of novel therapeutic targets.

  13. Immunological mechanisms involved in the protection against intestinal taeniosis elicited by oral immunization with Taenia solium calreticulin.

    Science.gov (United States)

    Leon-Cabrera, Sonia; Cruz-Rivera, Mayra; Mendlovic, Fela; Romero-Valdovinos, Mirza; Vaughan, Gilberto; Salazar, Ana María; Avila, Guillermina; Flisser, Ana

    2012-11-01

    Oral immunization with functional recombinant Taenia solium calreticulin (rTsCRT) induces 37% reduction in tapeworm burden in the experimental model of intestinal taeniosis in hamsters. Furthermore, tapeworms recovered from vaccinated animals exhibit diminished length, being frequently found in more posterior parts of the small intestine. The aim of this study was to analyze the immunological mechanisms involved in protection in response to rTsCRT oral immunization. Hamsters were orally immunized with rTsCRT using cholera toxin (CT) as adjuvant, weekly for 4 weeks. Fifteen days after the last boost animals were challenged with four T. solium cysticerci. Reduction in the adult worm recovery and increased transcription of mRNA for IL-4 and IFN-γ in the mucosa of rTsCRT+CT immunized animals were observed. Immunization also induced goblet cell hyperplasia in the mucosa surrounding the implantation site of the parasite. Specific IgG and IgA antibodies in serum and fecal supernatants were detected after the second immunization, being more pronounced after challenge. Our data suggest that oral vaccination with rTsCRT+CT regulates a local expression of IL-4 and IFN-γ, stimulating secretion of IgA that, together with the increase of goblet cells and mucin production, could result in an unfavorable environment for T. solium promoting an impaired tapeworm development. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Social Laughter Triggers Endogenous Opioid Release in Humans.

    Science.gov (United States)

    Manninen, Sandra; Tuominen, Lauri; Dunbar, Robin I; Karjalainen, Tomi; Hirvonen, Jussi; Arponen, Eveliina; Hari, Riitta; Jääskeläinen, Iiro P; Sams, Mikko; Nummenmaa, Lauri

    2017-06-21

    The size of human social networks significantly exceeds the network that can be maintained by social grooming or touching in other primates. It has been proposed that endogenous opioid release after social laughter would provide a neurochemical pathway supporting long-term relationships in humans (Dunbar, 2012), yet this hypothesis currently lacks direct neurophysiological support. We used PET and the μ-opioid-receptor (MOR)-specific ligand [ 11 C]carfentanil to quantify laughter-induced endogenous opioid release in 12 healthy males. Before the social laughter scan, the subjects watched laughter-inducing comedy clips with their close friends for 30 min. Before the baseline scan, subjects spent 30 min alone in the testing room. Social laughter increased pleasurable sensations and triggered endogenous opioid release in thalamus, caudate nucleus, and anterior insula. In addition, baseline MOR availability in the cingulate and orbitofrontal cortices was associated with the rate of social laughter. In a behavioral control experiment, pain threshold-a proxy of endogenous opioidergic activation-was elevated significantly more in both male and female volunteers after watching laughter-inducing comedy versus non-laughter-inducing drama in groups. Modulation of the opioidergic activity by social laughter may be an important neurochemical pathway that supports the formation, reinforcement, and maintenance of human social bonds. SIGNIFICANCE STATEMENT Social contacts are vital to humans. The size of human social networks significantly exceeds the network that can be maintained by social grooming in other primates. Here, we used PET to show that endogenous opioid release after social laughter may provide a neurochemical mechanism supporting long-term relationships in humans. Participants were scanned twice: after a 30 min social laughter session and after spending 30 min alone in the testing room (baseline). Endogenous opioid release was stronger after laughter versus the

  15. Why Don’t People Pay Attention?: Endogenous Sticky Information in a DSGE Model

    OpenAIRE

    Dräger, Lena

    2010-01-01

    Building on the models of sticky information, we endogenize the probability of obtaining new information by introducing a switching mechanism allowing agents to choose between costly rational expectations and costless expectations under sticky information. Thereby, the share of agents with rational expectations becomes endogenous and timevarying. While central results of sticky information models are retained, we find that the share of rational expectations is positively correlated with the v...

  16. Neural correlates of endogenous attention, exogenous attention and inhibition of return in touch

    OpenAIRE

    Jones, A.; Forster, B.

    2014-01-01

    Selective attention helps process the myriad of information constantly touching our body. Both endogenous and exogenous mechanisms are relied upon to effectively process this information; however, it is unclear how they relate in the sense of touch. In three tasks we contrasted endogenous and exogenous event-related potential (ERP) and behavioural effects. Unilateral tactile cues were followed by a tactile target at the same or opposite hand. Clear behavioural effects showed facilitation of e...

