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Sample records for foci potential role

  1. Immune responses to plague infection in wild Rattus rattus, in Madagascar: a role in foci persistence?

    Science.gov (United States)

    Andrianaivoarimanana, Voahangy; Telfer, Sandra; Rajerison, Minoarisoa; Ranjalahy, Michel A; Andriamiarimanana, Fehivola; Rahaingosoamamitiana, Corinne; Rahalison, Lila; Jambou, Ronan

    2012-01-01

    Plague is endemic within the central highlands of Madagascar, where its main reservoir is the black rat, Rattus rattus. Typically this species is considered susceptible to plague, rapidly dying after infection inducing the spread of infected fleas and, therefore, dissemination of the disease to humans. However, persistence of transmission foci in the same area from year to year, supposes mechanisms of maintenance among which rat immune responses could play a major role. Immunity against plague and subsequent rat survival could play an important role in the stabilization of the foci. In this study, we aimed to investigate serological responses to plague in wild black rats from endemic areas of Madagascar. In addition, we evaluate the use of a recently developed rapid serological diagnostic test to investigate the immune response of potential reservoir hosts in plague foci. We experimentally infected wild rats with Yersinia pestis to investigate short and long-term antibody responses. Anti-F1 IgM and IgG were detected to evaluate this antibody response. High levels of anti-F1 IgM and IgG were found in rats one and three weeks respectively after challenge, with responses greatly differing between villages. Plateau in anti-F1 IgM and IgG responses were reached for as few as 500 and 1500 colony forming units (cfu) inoculated respectively. More than 10% of rats were able to maintain anti-F1 responses for more than one year. This anti-F1 response was conveniently followed using dipsticks. Inoculation of very few bacteria is sufficient to induce high immune response in wild rats, allowing their survival after infection. A great heterogeneity of rat immune responses was found within and between villages which could heavily impact on plague epidemiology. In addition, results indicate that, in the field, anti-F1 dipsticks are efficient to investigate plague outbreaks several months after transmission.

  2. Immune responses to plague infection in wild Rattus rattus, in Madagascar: a role in foci persistence?

    Directory of Open Access Journals (Sweden)

    Voahangy Andrianaivoarimanana

    Full Text Available BACKGROUND: Plague is endemic within the central highlands of Madagascar, where its main reservoir is the black rat, Rattus rattus. Typically this species is considered susceptible to plague, rapidly dying after infection inducing the spread of infected fleas and, therefore, dissemination of the disease to humans. However, persistence of transmission foci in the same area from year to year, supposes mechanisms of maintenance among which rat immune responses could play a major role. Immunity against plague and subsequent rat survival could play an important role in the stabilization of the foci. In this study, we aimed to investigate serological responses to plague in wild black rats from endemic areas of Madagascar. In addition, we evaluate the use of a recently developed rapid serological diagnostic test to investigate the immune response of potential reservoir hosts in plague foci. METHODOLOGY/PRINCIPAL FINDINGS: We experimentally infected wild rats with Yersinia pestis to investigate short and long-term antibody responses. Anti-F1 IgM and IgG were detected to evaluate this antibody response. High levels of anti-F1 IgM and IgG were found in rats one and three weeks respectively after challenge, with responses greatly differing between villages. Plateau in anti-F1 IgM and IgG responses were reached for as few as 500 and 1500 colony forming units (cfu inoculated respectively. More than 10% of rats were able to maintain anti-F1 responses for more than one year. This anti-F1 response was conveniently followed using dipsticks. CONCLUSION/SIGNIFICANCE: Inoculation of very few bacteria is sufficient to induce high immune response in wild rats, allowing their survival after infection. A great heterogeneity of rat immune responses was found within and between villages which could heavily impact on plague epidemiology. In addition, results indicate that, in the field, anti-F1 dipsticks are efficient to investigate plague outbreaks several months after

  3. Intraprostatic locations of tumor foci of higher grade missed by diagnostic prostate biopsy among potential candidates for active surveillance

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    Kim, Kwangmo; Lee, Jung Keun; Choe, Gheeyoung; Hong, Sung Kyu

    2016-01-01

    To establish optimal biopsy scheme for selection of candidates for active surveillance (AS) among prostate cancer (PCa) patients, information on topographical distribution of tumor foci of higher grade missed by contemporary biopsy amongst potential candidates of AS would certainly be useful. Thus we analyzed topographic distribution of tumor foci by examining prostatectomy specimens in 444 patients who underwent radical prostatectomy for low risk PCa. Anterior and posterior prostate areas were demarcated by a horizontal line drawn at midpoint of prostatic urethra. Among 444 subjects, patients with upgrading showed relatively higher prevalence of index tumor foci in anterior prostate than those without upgrading, though not reaching statistical significance (p = 0.252). Meanwhile, among 135 (30.4%) patients with very low risk PCa, patients with upgrading showed significantly higher prevalence of index tumor foci in anterior prostate than those without upgrading (52.2% vs 33.8%; p = 0.031). In conclusions, tumor foci of higher grade missed by diagnostic biopsy were mostly located in anterior prostate among very low risk PCa patients. Such finding would be concrete evidence to support the notion that more efforts are needed to increase accuracy in detecting tumor foci in anterior prostate among potential candidates for AS. PMID:27827421

  4. Role Breadth Self-Efficacy and Foci of Proactive Behavior: Moderating Role of Collective, Relational, and Individual Self-Concept.

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    Hwang, Pin-Chyuan; Han, Ming-Chuan; Chiu, Su-Fen

    2015-01-01

    This study aims to identify the interactive effect of role breadth self-efficacy (RBSE) and the three levels of self-concept (collective, relational, and individual) in predicting of different foci of proactive behaviors. Results from 259 matched responses from an airline company in Taiwan showed that RBSE had a positive effect on (1) pro-organizational proactive behavior among those with higher collective self-concept, (2) pro-supervisor proactive behavior among those with higher relational self-concept, and (3) pro-self proactive behavior among those with higher individual self-concept. Our findings provide insights into the moderating role of different levels of self-concept on RBSE-proactive behavior process in terms of specific targets or beneficiaries. Further implications for organizational research and practice are discussed.

  5. Domestic animals as potential reservoir hosts of Trypanosoma brucei gambiense in sleeping sickness foci in Cameroon

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    Njiokou F.

    2010-03-01

    Full Text Available An explanation of the endemic nature and/or the resurgence of Human African Trypanosomiasis (HAT in the historic foci in West and Central Africa may be the existence of an animal reservoir. In some HAT foci, pigs were found infected by Trypanosoma brucei gambiense but the implication of the other domestic animals was not quite evaluated. This study aims to determine the prevalence of T. b. gambiense in domestic animal species (goat, sheep, pig and dog commonly found in the four active HAT foci in Cameroon (Bipindi, Fontem, Campo and Doumé. Blood samples were collected from 307 pigs, 264 goats, 267 sheep and 37 dogs and used for parasitological (QBC, immunological (LiTat 1.3 CATT and molecular (PCR analyses. QBC detected trypanosomes in 3.88 % domestic animals while 22.7 % were sero-positive with LiTat 1.3 CATT tests. Of the 875 animals analysed, 174 (19.88 % harboured T. brucei s.l. DNA, found in each of the four types of animal and in the four localities. The infection rate significantly differed among the animal species (p < 0.0001 and localities (p < 0.0001. The PCR also revealed T. b. gambiense group 1 DNA in 27 (3.08 % domestic animals. The specific infection rates were as follows: sheep (6.74 %, goats (3.08 %, pigs (0.32 % and dogs (0 %. T. b. gambiense was found in 8 (3.92 % animals from Bipindi, 15 (4.83 % from Campo, 4 (2.59 % from Fontem-Center and none from Doumé. The infection rates significantly differed between the localities, and correlated with the intensity of HAT transmission in the foci.

  6. SPO11-independent DNA repair foci and their role in meiotic silencing.

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    Fabrizia Carofiglio

    2013-06-01

    Full Text Available In mammalian meiotic prophase, the initial steps in repair of SPO11-induced DNA double-strand breaks (DSBs are required to obtain stable homologous chromosome pairing and synapsis. The X and Y chromosomes pair and synapse only in the short pseudo-autosomal regions. The rest of the chromatin of the sex chromosomes remain unsynapsed, contains persistent meiotic DSBs, and the whole so-called XY body undergoes meiotic sex chromosome inactivation (MSCI. A more general mechanism, named meiotic silencing of unsynapsed chromatin (MSUC, is activated when autosomes fail to synapse. In the absence of SPO11, many chromosomal regions remain unsynapsed, but MSUC takes place only on part of the unsynapsed chromatin. We asked if spontaneous DSBs occur in meiocytes that lack a functional SPO11 protein, and if these might be involved in targeting the MSUC response to part of the unsynapsed chromatin. We generated mice carrying a point mutation that disrupts the predicted catalytic site of SPO11 (Spo11(YF/YF, and blocks its DSB-inducing activity. Interestingly, we observed foci of proteins involved in the processing of DNA damage, such as RAD51, DMC1, and RPA, both in Spo11(YF/YF and Spo11 knockout meiocytes. These foci preferentially localized to the areas that undergo MSUC and form the so-called pseudo XY body. In SPO11-deficient oocytes, the number of repair foci increased during oocyte development, indicating the induction of S phase-independent, de novo DNA damage. In wild type pachytene oocytes we observed meiotic silencing in two types of pseudo XY bodies, one type containing DMC1 and RAD51 foci on unsynapsed axes, and another type containing only RAD51 foci, mainly on synapsed axes. Taken together, our results indicate that in addition to asynapsis, persistent SPO11-induced DSBs are important for the initiation of MSCI and MSUC, and that SPO11-independent DNA repair foci contribute to the MSUC response in oocytes.

  7. SPO11-independent DNA repair foci and their role in meiotic silencing.

    Science.gov (United States)

    Carofiglio, Fabrizia; Inagaki, Akiko; de Vries, Sandra; Wassenaar, Evelyne; Schoenmakers, Sam; Vermeulen, Christie; van Cappellen, Wiggert A; Sleddens-Linkels, Esther; Grootegoed, J Anton; Te Riele, Hein P J; de Massy, Bernard; Baarends, Willy M

    2013-06-01

    In mammalian meiotic prophase, the initial steps in repair of SPO11-induced DNA double-strand breaks (DSBs) are required to obtain stable homologous chromosome pairing and synapsis. The X and Y chromosomes pair and synapse only in the short pseudo-autosomal regions. The rest of the chromatin of the sex chromosomes remain unsynapsed, contains persistent meiotic DSBs, and the whole so-called XY body undergoes meiotic sex chromosome inactivation (MSCI). A more general mechanism, named meiotic silencing of unsynapsed chromatin (MSUC), is activated when autosomes fail to synapse. In the absence of SPO11, many chromosomal regions remain unsynapsed, but MSUC takes place only on part of the unsynapsed chromatin. We asked if spontaneous DSBs occur in meiocytes that lack a functional SPO11 protein, and if these might be involved in targeting the MSUC response to part of the unsynapsed chromatin. We generated mice carrying a point mutation that disrupts the predicted catalytic site of SPO11 (Spo11(YF/YF)), and blocks its DSB-inducing activity. Interestingly, we observed foci of proteins involved in the processing of DNA damage, such as RAD51, DMC1, and RPA, both in Spo11(YF/YF) and Spo11 knockout meiocytes. These foci preferentially localized to the areas that undergo MSUC and form the so-called pseudo XY body. In SPO11-deficient oocytes, the number of repair foci increased during oocyte development, indicating the induction of S phase-independent, de novo DNA damage. In wild type pachytene oocytes we observed meiotic silencing in two types of pseudo XY bodies, one type containing DMC1 and RAD51 foci on unsynapsed axes, and another type containing only RAD51 foci, mainly on synapsed axes. Taken together, our results indicate that in addition to asynapsis, persistent SPO11-induced DSBs are important for the initiation of MSCI and MSUC, and that SPO11-independent DNA repair foci contribute to the MSUC response in oocytes.

  8. Phylogenetic Analysis of Entomoparasitic Nematodes, Potential Control Agents of Flea Populations in Natural Foci of Plague

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    Koshel, E. I.; Aleshin, V. V.; Eroshenko, G. A.; Kutyrev, V. V.

    2014-01-01

    Entomoparasitic nematodes are natural control agents for many insect pests, including fleas that transmit Yersinia pestis, a causative agent of plague, in the natural foci of this extremely dangerous zoonosis. We examined the flea samples from the Volga-Ural natural focus of plague for their infestation with nematodes. Among the six flea species feeding on different rodent hosts (Citellus pygmaeus, Microtus socialis, and Allactaga major), the rate of infestation varied from 0 to 21%. The propagation rate of parasitic nematodes in the haemocoel of infected fleas was very high; in some cases, we observed up to 1,000 juveniles per flea specimen. Our study of morphology, life cycle, and rDNA sequences of these parasites revealed that they belong to three distinct species differing in the host specificity. On SSU and LSU rRNA phylogenies, these species representing three genera (Rubzovinema, Psyllotylenchus, and Spilotylenchus), constitute a monophyletic group close to Allantonema and Parasitylenchus, the type genera of the families Allantonematidae and Parasitylenchidae (Nematoda: Tylenchida). We discuss the SSU-ITS1-5.8S-LSU rDNA phylogeny of the Tylenchida with a special emphasis on the suborder Hexatylina. PMID:24804197

  9. Chemopreventive Potential of Synergy1 and Soybean in Reducing Azoxymethane-Induced Aberrant Crypt Foci in Fisher 344 Male Rats

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    V. P. Gourineni

    2011-01-01

    Full Text Available Synergy1, a prebiotic composed of Inulin and Oligofructose (1 : 1. Soybean meal is a natural source of isoflavones. The objective was to investigate the effects of feeding Synergy1 and SM on the incidence of azoxymethane- (AOM- induced aberrant crypt foci (ACF in Fisher 344 male rats. Rats (54 were randomly assigned to 9 groups (n=6. Control group (C was fed AIN-93G and treatment groups Syn1 and SM at 5% and 10% singly and in combinations. Rats were injected with two s/c injections of AOM at 7 and 8 weeks of age at 16 mg/kg body weight and killed at 17 weeks by CO2 asphyxiation. Colonic ACF enumeration and hepatic enzyme activities were measured. Reductions (% in total ACF among treatment groups fed combinations were higher (67–77 compared to groups fed singly (52–64. Synergistic mechanisms among phytochemicals may be responsible suggesting protective role in colon carcinogenesis with implications in food product development.

  10. The chemopreventive potential of Curcuma purpurascens rhizome in reducing azoxymethane-induced aberrant crypt foci in rats

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    Rouhollahi, Elham; Moghadamtousi, Soheil Zorofchian; Al-Henhena, Nawal; Kunasegaran, Thubasni; Hasanpourghadi, Mohadeseh; Looi, Chung Yeng; Abd Malek, Sri Nurestri; Awang, Khalijah; Abdulla, Mahmood Ameen; Mohamed, Zahurin

    2015-01-01

    Curcuma purpurascens BI. rhizome, a member of the Zingiberaceae family, is a popular spice in Indonesia that is traditionally used in assorted remedies. Dichloromethane extract of C. purpurascens BI. rhizome (DECPR) has previously been shown to have an apoptosis-inducing effect on colon cancer cells. In the present study, we examined the potential of DECPR to prevent colon cancer development in rats treated with azoxymethane (AOM) (15 mg/kg) by determining the percentage inhibition in incidence of aberrant crypt foci (ACF). Starting from the day immediately after AOM treatment, three groups of rats were orally administered once a day for 2 months either 10% Tween 20 (5 mL/kg, cancer control), DECPR (250 mg/kg, low dose), or DECPR (500 mg/kg, high dose). Meanwhile, the control group was intraperitoneally injected with 5-fluorouracil (35 mg/kg) for 5 consecutive days. After euthanizing the rats, the number of ACF was enumerated in colon tissues. Bax, Bcl-2, and proliferating cell nuclear antigen (PCNA) protein expressions were examined using immunohistochemical and Western blot analyses. Antioxidant enzymatic activity was measured in colon tissue homogenates and associated with malondialdehyde level. The percentage inhibition of ACF was 56.04% and 68.68% in the low- and high-dose DECPR-treated groups, respectively. The ACF inhibition in the treatment control group was 74.17%. Results revealed that DECPR exposure at both doses significantly decreased AOM-induced ACF formation, which was accompanied by reduced expression of PCNA. Upregulation of Bax and downregulation of Bcl-2 suggested the involvement of apoptosis in the chemopreventive effect of DECPR. In addition, the oxidative stress resulting from AOM treatment was significantly attenuated after administration of DECPR, which was shown by the elevated antioxidant enzymatic activity and reduced malondialdehyde level. Taken together, the present data clearly indicate that DECPR significantly inhibits ACF formation

  11. Do aberrant crypt foci have predictive value for the occurrence of colorectal tumours? Potential of gene expression profiling in tumours

    NARCIS (Netherlands)

    Wijnands, M.V.W.; Erk, van M.J.; Doornbos, R.P.; Krul, C.A.M.; Woutersen, R.A.

    2004-01-01

    The effects of different dietary compounds on the formation of aberrant crypt foci (ACF) and colorectal tumours and on the expression of a selection of genes were studied in rats. Azoxymethane-treated male F344 rats were fed either a control diet or a diet containing 10% wheat bran (WB), 0.2%

  12. Enzootic plague foci, Algeria

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    Malek, M.A.; Hammani, A.; Beneldjouzi, A.; Bitam, I.

    2014-01-01

    In Algeria, PCR sequencing of pla, glpD and rpoB genes found Yersinia pestis in 18/237 (8%) rodents of five species, including Apodemus sylvaticus, previously undescribed as pestiferous; and disclosed three new plague foci. Multiple spacer typing confirmed a new Orientalis variant. Rodent survey should be reinforced in this country hosting reemerging plague. PMID:25834736

  13. Enzootic plague foci, Algeria

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    M.A. Malek

    2015-03-01

    Full Text Available In Algeria, PCR sequencing of pla, glpD and rpoB genes found Yersinia pestis in 18/237 (8% rodents of five species, including Apodemus sylvaticus, previously undescribed as pestiferous; and disclosed three new plague foci. Multiple spacer typing confirmed a new Orientalis variant. Rodent survey should be reinforced in this country hosting reemerging plague.

  14. Foci of Volcanoes

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, I.

    1974-01-01

    One may assume a center of volcanic activities beneath the edifice of an active volcano, which is here called the focus of the volcano. Sometimes it may be a ''magma reservoir''. Its depth may differ with types of magma and change with time. In this paper, foci of volcanoes are discussed from the viewpoints of four items: (1) Geomagnetic changes related with volcanic activities; (2) Crustal deformations related with volcanic activities; (3) Magma transfer through volcanoes; and (4) Subsurface structure of calderas.

  15. [Possibilities of ultrasonic investigations in differentiation of a small-foci impairment of thyroid gland].

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    Reyti, A O; Vityuk, N V; Medvedev, V E; Starushok, I O

    2015-03-01

    The results of ultrasound investigation of microcarcinomas and nontumoral foci of thyroid gland up to 10 mm in diameter and malignant foci over 10 mm are presented. Ultrasound signs are depicted, in accordance to which a potentially malignant thyroid gland foci are delineated, what demands a morphological (cytological) verification conduction.

  16. γH2AX/53BP1 foci as a potential pre-treatment marker of HNSCC tumors radiosensitivity - preliminary methodological study and discussion

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    Falk, Martin; Horakova, Zuzana; Svobodova, Marketa; Masarik, Michal; Kopecna, Olga; Gumulec, Jaromir; Raudenska, Martina; Depes, Daniel; Bacikova, Alena; Falkova, Iva; Binkova, Hana

    2017-09-01

    In order to improve patients' post-treatment quality of life, a shift from surgery to non-surgical (chemo)radio-treatment is recognized in head and neck oncology. However, about half of HNSCC tumors are resistant to irradiation and an efficient marker of individual tumor radiosensitivity is still missing. We analyzed whether various parameters of DNA double strand break (DSB) repair determined in vitro can predict, prior to clinical treatment initiation, the radiosensitivity of tumors. We compared formation and decrease of γH2AX/53BP1 foci in 48 h after irradiating tumor cell primocultures with 2 Gy of γ-rays. To better understand complex tumor behavior, three different cell type primocultures - CD90-, CD90+, and a mixed culture of these cells - were isolated from 1 clinically radioresistant, 2 radiosensitive, and 4 undetermined HPV-HNSCC tumors and followed separately. While DSB repair was delayed and the number of persisting DSBs increased in the radiosensitive tumors, the results for the radioresistant tumor were similar to cultured normal human skin fibroblasts. Hence, DSB repair kinetics/efficiency may correlate with clinical response to radiotherapy for a subset of HNSCC tumors but the size (and therefore practical relevance) of this subset remains to be determined. The same is true for contribution of different cell type primocultures to tumor radioresistance.

  17. Dentigenous infectious foci – a risk factor of infective endocarditis

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    Wisniewska-Spychala, Beata; Sokalski, Jerzy; Grajek, Stefan; Jemielity, Marek; Trojnarska, Olga; Choroszy-Król, Irena; Sójka, Anna; Maksymiuk, Tomasz

    2012-01-01

    Summary Background Dentigenous, infectious foci are frequently associated with the development of various diseases. The role of such foci in the evolution of endocarditis still remains unclear. This article presents the concluding results of an interdisciplinary study verifying the influence of dentigenous, infectious foci on the development of infective endocarditis. Material/Methods The study subjects were 60 adult patients with history of infective endocarditis and coexistent acquired heart disease, along with the presence at least 2 odontogenic infectious foci (ie, 2 or more teeth with gangrenous pulp and periodontitis). The group had earlier been qualified for the procedure of heart valve replacement. Swabs of removed heart valve tissue with inflammatory lesions and blood were then examined microbiologically. Swabs of root canals and their periapical areas, of periodontal pockets, and of heart valves were also collected. Results Microbial flora, cultured from intradental foci, blood and heart valves, fully corresponded in 14 patients. This was accompanied in almost all cases by more advanced periodontitis (2nd degree, Scandinavian classification), irrespective of the bacterial co-occurrence mentioned. In the remaining patients, such consistency was not found. Conclusions Among various dentigenous, infectious foci, the intradental foci appear to constitute a risk factor for infective endocarditis. PMID:22293883

  18. Actin Foci Adhesion of D. discoideum

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    Flanders, Bret; Paneru, Govind

    2014-03-01

    Amoeboid migration is a fast (10 μm min-1) integrin-independent mode of migration that is important with D. discoideum, leukocytes, and breast cancer cells. It is poorly understood, but depends on the establishment of adhesive contacts to the substrate where the cell transmits traction forces. In pre-aggregative D. discoideum, a model system for learning about amoeboid migration, these adhesive contacts are discrete complexes that are known as actin-foci. They have an area of ~ 0.5 μm2 and a lifetime of ~ 20 s. This talk will present measurements of the adhesive character of actin foci that have been obtained using a submicron force transducer that was designed for this purpose. Results on the rupture stresses and lifetimes of individual acting foci under nano-newton level forces will be described in the context of a general theory for cellular adhesion. This theory depends on, essentially, three cellular properties: the membrane-medium surface tension, the number density of adhesion receptors in the membrane, and the receptor-substrate potential energy surface. Therefore, the use of the transducer to determine the surface tension will be presented, as well.

  19. Pomegranate polyphenolics suppressed azoxymethane-induced colorectal aberrant crypt foci and inflammation: possible role of miR-126/VCAM-1 and miR-126/PI3K/AKT/mTOR.

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    Banerjee, Nivedita; Kim, Hyemee; Talcott, Stephen; Mertens-Talcott, Susanne

    2013-12-01

    The antitumorigenic activities of polyphenols such as ellagitannins and anthocyanins in pomegranate (Punica granatum L.) have been previously studied where cytotoxic, anti-inflammatory and antioxidant effects were evident in various cancer models. The objective of this study was to investigate the role of miR-126/vascular cell adhesion molecule 1 (VCAM-1) and miR-126/phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) in pomegranate-mediated anti-inflammatory and anticarcinogenic effects in vivo and in vitro. Sprague-Dawley rats (n = 10 per group) received pomegranate juice (2504.74 mg gallic acid equivalents/l) or a polyphenol-free control beverage ad libitum for 10 weeks and were injected with azoxymethane (AOM) subcutaneously (15mg/kg) at weeks 2 and 3. Consumption of pomegranate juice suppressed the number of aberrant crypt foci (ACF) and dysplastic ACF by 29 and 53.5% (P = 0.05 and 0.04), respectively, and significantly lowered proliferation of mucosa cells. Pomegranate juice significantly downregulated proinflammatory enzymes nitric oxide synthase and cyclooxygenase-2 messenger RNA (mRNA) and protein expression. In addition, it suppressed nuclear factor-κB and VCAM-1 mRNA and protein expression in AOM-treated rats. Pomegranate also inhibited phosphorylation of PI3K/AKT and mTOR expression and increased the expression of miR-126. The specific target and functions of miR-126 were investigated in HT-29 colon cancer cell lines. In vitro, the involvement of miR-126 was confirmed using the antagomiR for miR-126, where pomegranate reversed the effects of the antagomiR on the expression of miR-126, VCAM-1 and PI3K p85β. In summary, therapeutic potentials of pomegranate in colon tumorigenesis were due in part to targeting miR-126-regulated pathways, which contributes in the underlying anti-inflammatory mechanisms.

  20. Understanding the persistence of plague foci in Madagascar.

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    Voahangy Andrianaivoarimanana

    2013-11-01

    Full Text Available Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar.

  1. Understanding the persistence of plague foci in Madagascar.

    Science.gov (United States)

    Andrianaivoarimanana, Voahangy; Kreppel, Katharina; Elissa, Nohal; Duplantier, Jean-Marc; Carniel, Elisabeth; Rajerison, Minoarisoa; Jambou, Ronan

    2013-11-01

    Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar.

  2. Understanding the Persistence of Plague Foci in Madagascar

    Science.gov (United States)

    Andrianaivoarimanana, Voahangy; Kreppel, Katharina; Elissa, Nohal; Duplantier, Jean-Marc; Carniel, Elisabeth; Rajerison, Minoarisoa; Jambou, Ronan

    2013-01-01

    Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar. PMID:24244760

  3. CDC25B overexpression stabilises centrin 2 and promotes the formation of excess centriolar foci.

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    Rose Boutros

    Full Text Available CDK-cyclin complexes regulate centriole duplication and microtubule nucleation at specific cell cycle stages, although their exact roles in these processes remain unclear. As the activities of CDK-cyclins are themselves positively regulated by CDC25 phosphatases, we investigated the role of centrosomal CDC25B during interphase. We report that overexpression of CDC25B, as is commonly found in human cancer, results in a significant increase in centrin 2 at the centrosomes of interphase cells. Conversely, CDC25B depletion causes a loss of centrin 2 from the centrosome, which can be rescued by treatment with the proteasome inhibitor MG132. CDC25B overexpression also promotes the formation of excess centrin 2 "foci". These foci can accumulate other centrosome proteins, including γ-tubulin and PCM-1, and can function as microtubule organising centres, indicating that these represent functional centrosomes. Formation of centrin 2 foci can be blocked by specific inhibition of CDK2 but not CDK1. CDK2-mediated phosphorylation of Monopolar spindle 1 (Mps1 at the G1/S transition is essential for the initiation of centrosome duplication, and Mps1 is reported to phosphorylate centrin 2. Overexpression of wild-type or non-degradable Mps1 exacerbated the formation of excess centrin 2 foci induced by CDC25B overexpression, while kinase-dead Mps1 has a protective effect. Together, our data suggest that CDC25B, through activation of a centrosomal pool of CDK2, stabilises the local pool of Mps1 which in turn regulates the level of centrin 2 at the centrosome. Overexpression of CDC25B may therefore contribute to tumourigenesis by perturbing the natural turnover of centrosome proteins such as Mps1 and centrin 2, thus resulting in the de novo assembly of extra-numerary centrosomes and potentiating chromosome instability.

  4. Ultramicrostructure and clinical implications of satellite foci in front of the head of pterygium

    Institute of Scientific and Technical Information of China (English)

    LIU Haixia; XIANG Nan; ZHOU Xiongwu; HU Weikun; LI Guigang; ZHANG Hong

    2007-01-01

    In our previous studies,grey satellite foci were found in the front of heads of pterygia.This research was designed to investigate the ultramicrostructure and clinical implications of these satellite foci.The satellite foci were observed and counted under slit lamp biomicroscope.The patients with eye pterygia were divided into groups in terms of occupation,sex,age,length of history,grade of congestion,and size of the heads.The SPSS 13.0 software was used for statistical analysis.The cap areas and satellite foci were ultramicrostructurally examined.Among the total 62 eyes with pterygium,satellite foci were found in 34.The overall incidence of satellite foci was 54.8%.There were no significant differences in incidence among the subjects of different sex,age,and length of history.There were significant differences in incidence among the patients of different occupation,grades of congestion,and size of heads.Higher grades of congestion,outdoor occupations and larger pterygium heads were associated with higher incidence of satellite foci.High grades of congestion and bigger heads were also correlated with the number of satellite foci.Length of history bore no correlation with number of satellite foci.Histologically,the components of the cap areas and the foci were identical,with both consisting of mass of active fibroblasts.The activated fibroblasts existed in the natural tissue planes between Bowman's layer and basal cell layer.The fibroblasts in the satellite foci and the cap areas of a pterygium show some features of tumor cells and may play a vital role in the development and progression of a pterygium.The presence and amount of satellite foci around a pterygium can be used as an indicator for the speed of its growth.

  5. Pelvic Gliomatosis within Foci of Endometriosis

    OpenAIRE

    Killeen, Vincent B.; Reich, Harry; McGlynn, Fran; Virgilio, Lawrence A.; Krawitz, Michael A.; Sekel, Lisa

    1997-01-01

    The third reported case of pelvic gliomatosis found within foci of endometriosis is documented 16 years after the removal of a benign cystic teratoma. Grossly at laparoscopy the lesions appear as typical deep fibrotic endometriotic implants.

  6. Locating Ectopic Foci on a Cylinder

    Science.gov (United States)

    Kuklik, Pawel; Zebrowski, Jan J.

    2003-07-01

    Arrhythmia is a condition in which an additional ectopic pacemaker is present in the tissue of the heart. Localization of ectopic foci is essential for successful radio-frequency ablation, an important surgical way of treating arrhythmia. In one of the possible mechanisms, arrhythmia induced by an ectopic foci located in one of the main blood vessels leading out or onto the heart. The therapeutic procedure in this case is usually ablation of the whole junction of the blood vessel with heart wall. In this way, whatever excitation occurs inside the vessel, it cannot penetrate the ventricles perturbing their contraction cycle. Such an ablation procedure is long and burdened with the risk of the perforation. A more safe method would involve the localization of the source of the excitation (i.e. the ectopic foci) and its ablation. The methods used in cardiology at present involve complicated localization systems and are time-consuming with the patient spending a long time on the operating table. Recently, Hall and Glass have developed numerical methods which allow to quickly to model the localization of the ectopic foci in a flat, square sample of an inhomogeneous medium. Here, we demonstrate an extension of this model for the case of a cylinder containing an ectopic foci, that can be a model of a blood vessel with the source of the ectopic beat inside it. Three methods of localization are implemented. Standard electrodes containing several active tips are used to stimulate the medium locally and locate the foci judging from the reaction of the system. The first one uses electrode activation times to compute the location of the ectopic site. The second one localizes it by measuring the resetting response of the foci, and the third one, uses wavefront curvature. Specifically for the cylindrical geometry of the blood vessel, we developed a localization procedure that allows to quickly localize the pacemaker.

  7. Mapping risk foci for endemic sheep scab.

    Science.gov (United States)

    Rose, H; Learmount, J; Taylor, M; Wall, R

    2009-10-28

    Psoroptic mange in sheep, resulting from infestation by the astigmatid mite Psoroptes ovis, is increasingly prevalent in Europe and other parts of the world. As a step towards improved national control, regional or local scab management programmes that target high-risk areas and aim to maintain the number of outbreaks below an acceptable level may be an effective initial use of time and resource. To facilitate such a management approach, in this paper scab outbreak farms are identified using a questionnaire survey of sheep farmers, the data from which are then used to build a national scab risk model for Great Britain. The questionnaire results indicate a national prevalence of scab, between March 2007 and February 2008, of 8.6% (+/-1.98). However, previous exposure to sheep scab significantly affected the respondent's probability of reporting a scab outbreak during the survey period (chi(2)=53.2, d.f.=1, P<0.001); 85% of the farms that reported at least one scab outbreak had experienced outbreaks in previous years, 27% had experienced outbreaks in more than five of the previous 10 years. In contrast, 76% of farms that did not report scab had not had a previous outbreak. The highest prevalence areas were in Northern England, Wales, Southwest England and Scotland. Modelling the distribution of the reported scab outbreaks identified height above sea level, temperature and rainfall as significant predictors of the probability of an outbreak, superimposed on an underlying pattern of sheep abundance. It is argued that scab management programmes directed at these foci have the potential to allow a more targeted approach to scab control and significantly reduce the prevalence of scab in the UK and other European countries.

  8. Extracellular Vesicles: potential roles in Regenerative Medicine

    Directory of Open Access Journals (Sweden)

    Olivier G de Jong

    2014-12-01

    Full Text Available Extracellular vesicles (EV consist of exosomes, which are released upon fusion of the multivesicular body with the cell membrane, and microvesicles, which are released directly from the cell membrane. EV can mediate cell-cell communication and are involved in many processes, including immune signaling, angiogenesis, stress response, senescence, proliferation, and cell differentiation. The vast amount of processes that EV are involved in and the versatility of manner in which they can influence the behavior of recipient cells make EV an interesting source for both therapeutic and diagnostic applications. Successes in the fields of tumor biology and immunology sparked the exploration of the potential of EV in the field of regenerative medicine. Indeed, EV are involved in restoring tissue and organ damage, and may partially explain the paracrine effects observed in stem cell based therapeutic approaches. The function and content of EV may also harbor information that can be used in tissue engineering, in which paracrine signaling is employed to modulate cell recruitment, differentiation, and proliferation. In this review, we discuss the function and role of EV in regenerative medicine and elaborate on potential applications in tissue engineering.

  9. Understanding migraine: Potential role of neurogenic inflammation

    Directory of Open Access Journals (Sweden)

    Rakesh Malhotra

    2016-01-01

    approach to treatment. With this objective, the present review summarizes the evidence supporting the involvement of neurogenic inflammation and neuropeptides in the pathophysiology and pharmacology of migraine headache as well as its potential significance in better tailoring therapeutic interventions in migraine or other neurological disorders. In addition, we have briefly highlighted the pathophysiological role of neurogenic inflammation in various other neurological disorders.

  10. Optimally enhanced heating for focused ultrasound surgery with split foci, dual-frequency, or multi foci

    Science.gov (United States)

    Lu, Mingzhu; Guan, Yubo; Dong, Tengju; Liu, Fenfen; Wan, Mingxi

    2017-03-01

    To substantially enhance heating in HIFU treatment, several methods such as split foci, multi foci, and dual-frequency modes are used. The enhanced-cavitation heating protocols are implemented experimentally in BSA gel-phantom using four-element split-focus array. Using dual frequency of 1.2 and 2.4 MHz, the superimposing of two frequency pressures at confocal region can enhance nucleation cavitation and inertial cavitation activity. When using 135° phase shift combined with dual frequency of 1.2 and 2.4 MHz, the peak negative pressure reach maximum due to peak-negative pressures of two frequencies occur at same time, resulting strong cavitation activities. When using dual frequency of 1.2 and 2.4 MHz, 25-Hz pulse-repetition frequency (PRF), both 135° and 180° phase shift protocols, the experiment results show the largest lesion size of 10.5 × 10.5 × 11 mm3, quickest lesion inception time of less than 0.2 s, therefore, both 135° and 180° phase shift protocols are most efficient in enhanced-cavitation heating. The filtered-PCD mean square waveforms reveal that the strong inertial-cavitation activities involve in those two treatments. The lesion size of four foci of 180° phase shift, single frequency, 25 Hz PRF, is 2 times that of 0° phase shift, single frequency even if the peak intensity of 180° case is half less than that of 0° phase shift case. When arrange multi foci using phased array in a style of a wavelength distance between neighbor foci in focal plane, the result is the same as that using split foci of 180° phase shift and single frequency.

  11. Potential role of tetrandrine in cancer therapy

    Institute of Scientific and Technical Information of China (English)

    CHEN Yu-Jen

    2002-01-01

    Tetrandrine, a bisbenylisoquinoline alkaloid isolated from the dried root of Stephenia tetrandra S Moore, exhibits very broad pharmacological actions, including anti-tumor activity. The beneficial effects of tetrandrine on tumor cell cytotoxicity and radiosensitization, multidrug resistance, normal tissue radioprotection, and angiogenesis are most promising and deserve great attention. Tetrandrine has potential either as a tumoricidal agent or as an adjunct to chemotherapy and radiotherapy. To evaluate the potential clinical efficacy of tetrandrine for cancer therapy,more mechanism-based pharmacological, pharmacokinetic, and pharmacodynamic studies are required.

  12. 67. Do prenatal intracardiac echogenic foci affect postnatal cardiac function?

    Directory of Open Access Journals (Sweden)

    R. Bader

    2016-07-01

    Full Text Available Echogenic foci in the prenatal hear is not an uncommon finding. To determine whether prenatally diagnosed intracardiac echogenic foci are associated with neonatal cardiac dysfunction and persistence. Fetuses in which intracardiac echogenic foci were shown on prenatal sonography at 1 perinatal center from (September 2009 to December 2013 underwent postnatal echocardiography at ages 1 month to1 year. A single pediatric cardiologist assessed cardiac function by measuring the left ventricular shortening fraction and myocardial performance index. The presence of tricuspid valve regurgitation was also sought. Prenatally 60 fetuses had intracardiac echogenic foci mean age ± SD at diagnosis (23 ± 3.1. 53 (88.3% had left ventricular intracardiac echogenic foci, and 7 (11.6% had right ventricular intracardiac echogenic foci. 12 preganant ladies were lost for follow up (2 fetuses of 7 (28.5% with right ventricular intracardiac echogenic foci., and 10 fetuses of 53 (18.8% with LV intracardiac echogenic foci %. Post natally, those infants, 32 (66.6% males and 16 (33.3% females were examined. At a mean age ± SD of 7.4 ± 3.1 months. Prenatally, all infants had a normal left ventricular shortening fraction. The overall mean left ventricular myocardial performance index (reference value, 0.36 ± 0.06, was normal for both infants with left ventricular intracardiac echogenic foci (0.32 ± 0.01 and those with right ventricular intracardiac echogenic foci (0.33 ± 0.05. Trace tricuspid valve regurgitation were noted in 15 (31% of the infants. Left ventricular intracardiac echogenic foci persisted in 15 infants (34.8%, whereas right ventricular intracardiac echogenic foci persisted in 1 infant (20%. Prenatally diagnosed intracardiac echogenic foci can be persistent but is not associated with myocardial dysfunction in the first year of life.

  13. [THE PRESENT STATE OF EPIZOOTOLOGICAL MONITORING OF THE NATURAL FOCI OF INFECTIONS IN THE RUSSIAN FEDERATION].

    Science.gov (United States)

    Trankvilevsky, D V; Tsarenko, V A; Zhukov, V I

    2016-01-01

    The facilities of the Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare play a leading role in epizootological monitoring. The specialists (zoologists and entomologists) of Hygiene and Epidemiology Centers do basic work in the subjects of the Russian Federation. The data obtained in the participation of different ministries and departments are used to analyze the results of monitoring. The latter is one of the important steps in the management of the epidemic, process in natural focal infections. In recent years, there has been an unjustified reduction in the volume of studies in the natural foci. This negatively affects the reliability of estimates and predictions of the epidemic activity of the natural foci of infections. Ensuring the national, security of the Russian Federation, epidemiological surveillance, and control of its natural foci requires staffing and appropriate professional training in the zoological and entomological subdivisions of the Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare.

  14. Daclatasvir: potential role in hepatitis C

    Directory of Open Access Journals (Sweden)

    Lee C

    2013-10-01

    Full Text Available Choongho Lee College of Pharmacy, Dongguk University-Seoul, Goyang, Republic of Korea  Abstract: Chronic hepatitis C virus (HCV infection is responsible for the development of liver cirrhosis and hepatocellular carcinoma. It has been a tremendous burden on global health care systems. With the advent of a number of new direct-acting and host-targeting antiviral agents, current interferon-α- and ribavirin-based HCV therapy has started to move towards an interferon-sparing or even interferon-free strategy. In this regard, a recently identified NS5A inhibitor, daclatasvir, showed a great promise in clinical trials as another new class of direct-acting anti-HCV therapeutics, with a distinct mechanism of action. In this review, a variety of preclinical as well as clinical proof-of-concept studies of daclatasvir, including the studies of its discovery, mechanism of action, viral resistance, and host polymorphism profiles are reviewed. In addition, a role of daclatasvir in the future therapy for HCV patients is discussed briefly. Keywords: hepatitis C virus, nonstructural protein 5A, NS5A inhibitor, hepatitis C treatment

  15. Identification of Chinese plague foci from long-term epidemiological data.

    Science.gov (United States)

    Ben-Ari, Tamara; Neerinckx, Simon; Agier, Lydiane; Cazelles, Bernard; Xu, Lei; Zhang, Zhibin; Fang, Xiye; Wang, Shuchun; Liu, Qiyong; Stenseth, Nils C

    2012-05-22

    Carrying out statistical analysis over an extensive dataset of human plague reports in Chinese villages from 1772 to 1964, we identified plague endemic territories in China (i.e., plague foci). Analyses rely on (i) a clustering method that groups time series based on their time-frequency resemblances and (ii) an ecological niche model that helps identify plague suitable territories characterized by value ranges for a set of predefined environmental variables. Results from both statistical tools indicate the existence of two disconnected plague territories corresponding to Northern and Southern China. Altogether, at least four well defined independent foci are identified. Their contours compare favorably with field observations. Potential and limitations of inferring plague foci and dynamics using epidemiological data is discussed.