  17. Contagion risk in endogenous financial networks

    International Nuclear Information System (INIS)

    Li, Shouwei; Sui, Xin

    2016-01-01

    Highlights: • We propose an endogenous financial network model. • Endogenous networks include interbank networks, inter-firm networks and bank-firm networks. • We investigate contagion risk in endogenous financial networks. - Abstract: In this paper, we investigate contagion risk in an endogenous financial network, which is characterized by credit relationships connecting downstream and upstream firms, interbank credit relationships and credit relationships connecting firms and banks. The findings suggest that: increasing the number of potential lenders randomly selected can lead to an increase in the number of bank bankruptcies, while the number of firm bankruptcies presents a trend of increase after the decrease; after the intensity of choice parameter rises beyond a threshold, the number of bankruptcies in three sectors (downstream firms, upstream firms and banks) shows a relatively large margin of increase, and keeps at a relatively high level; there exists different trends for bankruptcies in different sectors with the change of the parameter of credits’ interest rates.

  18. Endogenous Money, Output and Prices in India

    OpenAIRE

    Das, Rituparna

    2009-01-01

    This paper proposes to quantify the macroeconometric relationships among the variables broad money, lending by banks, price, and output in India using simultaneous equations system keeping in view the issue of endogeneity.

  19. Structure, Immunogenicity, and Protective Mechanism of an Engineered Enterovirus 71-Like Particle Vaccine Mimicking 80S Empty Capsid.

    Science.gov (United States)

    Wang, Xiaoli; Ku, Zhiqiang; Zhang, Xiang; Ye, Xiaohua; Chen, Jinhuan; Liu, Qingwei; Zhang, Wei; Zhang, Chao; Fu, Zhenglin; Jin, Xia; Cong, Yao; Huang, Zhong

    2018-01-01

    Enterovirus 71 (EV71) is the major causative agent of severe hand, foot, and mouth disease, which affects millions of young children in the Asia-Pacific region annually. In this study, we engineered a novel EV71 virus-like particle (VLP) that lacks VP4 (therefore designated VLP ΔVP4 ) and investigated its structure, antigenicity, and vaccine potential. The cryo-electron microscopy (cryo-EM) structure of VLP ΔVP4 was reconstructed to 3.71-Å resolution. Results from structural and biochemical analyses revealed that VLP ΔVP4 resembles the end product of the viral uncoating process, the 80S empty capsid. VLP ΔVP4 is able to elicit high-titer neutralizing antibodies and to fully protect mice against lethal viral challenge. Mechanistic studies showed that, at the cellular level, the anti-VLP ΔVP4 sera exert neutralization effects at both pre- and postattachment stages by inhibiting both virus attachment and internalization, and at the molecular level, the antisera can block multiple interactions between EV71 and its key receptors. Our study gives a better understanding of EV71 capsid assembly and provides important information for the design and development of new-generation vaccines for EV71, and perhaps for other enteroviruses, as well. IMPORTANCE Enterovirus 71 (EV71) infection may lead to severe hand, foot, and mouth disease, with significant morbidity and mortality. Knowledge regarding EV71 particle assembly remains limited. Here, we report the generation and characterization of a novel EV71 virus-like particle that lacks the VP4 capsid subunit protein. This particle, termed VLP ΔVP4 , structurally mimics the 80S empty capsid, which is the end stage of EV71 uncoating. We further show that VLP ΔVP4 exhibits desirable immunogenicity and protective efficacy in proof-of-concept studies. In addition, the inhibitory mechanisms of the VLP ΔVP4 -induced antibodies are unraveled at both the cellular and molecular levels. Our work provides the first evidence of

  20. Some observations about the endogenous money theory

    OpenAIRE

    Bertocco Giancarlo

    2006-01-01

    The endogenous money theory constitutes the core element of the post-keynesian monetary theory. The first formulation of this theory can be found in the works of Kaldor published in the 1970s. Taking these studies as a starting point, the post-keynesians elaborated two versions of the endogenous money theory which differ in their assumptions about the behaviour of the monetary authorities and the banking system, and hence offer different conclusions about the slope of the money supply curve. ...

  1. Invasive fungal infections in endogenous Cushing's syndrome

    Science.gov (United States)

    Scheffel, Rafael Selbach; Dora, José Miguel; Weinert, Letícia Schwerz; Aquino, Valério; Maia, Ana Luiza; Canani, Luis Henrique; Goldani, Luciano Z.

    2010-01-01

    Cushing's syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing's original description of the disease. We describe here a patient with endogenous Cushing's syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease. PMID:24470886

  2. Endogenous Money Supply and Money Demand

    OpenAIRE

    Woon Gyu Choi; Seonghwan Oh

    2000-01-01

    This paper explores the behavior of money demand by explicitly accounting for the money supply endogeneity arising from endogenous monetary policy and financial innovations. Our theoretical analysis indicates that money supply factors matter in the money demand function when the money supply partially responds to money demand. Our empirical results with U.S. data provide strong evidence for the relevance of the policy stance to the demand for MI under a regime in which monetary policy is subs...

  3. [Brain protection against cerebral ischemia].