  16. Identification of Chinese plague foci from long-term epidemiological data

    Science.gov (United States)

    Ben-Ari, Tamara; Neerinckx, Simon; Agier, Lydiane; Cazelles, Bernard; Xu, Lei; Zhang, Zhibin; Fang, Xiye; Wang, Shuchun; Liu, Qiyong; Stenseth, Nils C.

    2012-01-01

    Carrying out statistical analysis over an extensive dataset of human plague reports in Chinese villages from 1772 to 1964, we identified plague endemic territories in China (i.e., plague foci). Analyses rely on (i) a clustering method that groups time series based on their time-frequency resemblances and (ii) an ecological niche model that helps identify plague suitable territories characterized by value ranges for a set of predefined environmental variables. Results from both statistical tools indicate the existence of two disconnected plague territories corresponding to Northern and Southern China. Altogether, at least four well defined independent foci are identified. Their contours compare favorably with field observations. Potential and limitations of inferring plague foci and dynamics using epidemiological data is discussed. PMID:22570501

  17. Magnesium: Potential Roles in Neurovascular Disease

    Directory of Open Access Journals (Sweden)

    Jason J Chang

    2014-04-01

    Full Text Available Objective: Magnesium therapy has been studied extensively in pre-clinical and clinical trials in multiple organ systems. Cerebrovascular diseases are particularly likely to benefit from its neuroprotective properties. This review summarizes current studies of magnesium in a wide range of neurovascular diseases.Methods: We searched relevant terms in the National Library of Medicine PubMed database and selected research including basic science, translational reports, meta-analyses, and clinical studies.Results: Studies examining magnesium administration in ischemic stroke have failed to show any benefit in clinical outcome. Data on magnesium for intracerebral hemorrhage is limited. Preliminary investigations in subarachnoid hemorrhage were promising, but definitive studies did not reveal differences in clinical outcome between magnesium and placebo-treated groups. Studies examining magnesium administration in global ischemia following cardiac arrest suggest a trend toward improved clinical outcome. The strongest evidence for clinically relevant neuroprotection following magnesium administration derives from studies of pre-term infants and patients undergoing cardiac bypass and carotid endarterectomy procedures. Magnesium was found to have an excellent safety profile across all investigations.Conclusions: Magnesium is easy to administer and possesses a favorable safety profile. Its utility as a neuroprotectant in cardiac surgery, carotid enderaterectomy, and pre-term infant hypoxia remain promising. Value as a therapeutic agent in ischemic stroke, intracerebral hemorrhage and subarachnoid hemorrhage is unclear and appears to be limited by late administration. Ongoing clinical trials assessing magnesium administration in the first hours following symptom onset may help clarify the role of magnesium therapy in these disease processes.

  18. PMEL EcoFOCI Early Arctic Data, 1986-1991

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Pacific Marine Environmental Laboratory (PMEL) Fisheries-Oceanography Cooperative Investigations (FOCI) Early Arctic Data, 1987 - 1991

  19. PMEL EcoFOCI Shelikof Line 8 Data, 1981-open

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Pacific Marine Environmental Laboratory (PMEL) Fisheries-Oceanography Cooperative Investigations (FOCI) Shelikof Line 8 Data

  20. Fully automated analysis of chemically induced γH2AX foci in human peripheral blood mononuclear cells by indirect immunofluorescence.

    Science.gov (United States)

    Willitzki, Annika; Lorenz, Sebastian; Hiemann, Rico; Guttek, Karina; Goihl, Alexander; Hartig, Roland; Conrad, Karsten; Feist, Eugen; Sack, Ulrich; Schierack, Peter; Heiserich, Lisa; Eberle, Caroline; Peters, Vanessa; Roggenbuck, Dirk; Reinhold, Dirk

    2013-11-01

    Analysis of phosphorylated histone protein H2AX (γH2AX) foci is currently the most sensitive method to detect DNA double-strand breaks (DSB). This protein modification has the potential to become an individual biomarker of cellular stress, especially in the diagnosis and monitoring of neoplastic diseases. To make γH2AX foci analysis available as a routine screening method, different software approaches for automated immunofluorescence pattern evaluation have recently been developed. In this study, we used novel pattern recognition algorithms on the AKLIDES® platform to automatically analyze immunofluorescence images of γH2AX foci and compared the results with visual assessments. Dose- and time-dependent γH2AX foci formation was investigated in human peripheral blood mononuclear cells (PBMCs) treated with the chemotherapeutic drug etoposide (ETP). Moreover, the AKLIDES system was used to analyze the impact of different immunomodulatory reagents on γH2AX foci formation in PBMCs. Apart from γH2AX foci counting the use of novel pattern recognition algorithms allowed the measurement of their fluorescence intensity and size, as well as the analysis of overlapping γH2AX foci. The comparison of automated and manual foci quantification showed overall a good correlation. After ETP exposure, a clear dose-dependent increase of γH2AX foci formation was evident using the AKLIDES as well as Western blot analysis. Kinetic experiments on PBMCs incubated with 5 μM ETP demonstrated a peak in γH2AX foci formation after 4 to 8 h, while a removal of ETP resulted in a strong reduction of γH2AX foci after 1 to 4 h. In summary, this study demonstrated that the AKLIDES system can be used as an efficient automatic screening tool for γH2AX foci analysis by providing new evaluation features and facilitating the identification of drugs which induce or modulate DNA damage.

  1. Methylation of C9orf72 expansion reduces RNA foci formation and dipeptide-repeat proteins expression in cells.

    Science.gov (United States)

    Bauer, Peter O

    2016-01-26

    A hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of both frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), together referred to as c9FTD/ALS. It has been suggested that a loss of C9orf72 protein expression, the formation of toxic RNA foci and dipeptide-repeat proteins contribute to C9orf72-related diseases. Interestingly, it has been shown that trimethylation of histones and methylation of CpG islands near the repeat expansion may play a role in the pathogenesis c9FTD/ALS. Recently, methylation of expanded repeat itself has been reported. To further elucidate the mechanisms underlying these diseases, the influence of epigenetic modification in the repeat expansion on its pathogenic effect was assessed. Here, a reduced formation of toxic RNA foci and dipeptide-repeat proteins upon methylation of the GGGGCC repeat in a cellular model of c9FTD/ALS is shown. Additionally, a novel methylcytosine-capture DNA hybridization immunoassay for semi-quantitative detection of the repeat methylation levels is presented, potentially usable for methylation analysis in patients carrying C9orf72 repeat expansion carriers as a diagnostic tool. Presented results suggest that increased level of pathogenic GGGGCC expansion methylation may be sufficient to alleviate the molecular pathology of the C9orf72-related diseases.

  2. The influence of simple sugars and starch given during pre- or post-initiation on aberrant crypt foci in rat colon

    DEFF Research Database (Denmark)

    Poulsen, Morten; Mølck, Anne-Marie; Thorup, Inger;

    2001-01-01

    The aim of the present study was to investigate the enhancing effect of dietary sugar on the development of aberrant crypt foci (ACF) in male F344 rats initiated with azoxymethane (AOM). The potential role of sugar as either a co-initiator or a promoter was investigated by giving diets high...... was seen. The level of oxidative stress in the cytosol from the proximal colon and colonic glutathione transferase and quinone reductase was not affected by the sugar treatments. The overall results from this study show that sucrose and dextrin enhance the number of preneoplastic lesions in AOM...

  3. Are all pharmacy staff interested in potential future roles?

    Science.gov (United States)

    Braund, Rhiannon; Chesney, Kate Marie; Keast, Emilia Paulina; Ng, Lye Jinn; Qi, Sarah; Samaranayaka, Sashika; Wang, Eddie

    2012-12-01

    To determine the current perceived roles and responsibilities of pharmacy staff in community pharmacies in New Zealand, and attitudes to proposed new advanced roles for pharmacy staff. Structured interviews were conducted within five community pharmacies, including at least two pharmacists, two dispensary staff and two pharmacy assistants. The interviews were structured to determine previous experience, current roles and responsibilities and the perceived future roles of pharmacy staff within a community pharmacy setting. Thematic analysis from 27 interviews identified key findings. Current roles appeared to be fairly well defined. Pharmacy assistants listed key roles as customer interactions and sales focus, noting that the dispensary was outside their area of responsibility. Technicians identified their role as being dispensary focused while pharmacists saw their role as the 'final check' to ensure accuracy as well as providing dispensing, counselling and managerial roles. With potential future roles, the assistants were less interested than the other groups, citing contentment with current situation and training as a barrier. Some technicians indicated an interest in furthering their roles, but many were reluctant and saw that additional training was too time consuming. Whilst pharmacists appeared to be interested in further scopes of practice, they appeared more reluctant to do this at the expense of handing dispensing responsibility to a non-pharmacist. Whilst there is a push for pharmacists to provide advanced clinical services, it is important to acknowledge that many staff working within community pharmacies are satisfied with their current role. © 2012 The Authors. IJPP © 2012 Royal Pharmaceutical Society.

  4. Multiple coaxial foci generation by phase-only pupil filters

    Science.gov (United States)

    Valle, Pedro J.; Oti, José E.; Canales, Vidal F.; Cagigal, Manuel P.

    2007-04-01

    A new procedure for creating simultaneous multiple foci along the same optical axis with phase-only pupil-plane filters is proposed. Pupil-plane filters consist in phase-only masks described by simple circularly symmetric analytical functions. The axial separation between foci and their energy distribution are independently controlled by two different parameters of the filter. The main advantage of this new design is that, unlike other methods that required slow iterative algorithms, the proposed phase masks are straightforwardly calculated from analytical expressions. Moreover, real-time dynamic foci control could be achieved by using a computer addressed spatial light modulator that allowed the generation of variable phase patterns. The phase profiles we propose can be combined with multiple transversal foci phase patterns to actually form axial replicas of the transversal foci. Thus, it should be expected that three-dimensional structures were dynamically driven fast enough to perform real-time interactive multiple foci manipulation. Experimental verification of the multiple coaxial foci creation by static phase filters is shown.

  5. Fluorescent foci quantitation for high-throughput analysis

    Science.gov (United States)

    Ledesma-Fernández, Elena; Thorpe, Peter H.

    2015-01-01

    A number of cellular proteins localize to discrete foci within cells, for example DNA repair proteins, microtubule organizing centers, P bodies or kinetochores. It is often possible to measure the fluorescence emission from tagged proteins within these foci as a surrogate for the concentration of that specific protein. We wished to develop tools that would allow quantitation of fluorescence foci intensities in high-throughput studies. As proof of principle we have examined the kinetochore, a large multi-subunit complex that is critical for the accurate segregation of chromosomes during cell division. Kinetochore perturbations lead to aneuploidy, which is a hallmark of cancer cells. Hence, understanding kinetochore homeostasis and regulation are important for a global understanding of cell division and genome integrity. The 16 budding yeast kinetochores colocalize within the nucleus to form a single focus. Here we have created a set of freely-available tools to allow high-throughput quantitation of kinetochore foci fluorescence. We use this ‘FociQuant’ tool to compare methods of kinetochore quantitation and we show proof of principle that FociQuant can be used to identify changes in kinetochore protein levels in a mutant that affects kinetochore function. This analysis can be applied to any protein that forms discrete foci in cells. PMID:26290880

  6. Correspondence between flat aberrant crypt foci and mucin-depleted foci in rodent colon carcinogenesis.

    Science.gov (United States)

    Femia, Angelo Pietro; Paulsen, Jan Erik; Dolara, Piero; Alexander, Jan; Caderni, Giovanna

    2008-01-01

    Flat aberrant crypt foci (flat ACF) and mucin-depleted foci (MDF) are preneoplastic lesions identified in the colon of carcinogen-treated rodents stained with methylene blue (MB) and high iron diamine-alcian blue (HID-AB), respectively. The correspondence between flat ACF and MDF in the same colon of Min mice treated with azoxymethane (AOM) and of F344 rats treated with 1,2-dimethylhydrazine (DMH) was explored. The position of each flat ACF was recorded on a digitally constructed photographic map of the MB-stained colon. The same colons were then stained with HID-AB and the position of each MDF was compared with that of flat ACF. The fraction of coincident lesions, identified as both flat ACF and MDF with the two staining methods, was 57% and 42%, in the Min mice and F344 rats, respectively. Flat ACF or MDF not coincident with the two staining methods were either undetectable or ACF with one of the two methods. Flat ACF and MDF show considerable, but not total, overlap.

  7. The Potential Role of Artificial Intelligence Technology in Education.

    Science.gov (United States)

    Salem, Abdel-Badeeh M.

    The field of Artificial Intelligence (AI) and Education has traditionally a technology-based focus, looking at the ways in which AI can be used in building intelligent educational software. In addition AI can also provide an excellent methodology for learning and reasoning from the human experiences. This paper presents the potential role of AI in…

  8. Conceptualising the Potential Role of L1 in CLIL

    Science.gov (United States)

    Lin, Angel M. Y.

    2015-01-01

    Content and language integrated learning (CLIL) is a rapidly growing area of both research and practice in all parts of the world, especially in Europe and Asia. As a young discipline, CLIL has a good potential of distinguishing itself from monolingual L2 immersion education models by becoming more flexible and balanced about the role of L1 in…

  9. Conceptualising the Potential Role of L1 in CLIL

    Science.gov (United States)

    Lin, Angel M. Y.

    2015-01-01

    Content and language integrated learning (CLIL) is a rapidly growing area of both research and practice in all parts of the world, especially in Europe and Asia. As a young discipline, CLIL has a good potential of distinguishing itself from monolingual L2 immersion education models by becoming more flexible and balanced about the role of L1 in…

  10. Histopathological changes in tendinopathy--potential roles of BMPs?

    Science.gov (United States)

    Lui, Pauline Po Yee

    2013-12-01

    The pathogenesis of tendinopathy remains unclear. Chondro-osteogenic BMPs such as BMP-2, BMP-4 and BMP-7 have been reported in clinical samples and animal models of tendinopathy. As chondrocyte-like cells and ossified deposits have been observed in both clinical samples and animal models of failed tendon healing tendinopathy, chondro-osteogenic BMPs might contribute to tissue metaplasia and other histopathological changes in tendinopathy. In this review I have summarized the current evidence supporting the roles of chondro-osteogenic BMPs in the histopathological changes of tendinopathy. The potential targets, effects and sources of these BMPs are discussed. I have also provided directions for future studies about the potential roles of BMPs in the pathogenesis of tendinopathy. Better understanding of the roles of these BMPs in the histopathological changes of tendinopathy could provide new options for the prevention and treatment of this disabling tendon disorder.

  11. Aberrant crypt foci as microscopic precursors of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Lei Cheng; Mao-De Lai

    2003-01-01

    Since the first detection of aberrant crypt foci (ACF) in carcinogen-treated mice, there have been numerous studies focusing on these microscopically visible lesions both in rodents and in humans. ACF have been generally accepted as precancerous lesions in regard to histopathological characteristics, biochemical and immunohistochemical alterations, and genetic and epigenetic alterations. ACF show variable histological features, ranging from hyperplasia to dysplasia. ACF in human colon are more frequently located in the distal parts than in the proximal parts, which is in accordance with those in colorectal cancer (CRC). The immunohistochemical expressions of carcinoembryonic antigen (CEA), β-catenin, placental cadherin (P-cadherin),epithelial cadherin (E-cadherin), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and P16INK4a are found to be altered. Genetic mutations of K-ras, APC and p53, and the epigenetic alterations of CpG island methylation of ACF have also been demonstrated. Genomic instabilities due to the defect of mismatch repair (MMR) system are detectable in ACF Two hypotheses have been proposed.One is the "dysplasia ACF-adenoma-carcinoma sequence",the other is "heteroplastic ACF-adenoma-carcinoma sequence". The malignant potential of ACF, especially dyspiastic ACF, makes it necessary to reveal the nature of these lesions, and to prevent CRC from the earliest possible stage. The technique of magnifying chromoscope makes it possible to detect "in vivo' ACF, which is beneficial to colon cancer research, identifying high-risk populations for CRC,and developing preventive procedures.

  12. PCNA-dependent accumulation of CDKN1A into nuclear foci after ionizing irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Wiese, Claudia [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Rudolph, Jeanette Heede [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany); Jakob, Burkhard [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany); Fink, Daniela [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany); Tobias, Frank [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany); Blattner, Christine [Karlsruhe Inst. of Technology (KIT) (Germany). Inst. of Toxicology and Genetics; Taucher-Scholz, Gisela [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany)

    2012-03-26

    The cyclin-dependent kinase inhibitor CDKN1A/p21 confers cell-cycle arrest in response to DNA damage and inhibits DNA replication through its direct interaction with the proliferating cell nuclear antigen (PCNA) and cyclin/cyclin-dependent kinase complexes. Previously, we reported that in response to densely ionizing radiation CDKN1A rapidly is recruited to the sites of particle traversal, and that CDKN1A foci formation in response to heavy ions is independent of its transactivation by TP53. In this paper, we show that exposure of normal human fibroblasts to X-rays or to H2O2 also induces nuclear accumulations of CDKN1A. We find that CDKN1A foci formation in response to radiation damage is dependent on its dephosphorylation and on its direct physical interaction with PCNA. Live cell imaging analyses of ectopically expressed EGFP-CDKN1A and dsRed-PCNA show rapid recruitment of both proteins into foci after radiation damage. Detailed dynamic measurements reveal a slightly delayed recruitment of CDKN1A compared to PCNA, which is best described by bi-exponential curve fitting, taking the preceding binding of PCNA to DNA into account. Finally, we propose a regulatory role for CDKN1A in mediating PCNA function after radiation damage, and provide evidence that this role is distinct from its involvement in nucleotide excision repair and unrelated to double-strand break repair.

  13. Potential roles of optical interconnections within broadband switching modules

    Science.gov (United States)

    Lalk, Gail R.; Habiby, Sarry F.; Hartman, Davis H.; Krchnavek, Robert R.; Wilson, Donald K.; Young, Kenneth C., Jr.

    1991-04-01

    An investigation of potential physical design bottlenecks in future broadband telecommunication switches has led to the identification of several areas where optical interconnections may play a role in the practical realization of required system performance. In the model used the speed and interconnection densities as well as requirements for ease-of-access and efficient power utilization challenge conventional partitioning and packaging strategies. Potential areas where optical interconnections may relieve some of the physical design bottlenecks include fiber management at the customer interface to the switch routing and distribution of high-density interconnections within the fabric of the switch and backplane interconnections to increase system throughput.

  14. Apparent diffusive motion of centrin foci in living cells: implications for diffusion-based motion in centriole duplication

    Science.gov (United States)

    Rafelski, Susanne M.; Keller, Lani C.; Alberts, Jonathan B.; Marshall, Wallace F.

    2011-04-01

    The degree to which diffusion contributes to positioning cellular structures is an open question. Here we investigate the question of whether diffusive motion of centrin granules would allow them to interact with the mother centriole. The role of centrin granules in centriole duplication remains unclear, but some proposed functions of these granules, for example, in providing pre-assembled centriole subunits, or by acting as unstable 'pre-centrioles' that need to be captured by the mother centriole (La Terra et al 2005 J. Cell Biol. 168 713-22), require the centrin foci to reach the mother. To test whether diffusive motion could permit such interactions in the necessary time scale, we measured the motion of centrin-containing foci in living human U2OS cells. We found that these centrin foci display apparently diffusive undirected motion. Using the apparent diffusion constant obtained from these measurements, we calculated the time scale required for diffusion to capture by the mother centrioles and found that it would greatly exceed the time available in the cell cycle. We conclude that mechanisms invoking centrin foci capture by the mother, whether as a pre-centriole or as a source of components to support later assembly, would require a form of directed motility of centrin foci that has not yet been observed.

  15. Apparent diffusive motion of centrin foci in living cells: implications for diffusion-based motion in centriole duplication.

    Science.gov (United States)

    Rafelski, Susanne M; Keller, Lani C; Alberts, Jonathan B; Marshall, Wallace F

    2011-04-01

    The degree to which diffusion contributes to positioning cellular structures is an open question. Here we investigate the question of whether diffusive motion of centrin granules would allow them to interact with the mother centriole. The role of centrin granules in centriole duplication remains unclear, but some proposed functions of these granules, for example, in providing pre-assembled centriole subunits, or by acting as unstable 'pre-centrioles' that need to be captured by the mother centriole (La Terra et al 2005 J. Cell Biol. 168 713-22), require the centrin foci to reach the mother. To test whether diffusive motion could permit such interactions in the necessary time scale, we measured the motion of centrin-containing foci in living human U2OS cells. We found that these centrin foci display apparently diffusive undirected motion. Using the apparent diffusion constant obtained from these measurements, we calculated the time scale required for diffusion to capture by the mother centrioles and found that it would greatly exceed the time available in the cell cycle. We conclude that mechanisms invoking centrin foci capture by the mother, whether as a pre-centriole or as a source of components to support later assembly, would require a form of directed motility of centrin foci that has not yet been observed.

  16. Role of the Ionic Potential in High Harmonic Generation

    CERN Document Server

    Shafir, D; Higuet, J; Soifer, H; Dagan, M; Descamps, D; Mevel, E; Petit, S; Worner, H J; Pons, B; Dudovich, N; Mairesse, Y

    2013-01-01

    Recollision processes provide direct insight into the structure and dynamics of electronic wave functions. However, the strength of the process sets its basic limitations - the interaction couples numerous degrees of freedom. In this Letter we decouple the basic steps of the process and resolve the role of the ionic potential which is at the heart of a broad range of strong field phenomena. Specifically, we measure high harmonic generation from argon atoms. By manipulating the polarization of the laser field we resolve the vectorial properties of the interaction. Our study shows that the ionic core plays a significant role in all steps of the interaction. In particular, Coulomb focusing induces an angular deflection of the electrons before recombination. A complete spatiospectral analysis reveals the influence of the potential on the spatiotemporal properties of the emitted light.

  17. A potential role for tetranectin in mineralization during osteogenesis

    DEFF Research Database (Denmark)

    Wewer, U M; Ibaraki, K; Schjørring, P;

    1994-01-01

    cartilage or in the surrounding skeletal muscle. Using an in vitro mineralizing system, we examined osteoblastic cells at different times during their growth and differentiation. Tetranectin mRNA appeared in the cultured osteoblastic cells in parallel with mineralization, in a pattern similar...... osteogenesis. In conclusion, we have established a potential role for tetranectin as a bone matrix protein expressed in time and space coincident with mineralization in vivo and in vitro....

  18. Chikungunya Virus nsP3 Blocks Stress Granule Assembly by Recruitment of G3BP into Cytoplasmic Foci

    NARCIS (Netherlands)

    Fros, J.J.; Domeradzka, N.E.; Baggen, J.; Geertsema, C.; Flipse, J.; Vlak, J.M.; Pijlman, G.P.

    2012-01-01

    Chikungunya virus nonstructural protein nsP3 has an essential but unknown role in alphavirus replication and interacts with Ras-GAP SH3 domain-binding protein (G3BP). Here we describe the first known function of nsP3, to inhibit stress granule assembly by recruiting G3BP into cytoplasmic foci. A con

  19. Chikungunya Virus nsP3 Blocks Stress Granule Assembly by Recruitment of G3BP into Cytoplasmic Foci

    NARCIS (Netherlands)

    Fros, J.J.; Domeradzka, N.E.; Baggen, J.; Geertsema, C.; Flipse, J.; Vlak, J.M.; Pijlman, G.P.

    2012-01-01

    Chikungunya virus nonstructural protein nsP3 has an essential but unknown role in alphavirus replication and interacts with Ras-GAP SH3 domain-binding protein (G3BP). Here we describe the first known function of nsP3, to inhibit stress granule assembly by recruiting G3BP into cytoplasmic foci. A con

  20. Three-dimensional array foci of generalized Fibonacci photon sieves

    CERN Document Server

    Zhang, Junyong; Zhu, Jianqiang; Lin, Zunqi

    2015-01-01

    We present a new kind of photon sieves on the basis of the generalized Fibonacci sequences. The required numbers and locations of axial foci can be designed by generalized Fibonacci photon sieves (GFiPS). Furthermore, the three-dimensional array foci can be controllable and adjustable by the optical path difference scaling factor (OPDSF) when the amplitude modulation is replaced with the phase modulation. Multi-focal technologies can be applied to nano-imaging, THZ, laser communications, direct laser writing, optical tweezers or atom trapping, etc.

  1. Potential role of miRNAs in developmental haemostasis.

    Directory of Open Access Journals (Sweden)

    Raúl Teruel

    Full Text Available MicroRNAs (miRNAs are an abundant class of small non-coding RNAs that are negative regulators in a crescent number of physiological and pathological processes. However, their role in haemostasis, a complex physiological process involving multitude of effectors, is just beginning to be characterized. We evaluated the changes of expression of miRNAs in livers of neonates (day one after birth and adult mice by microarray and qRT-PCR trying to identify miRNAs that potentially may also be involved in the control of the dramatic change of hepatic haemostatic protein levels associated with this transition. Twenty one out of 41 miRNAs overexpressed in neonate mice have hepatic haemostatic mRNA as potential targets. Six of them identified by two in silico algorithms potentially bind the 3'UTR regions of F7, F9, F12, FXIIIB, PLG and SERPINC1 mRNA. Interestingly, miR-18a and miR-19b, overexpressed 5.4 and 8.2-fold respectively in neonates, have antithrombin, a key anti-coagulant with strong anti-angiogenic and anti-inflammatory roles, as a potential target. The levels of these two miRNAs inversely correlated with antithrombin mRNA levels during development (miR-19b: R = 0.81; p = 0.03; miR-18a: R = 0.91; p<0.001. These data suggest that miRNAs could be potential modulators of the haemostatic system involved in developmental haemostasis.

  2. Ergothioneine; antioxidant potential, physiological function and role in disease.

    Science.gov (United States)

    Cheah, Irwin K; Halliwell, Barry

    2012-05-01

    Since its discovery, the unique properties of the naturally occurring amino acid, L-ergothioneine (EGT; 2-mercaptohistidine trimethylbetaine), have intrigued researchers for more than a century. This widely distributed thione is only known to be synthesized by non-yeast fungi, mycobacteria and cyanobacteria but accumulates in higher organisms at up to millimolar levels via an organic cation transporter (OCTN1). The physiological role of EGT has yet to be established. Numerous in vitro assays have demonstrated the antioxidant and cytoprotective capabilities of EGT against a wide range of cellular stressors, but an antioxidant role has yet to be fully verified in vivo. Nevertheless the accumulation, tissue distribution and scavenging properties, all highlight the potential for EGT to function as a physiological antioxidant. This article reviews our current state of knowledge. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.

  3. Vitamin D and cardiovascular disease: potential role in health disparities.

    Science.gov (United States)

    Artaza, Jorge N; Contreras, Sandra; Garcia, Leah A; Mehrotra, Rajnish; Gibbons, Gary; Shohet, Ralph; Martins, David; Norris, Keith C

    2011-01-01

    Cardiovascular disease (CVD), which includes coronary artery disease and stroke, is the leading cause of mortality in the nation. Excess CVD morbidity and premature mortality in the African American community is one of the most striking examples of racial/ ethnic disparities in health outcomes. African Americans also suffer from increased rates of hypovitaminosis D, which has emerged as an independent risk factor for all-cause and cardiovascular mortality. This overview examines the potential role of hypovitaminosis D as a contributor to racial and ethnic disparities in cardiovascular disease (CVD). We review the epidemiology of vitamin D and CVD in African Americans and the emerging biological roles of vitamin D in key CVD signaling pathways that may contribute to the epidemiological findings and provide the foundation for future therapeutic strategies for reducing health disparities.

  4. Lack of promoting activity of four pesticides on induction of preneoplastic liver cell foci in rats.

    Science.gov (United States)

    Kato, T; Ogiso, T; Kato, K; Sano, M; Hasegawa, R; Shirai, T; Ito, N

    1995-01-01

    Four pesticides were examined for hepatopromoting activity using a medium-term bioassay based upon induction of glutathione S-transferase placental form (GST-P) positive foci in the rat liver. Male F344 rats were initially injected with diethylnitrosamine (DEN; 200 mg/kg body weight) intraperitoneally and 2 weeks later were treated with O-ethyl O-4-nitrophenyl phenylphosphonothioate (EPN; 75 and 150 ppm), diazinon (500 and 1,000 ppm), phenthoate (500 and 1,000 ppm), or iprobenfos (500 and 1,000 ppm) in the diet for 6 weeks and then killed, all rats being subjected to partial hepatectomy at week 3. All of the pesticides gave negative results, the numbers and areas of GST-P positive foci not exceeding the control values for animals given DEN alone. Indeed, a significant reduction of foci development was seen for EPN (75 ppm). These findings provide experimental evidence that the presently examined four pesticides do not have hepatocarcinogenic potential in rats.

  5. A specific inhibitor of protein kinase CK2 delays gamma-H2Ax foci removal and reduces clonogenic survival of irradiated mammalian cells

    Directory of Open Access Journals (Sweden)

    Huber Peter E

    2011-02-01

    Full Text Available Abstract Background The protein kinase CK2 sustains multiple pro-survival functions in cellular DNA damage response and its level is tightly regulated in normal cells but elevated in cancers. Because CK2 is thus considered as potential therapeutic target, DNA double-strand break (DSB formation and rejoining, apoptosis induction and clonogenic survival was assessed in irradiated mammalian cells upon chemical inhibition of CK2. Methods MRC5 human fibroblasts and WIDR human colon carcinoma cells were incubated with highly specific CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB, or mock-treated, 2 hours prior to irradiation. DSB was measured by pulsed-field electrophoresis (PFGE as well as gamma-H2AX foci formation and removal. Apoptosis induction was tested by DAPI staining and sub-G1 flow cytometry, survival was quantified by clonogenic assay. Results TBB treatment did not affect initial DNA fragmention (PFGE; up to 80 Gy or foci formation (1 Gy. While DNA fragment rejoining (PFGE was not inhibited by the drug, TBB clearly delayed gamma-H2AX foci disappearence during postirradiation incubation. No apoptosis induction could be detected for up to 38 hours for both cell lines and exposure conditions (monotherapies or combination, but TBB treatment at this moderately toxic concentration of 20 μM (about 40% survival enhanced radiation-induced cell killing in the clonogenic assay. Conclusions The data imply a role of CK2 in gamma-H2AX dephosporylation, most likely through its known ability to stimulate PP2A phosphatase, rather than DSB rejoining. The slight but definite clonogenic radiosensitization by TBB does apparently not result from interference with an apoptosis suppression function of CK2 in these cells but could reflect inhibitor-induced uncoupling of DNA damage response decay from break ligation.

  6. The role of cytokines in immunological tolerance: potential for therapy.

    Science.gov (United States)

    Harber, M; Sundstedt, A; Wraith, D

    2000-11-27

    Current immunosuppression protocols, although often effective, are nonspecific and therefore hazardous. Consequently, immunological tolerance that is antigen specific and does not globally depress the patient's immune system has become one of the Holy Grails of immunology. Since the discovery that cytokines have immunomodulatory effects, extensive research has investigated the potential of these molecules to induce and maintain specific immunological tolerance in the context of transplantation, allergy and autoimmunity. In this article, we review the possible mechanisms by which cytokines can modulate the immune response and the animal models that frequently confound the theory that a single cytokine, or group of cytokines, can induce tolerance in a predictable manner. Finally, we discuss the role of cytokines at a paracrine level, particularly in the context of inducing and maintaining antigen-specific, regulatory T cells with the clinical potential to suppress specific immune responses.

  7. Role of transdermal potential difference during iontophoretic drug delivery.

    Science.gov (United States)

    Bandrivskyy, Andriy; Bernjak, Alan; McClintock, Peter V E; Stefanovska, Aneta

    2004-09-01

    Potential differences have been measured during transdermal iontophoresis in order to establish the effect of voltage, as opposed to current, on cutaneous blood flow. It is known that, even in the absence of drugs, the iontophoresis current can sometimes produce increased blood flow. The role of voltage in this process is studied through single-ended measurements (between electrode and body) of the potential difference during iontophoresis with 100-microA, 20-s current pulses through deionized water, saturated 20.4% NaCl solution, 1% acetylcholine, and 1% sodium nitroprusside. It is found that the voltage needed to deliver the current varied by orders of magnitudes less than the differences in the conductance of these different electrolytes, and it is concluded that, at least for the present current protocol, the voltage as such is not an important factor in increasing the blood flow.

  8. Porifera Lectins: Diversity, Physiological Roles and Biotechnological Potential.

    Science.gov (United States)

    Gardères, Johan; Bourguet-Kondracki, Marie-Lise; Hamer, Bojan; Batel, Renato; Schröder, Heinz C; Müller, Werner E G

    2015-08-07

    An overview on the diversity of 39 lectins from the phylum Porifera is presented, including 38 lectins, which were identified from the class of demosponges, and one lectin from the class of hexactinellida. Their purification from crude extracts was mainly performed by using affinity chromatography and gel filtration techniques. Other protocols were also developed in order to collect and study sponge lectins, including screening of sponge genomes and expression in heterologous bacterial systems. The characterization of the lectins was performed by Edman degradation or mass spectrometry. Regarding their physiological roles, sponge lectins showed to be involved in morphogenesis and cell interaction, biomineralization and spiculogenesis, as well as host defense mechanisms and potentially in the association between the sponge and its microorganisms. In addition, these lectins exhibited a broad range of bioactivities, including modulation of inflammatory response, antimicrobial and cytotoxic activities, as well as anticancer and neuromodulatory activity. In view of their potential pharmacological applications, sponge lectins constitute promising molecules of biotechnological interest.

  9. Computationally Discovered Potentiating Role of Glycans on NMDA Receptors

    Science.gov (United States)

    Sinitskiy, Anton V.; Stanley, Nathaniel H.; Hackos, David H.; Hanson, Jesse E.; Sellers, Benjamin D.; Pande, Vijay S.

    2017-01-01

    N-methyl-D-aspartate receptors (NMDARs) are glycoproteins in the brain central to learning and memory. The effects of glycosylation on the structure and dynamics of NMDARs are largely unknown. In this work, we use extensive molecular dynamics simulations of GluN1 and GluN2B ligand binding domains (LBDs) of NMDARs to investigate these effects. Our simulations predict that intra-domain interactions involving the glycan attached to residue GluN1-N440 stabilize closed-clamshell conformations of the GluN1 LBD. The glycan on GluN2B-N688 shows a similar, though weaker, effect. Based on these results, and assuming the transferability of the results of LBD simulations to the full receptor, we predict that glycans at GluN1-N440 might play a potentiator role in NMDARs. To validate this prediction, we perform electrophysiological analysis of full-length NMDARs with a glycosylation-preventing GluN1-N440Q mutation, and demonstrate an increase in the glycine EC50 value. Overall, our results suggest an intramolecular potentiating role of glycans on NMDA receptors. PMID:28378791

  10. The Potential Roles of Bisphenol A (BPA Pathogenesis in Autoimmunity

    Directory of Open Access Journals (Sweden)

    Datis Kharrazian

    2014-01-01

    Full Text Available Bisphenol A (BPA is a monomer found in commonly used consumer plastic goods. Although much attention in recent years has been placed on BPA’s impact as an endocrine disruptor, it also appears to activate many immune pathways involved in both autoimmune disease development and autoimmune reactivity provocation. The current scientific literature is void of research papers linking BPA directly to human or animal onset of autoimmunity. This paper explores the impact of BPA on immune reactivity and the potential roles these mechanisms may have on the development or provocation of autoimmune diseases. Potential mechanisms by which BPA may be a contributing risk factor to autoimmune disease development and progression include its impact on hyperprolactinemia, estrogenic immune signaling, cytochrome P450 enzyme disruption, immune signal transduction pathway alteration, cytokine polarization, aryl hydrocarbon activation of Th-17 receptors, molecular mimicry, macrophage activation, lipopolysaccharide activation, and immunoglobulin pathophysiology. In this paper a review of these known autoimmune triggering mechanisms will be correlated with BPA exposure, thereby suggesting that BPA has a role in the pathogenesis of autoimmunity.

  11. Notch signaling: its roles and therapeutic potential in hematological malignancies.

    Science.gov (United States)

    Gu, Yisu; Masiero, Massimo; Banham, Alison H

    2016-05-17

    Notch is a highly conserved signaling system that allows neighboring cells to communicate, thereby controlling their differentiation, proliferation and apoptosis, with the outcome of its activation being highly dependent on signal strength and cell type. As such, there is growing evidence that disturbances in physiological Notch signaling contribute to cancer development and growth through various mechanisms. Notch was first reported to contribute to tumorigenesis in the early 90s, through identification of the involvement of the Notch1 gene in the chromosomal translocation t(7;9)(q34;q34.3), found in a small subset of T-cell acute lymphoblastic leukemia. Since then, Notch mutations and aberrant Notch signaling have been reported in numerous other precursor and mature hematological malignancies, of both myeloid and lymphoid origin, as well as many epithelial tumor types. Of note, Notch has been reported to have both oncogenic and tumor suppressor roles, dependent on the cancer cell type. In this review, we will first give a general description of the Notch signaling pathway, and its physiologic role in hematopoiesis. Next, we will review the role of aberrant Notch signaling in several hematological malignancies. Finally, we will discuss current and potential future therapeutic approaches targeting this pathway.

  12. The dual roles of rural midwives: the potential for role conflict and impact on retention.

    Science.gov (United States)

    Yates, Karen; Usher, Kim; Kelly, Jenny

    2011-01-01

    Nurses and midwives continue to make up the largest proportion of the health workforce. As a result, shortages of nurses and midwives have a significant impact on the delivery of effective health care. Shortages of nurses and midwives are known to be more pronounced in rural and remote areas where recruitment and retention remain problematic. However, rural nurses are often required to be multi-skilled, which has led to expectations that nurses who are also midwives, are required to work across areas of the hospital to help to address shortages. For midwives this issue is even more problematic as they may actually end up spending a very small percentage of their working day involved in the delivery of maternity care. This workforce strategy has the potential to seriously erode the skills of the midwives. Situations such as this are implicated in attrition of midwives because of the role stress that results when they are required to work in models of care where they experience the constant pull to work between departments and across roles. This paper addresses the requirement for midwives in some rural facilities to work across roles of general nurse and midwife and outlines the issues that arise as a result. In particular, the paper links the concepts of Role Theory to the requirement for midwives to work in dual roles and the potential for role stress to develop.

  13. Bacteriophage and their potential roles in the human oral cavity

    Directory of Open Access Journals (Sweden)

    Anna Edlund

    2015-04-01

    Full Text Available The human oral cavity provides the perfect portal of entry for viruses and bacteria in the environment to access new hosts. Hence, the oral cavity is one of the most densely populated habitats of the human body containing some 6 billion bacteria and potentially 35 times that many viruses. The role of these viral communities remains unclear; however, many are bacteriophage that may have active roles in shaping the ecology of oral bacterial communities. Other implications for the presence of such vast oral phage communities include accelerating the molecular diversity of their bacterial hosts as both host and phage mutate to gain evolutionary advantages. Additional roles include the acquisitions of new gene functions through lysogenic conversions that may provide selective advantages to host bacteria in response to antibiotics or other types of disturbances, and protection of the human host from invading pathogens by binding to and preventing pathogens from crossing oral mucosal barriers. Recent evidence suggests that phage may be more involved in periodontal diseases than were previously thought, as their compositions in the subgingival crevice in moderate to severe periodontitis are known to be significantly altered. However, it is unclear to what extent they contribute to dysbiosis or the transition of the microbial community into a state promoting oral disease. Bacteriophage communities are distinct in saliva compared to sub- and supragingival areas, suggesting that different oral biogeographic niches have unique phage ecology shaping their bacterial biota. In this review, we summarize what is known about phage communities in the oral cavity, the possible contributions of phage in shaping oral bacterial ecology, and the risks to public health oral phage may pose through their potential to spread antibiotic resistance gene functions to close contacts.