    Science.gov (United States)

    Kitagawa, Kazuo

    2013-01-01

    Previous clinical trials failed to show the benefit of several potentially protective drugs in acute ischemic stroke. However, there would be three main approaches for brain protection against stroke. The first is to develop a novel thrombolytic agent which is more efficient and safer than alteplase. Tenecteplase and desmoteplase are in progress as a new thrombolytic drug. The second strategy is to augment collateral circulation through leptomeningeal anastomosis. Administration of G-CSF could enhance arteriogenesis, but it takes several days to develop functional collateral. For this purpose, partial aortic balloon clumping or stimulation of pterygopalatine ganglion may be promising. The third one is to protect neurovascular unit against reperfusion injury. Brain hypothermia is the most effective strategy in experimental ischemia, and the clinical trial for hypothermia combined with thrombolysis therapy is in progress. Activation of endogenous protective response, as presented by ischemic tolerance, has focused on remote ischemic conditioning. Although the precise mechanisms of remote preconditioning remain unclear, intermittent limb ischemia is a safe approach. Remote ischemic conditioning is now investigated in acute patients with thrombolysis therapy.

  4. Properties of protective oxide scales containing cerium on Incoloy 800H in oxidizing and sulfidizing environments. I. Constant-extension-rate study of mechanical properties

    NARCIS (Netherlands)

    Haanappel, V.A.C.; Fransen, T.; Geerdink, Bert; Gellings, P.J.

    1988-01-01

    The mechanical properties of ceramic coatings containing cerium oxide, prepared by the sol-gel method and used to protect Incoloy 800H against aggressive environments, are reported. Deformation and cracking behavior in oxidizing and sulfidizing environments has been investigated by

  5. Inhibition of protein translation as a mechanism of acidotic pH protection against ischaemic injury through inhibition of CREB mediated tRNA synthetase expression

    NARCIS (Netherlands)

    Crean, Daniel; Felice, Luca; Pierre, Philippe; Jennings, Paul; Leonard, Martin O

    2013-01-01

    Ischaemia associated reduction in local tissue pH is well documented but the mechanisms through which it influences cell survival remain poorly understood. Using renal epithelial HK-2 cells we demonstrate acidotic pH6.4 protects against oxygen glucose deprivation (OGD) induced cell death. Initial

  6. Ciliary neurotrophic factor is an endogenous pyrogen.

    Science.gov (United States)

    Shapiro, L; Zhang, X X; Rupp, R G; Wolff, S M; Dinarello, C A

    1993-09-15

    Fever is initiated by the action of polypeptide cytokines called endogenous pyrogens, which are produced by the host during inflammation, trauma, or infection and which elevate the thermoregulatory set point in the hypothalamus. Ciliary neurotrophic factor (CNTF) supports the differentiation and survival of central and peripheral neurons. We describe the activity of CNTF as intrinsically pyrogenic in the rabbit. CNTF induced a monophasic fever which rose rapidly (within the first 12 min) following intravenous injection; CNTF fever was blocked by pretreatment with indomethacin. The fever induced by CNTF was not due to contaminating endotoxins. Increasing doses of CNTF resulted in prolongation of the fever, suggesting the subsequent induction of additional endogenous pyrogenic activity. After passive transfer of plasma obtained during CNTF-induced fever, endogenous pyrogen activity was not present in the circulation; CNTF also did not induce the endogenous pyrogens interleukin 1, tumor necrosis factor, or interleukin 6 in vitro. Nevertheless, a second endogenous pyrogen may originate within the central nervous system following the systemic injection of CNTF. Of the four endogenous pyrogens described to date (interleukin 1, tumor necrosis factor, interferon, and interleukin 6), CNTF, like interleukin 6, utilizes the cell-surface gp 130 signal-transduction apparatus.

  7. Genetic Mechanisms of Coffee Extract Protection in a Caenorhabditis elegans Model of β-Amyloid Peptide Toxicity

    OpenAIRE

    Dostal, Vishantie; Roberts, Christine M.; Link, Christopher D.

    2010-01-01

    Epidemiological studies have reported that coffee and/or caffeine consumption may reduce Alzheimer's disease (AD) risk. We found that coffee extracts can similarly protect against β-amyloid peptide (Aβ) toxicity in a transgenic Caenorhabditis elegans Alzheimer's disease model. The primary protective component(s) in this model is not caffeine, although caffeine by itself can show moderate protection. Coffee exposure did not decrease Aβ transgene expression and did not need to be present during...

  8. Place of Mitochondrial Potassium-ATP Channels in The Mechanism of Effect of Ischemic Conditionings

    Directory of Open Access Journals (Sweden)

    İlker Şengül

    2012-07-01

    Full Text Available Ischemia-reperfusion episodes in a short interval “just before” ischemia performed experimentally have been called preconditioning, where as “just after” ischemia have been called postconditioning and tissue protective effects of these endogenous mechanisms have been shown in various organs via various studies. Although multipl mechanisms have been being propounded about these phenomenons which have been found area of usage from hearth surgery to organ transplantation, mitochondrial potassium ATP-channels have been maintaining its importance.

  9. Dynamic equilibrium of endogenous selenium nanoparticles in selenite-exposed cancer cells: a deep insight into the interaction between endogenous SeNPs and proteins.