  14. The potential protective role of taurine against experimental allergic inflammation.

    Science.gov (United States)

    Nam, Sun-Young; Kim, Hyung-Min; Jeong, Hyun-Ja

    2017-09-01

    Taurine has been widely evaluated as a potential therapeutic agent in chronic inflammatory disorders and various infections. However, the potential role of taurine in regulating allergic inflammatory responses is currently unknown. The present study was designed to evaluate the in vitro effects of taurine on the levels of thymic stromal lymphopoietin (TSLP) and other pro-inflammatory cytokines and activation of caspase-1 and nuclear factor (NF)-κB as well as the phosphorylations of c-Jun N-terminal kinase (JNK) and p38 in phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-triggered human mast cell line, HMC-1 cells. Furthermore, we assessed the therapeutic effects of taurine on ovalbumin (OVA)-induced allergic rhinitis (AR) animal models. Here, the obtained results showed that taurine dose-dependently inhibited the production and mRNA expression of TSLP and pro-inflammatory cytokines in HMC-1 cells exposed to PMACI. Taurine attenuated the phosphorylation of JNK and p38 in activated HMC-1 cells. Moreover, taurine brought a significant inhibition of the activities of NF-κB and caspase-1. In an OVA-induced AR animal model, the increased levels of nose rubbing, histamine, immunoglobulin E, TSLP, and interleukin IL-1β were dramatically reduced by the administration of taurine. In summary, taurine could serve as potential novel remedy of allergic inflammatory disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Quantitative analysis of liver GST-P foci promoted by a chemical mixture of hexachlorobenzene and PCB 126: implication of size-dependent cellular growth kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Yasong [Colorado State University, Quantitative and Computational Toxicology Group, Department of Environmental and Radiological Health Sciences, Fort Collins, CO (United States); Translational Pharmacology Group, PDM, Pfizer Inc, Groton, CT (United States); Lohitnavy, Manupat; Lohitnavy, Ornrat; Eickman, Elizabeth; Gerjevic, Lisa; Yang, Raymond S.H. [Colorado State University, Quantitative and Computational Toxicology Group, Department of Environmental and Radiological Health Sciences, Fort Collins, CO (United States); Reddy, Micaela [DMPK Group, Preclinical Sciences, Roche Palo Alto LLC, CA (United States); Ashley, Amanda [Colorado State University, Department of Cell and Molecular Biology, Fort Collins, CO (United States); Xu, Yihua [University of Wisconsin, McArdle Laboratory for Cancer Research, Madison, WI (United States); Conolly, Rory B. [USEPA, National Center for Computational Toxicology, Research Triangle Park, NC (United States)

    2008-02-15

    The objectives of this study were twofold: (1) evaluating the carcinogenic potential of the mixture of two persistent environmental pollutants, hexachlorobenzene (HCB) and 3,3',4,4',5-pentachlorobiphenyl (PCB 126), in an initiation-promotion bioassay involving the development of {pi} glutathione S-transferase (GST-P) liver foci, and (2) analyzing the GST-P foci data using a biologically-based computer model (i.e., clonal growth model) with an emphasis on the effect of focal size on the growth kinetics of initiated cells. The 8-week bioassay involved a series of treatments of initiator, two-thirds partial hepatectomy, and daily oral gavage of the mixture of two doses in male F344 rats. The mixture treatment significantly increased liver GST-P foci development, indicating carcinogenic potential of this mixture. Our clonal growth model was developed to simulate the appearance and development of initiated GST-P cells in the liver over time. In the model, the initiated cells were partitioned into two subpopulations with the same division rate but different death rates. Each subpopulation was further categorized into single cells, mini- (2-11 cells), medium- (12-399 cells), and large-foci (>399 cells) with different growth kinetics. Our modeling suggested that the growth of GST-P foci is size-dependent; in general, the larger the foci, the higher the rate constants of division and death. In addition, the modeling implied that the two doses promoted foci development in different manners even though the experimental foci data appeared to be similar between the two doses. This study further illustrated how clonal growth modeling may facilitate our understanding in chemical carcinogenic process. (orig.)

  16. The role of transient receptor potential channels in metabolic syndrome

    DEFF Research Database (Denmark)

    Liu, Daoyan; Zhu, Zhiming; Tepel, Martin

    2008-01-01

    Metabolic syndrome is correlated with increased cardiovascular risk and characterized by several factors, including visceral obesity, hypertension, insulin resistance, and dyslipidemia. Several members of a large family of nonselective cation entry channels, e.g., transient receptor potential (TRP......) canonical (TRPC), vanilloid (TRPV), and melastatin (TRPM) channels, have been associated with the development of cardiovascular diseases. Thus, disruption of TRP channel expression or function may account for the observed increased cardiovascular risk in metabolic syndrome patients. TRPV1 regulates...... there is no evidence that a single TRP channelopathy may be the cause of all metabolic syndrome characteristics, further studies will help to clarify the role of specific TRP channels involved in the metabolic syndrome. (Hypertens Res 2008; 31: 1989-1995)....

  17. Potential role of NADPH oxidase in pathogenesis of pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Wei-Li; Cao; Xiao-Hui; Xiang; Kai; Chen; Wei; Xu; Shi-Hai; Xia

    2014-01-01

    Studies have demonstrated that reactive oxygen species(ROS) are closely related to inflammatory disorders. Nicotinamide adenine dinucleotide phosphate oxidase(NOX), originally found in phagocytes, is the main source of ROS in nonphagocytic cells. Besides directly producing the detrimental highly reactive ROS to act on biomolecules(lipids, proteins, and nucleic acids), NOX can also activate multiple signal transduction pathways, which regulate cell growth, proliferation, differentiation and apoptosis by producing ROS. Recently, research on pancreatic NOX is no longer limited to inflammatory cells, but extends to the aspect of pancreatic acinar cells and pancreatic stellate cells, which are considered to be potentially associated with pancreatitis. In this review, we summarize the literature on NOX protein structure, activation, function and its role in the pathogenesis of pancreatitis.

  18. Cannabinoid receptor 2: potential role in immunomodulation and neuroinflammation.

    Science.gov (United States)

    Rom, Slava; Persidsky, Yuri

    2013-06-01

    An accumulating body of evidence suggests that endocannabinoids and cannabinoid receptors type 1 and 2 (CB(1), CB(2)) play a significant role in physiologic and pathologic processes, including cognitive and immune functions. While the addictive properties of marijuana, an extract from the Cannabis plant, are well recognized, there is growing appreciation of the therapeutic potential of cannabinoids in multiple pathologic conditions involving chronic inflammation (inflammatory bowel disease, arthritis, autoimmune disorders, multiple sclerosis, HIV-1 infection, stroke, Alzheimer's disease to name a few), mainly mediated by CB(2) activation. Development of CB(2) agonists as therapeutic agents has been hampered by the complexity of their intracellular signaling, relative paucity of highly selective compounds and insufficient data regarding end effects in the target cells and organs. This review attempts to summarize recent advances in studies of CB(2) activation in the setting of neuroinflammation, immunomodulation and HIV-1 infection.

  19. Role Playing Game (RPG on nursing undergraduate course: educational potentials

    Directory of Open Access Journals (Sweden)

    Amanda Nathale Soares

    2016-12-01

    Full Text Available The objective of this study was to evaluate the potential of a Role Playing Game as an educational strategy in Undergraduate Nursing course, emphasizing its subjective implications in understanding aspects of the profession. This is a qualitative study, conducted through an evaluative research, of deployment analysis type. Nursing students of the 3rd period participated. The instrument to collection was Memories of Game, reports prepared by students after game sessions. The game is a non-traditional educational strategy that enabled approach to students through professional practice, active participation, self-reflection and reflection on professional practice. This strategy favored individualization processes, allowing students to experience situations similar to the nursing practice and exercise skills such as teamwork and creativity. The expansion of studies that address the subjective processes in higher education, through simulation games, can contribute to better design of health development processes.

  20. The potential roles for adipose tissue in peripheral nerve regeneration.

    Science.gov (United States)

    Walocko, Frances M; Khouri, Roger K; Urbanchek, Melanie G; Levi, Benjamin; Cederna, Paul S

    2016-01-01

    This review summarizes current understanding about the role of adipose-derived tissues in peripheral nerve regeneration and discusses potential advances that would translate this approach into the clinic. We searched PubMed for in vivo, experimental studies on the regenerative effects of adipose-derived tissues on peripheral nerve injuries. We summarized the methods and results for the 42 experiments. Adipose-derived tissues enhanced peripheral nerve regeneration in 86% of the experiments. Ninety-five percent evaluated purified, cultured, or differentiated adipose tissue. These approaches have regulatory and scaling burdens, restricting clinical usage. Only one experiment tested the ability of adipose tissue to enhance nerve regeneration in conjunction with nerve autografts, the clinical gold standard. Scientific studies illustrate that adipose-derived tissues enhance regeneration of peripheral nerves. Before this approach achieves clinical acceptance, fat processing must become automated and regulatory approval achieved. Animal studies using whole fat grafts are greatly needed for clinical translation. © 2015 Wiley Periodicals, Inc.

  1. Potential role of microorganisms in the pathogenesis of rosacea.

    Science.gov (United States)

    Holmes, Anna D

    2013-12-01

    Rosacea is a skin condition of abnormal inflammation and vascular dysfunction. The active contribution of a microbial agent in the development or progression of rosacea continues to be debated. Research supports the presence of commensal Demodex folliculorum mites at increased density in the skin and associates Helicobacter pylori infection of the gut with rosacea. Fewer studies implicate Staphylococcus epidermidis, Chlamydophila pneumoniae, and the Demodex-associated bacteria Bacillus oleronius. No research, however, provides a mechanism by which colonization by a microorganism translates to manifestation of the condition. Prevailing and emerging principles in the biology of the microbiome and the pathophysiology of rosacea may help to reconcile these lingering questions. Here the microorganisms implicated in rosacea are reviewed and the reaction of the microbiome to inflammation and to changes in microenvironments and macroenvironments are discussed to explain potential roles for microorganisms in rosacea pathophysiology.

  2. Expression Patterns and Potential Biological Roles of Dip2a.

    Directory of Open Access Journals (Sweden)

    Luqing Zhang

    Full Text Available Disconnected (disco-interacting protein 2 homolog A is a member of the DIP2 protein family encoded by Dip2a gene. Dip2a expression pattern has never been systematically studied. Functions of Dip2a in embryonic development and adult are not known. To investigate Dip2a gene expression and function in embryo and adult, a Dip2a-LacZ mouse model was generated by insertion of β-Gal cDNA after Dip2a promoter using CRISPR/Cas9 technology. Dip2a-LacZ mouse was designed to be a lacZ reporter mouse as well as a Dip2a knockout mouse. Heterozygous mice were used to study endogenous Dip2a expression and homozygotes to study DIP2A-associated structure and function. LacZ staining indicated that Dip2a is broadly expressed in neuronal, reproductive and vascular tissues, as well as in heart, kidney, liver and lung. Results demonstrate that Dip2a is expressed in ectoderm-derived tissues in developing embryos. Adult tissues showed rich staining in neurons, mesenchymal, endothelial, smooth muscle cells and cardiomyocytes by cell types. The expression pattern highly overlaps with FSTL1 and supports previous report that DIP2A to be potential receptor of FSTL1 and its protective roles of cardiomyocytes. Broad and intense embryonic and adult expression of Dip2a has implied their multiple structural and physiological roles.

  3. Potential role of folate in pre-eclampsia.

    Science.gov (United States)

    Singh, Mansi Dass; Thomas, Philip; Owens, Julie; Hague, William; Fenech, Michael

    2015-10-01

    Dietary deficiencies of folate and other B vitamin cofactors involved in one-carbon metabolism, together with genetic polymorphisms in key folate-methionine metabolic pathway enzymes, are associated with increases in circulating plasma homocysteine, reduction in DNA methylation patterns, and genome instability events. All of these biomarkers have also been associated with pre-eclampsia. The aim of this review was to explore the literature and identify potential knowledge gaps in relation to the role of folate at the genomic level in either the etiology or the prevention of pre-eclampsia. A systematic search strategy was designed to identify citations in electronic databases for the following terms: folic acid supplementation AND pre-eclampsia, folic acid supplementation AND genome stability, folate AND genome stability AND pre-eclampsia, folic acid supplementation AND DNA methylation, and folate AND DNA methylation AND pre-eclampsia. Forty-three articles were selected according to predefined selection criteria. The studies included in the present review were not homogeneous, which made pooled analysis of the data very difficult. The present review highlights associations between folate deficiency and certain biomarkers observed in various tissues of women at risk of pre-eclampsia. Further investigation is required to understand the role of folate in either the etiology or the prevention of pre-eclampsia.

  4. Sensory impairment in mental retardation: a potential role for NGF.

    Science.gov (United States)

    Battaglia, Anna

    2011-06-01

    Sensory impairment is defined as the inability to interpret outside stimuli such as visual, auditory, verbal, sense of touch, taste or smell or feelings of pain. This leads to absence of sensation and neuronal coordination. The impairment may be caused by ageing and other physiological changes, accident or injuries or can be found in some cases of mental retardation (MR) also referred to as intellectual disability. Known cases of MR involving inability to accurately interpret an outside source or stimuli are: Fragile-X syndrome; Tuberous sclerosis complex (TSC) with associated autism spectrum disorder (ASD); Rett syndrome; Autism and ASD with or without MR; Chromosome 22q13.3 deletion syndrome; familial dysautonomia, Prader-Willi's syndrome, Williams syndrome. In this review we will discuss in particular form of ASD and altered sensory sensitivity. The role of NGF in causing pronociceptive activity and its role in peripheral sensitisation is discussed under the light of its involvement in forms of MR where loss of pain perception is a main feature due to mutations to NGF receptors or NGF genes during development. Other forms of MR with altered sensory impairment will be considered as well as additional potential mechanisms involved.

  5. Potential Role of Activating Transcription Factor 5 during Osteogenesis

    Directory of Open Access Journals (Sweden)

    Luisa Vicari

    2016-01-01

    Full Text Available Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2, encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

  6. Porifera Lectins: Diversity, Physiological Roles and Biotechnological Potential

    Directory of Open Access Journals (Sweden)

    Johan Gardères

    2015-08-01

    Full Text Available An overview on the diversity of 39 lectins from the phylum Porifera is presented, including 38 lectins, which were identified from the class of demosponges, and one lectin from the class of hexactinellida. Their purification from crude extracts was mainly performed by using affinity chromatography and gel filtration techniques. Other protocols were also developed in order to collect and study sponge lectins, including screening of sponge genomes and expression in heterologous bacterial systems. The characterization of the lectins was performed by Edman degradation or mass spectrometry. Regarding their physiological roles, sponge lectins showed to be involved in morphogenesis and cell interaction, biomineralization and spiculogenesis, as well as host defense mechanisms and potentially in the association between the sponge and its microorganisms. In addition, these lectins exhibited a broad range of bioactivities, including modulation of inflammatory response, antimicrobial and cytotoxic activities, as well as anticancer and neuromodulatory activity. In view of their potential pharmacological applications, sponge lectins constitute promising molecules of biotechnological interest.

  7. Novel characteristics of CtIP at damage-induced foci following the initiation of DNA end resection

    Energy Technology Data Exchange (ETDEWEB)

    Fujisawa, Hiroshi [School of Engineering, The University of Tokyo, Tokyo 113-8656 (Japan); Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Fujimori, Akira [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Okayasu, Ryuichi [International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Uesaka, Mitsuru [School of Engineering, The University of Tokyo, Tokyo 113-8656 (Japan); Yajima, Hirohiko, E-mail: hyajima@nirs.go.jp [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2015-01-15

    Highlights: • CtIP becomes hyperphosphorylated and forms foci following cell irradiation. • CtIP accumulates in foci subsequent to the peak of hyperphosphorylation. • CtIP is maintained in a hypophosphorylated state at later times. • CtIP is continuously recruited to DNA double strand breaks downstream of resection. • CtIP presumably have a distinct role following the initiation of resection. - Abstract: Homologous recombination (HR) is a major repair pathway for DNA double strand breaks (DSBs), and end resection, which generates a 3′-single strand DNA tail at the DSB, is an early step in the process. Resection is initiated by the Mre11 nuclease together with CtIP. Here, we describe novel characteristics of CtIP at DSBs. At early times following exposure of human cells to ionizing radiation, CtIP localized to the DSB, became hyperphosphorylated and formed foci in an ATM-dependent manner. At later times, when the initiation of resection had occurred, CtIP foci persist but CtIP is maintained in a hypophosphorylated state, which is dependent on ATM and ATR. Exposure to cycloheximide revealed that CtIP turns over at DSB sites downstream of resection. Our findings provide strong evidence that CtIP is continuously recruited to DSBs downstream of both the initiation and extension step of resection, strongly suggesting that CtIP has functions in addition to promoting the initiation of resection during HR.

  8. PMEL EcoFOCI Chukchi Sea profile data, 2010-2012

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Pacific Marine Environmental Laboratory (PMEL) Fisheries-Oceanography Cooperative Investigations (FOCI) Chukchi Sea. PMEL EcoFOCI data from a local source.

  9. Features of direct implantation in chronic foci of odontogenic infection

    Directory of Open Access Journals (Sweden)

    Gudaryan А.А.

    2016-12-01

    Full Text Available The article presents the results of the developed therapeutic and prophylactic complex and efficacy of immediate implantation in 66 patients with chronic foci of odontogenic infection in the periapical region. Objective: to increase preventive measures of inflammatory and infectious complications and optimization of osteo-integrative processes in immediate implantation after tooth extraction, with periapical foci of chronic infection. It was found that the use of the developed medical complex of following up direct implantation includes the use of local photodynamic therapy, platelet, rich in fibrin as a injection and membranes; this allowed to create a favorable background for the prevention of inflammatory and infectious complications in the peri-implant area and created a favorable background for the osseo-integration of implants in 97.1% of the investigated.

  10. [The implantation of bipolar coagulation to remove endometriosis foci].

    Science.gov (United States)

    Sobkiewicz, S; Palatyński, A; Salata, I

    2001-05-01

    The paper compares the results of bipolar coagulation bey means of ERBE ICC 300 diatermy coagulator and WISAP endocoagulator. The results of both types of coagulation were assessed with reference to the changes occurring on peritoneum ligamenti sacro-uterini, Douglas pouch and ovary. The best results of endometriosis foci coagulation were obtained with bipolar ball at 20-30 W; no side effects or feelings of malaise were observed in patients just after the operation or over a longer period of convalescence.

  11. The potential role of amlodipine on experimentally induced bacterial rhinosinusitis.

    Science.gov (United States)

    Tatar, Arzu; Korkmaz, Mukadder; Yayla, Muhammed; Polat, Elif; Uslu, Hakan; Halici, Zekai; Parlak, Secil N

    2016-09-28

    For the treatment of rhinosinusitis antibiotics are used frequently. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of discovery of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity. In this study we aimed to investigate the potential role of amlodipine in treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation. Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte (PMNL) infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione) and an oxidative product (malondialdehyde) were determined. In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline) and although not superior to cefazolin, amlodipine decreased PMNL infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups. The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All

  12. Acanthomatous ameloblastoma with atypical foci in five dogs.

    Science.gov (United States)

    Malmberg, Jennifer L; Howerth, Elizabeth W; Powers, Barb E; Schaffer, Paula A

    2017-03-01

    Acanthomatous ameloblastoma is a common, locally invasive, nonmetastasizing tumor of the canine oral cavity. The long-term prognosis for canine acanthomatous ameloblastoma is good if complete excision can be achieved, usually by maxillectomy or mandibulectomy. A variant of acanthomatous ameloblastoma with atypical foci was noted in 5 dogs. There was no age, breed, or sex predisposition. Atypical cells were pleomorphic with a high mitotic rate. They were immunohistochemically negative for cytokeratin, vimentin, melan A, PNL2, CD3, Pax5, CD18, chromogranin A, and synaptophysin. Ultrastructurally, the atypical cells had modest amounts of electron-lucent cytoplasm, abundant rough endoplasmic reticulum, zonula adherens junctions, cleaved or irregular nuclei, and occasional cytoplasmic structures consistent with secretory granules or lysosomes. Complete excision was achieved by maxillectomy or mandibulectomy in 3 dogs; the lesion was incompletely excised in 2 dogs. No ancillary therapy was elected in any patient. No local recurrence or distant metastasis was reported in any case. One patient died of heart failure 20 mo following complete excision; all other patients were alive at last follow-up (average follow-up: 18.8 mo, range: 6-30 mo). The histogenesis of the atypical foci is unclear, but atypical foci within acanthomatous ameloblastoma do not appear to be associated with metastasis or with a poor prognosis relative to acanthomatous ameloblastoma with typical histologic morphology.

  13. Reliability of seizure semiology in patients with 2 seizure foci.

    Science.gov (United States)

    Rathke, Kevin M; Schäuble, Barbara; Fessler, A James; So, Elson L

    2011-06-01

    To determine whether seizure semiology is reliable in localizing and distinguishing seizures at 2 independent brain foci in the same patient. Two masked reviewers localized seizures from 2 foci by their clinical semiology and intracranial electroencephalograms (EEGs). Epilepsy monitoring unit of referral comprehensive epilepsy program. Seventeen consecutive patients (51 seizures) with sufficient video and intracranial EEG data were identified by reviewing medical records of 366 patients older than 10 years. The primary outcome measures were interobserver agreement between the 2 masked reviewers; the proportion of seizures localized by semiology; the proportion of localized seizures concordant with intracranial EEG localization; and comparison between concordant and nonconcordant seizures in latency of intracranial EEG seizure spread. Interobserver agreement was 41% (κ score, 0.16). Only 30 of 51 seizures (59%) were localized by seizure semiology. The focus localized by semiology was concordant with the location of intracranial EEG seizure onset in 16 of 30 seizures (53%). No significant difference was observed between concordant and nonconcordant seizures in relation to the speed with which the EEG discharge spread from the location of seizure onset to another lobar region (P = .09, Wilcoxon rank sum test). Clinical seizure semiology is not as useful as intracranial EEG in localizing seizure onset in patients with dual seizure foci.