    Science.gov (United States)

    Bao, Peng; Chen, Song-Can; Xiao, Ke-Qing

    2015-12-01

    Elemental selenium (Se) was recently found to exist as endogenous nanoparticles (i.e., SeNPs) in selenite-exposed cancer cells. By sequestrating critical intracellular proteins, SeNPs appear capable of giving rise to multiple cytotoxicity mechanisms including inhibition of glycolysis, glycolysis-dependent mitochondrial dysfunction, microtubule depolymerization and inhibition of autophagy. In this work, we reveal a dynamic equilibrium of endogenous SeNP assembly and disassembly in selenite-exposed H157 cells. Endogenous SeNPs are observed both in the cytoplasm and in organelles. There is an increase in endogenous SeNPs between 24 h and 36 h, and a decrease between 36 h and 72 h according to transmission electron microscopy results and UV-Vis measurements. These observations imply that elemental Se in SeNPs could be oxidized back into selenite by scavenging superoxide radicals and ultimately re-reduced into selenide; then the assembly and disassembly of SeNPs proceed simultaneously with the sequestration and release of SeNP high-affinity proteins. There is also a possibility that the reduction of elemental Se to selenide pathway may lie in selenite-exposed cancer cells, which results in the assembly and disassembly of endogenous SeNPs. Genome-wide expression analysis results show that endogenous SeNPs significantly altered the expression of 504 genes, compared to the control. The endogenous SeNPs induced mitochondrial impairment and decreasing of the annexin A2 level can lead to inhibition of cancer cell invasion and migration. This dynamic flux of endogenous SeNPs amplifies their cytotoxic potential in cancer cells, thus provide a starting point to design more efficient intracellular self-assembling systems for overcoming multidrug resistance.

  10. Do Soy Isoflavones Provide Protection Against Prostate Cancer Via a Classical Estrogen Receptor-Alpha (Era) Independent Mechanism?

    National Research Council Canada - National Science Library

    Lubahn, Dennis

    2001-01-01

    .... Our hypothesis is that soy isoflavones, specifically genistein and daidzein, will provide protection from development and progression of prostate cancer in mice lacking functional estrogen receptor...

  11. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity.

    Science.gov (United States)

    Panossian, Alexander; Wikman, Georg

    2009-09-01

    The aim of this review article is to assess the level of scientific evidence presented by clinical trials of adaptogens in fatigue, and to provide a rationale at the molecular level for verified effects. Strong scientific evidence is available for Rhodiola rosea SHR-5 extract, which improved attention, cognitive function and mental performance in fatigue and in chronic fatigue syndrome. Good scientific evidence has been documented in trails in which Schisandra chinensis and Eleutherococcus senticosus increased endurance and mental performance in patients with mild fatigue and weakness. Based on their efficacy in clinical studies, adaptogens can be defined as a pharmacological group of herbal preparations that increase tolerance to mental exhaustion and enhance attention and mental endurance in situations of decreased performance. The beneficial stress-protective effect of adaptogens is related to regulation of homeostasis via several mechanisms of action associated with the hypothalamic-pituitary-adrenal axis and the control of key mediators of stress response such as molecular chaperons (e.g. Hsp70), stress-activated c-Jun N-terminal protein kinase (JNK1), Forkhead Box O transcription factor DAF-16, cortisol and nitric oxide (NO). The key point of action of phytoadaptogens appears to be their up-regulating and stress-mimetic effects on the "stress-sensor" protein Hsp70, which plays an important role in cell survival and apoptosis. Hsp70 inhibits the expression of NO synthase II gene and interacts with glucocorticoid receptors directly and via the JNK pathway, thus affecting the levels of circulating cortisol and NO. Prevention of stress-induced increase in NO, and the associated decrease in ATP production, results in increased performance and endurance. Adaptogen-induced up-regulation of Hsp70 triggers stress-induced JNK-1 and DAF-16-mediated pathways regulating the resistance to stress and resulting in enhanced mental and physical performance and, possibly

  12. Mechanism of melatonin protection against copper-ascorbate-induced oxidative damage in vitro through isothermal titration calorimetry.

    Science.gov (United States)

    Ghosh, Arnab K; Naaz, Shamreen; Bhattacharjee, Bharati; Ghosal, Nirajan; Chattopadhyay, Aindrila; Roy, Souvik; Reiter, Russel J; Bandyopadhyay, Debasish

    2017-07-01

    Involvement of oxidative stress in cardiovascular diseases is well established. Melatonin's role as an antioxidant and free radical scavenger via its receptor dependent and receptor independent pathways is well known. The aim of this study is to identify and elaborate upon a third mechanism by which melatonin is able to abrogate oxidative stress. Oxidative stress was induced in vitro, by copper (0.2mM)-ascorbate (1mM) in isolated goat heart mitochondria, cytosol and peroxisomes and they were co-incubated with graded doses of melatonin. Similar experiments in a cell-free chemical system involving two pure antioxidant enzymes, Cu-Zn superoxide dismutase and catalase was also carried out. Biochemical changes in activity of these antioxidant enzymes were analysed. Isothermal titration calorimetric studies with pure Cu-Zn superoxide dismutase and catalase were also carried out. Incubation with copper-ascorbate led to alteration in activity of Cu-Zn superoxide dismutase and catalase which were found to be protected upon co-incubation with melatonin (80μM for catalase and 1μM for others). Results of isothermal titration calorimetric studies with pure Cu-Zn superoxide dismutase and catalase along with different combinations of copper chloride, ascorbic acid and melatonin suggest that when melatonin is present in the reaction medium along with copper-ascorbate, it restrains the copper-ascorbate molecules by binding with them physically along with scavenging the free radicals generated by them. The present study suggests that possibly, binding of melatonin with antioxidant enzymes masks the vulnerable sites of these antioxidant enzymes, thus preventing oxidative damage by copper-ascorbate molecules. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Molecular mechanism of cell damage and protection against ionizing radiation. Communication 3. Correlation between the protective effect and development of a non-specific reaction