  14. Metallothioneins in human tumors and potential roles in carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Cherian, M. George; Jayasurya, A.; Bay, Boon-Huat

    2003-12-10

    Metallothioneins (MT) are a group of low-molecular weight, cysteine rich intracellular proteins, which are encoded by a family of genes containing at least 10 functional isoforms in human. The expression and induction of these proteins have been associated with protection against DNA damage, oxidative stress and apoptosis. Moreover, MT may potentially activate certain transcriptional factors by donating zinc. Although MT is a cytosolic protein in resting cells, it can be translocated transiently to the cell nucleus during cell proliferation and differentiation. A number of studies have shown an increased expression of MT in various human tumors of the breast, colon, kidney, liver, lung, nasopharynx, ovary, prostate, salivary gland, testes, thyroid and urinary bladder. However, MT is down-regulated in certain tumors such as hepatocellular carcinoma and liver adenocarcinoma. Hence, the expression of MT is not universal to all human tumors, but may depend on the differentiation status and proliferative index of tumors, along with other tissue factors and gene mutations. In certain tumors such as germ cell carcinoma, the expression of MT is closely related to the tumor grade and proliferative activity. Increased expression of MT has also been observed in less differentiated tumors. Thus, expression of MT may be a potential prognostic marker for certain tumors. There are few reports on the expression of the different isoforms of MT which have been analyzed by specific gene probes. They reveal that certain isoforms are expressed in specific cell types. The factors which can influence MT induction in human tumors are not yet understood. Down-regulation of MT synthesis in hepatic tumors may be related to hypermethylation of the MT-promoter or mutation of other genes such as the p53 tumor suppressor gene. In vitro studies using human cancer cells suggest a possible role for p53 and the estrogen-receptor on the expression and induction of MT in epithelial neoplastic cells

  15. HDAC inhibitor sodium butyrate sensitizes E1A+Ras-transformed cells to DNA damaging agents by facilitating formation and persistence of γH2AX foci.

    Science.gov (United States)

    Abramova, Maria V; Svetlikova, Svetlana B; Kukushkin, Alexander N; Aksenov, Nikolai D; Pospelova, Tatiana V; Pospelov, Valery A

    2011-12-15

    HDAC inhibitors (HDACi) suppress the growth of tumor cells due to induction of cell cycle arrest, senescence or apoptosis. Recent data demonstrate that HDACi can interfere with DNA Damage Response (DDR) thereby sensitizing the cells to DNA damaging agents. Here, we show that HDACi sodium butyrate (NaBut) potentiates the formation of γH2AX foci predominantly in S-phase E1A+Ras cells. Accumulation of γH2AX foci sensitizes the cells toward such DNA damaging agents as irradiation (IR) and adriamycin. In fact, NaBut potentiates the persistence of γH2AX foci induced by genotoxic agents. The synergizing effects depend on DNA damaging factors and on the order of NaBut treatment. Indeed, NaBut treatment for 24 h leads to an accumulation of G 1-phase cells and a lack of S-phase cells, therefore, adriamycin, a powerful S-phase-specific inhibitor, when added to NaBut-treated cells, is unable to substantially add γH2AX foci. In contrast, IR produces both single- and double-strand DNA breaks at any stage of the cell cycle and was shown to increase γH2AX foci in NaBut-treated cells. Further, a lifetime of IR-induced γH2AX foci depends on the subsequent presence of HDACi. Correspondingly, NaBut withdrawal leads to the extinction of IR-induced γH2AX foci. This necessitates HDACi to hold the IR-induced γH2AX foci unrepaired. However, the IR-induced γH2AX foci persist after long-term NaBut treatment (72 h) even after washing the drug. Thus, although signaling pathways regulating H2AX phosphorylation in NaBut-treated cells remain to be investigated, the obtained results show that NaBut potentiates effects of DNA damaging agents by facilitating formation and persistence of γH2AX foci.

  16. Exploring the potential roles of biochars on land degradation mitigation

    Directory of Open Access Journals (Sweden)

    A.K. Berek

    2014-04-01

    Full Text Available Land degradation was exacerbated and its management was challenged by population growth and global climate change. The impacts of land degradation on food security, ecosystem services and biodiversity become a more serious problem particularly in developing countries. Biochar, based on the current research findings, is capable to amend degraded lands. This paper reviewed relevant biocharproperties and identified the opportunities of its using for recovering deteriorated lands.Biochar was traditionally recognized as a good absorbent, energy source, and its ash was used by farmers to recover soil fertility. Recent findings revealed that application of biochar improved soil water retention, enhanced soil aggregation, decreased soil bulk density and increased soil infiltration. It also increased soil cation exchange capacity, soil pH, mineral nutrients, reduced nutrient leaching, support microbial population and activities, and suppressed the pest. The sorption capacity of biochar to soil and water pollutants such as Pb, Cu, Ni, Cr, Cd,dioxine, atrazine, and concurrently eliminatedthe environmental problems such as hypoxia, eutrophication, and algae bloom, have also been investigated. Investigation on its role to mitigate climate change revealed that biochar is capable in reducing greenhouse gasesemissions such as CO2, N2O, and CH4. All those beneficial effects of biochars were attributed to its high porosity, large surface area and surface charge, high carbon, ash and nutrient content, and its stability to be degraded. Thus, biochar could be potential for ameliorating degraded lands

  17. Potential role of seismic base isolation in the DOE

    Energy Technology Data Exchange (ETDEWEB)

    Sommer, S.C.

    1993-08-01

    For nearly two decades, the United States Department of Energy (DOE) has substantially increased its efforts to reduce the effects of earthquakes on its facilities. Traditional means within the DOE for designing or retrofitting structures to mitigate earthquake effects include strengthening and anchoring. A nontraditional and an increasingly popular concept for mitigating the effects of earthquakes on structures is seismic base isolation. Because base isolation is emerging as a promising technology for mitigating seismic effects, its potential role in the DOE must be evaluated. In order to use the technology within the DOE, criteria and guidance need to be developed since base isolation may provide a viable design option for mitigating the effects of earthquakes on DOE facilities. This paper discusses the fundamentals of seismic base isolation, applications of the technology, and how the technology might be applied within the DOE. The future involvement of the DOE in base isolation will be part of its efforts to be a leader in meeting the Federal requirements for seismic safety.

  18. Potential Role of Epigenetic Mechanism in Manganese Induced Neurotoxicity

    Science.gov (United States)

    Tarale, Prashant; Chakrabarti, Tapan; Sivanesan, Saravanadevi; Naoghare, Pravin; Bafana, Amit; Krishnamurthi, Kannan

    2016-01-01

    Manganese is a vital nutrient and is maintained at an optimal level (2.5–5 mg/day) in human body. Chronic exposure to manganese is associated with neurotoxicity and correlated with the development of various neurological disorders such as Parkinson's disease. Oxidative stress mediated apoptotic cell death has been well established mechanism in manganese induced toxicity. Oxidative stress has a potential to alter the epigenetic mechanism of gene regulation. Epigenetic insight of manganese neurotoxicity in context of its correlation with the development of parkinsonism is poorly understood. Parkinson's disease is characterized by the α-synuclein aggregation in the form of Lewy bodies in neuronal cells. Recent findings illustrate that manganese can cause overexpression of α-synuclein. α-Synuclein acts epigenetically via interaction with histone proteins in regulating apoptosis. α-Synuclein also causes global DNA hypomethylation through sequestration of DNA methyltransferase in cytoplasm. An individual genetic difference may also have an influence on epigenetic susceptibility to manganese neurotoxicity and the development of Parkinson's disease. This review presents the current state of findings in relation to role of epigenetic mechanism in manganese induced neurotoxicity, with a special emphasis on the development of Parkinson's disease. PMID:27314012

  19. Potential Role of Honey in Learning and Memory

    Directory of Open Access Journals (Sweden)

    Zahiruddin Othman

    2015-04-01

    Full Text Available The composition and physicochemical properties of honey are variable depending on its floral source and often named according to the geographical location. The potential medicinal benefits of Tualang honey, a multifloral jungle honey found in Malaysia, have recently been attracting attention because of its reported beneficial effects in various diseases. This paper reviews the effects of honey, particularly Tualang honey, on learning and memory. Information regarding the effects of Tualang honey on learning and memory in human as well as animal models is gleaned to hypothesize its underlying mechanisms. These studies show that Tualang honey improves morphology of memory-related brain areas, reduces brain oxidative stress, increases brain-derived neurotrophic factor (BDNF and acetylcholine (ACh concentrations, and reduces acetylcholinesterase (AChE in the brain homogenates. Its anti-inflammatory roles in reducing inflammatory trigger and microglial activation have yet to be investigated. It is hypothesized that the improvement in learning and memory following Tualang honey supplementation is due to the significant improvement in brain morphology and enhancement of brain cholinergic system secondary to reduction in brain oxidative damage and/or upregulation of BDNF concentration. Further studies are imperative to elucidate the molecular mechanism of actions.

  20. Potential Antidepressant Role of Neurotransmitter CART: Implications for Mental Disorders

    Directory of Open Access Journals (Sweden)

    Peizhong Mao

    2011-01-01

    Full Text Available Depression is one of the most prevalent and debilitating public health concerns. Although no single cause of depression has been identified, it appears that interaction among genetic, epigenetic, biochemical, environmental, and psychosocial factors may explain its etiology. Further, only a fraction of depressed patients show full remission while using current antidepressants. Therefore, identifying common pathways of the disorder and using that knowledge to develop more effective pharmacological treatments are two primary targets of research in this field. Brain-enriched neurotransmitter CART (cocaine- and amphetamine-regulated transcript has multiple functions related to emotions. It is a potential neurotrophic factor and is involved in the regulation of hypothalamic-pituitary-adrenal axis and stress response as well as in energy homeostasis. CART is also highly expressed in limbic system, which is considered to have an important role in regulating mood. Notably, adolescents carrying a missense mutation in the CART gene exhibit increased depression and anxiety. Hence, CART peptide may be a novel promising antidepressant agent. In this paper, we summarize recent progress in depression and CART. In particular, we emphasize a new antidepressant function for CART.

  1. Potential role of aromatase inhibitors in the treatment of endometriosis.

    Science.gov (United States)

    Abu Hashim, Hatem

    2014-01-01

    Endometriosis is an estrogen-dependent chronic inflammatory disease affecting 5%-10% of reproductive-age women, with a prevalence of 5%-50% in infertile women and >33% of women with chronic pelvic pain. Third-generation aromatase inhibitors (AIs) are approved adjuvants for the treatment of estrogen receptor-positive breast cancer. Molecular studies have revealed the presence of aromatase P450, the key enzyme in the biosynthesis of ovarian estradiol, inside the endometriotic tissue, indicating local synthesis of estradiol. Thereby, AIs represent an appealing medical option for the management of different aspects of this enigmatic disease, especially pelvic pain and infertility. Accordingly, this review aims to evaluate the potential role of AIs in the treatment of endometriosis-associated symptoms, mainly pain and infertility. Notably, several studies have demonstrated that the combination of AIs with conventional therapy as oral contraceptive pills, progestins, or gonadotropin-releasing hormone analogs can be used to control endometriosis-associated pain and pain recurrence in premenopausal women, particularly those with pain due to rectovaginal endometriosis refractory to other medical or surgical treatment. Some case reports have shown promising results in the treatment of postmenopausal endometriosis as first-line treatment, when surgery is contraindicated, or as second-line treatment in the case of postoperative recurrence. Third-generation AIs, especially letrozole, have challenged clomiphene citrate as an ovulation-induction agent in patients with polycystic ovary syndrome and in cases of unexplained infertility. However, few studies are available regarding the use of AIs to treat endometriosis-associated infertility. Therefore, larger multicenter randomized trials using AIs for the treatment of endometriosis-associated infertility are needed to clarify its effect. The safety of AIs for ovulation induction or superovulation has generated a lively discussion

  2. Objective scoring of transformed foci in BALB/c 3T3 cell transformation assay by statistical image descriptors

    OpenAIRE

    Urani, Chiara; Corvi, Raffaella; CALLEGARO G.; Stefanini, Federico Mattia

    2013-01-01

    In vitro cell transformation assays (CTAs) have been shown to model important stages of in vivo carcinogenesis and have the potential to predict carcinogenicity in humans. Advantages of CTAs are their ability of revealing both genotoxic and non-genotoxic carcinogens while reducing both experimental costs and the number of animals used. The endpoint of the CTA is foci formation, and requires classification under light microscopy based on morphology. Thus current limitations for the wide ado...

  3. Detecting and localizing the foci in human epileptic seizures

    CERN Document Server

    Ben-Jacob, E; Pomyalov, A; Procaccia, I; Towle, V L; Ben-Jacob, Eshel; Boccaletti, Stefano; Pomyalov, Anna; Procaccia, Itamar; Towle, Vernon L.

    2007-01-01

    We consider the electrical signals recorded from a subdural ECoG grid of electrodes placed on the pial surface of the brain for chronic evaluation of epileptic patients before surgical resection. A simple and computationally fast method to analyze the inter-ictal phase synchrony between such electrodes is introduced and developed with the aim of detecting and localizing the foci of the epileptic events. We evaluate the method by comparing the results of surgery to the localization predicted here. We find an indication of good correspondence between the success or failure in the surgery and the agreement between our identification and the regions actually operated on.

  4. Electrical stimulation for epilepsy: stimulation of hippocampal foci.

    Science.gov (United States)

    Velasco, F; Velasco, M; Velasco, A L; Menez, D; Rocha, L

    2001-01-01

    Subacute and chronic continuous electrical stimulation at the epileptic focus in the hippocampus or parahippocampal cortex at 130 Hz, 0.21-1.0 ms, 2.5-3.5 V (about 200-300 microA) induces a decrease in focal EEG epileptic interictal activity and also in the occurrence of clinical seizures. This may represent an alternative for the treatment of temporal lobe seizures originated in bilateral independent temporal lobe foci or occurring in patients where one is uncertain whether memory deficit might result from ablative procedures.

  5. Potential role of aromatase inhibitors in the treatment of endometriosis

    Directory of Open Access Journals (Sweden)

    Abu Hashim H

    2014-07-01

    Full Text Available Hatem Abu HashimDepartment of Obstetrics and Gynecology, Faculty of Medicine, Mansoura University, Mansoura, EgyptAbstract: Endometriosis is an estrogen-dependent chronic inflammatory disease affecting 5%–10% of reproductive-age women, with a prevalence of 5%–50% in infertile women and >33% of women with chronic pelvic pain. Third-generation aromatase inhibitors (AIs are approved adjuvants for the treatment of estrogen receptor-positive breast cancer. Molecular studies have revealed the presence of aromatase P450, the key enzyme in the biosynthesis of ovarian estradiol, inside the endometriotic tissue, indicating local synthesis of estradiol. Thereby, AIs represent an appealing medical option for the management of different aspects of this enigmatic disease, especially pelvic pain and infertility. Accordingly, this review aims to evaluate the potential role of AIs in the treatment of endometriosis-associated symptoms, mainly pain and infertility. Notably, several studies have demonstrated that the combination of AIs with conventional therapy as oral contraceptive pills, progestins, or gonadotropin-releasing hormone analogs can be used to control endometriosis-associated pain and pain recurrence in premenopausal women, particularly those with pain due to rectovaginal endometriosis refractory to other medical or surgical treatment. Some case reports have shown promising results in the treatment of postmenopausal endometriosis as first-line treatment, when surgery is contraindicated, or as second-line treatment in the case of postoperative recurrence. Third-generation AIs, especially letrozole, have challenged clomiphene citrate as an ovulation-induction agent in patients with polycystic ovary syndrome and in cases of unexplained infertility. However, few studies are available regarding the use of AIs to treat endometriosis-associated infertility. Therefore, larger multicenter randomized trials using AIs for the treatment of endometriosis

  6. Schistosomiasis mansoni in areas of low transmission: epidemiological characterization of Venezuelan foci

    Directory of Open Access Journals (Sweden)

    Alarcón de Noya B

    2002-01-01

    Full Text Available Severe schistosomiasis is a rare event in Venezuela nowadays, after a successful national campaign by the Schistosomiasis Control Program. Unfortunately, this program has practically disappeared, and snail surveillance in field is not a priority, anymore. Thus, schistosomiasis has become a neglected disease in this country. However, surveys in different populations from the endemic area have shown particular epidemiological features described herein. In five communities we evaluated 2,175 persons and searched for the presence of Biomphalaria glabrata snails. Some markers were used for classifying schistosomiasis foci: mean age of the persons with Schistosoma mansoni eggs in the stools, serological tests, presence of B. glabrata snails, and intensity of infection. Places without B. glabrata snails and with few schistosomiasis cases were defined as "past transmission sites"; a site with abundant snails but few cases was defined as "potential risk"; "new transmission" foci were characterized by the presence of infected snails and young people passing eggs in the stools. A "re-emergent" focus has shared these last features, showing in addition a place where schistosomiasis had been reported before. Recent evidences of active transmission with the increasing dispersion of B. glabrata snails, point out the necessity for the re-establishment of the Schistosomiasis Control Program in Venezuela.

  7. Characteristics of {gamma}-H2AX foci at DNA double-strand breaks sites

    Energy Technology Data Exchange (ETDEWEB)

    Pilch, D.R.; Sedelnikova, O.A.; Redon, C. [National Cancer Institute, National Institutes of Health, Lab. of Molecular Pharmacology, Bethesda, Maryland (United States); Celeste, A.; Nussenzweig, A. [National Cancer Institute, National Institutes of Health, Experimental Immunology Branch, Bethesda, Maryland (United States); Bonner, W.M. [National Cancer Institute, National Institutes of Health, Lab. of Molecular Pharmacology, Bethesda, Maryland (United States)

    2003-06-01

    Phosphorylated H2AX ({gamma}-H2AX) is essential to the efficient recognition and (or) repair of DNA double strand breaks (DSBs), and many molecules, often thousands, of H2AX become rapidly phosphorylated at the site of each nascent DSB. An antibody to {gamma}-H2AX reveals that this highly amplified process generates nuclear foci. The phosphorylation site is a serine four residues from the C-terminus which has been evolutionarily conserved in organisms from giardia intestinalis to humans. Mice and yeast lacking the conserved serine residue demonstrate a variety of defects in DNA DSB processing. H2AX{sup {delta}}{sup /{delta}} mice are smaller, sensitive to ionizing radiation, defective in class switch recombination and spermatogenesis while cells from the mice demonstrate substantially increased numbers of genomic defects. {gamma}-H2AX foci formation is a sensitive biological dosimeter and presents new and exciting opportunities to understand important biological processes, human diseases, and individual variations in radiation sensitivity. These potentialities demonstrate the importance of understanding the parameters and functions of {gamma}-H2AX formation. (author)

  8. Controllable design of super-oscillatory lenses with multiple sub-diffraction-limit foci.

    Science.gov (United States)

    Li, Muyuan; Li, Wenli; Li, Haoyong; Zhu, Yechuan; Yu, Yiting

    2017-05-02

    The conventional multifocal optical elements cannot precisely control the focal number, spot size, as well as the energy distribution in between. Here, the binary amplitude-type super-oscillatory lens (SOL) is utilized, and a robust and universal optimization method based on the vectorial angular spectrum (VAS) theory and the genetic algorithm (GA) is proposed, aiming to achieve the required focusing performance with arbitrary number of foci in preset energy distribution. Several typical designs of multifocal SOLs are demonstrated. Verified by the finite-difference time-domain (FDTD) numerical simulation, the designed multifocal SOLs agree well with the specific requirements. Moreover, the full-width at half-maximum (FWHM) of the achieved focal spots is close to λ/3 for all the cases (λ being the operating wavelength), which successfully breaks the diffraction limit. In addition, the designed SOLs are partially insensitive to the incident polarization state, functioning very well for both the linear polarization and circular polarization. The optimization method presented provides a useful design strategy for realizing a multiple sub-diffraction-limit foci field of SOLs. This research can find its potentials in such fields as parallel particle trapping and high-resolution microscopy imaging.

  9. [Monitoring the natural foci of tularemia on Wrangel Island].