    International Nuclear Information System (INIS)

    Veksler, A.M.; Ermekova, V.M.; Kozlovich, L.I.

    1975-01-01

    The dynamics of reversible unspecific reaction (UR) of chinese hamster fibroblast cell culture to hypothermia and cysteamine addition has been studied. A correlation between UR development and radioresistance has been established. The post-irradiation protection has been shown to grow undulatorilly o cysteamine addition at different times after irradiation. This is explained by superimposition of two processes: realization of latent lesions which is delayed by UR development, and repair of these lesions by the enzymatic system the activity of which changes periodicallY, also as a result of UR development

  14. Endogenous neurogenesis in the human brain following cerebral infarction.

    Science.gov (United States)

    Minger, Stephen L; Ekonomou, Antigoni; Carta, Eloisa M; Chinoy, Amish; Perry, Robert H; Ballard, Clive G

    2007-01-01

    Increased endogenous neurogenesis has a significant regenerative role in many experimental models of cerebrovascular diseases, but there have been very few studies in humans. We therefore examined whether there was evidence of altered endogenous neurogenesis in an 84-year-old patient who suffered a cerebrovascular accident 1 week prior to death. Using antibodies that specifically label neural stem/neural progenitor cells, we examined the presence of immunopositive cells around and distant from the infarcted area, and compared this with a control, age-matched individual. Interestingly, a large number of neural stem cells, vascular endothelial growth factor-immunopositive cells and new blood vessels were observed only around the region of infarction, and none in the corresponding brain areas of the healthy control. In addition, an increased number of neural stem cells was observed in the neurogenic region of the lateral ventricle wall. Our results suggest increased endogenous neurogenesis associated with neovascularization and migration of newly-formed cells towards a region of cerebrovascular damage in the adult human brain and highlight possible mechanisms underlying this process.

  15. The Deacetylase HDAC6 Mediates Endogenous Neuritic Tau Pathology

    Directory of Open Access Journals (Sweden)

    Jui-Heng Tseng

    2017-08-01

    Full Text Available The initiating events that promote tau mislocalization and pathology in Alzheimer’s disease (AD are not well defined, partly because of the lack of endogenous models that recapitulate tau dysfunction. We exposed wild-type neurons to a neuroinflammatory trigger and examined the effect on endogenous tau. We found that tau re-localized and accumulated within pathological neuritic foci, or beads, comprised of mostly hypo-phosphorylated, acetylated, and oligomeric tau. These structures were detected in aged wild-type mice and were enhanced in response to neuroinflammation in vivo, highlighting a previously undescribed endogenous age-related tau pathology. Strikingly, deletion or inhibition of the cytoplasmic shuttling factor HDAC6 suppressed neuritic tau bead formation in neurons and mice. Using mass spectrometry-based profiling, we identified a single neuroinflammatory factor, the metalloproteinase MMP-9, as a mediator of neuritic tau beading. Thus, our study uncovers a link between neuroinflammation and neuritic tau beading as a potential early-stage pathogenic mechanism in AD.

  16. Triggering endogenous immunosuppressive mechanisms by combined targeting of Dipeptidyl peptidase IV (DPIV/CD26) and Aminopeptidase N (APN/ CD13)--a novel approach for the treatment of inflammatory bowel disease.

    Science.gov (United States)

    Bank, Ute; Heimburg, Anke; Helmuth, Martin; Stefin, Sofia; Lendeckel, Uwe; Reinhold, Dirk; Faust, Jürgen; Fuchs, Petra; Sens, Bianca; Neubert, Klaus; Täger, Michael; Ansorge, Siegfried

    2006-12-20

    The ectopeptidases Dipeptidylpeptidase IV and Alanyl-Aminopeptidase N, strongly expressed by both, activated and regulatory T cells were shown to co-operate in T cell regulation. Based on the findings that DPIV and APN inhibitors induce the TGF-beta1 and IL-10 production and a suppression of T helper cell proliferation in parallel, and that particularly APN inhibitors amplify the suppressing activity of regulatory T cells, both peptidases represent a promising target complex for treatment of diseases associated with an imbalanced T cell response, such as inflammatory bowel diseases (IBD). The aim of the present study was to analyze the therapeutic potential of DPIV and APN inhibitors in vivo in a mouse model of colitis. Balb/c mice received 3% (w/v) dextran sulphate sodium with the drinking water for 7 days. After onset of colitis symptoms, inhibitor treatment started at day 3. Disease activity index (DAI) was assessed daily, supplemented by histological and immunological analysis. While the DPIV inhibitor Lys-[Z(NO])(2)]-pyrrolidide or the APN-inhibitor Actinonin alone had marked but no significant therapeutic effects, the simultaneous administration of both inhibitors reduced colitis activity in comparison to placebo treated mice, significantly (DAI 4.8 vs. 7.7, pendogenous immunosuppressive mechanisms.