    Science.gov (United States)

    Podobedova, Ia S; Meshcheriakova, I S; Demidova, T N; Kormilitsyna, M I; Mikhaĭlova, T V; Baraniuk, V V

    2013-01-01

    Long-term annual monitoring of the natural foci of tularemia was first made on Wrangel Island. The objects of the investigation were pellets of birds-myophages, blood samples from rodents, and excrements from carnivorous mammals. A total of 2626 biological samples were examined in the period 2002 to 2011. A serological test was ascertained to be the most effective method for the detection of tularemia epizooties; polymerase chain reaction should be used as an additional technique to examine blood samples, as well as rodent tubular bone debris taken from the pellets. Tularemia epizooties were registered in the populations of two species of lemmings every year, except in 2003. An intensive diffuse tularemia epizooty was first detected in this area, which emerged in 2019, peaked by spring 2011, and covered most of the island. The antigen of tularemia pathogen was identified in 43.46% of the samples under examination,which is a high quantitative indicator of the intensity of an epizootic process. The fact that positive samples are annually found in the same areas of the island suggests that the causative agent is steadily and long preserved in the parasitic system. The availability of stable and active natural tularemia foci on Wrangel Island calls for preventive measures, particularly vaccination of risk groups coming to the island to conduct researches.

  10. The role of local field potential coupling in epileptic synchronization

    Institute of Scientific and Technical Information of China (English)

    Jiongxing Wu; Heng Yang; Yufeng Peng; Liangjuan Fang; Wen Zheng; Zhi Song

    2013-01-01

    This review hopes to clearly explain the following viewpoints: (1) Neuronal synchronization underlies brain functioning, and it seems possible that blocking excessive synchronization in an epileptic neural network could reduce or even control seizures. (2) Local field potential coupling is a very common phenomenon during synchr in networks. Removal of neurons or neuronal networks that are coupled can significantly alter the extracellular field potential. Interventions of coupling mediated by local field potentials could result in desynchronization of epileptic seizures. (3) The synchronized electrical activity generated by neurons is sensitive to changes in the size of the extracellular space, which affects the efficiency of field potential transmission and the threshold of cell excitability. (4) Manipulations of the field potential fluctuations could help block synchronization at seizure onset.

  11. Plant γH2AX foci are required for proper DNA DSB repair responses and colocalize with E2F factors.

    Science.gov (United States)

    Lang, Julien; Smetana, Ondrej; Sanchez-Calderon, Lenin; Lincker, Frédéric; Genestier, Julie; Schmit, Anne-Catherine; Houlné, Guy; Chabouté, Marie-Edith

    2012-04-01

    Cellular responses to DNA double-strand breaks (DSBs) are linked in mammals and yeasts to the phosphorylated histones H2AX (γH2AX) repair foci which are multiproteic nuclear complexes responsible for DSB sensing and signalling. However, neither the components of these foci nor their role are yet known in plants. In this paper, we describe the effects of γH2AX deficiency in Arabidopsis thaliana plants challenged with DSBs in terms of genotoxic sensitivity and E2F-mediated transcriptional responses. We further establish the existence, restrictive to the G1/S transition, of specific DSB-induced foci containing tobacco E2F transcription factors, in both A. thaliana roots and BY-2 tobacco cells. These E2F foci partially colocalize with γH2AX foci while their formation is ataxia telangiectasia mutated (ATM)-dependent, requires the E2F transactivation domain with its retinoblastoma-binding site and is optimal in the presence of functional H2AXs. Overall, our results unveil a new interplay between plant H2AX and E2F transcriptional activators during the DSB response.

  12. The potential role of sports psychology in the obesity epidemic.

    Science.gov (United States)

    Morelli, Vincent; Davis, Carolyn

    2013-06-01

    Sports psychologists play an important role in enhancing performance among athletes. In conjunction with team physicians, they can also shed light on psychological disorders common in athletes, such as mood and eating disorders, and overtraining syndrome. Sports psychologists can also lend their expertise to assist with injury prevention and recovery and compliance issues. Sports psychology has a role in helping to reverse the growing obesity epidemic among school-aged children. These professionals, working with coaches, can increase children's levels of physical activity. Cognitive-behavioral techniques could lead to enhanced enjoyment, increased participation, improved school performance, and a reduction in obesity.

  13. The potential role of thrombopoietin in idiopathic thrombocytopenic purpura

    NARCIS (Netherlands)

    von dem Borne, A; Folman, C; van den Oudenrijn, S; de Jong, S; de Haas, M

    2002-01-01

    Thrombopoietin (TPO) plays a central role in the pathogenesis of idiopathic thrombocytopenic purpura (ITP), as it does in other immune-mediated thrombocytopenias. Because TPO is bound and internalized by platelets, it is destroyed together with platelets at an accelerated rate in the macrophage syst

  14. The Potential Role of Virtual Reality in Environmental Education.

    Science.gov (United States)

    Taylor, Gregory L.; Disinger, John F.

    1997-01-01

    Investigates the acceptability and possible role of virtual reality (VR) in environmental education. Among the principal findings were that the sample population of environmental educators indicated an acceptance of VR as a teaching tool. VR applications that allow students to have an experience not available in the physical world were perceived…

  15. The potential role of agroforestry in maintaining soil fertility on ...

    African Journals Online (AJOL)

    Organic fertilizers play a significant role in maintaining soil fertility on these ... soil and aid in nutrient cycling by providing prunings as a source of organic matter. ... that include improving soil fertility, and the conservation of soil and moisture, ...

  16. Surveillance of endemic foci of tick-borne encephalitis in Finland 1995-2013: evidence of emergence of new foci.

    Science.gov (United States)

    Tonteri, Elina; Kurkela, Satu; Timonen, Suvi; Manni, Tytti; Vuorinen, Tytti; Kuusi, Markku; Vapalahti, Olli

    2015-01-01

    The geographical risk areas for tick-borne encephalitis (TBE) in Finland remained the same until the beginning of the 21st century, but a considerable geographical expansion has been observed in the past 10 years. In order to support public health measures, the present study describes the number of laboratory-confirmed TBE cases and laboratory tests conducted and the associated trends by hospital district, with a particular emphasis on the suspected geographical risk areas. An additional investigation was conducted on 1,957 clinical serum samples throughout the country taken from patients with neurological symptoms to screen for undiagnosed TBE cases. This study identified new TBE foci in Finland, reflecting the spread of the disease into new areas. Even in the most endemic municipalities, transmission of TBE to humans occurred in very specific and often small foci. The number of antibody tests for TBE virus more than doubled (an increase by 105%) between 2007 and 2013. Analysis of the number of tests also revealed areas in which the awareness of clinicians may be suboptimal at present. However, it appears that underdiagnosis of neuroinvasive TBE is not common.

  17. Role of Sodium Channel on Cardiac Action Potential

    Directory of Open Access Journals (Sweden)

    S. H. Sabzpoushan

    2012-06-01

    Full Text Available Sudden cardiac death is a major cause of death worldwide. In most cases, it's caused by abnormal action potential propagation that leads to cardiac arrhythmia. The aim of this article is to study the abnormal action potential propagation through sodium ion concentration variations. We use a new electrophysiological model that is both detailed and computationally efficient. This efficient model is based on the partial differential equation method. The central finite difference method is used for numerical solving of the two-dimensional (2D wave propagation equation. Simulations are implemented in two stages, as a single cardiac cell and as a two-dimensional grid of cells. In both stages, the normal action potential formation in case of a single cell and it's normal propagation in case of a two-dimensional grid of cells were simulated with nominal sodium ion conductance. Then, the effect of sodium ion concentration on the action potential signal was studied by reducing the sodium ion conductance. It is concluded that reducing the sodium ion conductance, decreases both passing ability and conduction velocity of the action potential wave front.

  18. The role of local voltage potentials in outflow tract ectopy

    DEFF Research Database (Denmark)

    Thomsen, P.E.B.; Johannessen, A.; Jons, C.;

    2010-01-01

    Discrete, fragmented, local voltage potentials (LVPs) have been observed in electrograms recorded at the ablation site in patients undergoing radiofrequency ablation for arrhythmias originating in both the right and left ventricular outflow tract; however, the incidence and the significance...... for supraventricular arrhythmias served as controls. During sinus rhythm, LVPs were recorded in 24 of the 25 patients, 10-85 ms (41 +/- 19 ms) after the onset of the QRS complex, duration 33 +/- 11 ms, voltage 2.0 +/- 1.5 mV. The same potential was recorded 10-52 ms (mean 37 +/- 11 ms) prior to the V potential...... in the ventricular premature beats. In 10 patients, ventricular parasystole was suggested by varying coupling intervals > 100 ms, and fusion beats allowing for the estimation of the least common denominator of R-R intervals. In 23 of the 25 patients, the 12-lead electrocardiogram (ECG) and intracardiac contact...

  19. The role of fullerene shell upon stuffed atom polarization potential

    CERN Document Server

    Amusia, M Ya

    2015-01-01

    We have demonstrated that the polarization of the fullerene shell considerably alters the polarization potential of an atom, stuffed inside a fullerene. This essentially affects the electron elastic scattering phases as well as corresponding cross-sections. We illustrate the general trend by concrete examples of electron scattering by endohedrals of Neon and Argon. To obtain the presented results, we have suggested a simplified approach that permits to incorporate the effect of fullerenes polarizability into the Neon and Argon endohedrals polarization potential. As a result, we obtained numeric results that show strong variations in shape and magnitudes of scattering phases and cross-sections due to effect of fullerene polarization upon the endohedral polarization potential.

  20. Nuclear dynamics of radiation-induced foci in euchromatin and heterochromatin

    Energy Technology Data Exchange (ETDEWEB)

    Chiolo, Irene; Tang, Jonathan; Georgescu, Walter; Costes, Sylvain V.

    2013-10-01

    Repair of double strand breaks (DSBs) is essential for cell survival and genome integrity. While much is known about the molecular mechanisms involved in DSB repair and checkpoint activation, the roles of nuclear dynamics of radiation-induced foci (RIF) in DNA repair are just beginning to emerge. Here, we summarize results from recent studies that point to distinct features of these dynamics in two different chromatin environments: heterochromatin and euchromatin. We also discuss how nuclear architecture and chromatin components might control these dynamics, and the need of novel quantification methods for a better description and interpretation of these phenomena. These studies are expected to provide new biomarkers for radiation risk and new strategies for cancer detection and treatment.

  1. Nuclear dynamics of radiation-induced foci in euchromatin and heterochromatin

    Energy Technology Data Exchange (ETDEWEB)

    Chiolo, Irene; Georgescu, Walter; Tang, Jonathan; Costes, Sylvain V.

    2013-09-03

    Repair of double strand breaks (DSBs) is essential for cell survival and genome integrity. While much is known about the molecular mechanisms involved in DSB repair and checkpoint activation, the roles of nuclear dynamics of radiation-induced foci (RIF) in DNA repair are just beginning to emerge. Here, we summarize results from recent studies that point to distinct features of these dynamics in two different chromatin environments: heterochromatin and euchromatin. We also discuss how nuclear architecture and chromatin components might control these dynamics, and the need of novel quantification methods for a better description and interpretation of these phenomena. These studies are expected to provide new biomarkers for radiation risk and new strategies for cancer detection and treatment.

  2. The role of transient receptor potential channels in kidney disease.

    NARCIS (Netherlands)

    Woudenberg-Vrenken, T.E.; Bindels, R.J.M.; Hoenderop, J.G.J.

    2009-01-01

    The transient receptor potential (TRP) superfamily consists, in mammals, of six protein subfamilies, TRPC, TRPM, TRPV, TRPA, TRPML and TRPP. TRPs are cation channels involved in many physiological processes and in the pathogenesis of various disorders. In the kidney, TRP channels are expressed along

  3. The mathematics of mosaic analysis. II. Formulae for interacting foci.

    Science.gov (United States)

    Wyman, R J; Salkoff, L

    1982-04-01

    Mosaic fate mapping requires first a measurement of the frequency of separation (by genotype) of two structures and then a conversion of this frequency of separation to distance (WYMAN and THOMAS 1982). If the genotype of two structures is visible, the frequency of separation (sturt distance) may be directly obtained. If the genotype is not visible (e.g., for behavioral foci) then the frequency of separation (sturt distance) itself must be calculated. The formulae introduced by HOTTA and BENZER (1972) for calculating frequency of separation are appropriate only for a set of mosaics in which each fly has half normal and half mutant tissue. Using these formulae for a set of mosaics with a different fraction of mutant tissue can give enormously incorrect results.--In this paper we use intuitive lines of reasoning to obtain simple formulae for frequencies of separation that are algebraically equal to the more elaborate HOTTA and BENZER (1972) formulae.--We show that when calculating sturt distances, data from a collection of mosaics with a range of malenesses, even if the average maleness is 1/2, cannot be lumped together. We prove that applying any formula appropriate for m = 1/2 to a set of mosaics all of maleness m, and then to a set of maleness 1-m, and then averaging the two results, does give the correct value for sturt distances. In this way all the mapping distances may be obtained.--Another method for locating foci is called "contour mapping". We show that the currently available contour formulae are inaccurate. We suggest that contour maps be drawn using the accurate sturt distances.

  4. Potential role of remote sensing in disaster relief management

    Science.gov (United States)

    Rush, M.; Holguin, A.; Vernon, S.

    1976-01-01

    Baseline or predisaster data which would be useful to decision making in the immediate postdisaster period were suggested for the six areas of public health concern along with guidelines for organizing these data. Potential sources of these data are identified. In order to fully assess the impact of a disaster on an area, information about its predisaster status must be known. Aerial photography is one way of acquiring and recording such data.

  5. The potential role of Neutral Beam Injection in EU DEMO

    Science.gov (United States)

    Vincenzi, Pietro; Artaud, Jean-Francois; Bolzonella, Tommaso; Giruzzi, Gerardo

    2016-10-01

    EU DEMO studies for pulsed (DEMO1) and steady-state (DEMO2) concepts are currently in the pre-conceptual phase. Present DEMO1 design is based on ITER baseline H-mode scenario, while DEMO2 is based on advanced scenarios with moderate reversed q profile sustained by non-inductive currents. One of the possible flattop heating power systems currently considered is Neutral Beam Injection (NBI). In this work the role of NBI in DEMO1 and DEMO2 is investigated by means of integrated simulations of DEMO scenarios using METIS fast tokamak modelling tool. Limitations, requirements and benefits of the use of a NBI system are discussed. For DEMO1 pulsed concept, the role of NBI is mainly central plasma heating for scenario stability (high fusion power H-mode). As a by-product of the tangential injection, NBI is capable of current drive, which is favorable in order to extend the discharge duration. Regarding a steady-state DEMO2 concept, in addition to plasma heating, NBI becomes a direct actuator for the advanced scenario by driving a considerable part of the plasma current. This requires more than 100MW with off-axis injection. The effect of an increase of the injection energy on the driven current density profile is also presented for DEMO2.

  6. Potential Immune Modularly Role of Glycine in Oral Gingival Inflammation

    Directory of Open Access Journals (Sweden)

    Teresa Schaumann

    2013-01-01

    Full Text Available Gingival epithelial cells (GECs represent a physical barrier against bacteria and are involved in the processes of innate immunity. Recently, an anti-inflammatory and immune-modulatory effect of the amino acid glycine has been demonstrated. However, there is only little information about the immune-modulatory effects of glycine in oral tissues. This study aimed to investigate the existence and role of the glycine receptor in gingival tissue analyzing tissues/cells from extracted human molars via immunohistochemical analysis. In vitro, GECs were challenged by inflammatory conditions with IL-1β alone or in combination with glycine and analyzed for cytokine expression of IL6/IL8 via real-time PCR. On protein level, the effect of nuclear translocalization of NFκB protein p65 was analyzed using immunofluorescence analysis. A distinct proof of the GlyR in oral gingival tissue and keratinocytes could be demonstrated. Isolated challenge of the keratinocytes with IL-1β as well as with glycine resulted in an upregulation of IL6 and IL8 mRNA expression and activation of NFκB pathway. The presence of glycine in combination with the inflammatory stimulus led to a significant decrease in inflammatory parameters. These results indicate a possible anti-inflammatory role of glycine in gingival inflammation and encourage further research on the utility of glycine in the prevention or therapy of inflammatory periodontitis.

  7. Differential gene expression in CD45 cells at para-aortic foci stage of chicken haematopoiesis.

    Science.gov (United States)

    Säynäjäkangas, R; Uchida, T; Vainio, O

    2009-09-01

    Para-aortic foci of chicken embryos at 6-7 days of development are considered to provide a microenvironment for haematopoietic stem cell proliferation and initial differentiation similar to that of fetal liver in mammals. Here, we have investigated the genes involved in this process by constructing and analysing a subtractive cDNA library from CD45(+) cells in para-aortic region. Among 394 analysed clones 99 distinct genes were identified by sequence homology search. Classification of the identified genes according to biological processes revealed that innate immunity-related genes are highly expressed at this stage. This can be explained by the presence of yolk sac-derived macrophages in the original tissue sample but also by the indiscriminate expression of multiple lineage-specific genes in haematopoietic stem cells and primitive progenitors. Differentially expressed genes related to transcription, signalling and lymphocyte functions are potential candidates involved in lineage commitment.

  8. Creation of multiple on-axis foci and ultra-long focal depth for SPPs.

    Science.gov (United States)

    Wang, Jiayuan; Chen, Cuiyun; Sun, Zhijun

    2017-01-23

    We present the design of a plasmonic lens (PL) which is composed of pixelated nano-grooves on a gold film for the coupling and focusing of surface plasmon polaritons (SPPs) into multiple focal spots on the optical axis. The pixelated grooves are arranged along the y-axis and the x-position of each groove is optimized by the simulated annealing algorithm. PLs that implement two and three on-axis foci are presented and the designed structures have been validated with FDTD simulations. We also successfully constructed a long-focal-depth PL with a longitudinal FWHM of the focus that reached 25 plasmonic wavelengths, while its transverse field profile is maintained over 15 µm distance. The presented design method constitutes a new basis for plasmonic beam engineering, and the proposed particular SPP focal fields have potential applications in multiple imaging, particle manipulating, and plasmonic on-chip signal transmission.

  9. Potential Role of Probiotics in Mechanism of Intestinal Immunity

    Directory of Open Access Journals (Sweden)

    Imran Rashid Rajput and Wei Fen Li*

    2012-06-01

    Full Text Available Probiotics are nonpathogenic bacteria exert a constructive influence on health or physiology of the host. Effect of probiotics in the intestinal defense against variety of diseases is well known. The probiotics are involved in the mechanism of intestinal defense, support as antagonist against pathogens, improve intestinal epithelial layer and boost the innate as well as adaptive immunity. However these responses are also exerted by intestinal components. The intestinal components as well as probiotics play a reciprocal role to enhance the immune response of the individual. The possibilities of mechanism of action include the stimulation of epithelial cells, activation of dendritic cells via toll-like receptors (TLRs, conversely produce cytokines. These observations reviewed together advocate that specific immunomodulatory properties of probiotic bacteria should be focusing on mechanism of action via antigen presenting cells (APC.

  10. Probiotics: a potential role in the prevention of gestational diabetes?

    Science.gov (United States)

    Barrett, Helen L; Callaway, Leonie K; Nitert, Marloes Dekker

    2012-12-01

    The gut microbiome has a complex relationship with host metabolism and immune function. Host health and diet influence the composition of the gut microbiome, and conversely, different microbiome compositions influence host metabolism. Gestational diabetes mellitus is increasingly common and has serious implications for maternal and foetal health both during pregnancy and later in life. To date, clinical trials of exercise and dietary interventions to prevent the onset of gestational diabetes have had heterogeneous results and have proven disappointingly difficult. Alternative prevention strategies of gestational diabetes mellitus need to be considered and trialled in a placebo-controlled manner in combination with dietary and behavioural measures. One such potential preventative therapy is probiotic supplementation, that is, ingestion of specific bacterial strains with beneficial effects on the host. Probiotic supplements have been shown to improve metabolism by increasing host insulin sensitivity, cholesterol metabolism and also have a beneficial effect on the immune system. This discussion paper examines the evidence for the influence of the gut microbiome on host metabolism and the potential metabolic impact of probiotic supplementation, with particular regard for the evidence surrounding a possible use of probiotic supplements for the prevention of gestational diabetes. Probiotics offer the tantalising possibility of a feasible intervention for the prevention of gestational diabetes and improvement of metabolic syndromes, but there is a pressing need for further studies of the mechanisms underlying the apparent metabolic benefits and for the use of randomised controlled trials to allow examination of the effectiveness of probiotic supplementation in this setting.