  17. Measuring endogenous 5-HT release by emission tomography: promises and pitfalls

    DEFF Research Database (Denmark)

    Paterson, Louise M; Tyacke, Robin J; Nutt, David J

    2010-01-01

    Molecular in vivo neuroimaging techniques can be used to measure regional changes in endogenous neurotransmitters, evoked by challenges that alter synaptic neurotransmitter concentration. This technique has most successfully been applied to the study of endogenous dopamine release using positron......, with reference to the dopaminergic system. Studies that aim to image acute, endogenous 5-HT release or depletion at 5-HT receptor targets are summarised, with particular attention to studies in humans. Radiotracers targeting the 5-HT(1A), 5-HT(2A), and 5-HT(4) receptors and the serotonin reuptake transporter...... have been explored for their sensitivity to 5-HT fluctuations, but with mixed outcomes; tracers for these targets cannot reliably image endogenous 5-HT in humans. Shortcomings in our basic knowledge of the mechanisms underlying changes in binding potential are addressed, and suggestions are made...

  18. Estradiol Uses Different Mechanisms in Astrocytes from the Hippocampus of Male and Female Rats to Protect against Damage Induced by Palmitic Acid

    Directory of Open Access Journals (Sweden)

    Laura M. Frago

    2017-10-01

    Full Text Available An excess of saturated fatty acids can be toxic for tissues, including the brain, and this has been associated with the progression of neurodegenerative diseases. Since palmitic acid (PA is a free fatty acid that is abundant in the diet and circulation and can be harmful, we have investigated the effects of this fatty acid on lipotoxicity in hippocampal astrocytes and the mechanism involved. Moreover, as males and females have different susceptibilities to some neurodegenerative diseases, we accessed the responses of astrocytes from both sexes, as well as the possible involvement of estrogens in the protection against fatty acid toxicity. PA increased endoplasmic reticulum stress leading to cell death in astrocytes from both males and females. Estradiol (E2 increased the levels of protective factors, such as Hsp70 and the anti-inflammatory cytokine interleukin-10, in astrocytes from both sexes. In male astrocytes, E2 decreased pJNK, TNFα, and caspase-3 activation. In contrast, in female astrocytes E2 did not affect the activation of JNK or TNFα levels, but decreased apoptotic cell death. Hence, although E2 exerted protective effects against the detrimental effects of PA, the mechanisms involved appear to be different between male and female astrocytes. This sexually dimorphic difference in the protective mechanisms induced by E2 could be involved in the different susceptibilities of males and females to some neurodegenerative processes.

  19. Correlation between endogenous glutathione content and sensitivity of cultured human skin cells to radiation at defined wavelengths in the solar ultraviolet range

    International Nuclear Information System (INIS)

    Tyrrell, R.M.; Pidoux, M.

    1988-01-01

    Glutathione depletion of cultured human skin fibroblasts by treatment with buthionine-S.R.-sulfoximine (BSO) sensitises them to solar UV radiation. We now show that there is a close quantitative correlation between cellular glutathione content and sensitivity to radiation at 365 nm. A weaker correlation is observed when cells are depleted of glutathione using diethylmaleimide. Both fibroblasts and epidermal keratinocytes derived from the same foreskin biopsy are sensitised to radiation at 313 nm by glutathione depletion. At low to intermediate fluence levels, 10 mM cysteamine present during irradiation at 302 nm is able to almost completely reverse the sensitising effects of glutathione depletion suggesting that the endogenous thiol protects against radiation at this wavelength by a free radical scavenging mechanism. At 313 nm, the sensitisation is not reversed by cysteamine suggesting that glutathione plays a more specific role in protection against radiation at longer wavelengths. Xeroderma pigmentosum group A fibroblasts (excision deficient) are also sensitised to radiation at 313 and 365 nm by depletion of glutathione. The results provide further evidence that endogenous glutathione is involved in protecting human skin cells against a wide range of solar radiation damage. (author)

  20. IFN-Gamma-Dependent and Independent Mechanisms of CD4⁺ Memory T Cell-Mediated Protection from Listeria Infection.

    Science.gov (United States)

    Meek, Stephanie M; Williams, Matthew A

    2018-02-13

    While CD8⁺ memory T cells can promote long-lived protection from secondary exposure to intracellular pathogens, less is known regarding the direct protective mechanisms of CD4⁺ T cells. We utilized a prime/boost model in which mice are initially exposed to an acutely infecting strain of lymphocytic choriomeningitis virus (LCMV), followed by a heterologous rechallenge with Listeria monocytogenes recombinantly expressing the MHC Class II-restricted LCMV epitope, GP 61-80 (Lm-gp61). We found that heterologous Lm-gp61 rechallenge resulted in robust activation of CD4⁺ memory T cells and that they were required for rapid bacterial clearance. We further assessed the relative roles of TNF and IFNγ in the direct anti-bacterial function of CD4⁺ memory T cells. We found that disruption of TNF resulted in a complete loss of protection mediated by CD4⁺ memory T cells, whereas disruption of IFNγ signaling to macrophages results in only a partial loss of protection. The protective effect mediated by CD4⁺ T cells corresponded to the rapid accumulation of pro-inflammatory macrophages in the spleen and an altered inflammatory environment in vivo. Overall, we conclude that protection mediated by CD4⁺ memory T cells from heterologous Listeria challenge is most directly dependent on TNF, whereas IFNγ only plays a minor role.

  1. Neural correlates of endogenous attention, exogenous attention and inhibition of return in touch.

    Science.gov (United States)

    Jones, Alexander; Forster, Bettina

    2014-07-01

    Selective attention helps process the myriad of information constantly touching our body. Both endogenous and exogenous mechanisms are relied upon to effectively process this information; however, it is unclear how they relate in the sense of touch. In three tasks we contrasted endogenous and exogenous event-related potential (ERP) and behavioural effects. Unilateral tactile cues were followed by a tactile target at the same or opposite hand. Clear behavioural effects showed facilitation of expected targets both when the cue predicted targets at the same (endogenous predictive task) and opposite hand (endogenous counter-predictive task), and these effects also correlated with ERP effects of endogenous attention. In an exogenous task, where the cue was non-informative, inhibition of return (IOR) was observed. The electrophysiological results demonstrated early effects of exogenous attention followed by later endogenous attention modulations. These effects were independent in both the endogenous predictive and exogenous tasks. However, voluntarily directing attention away from a cued body part influenced the early exogenous marker (N80). This suggests that the two mechanisms are interdependent, at least when the task requires more demanding shifts of attention. The early marker of exogenous tactile attention, the N80, was not directly related to IOR, which may suggest that exogenous attention and IOR are not necessarily two sides of the same coin. This study adds valuable new insight into how we process and select information presented to our body, showing both independent and interdependent effects of endogenous and exogenous attention in touch. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  2. Ciliary derived neurotrophic factor protects oligodendrocytes against radiation induced damage in vitro by a mechanism independent of a proliferative effect

    International Nuclear Information System (INIS)

    Evans, Andrew J.; Mabie, Peter C.; Kessler, Jack A.; Vikram, Bhadrasain

    1997-01-01

    U studies showed that CNTF did not function as a mitogen when added to the mature oligodendrocyte cultures. Following radiation, cells incorporating BrdU appeared to be non-viable. Conclusion: CNTF appeared to protect mature oligodendrocytes from irradiation by a mechanism other than proliferation. Our in vitro studies suggest that CNTF might have the potential for preventing or alleviating radiation induced myelopathy

  3. Exploring Institutional Mechanisms for Scientific Input into the Management Cycle of the National Protected Area Network of Peru: Gaps and Opportunities.

    Science.gov (United States)

    López-Rodríguez, M D; Castro, H; Arenas, M; Requena-Mullor, J M; Cano, A; Valenzuela, E; Cabello, J

    2017-12-01

    Understanding how to improve decision makers' use of scientific information across their different scales of management is a core challenge for narrowing the gap between science and conservation practice. Here, we present a study conducted in collaboration with decision makers that aims to explore the functionality of the mechanisms for scientific input within the institutional setting of the National Protected Area Network of Peru. First, we analyzed institutional mechanisms to assess the scientific information recorded by decision makers. Second, we developed two workshops involving scientists, decision makers and social actors to identify barriers to evidence-based conservation practice. Third, we administered 482 questionnaires to stakeholders to explore social perceptions of the role of science and the willingness to collaborate in the governance of protected areas. The results revealed that (1) the institutional mechanisms did not effectively promote the compilation and application of scientific knowledge for conservation practice; (2) six important barriers hindered scientific input in management decisions; and (3) stakeholders showed positive perceptions about the involvement of scientists in protected areas and expressed their willingness to collaborate in conservation practice. This collaborative research helped to (1) identify gaps and opportunities that should be addressed for increasing the effectiveness of the institutional mechanisms and (2) support institutional changes integrating science-based strategies for strengthening scientific input in decision-making. These insights provide a useful contextual orientation for scholars and decision makers interested in conducting empirical research to connect scientific inputs with operational aspects of the management cycle in other institutional settings around the world.

  4. Exploring Institutional Mechanisms for Scientific Input into the Management Cycle of the National Protected Area Network of Peru: Gaps and Opportunities

    Science.gov (United States)

    López-Rodríguez, M. D.; Castro, H.; Arenas, M.; Requena-Mullor, J. M.; Cano, A.; Valenzuela, E.; Cabello, J.

    2017-12-01

    Understanding how to improve decision makers' use of scientific information across their different scales of management is a core challenge for narrowing the gap between science and conservation practice. Here, we present a study conducted in collaboration with decision makers that aims to explore the functionality of the mechanisms for scientific input within the institutional setting of the National Protected Area Network of Peru. First, we analyzed institutional mechanisms to assess the scientific information recorded by decision makers. Second, we developed two workshops involving scientists, decision makers and social actors to identify barriers to evidence-based conservation practice. Third, we administered 482 questionnaires to stakeholders to explore social perceptions of the role of science and the willingness to collaborate in the governance of protected areas. The results revealed that (1) the institutional mechanisms did not effectively promote the compilation and application of scientific knowledge for conservation practice; (2) six important barriers hindered scientific input in management decisions; and (3) stakeholders showed positive perceptions about the involvement of scientists in protected areas and expressed their willingness to collaborate in conservation practice. This collaborative research helped to (1) identify gaps and opportunities that should be addressed for increasing the effectiveness of the institutional mechanisms and (2) support institutional changes integrating science-based strategies for strengthening scientific input in decision-making. These insights provide a useful contextual orientation for scholars and decision makers interested in conducting empirical research to connect scientific inputs with operational aspects of the management cycle in other institutional settings around the world.

  5. The effects of dexketoprofen on endogenous leptin and lipid peroxidation during liver ischemia reperfusion injury.

    Science.gov (United States)

    Ustun, Yasemin Burcu; Koksal, Ersin; Kaya, Cengiz; Sener, Elif Bengi; Aksoy, Abdurrahman; Yarim, Gul; Kabak, Yonca; Gulbahar, Yavuz

    2014-01-01

    Hepatic ischemia reperfusion (IR) injury has complex mechanisms. We investigated the effect of dexketoprofen on endogenous leptin and malondialdehyde (MDA) levels. Wistar albino rats were divided into 4 equal groups and were subjected to 1-hour ischemia and different subsequent reperfusion intervals. Dexketoprofen was administered in a dose of 25 mg/kg 15 minutes before ischemia induction and 1-hour reperfusion to the Dexketoprofen one-hour reperfusion group, n = 6 (DIR1) group and 6-hour reperfusion to the Dexketoprofen six-hour reperfusion group, n = 6 (DIR6) group. In the control groups, 0.9% physiologic serum (SF) was administered 15 minutes before ischemia induction and 1-hour reperfusion to the one-hour reperfusion group, n = 6 (IR1) group and 6-hour reperfusion to the six-hour reperfusion group, n = 6 (IR6) group. Although serum leptin (P = 0.044) and hepatic tissue MDA levels (P = 0.004) were significantly higher in the IR6 group than in the IR1 group, there were no significant differences in dexketoprofen pretreatment between the DIR1 and DIR6 groups. There were no differences in serum MDA levels among the 4 groups, and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were significantly higher in the IR1 (P = 0.026 and P = 0.018, respectively) and IR6 (P = 0.000 and P = 0.002, respectively) groups than in the DIR1 and DIR6 groups. Dexketoprofen pretreatment can protect the liver from IR injury by decreasing inflammation and lipid peroxidation. Our study shows that dexketoprofen has no effects on endogenous leptin during IR injury.

  6. Plasminogen activator inhibitor-1 suppresses endogenous fibrinolysis in a canine model of pulmonary embolism

    International Nuclear Information System (INIS)

    Reilly, C.F.; Fujita, T.; Hutzelmann, J.E.; Mayer, E.J.; Shebuski, R.J.

    1991-01-01

    Plasminogen activator inhibitor-1 (PAI-1), the specific, fast-acting inhibitor of tissue-type plasminogen activator (t-PA), binds to fibrin and has been found in high concentrations within arterial thrombi. These findings suggest that the localization of PAI-1 to a thrombus protects that same thrombus from fibrinolysis. In this study, clot-bound PAI-1 was assessed for its ability to suppress clot lysis in vivo. Autologous, canine whole blood clots were formed in the presence of increasing amounts of activated PAI-1 (0-30 micrograms/ml). Approximately 6-8% of the PAI-1 bound to the clots under the experimental conditions. Control and PAI-1-enriched clots containing iodine-125-labeled fibrin (ogen) were homogenized, washed to remove nonbound elements, and delivered to the lungs of anesthetized dogs where the homogenates subsequently underwent lysis by the endogeneous fibrinolytic system. 125I-labeled fibrin degradation products appeared in the blood of control animals within 10 minutes and were maximal by 90 minutes. PAI-1 reduced fibrin degradation product release in a dose-responsive manner at all times between 30 minutes and 5 hours (greater than or equal to 76% inhibition at 30 minutes, PAI-1 greater than or equal to 6 micrograms/ml). PAI-1 also suppressed D-dimer release from clots containing small amounts of human fibrin (ogen). t-PA administration attenuated the effects of PAI-1, whereas latent PAI-1 (20 micrograms/ml) had no effect on clot lysis. Blood levels of PA and PAI activity remained unaltered during these experiments. The results indicate that PAI-1 markedly inhibits endogenous fibrinolysis in vivo and, moreover, suggest that the localization of PAI-1 to a forming thrombus is an important physiological mechanism for subsequent thrombus stabilization

  7. The first sequenced carnivore genome shows complex host-endogenous r