  11. Rain simulator role in creating of Erosion Potential Method (EPM)

    Science.gov (United States)

    Gavrilovic, Zoran; Stefanovic, Milutin; Milovanovic, Irina

    2010-05-01

    Soil erosion is a natural process that depends on many variables factor. Unlike the other factors rain is meteoric phenomenon of short duration and intensity variation. This feature caused the application of rain simulators in the field of erosion research. During the development of erosion potential method, it was concluded that there is too large dissipation of observed erosion data. The first use of simulators did not give better results, because the rain simulator had no impact on other factors of erosion. Therefore, the research continued in the laboratory where the use of rain simulators takes a series of data for various intensity and duration of rain. Other factors are controlled for each series of measurements were constant. These data enabled more precise definition of the numerical coefficients and procedures of erosion potential method (EPM), which is known in the scientific public as Gavrilovic method. The paper will appear applied a combination of experimental erosion field and laboratory measurements obtained using rain simulators. Key words: Erosion, torrents, meteorology, climate, Rain simulator

  12. Diagnosis of inflammatory bowel disease: Potential role of molecular biometrics.

    Science.gov (United States)

    M'Koma, Amosy E

    2014-11-27

    Accurate diagnosis of predominantly colonic inflammatory bowel disease (IBD) is not possible in 30% of patients. For decades, scientists have worked to find a solution to improve diagnostic accuracy for IBD, encompassing Crohn's colitis and ulcerative colitis. Evaluating protein patterns in surgical pathology colectomy specimens of colonic mucosal and submucosal compartments, individually, has potential for diagnostic medicine by identifying integrally independent, phenotype-specific cellular and molecular characteristics. Mass spectrometry (MS) and imaging (I) MS are analytical technologies that directly measure molecular species in clinical specimens, contributing to the in-depth understanding of biological molecules. The biometric-system complexity and functional diversity is well suited to proteomic and diagnostic studies. The direct analysis of cells and tissues by Matrix-Assisted-Laser Desorption/Ionization (MALDI) MS/IMS has relevant medical diagnostic potential. MALDI-MS/IMS detection generates molecular signatures obtained from specific cell types within tissue sections. Herein discussed is a perspective on the use of MALDI-MS/IMS and bioinformatics technologies for detection of molecular-biometric patterns and identification of differentiating proteins. I also discuss a perspective on the global challenge of transferring technologies to clinical laboratories dealing with IBD issues. The significance of serologic-immunometric advances is also discussed.

  13. Diagnosis of inflammatory bowel disease: Potential role of molecular biometrics

    Institute of Scientific and Technical Information of China (English)

    Amosy; E; M’Koma

    2014-01-01

    Accurate diagnosis of predominantly colonic inflammatory bowel disease(IBD) is not possible in 30% of patients. For decades, scientists have worked to find a solution to improve diagnostic accuracy for IBD, encompassing Crohn’s colitis and ulcerative colitis. Evaluating protein patterns in surgical pathology colectomy specimens of colonic mucosal and submucosal compartments, individually, has potential for diagnostic medicine by identifying integrally independent, phenotype-specific cellular and molecular characteristics. Mass spectrometry(MS) and imaging(I) MS are analytical technologies that directly measure molecular species in clinical specimens, contributing to the in-depth understanding of biological molecules. The biometric-system complexity and functional diversity is well suited to proteomic and diagnostic studies. The direct analysis of cells and tissues by Matrix-Assisted-Laser Desorption/Ionization (MALDI) MS/IMS has relevant medical diagnostic potential. MALDI-MS/IMS detection generates molecular signatures obtained from specific cell types within tissue sections. Herein discussed is a perspective on the use of MALDI-MS/IMS and bioinformatics technologies for detection of molecular-biometric patterns and identification of differentiating proteins. I also discuss a perspective on the global challenge of transferring technologies to clinical laboratories dealing with IBD issues. The significance of serologic-immunometric advances is also discussed.

  14. Cytoplasmic CUG RNA foci are insufficient to elicit key DM1 features.

    Directory of Open Access Journals (Sweden)

    Warunee Dansithong

    Full Text Available The genetic basis of myotonic dystrophy type I (DM1 is the expansion of a CTG tract located in the 3' untranslated region of DMPK. Expression of mutant RNAs encoding expanded CUG repeats plays a central role in the development of cardiac disease in DM1. Expanded CUG tracts form both nuclear and cytoplasmic aggregates, yet the relative significance of such aggregates in eliciting DM1 pathology is unclear. To test the pathophysiology of CUG repeat encoding RNAs, we developed and analyzed mice with cardiac-specific expression of a beta-galactosidase cassette in which a (CTG(400 repeat tract was positioned 3' of the termination codon and 5' of the bovine growth hormone polyadenylation signal. In these animals CUG aggregates form exclusively in the cytoplasm of cardiac cells. A key pathological consequence of expanded CUG repeat RNA expression in DM1 is aberrant RNA splicing. Abnormal splicing results from the functional inactivation of MBNL1, which is hypothesized to occur due to MBNL1 sequestration in CUG foci or from elevated levels of CUG-BP1. We therefore tested the ability of cytoplasmic CUG foci to elicit these changes. Aggregation of CUG RNAs within the cytoplasm results both in Mbnl1 sequestration and in approximately a two fold increase in both nuclear and cytoplasmic Cug-bp1 levels. Significantly, despite these changes RNA splice defects were not observed and functional analysis revealed only subtle cardiac dysfunction, characterized by conduction defects that primarily manifest under anesthesia. Using a human myoblast culture system we show that this transgene, when expressed at similar levels to a second transgene, which encodes expanded CTG tracts and facilitates both nuclear focus formation and aberrant splicing, does not elicit aberrant splicing. Thus the lack of toxicity of cytoplasmic CUG foci does not appear to be a consequence of low expression levels. Our results therefore demonstrate that the cellular location of CUG RNA

  15. γH2AX Foci Form Preferentially in Euchromatin after Ionising-Radiation

    Science.gov (United States)

    Cowell, Ian G.; Sunter, Nicola J.; Singh, Prim B.; Austin, Caroline A.; Durkacz, Barbara W.; Tilby, Michael J.

    2007-01-01

    Background The histone variant histone H2A.X comprises up to 25% of the H2A complement in mammalian cells. It is rapidly phosphorylated following exposure of cells to double-strand break (DSB) inducing agents such as ionising radiation. Within minutes of DSB generation, H2AX molecules are phosphorylated in large chromatin domains flanking DNA double-strand breaks (DSBs); these domains can be observed by immunofluorescence microscopy and are termed γH2AX foci. H2AX phosphorylation is believed to have a role mounting an efficient cellular response to DNA damage. Theoretical considerations suggest an essentially random chromosomal distribution of X-ray induced DSBs, and experimental evidence does not consistently indicate otherwise. However, we observed an apparently uneven distribution of γH2AX foci following X-irradiation with regions of the nucleus devoid of foci. Methodology/Principle Findings Using immunofluorescence microscopy, we show that focal phosphorylation of histone H2AX occurs preferentially in euchromatic regions of the genome following X-irradiation. H2AX phosphorylation has also been demonstrated previously to occur at stalled replication forks induced by UV radiation or exposure to agents such as hydroxyurea. In this study, treatment of S-phase cells with hydroxyurea lead to efficient H2AX phosphorylation in both euchromatin and heterochromatin at times when these chromatin compartments were undergoing replication. This suggests a block to H2AX phosphorylation in heterochromatin that is at least partially relieved by ongoing DNA replication. Conclusions/Significance We discus a number of possible mechanisms that could account for the observed pattern of H2AX phosphorylation. Since γH2AX is regarded as forming a platform for the recruitment or retention of other DNA repair and signaling molecules, these findings imply that the processing of DSBs in heterochromatin differs from that in euchromatic regions. The differential responses of

  16. The potential role of perfluorocarbon emulsions in decompression illness.

    Science.gov (United States)

    Spiess, Bruce D

    2010-03-01

    Decompression illness (DCI) is an occasional occurrence in sport, professional, and military diving as well as a potential catastrophe in high-altitude flight, space exploration, mining, and caisson bridge construction. DCI theoretically could be a success-limiting problem in escape from a disabled submarine (DISSUB). Perfluorocarbon emulsions (PFCs) have previously been investigated as 'blood substitutes' with one approved by the United States Food and Drug Administration for the treatment of myocardial ischaemia. PFCs possess enhanced (as compared to plasma) respiratory gas solubility characteristics, including oxygen, nitrogen and carbon dioxide. This review examines approximately 30 years of research regarding the utilization of PFCs in gas embolism as well as experimental DCI. To date, no humans have been treated with PFCs for DCI.

  17. The Anticancer Activity of Organotelluranes: Potential Role in Integrin Inactivation.

    Science.gov (United States)

    Silberman, Alon; Kalechman, Yona; Hirsch, Shira; Erlich, Ziv; Sredni, Benjamin; Albeck, Amnon

    2016-05-17

    Organic Te(IV) compounds (organotelluranes) differing in their labile ligands exhibited anti-integrin activities in vitro and anti-metastatic properties in vivo. They underwent ligand substitution with l-cysteine, as a thiol model compound. Unlike inorganic Te(IV) compounds, the organotelluranes did not form a stable complex with cysteine, but rather immediately oxidized it. The organotelluranes inhibited integrin functions, such as adhesion, migration, and metalloproteinase secretion mediation in B16F10 murine melanoma cells. In comparison, a reduced derivative with no labile ligand inhibited adhesion of B16F10 cells to a significantly lower extent, thus pointing to the importance of the labile ligands of the Te(IV) atom. One of the organotelluranes inhibited circulating cancer cells in vivo, possibly by integrin inhibition. Our results extend the current knowledge on the reactivity and mechanism of organotelluranes with different labile ligands and highlight their clinical potential.

  18. The potential roles of nanobiomaterials in distraction osteogenesis.

    Science.gov (United States)

    Makhdom, Asim M; Nayef, Lamees; Tabrizian, Maryam; Hamdy, Reggie C

    2015-01-01

    Distraction osteogenesis (DO) technique is used worldwide to treat many orthopedic conditions. Although successful, one limitation of this technique is the extended period of fixators until the bone is consolidated. The application of growth factors (GFs) is one promising approach to accelerate bone regeneration during DO. Despite promising in vivo results, its use is still limited in the clinic. This is secondary to inherent limitations of these GFs. Therefore, a development of delivery systems that allow sustained sequential release is necessary. Nanoparticles and nanocomposites have prevailing properties that can overcome the limitations of the current delivery systems. In addition, their use can overcome the current challenges associated with the insufficient mechanical properties of scaffolds and suboptimal osteogenic differentiation of transplanted cells in the distraction gap. We discuss the clinical implications, and potential early applications of the nanoparticles and nanocomposites for developing new treatments to accelerate bone regeneration in DO.

  19. Cannabinoids: is there a potential treatment role in epilepsy?

    Science.gov (United States)

    Blair, Robert E; Deshpande, Laxmikant S; DeLorenzo, Robert J

    2015-01-01

    Cannabinoids have been used medicinally for centuries, and in the last decade, attention has focused on their broad therapeutic potential particularly in seizure management. While some cannabinoids have demonstrated anticonvulsant activity in experimental studies, their efficacy for managing clinical seizures has not been fully established. This commentary will touch on our understanding of the brain endocannabinoid system's regulation of synaptic transmission in both physiological and pathophysiological conditions, and review the findings from both experimental and clinical studies on the effectiveness of cannabinoids to suppress epileptic seizures. At present, there is preliminary evidence that non-psychoactive cannabinoids may be useful as anticonvulsants, but additional clinical trials are needed to fully evaluate the efficacy and safety of these compounds for the treatment of epilepsy.

  20. Treatment of systemic sclerosis: potential role for stem cell transplantation

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    Wen Xiong

    2009-11-01

    Full Text Available Wen Xiong, Chris T DerkDivision of Rheumatology, Thomas Jefferson University, Philadelphia, PA, 19107, USAAbstract: Hematopoietic stem cell transplantation may “reset” the immune reconstitution and induce self tolerance of autoreactive lymphocytes, and has been explored in the treatments for systemic sclerosis. Phase I/II trials have shown a satisfactory risk benefit ratio. The true benefit will be identified by two ongoing prospective, randomized phase III trials. Multipotent mesenchymal stromal cells (MSCs possess antiproliferative, anti-inflammatory, and immunosuppressive properties. The use of MSCs has showed successful responses in patients with severe steroid-resistant acute graft versus host disease in phase II trials, and may be a potentially promising option for patients with systemic sclerosis.Keywords: scleroderma, systemic sclerosis, treatment, stem cells, transplant

  1. The potential role of breast ductoscopy in breast cancer screening.

    Science.gov (United States)

    Sarakbi, W Al; Escobar, Pedro F; Mokbel, Kefah

    2005-01-01

    Breast cancer remains the most common malignancy among women in the Western world. Mammography, which is currently the main screening modality for early detection, has a low positive predictive value of only 25%, especially in young women with very dense breasts. Therefore, new screening approaches are needed for the early detection of breast cancer in all age groups. Mammary ductoscopy (MD) is a newly developed endoscopic technique that allows direct visualization and biopsy of the mammary ductal epithelium where most cancers originate. The procedure can be performed under local anesthesia in the office setting. At present, MD is used as a diagnostic adjunct in patients with pathological nipple discharge and to guide duct excision surgery. This article focuses on the potential of this technique in breast cancer screening and highlights its limitations in this context.

  2. On the potential role of glutamate transport in mental fatigue

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    Hansson Elisabeth

    2004-11-01

    Full Text Available Abstract Mental fatigue, with decreased concentration capacity, is common in neuroinflammatory and neurodegenerative diseases, often appearing prior to other major mental or physical neurological symptoms. Mental fatigue also makes rehabilitation more difficult after a stroke, brain trauma, meningitis or encephalitis. As increased levels of proinflammatory cytokines are reported in these disorders, we wanted to explore whether or not proinflammatory cytokines could induce mental fatigue, and if so, by what mechanisms. It is well known that proinflammatory cytokines are increased in major depression, "sickness behavior" and sleep deprivation, which are all disorders associated with mental fatigue. Furthermore, an influence by specific proinflammatory cytokines, such as interleukin (IL-1, on learning and memory capacities has been observed in several experimental systems. As glutamate signaling is crucial for information intake and processing within the brain, and due to the pivotal role for glutamate in brain metabolism, dynamic alterations in glutamate transmission could be of pathophysiological importance in mental fatigue. Based on this literature and observations from our own laboratory and others on the role of astroglial cells in the fine-tuning of glutamate neurotransmission we present the hypothesis that the proinflammatory cytokines tumor necrosis factor-α, IL-1β and IL-6 could be involved in the pathophysiology of mental fatigue through their ability to attenuate the astroglial clearance of extracellular glutamate, their disintegration of the blood brain barrier, and effects on astroglial metabolism and metabolic supply for the neurons, thereby attenuating glutamate transmission. To test whether our hypothesis is valid or not, brain imaging techniques should be applied with the ability to register, over time and with increasing cognitive loading, the extracellular concentrations of glutamate and potassium (K+ in humans suffering from

  3. Potential role of probiotics on colorectal cancer prevention

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    Uccello Mario

    2012-11-01

    Full Text Available Abstract Background Colorectal cancer represents the most common malignancy of the gastrointestinal tract. Owing to differences in dietary habits and lifestyle, this neoplasm is more common in industrialized countries than in developing ones. Evidence from a wide range of sources supports the assumption that the link between diet and colorectal cancer may be due to an imbalance of the intestinal microflora. Discussion Probiotic bacteria are live microorganisms that, when administered in adequate amounts, confer a healthy benefit on the host, and they have been investigated for their protective anti-tumor effects. In vivo and molecular studies have displayed encouraging findings that support a role of probiotics in colorectal cancer prevention. Summary Several mechanisms could explain the preventive action of probiotics against colorectal cancer onset. They include: alteration of the intestinal microflora; inactivation of cancerogenic compounds; competition with putrefactive and pathogenic microbiota; improvement of the host’s immune response; anti-proliferative effects via regulation of apoptosis and cell differentiation; fermentation of undigested food; inhibition of tyrosine kinase signaling pathways.

  4. Peripheral artery disease: potential role of ACE-inhibitor therapy

    Directory of Open Access Journals (Sweden)

    Giuseppe Coppola

    2008-12-01

    Full Text Available Giuseppe Coppola, Giuseppe Romano, Egle Corrado, Rosa Maria Grisanti, Salvatore NovoDepartment of Internal Medicine, Cardiovascular and Nephro-Urological Diseases, Chair of Cardiovascular Disease, University of Palermo, Palermo, ItalyAbstract: Subjects with peripheral arterial disease (PAD of the lower limbs are at high risk for cardiovascular and cerebrovascular events and the prevalence of coronary artery disease in such patients is elevated. Recent studies have shown that regular use of cardiovascular medications, such as therapeutic and preventive agents for PAD patients, seems to be promising in reducing long-term mortality and morbidity. The angiotensin-converting-enzyme (ACE system plays an important role in the pathogenesis and progression of atherosclerosis, and ACE-inhibitors (ACE-I seem to have vasculoprotective and antiproliferative effects as well as a direct antiatherogenic effect. ACE-I also promote the degradation of bradykinin and the release of nitric oxide, a potent vasodilator; further, thay have shown important implications for vascular oxidative stress. Other studies have suggested that ACE-I may also improve endothelial dysfunction. ACE-I are useful for reducing the risk of cardiovascular events in clinical and subclinical PAD. Particularly, one agent of the class (ie, ramipril has shown in many studies to able to significantly reduce cardiovascular morbidity and mortality in patients with PAD.Keywords: atherosclerosis, peripheral arterial disease, endothelial dysfunction, ACE-inhibitors

  5. The potential role of dopamine D₃ receptor neurotransmission in cognition.

    Science.gov (United States)

    Nakajima, Shinichiro; Gerretsen, Philip; Takeuchi, Hiroyoshi; Caravaggio, Fernando; Chow, Tiffany; Le Foll, Bernard; Mulsant, Benoit; Pollock, Bruce; Graff-Guerrero, Ariel

    2013-08-01

    Currently available treatments have limited pro-cognitive effects for neuropsychiatric disorders, such as schizophrenia, Parkinson's disease and Alzheimer's disease. The primary objective of this work is to review the literature on the role of dopamine D₃ receptors in cognition, and propose dopamine D₃ receptor antagonists as possible cognitive enhancers for neuropsychiatric disorders. A literature search was performed to identify animal and human studies on D₃ receptors and cognition using PubMed, MEDLINE and EMBASE. The search terms included "dopamine D₃ receptor" and "cognition". The literature search identified 164 articles. The results revealed: (1) D₃ receptors are associated with cognitive functioning in both healthy individuals and those with neuropsychiatric disorders; (2) D₃ receptor blockade appears to enhance while D₃ receptor agonism seems to impair cognitive function, including memory, attention, learning, processing speed, social recognition and executive function independent of age; and (3) D₃ receptor antagonists may exert their pro-cognitive effect by enhancing the release of acetylcholine in the prefrontal cortex, disinhibiting the activity of dopamine neurons projecting to the nucleus accumbens or prefrontal cortex, or activating CREB signaling in the hippocampus. These findings suggest that D₃ receptor blockade may enhance cognitive performance in healthy individuals and treat cognitive dysfunction in individuals with a neuropsychiatric disorder. Clinical trials are needed to confirm these effects.

  6. Sustainable life support on Mars - the potential roles of cyanobacteria

    Science.gov (United States)

    Verseux, Cyprien; Baqué, Mickael; Lehto, Kirsi; de Vera, Jean-Pierre P.; Rothschild, Lynn J.; Billi, Daniela

    2016-01-01

    Even though technological advances could allow humans to reach Mars in the coming decades, launch costs prohibit the establishment of permanent manned outposts for which most consumables would be sent from Earth. This issue can be addressed by in situ resource utilization: producing part or all of these consumables on Mars, from local resources. Biological components are needed, among other reasons because various resources could be efficiently produced only by the use of biological systems. But most plants and microorganisms are unable to exploit Martian resources, and sending substrates from Earth to support their metabolism would strongly limit the cost-effectiveness and sustainability of their cultivation. However, resources needed to grow specific cyanobacteria are available on Mars due to their photosynthetic abilities, nitrogen-fixing activities and lithotrophic lifestyles. They could be used directly for various applications, including the production of food, fuel and oxygen, but also indirectly: products from their culture could support the growth of other organisms, opening the way to a wide range of life-support biological processes based on Martian resources. Here we give insights into how and why cyanobacteria could play a role in the development of self-sustainable manned outposts on Mars.

  7. Quantum Dots and their Potential Role in Cancer Theranostics.

    Science.gov (United States)

    Tripathi, S K; Kaur, Gurvir; Khurana, Rajneet Kaur; Kapoor, Sonia; Singh, Bhupinder

    2015-01-01

    The emergence of cancer nanomedicine is the result of fruitful advances in the fields of nanotechnology, bioimaging, formulation development, and molecular biology. Quantum dots (QDs) are the luminescent nanocrystals (NCs) that provide a multifunctional platform for imaging the biosystems following controlled delivery of therapeutic drugs, proteins, peptides, oligonucleotides, and genes. These engineered fluorescent probes with integrated imaging and carrier functionalities have become excellent tools for molecular diagnostics and delivery of therapeutics molecules. Flexible surface chemistry, unique optical properties, high sensitivity, and multiplexing capabilities of QDs certainly make them a most promising tool for personalized medicine. This review focuses on state-of-art advances in synthesizing QDs and highlights the approaches used for functionalization of QDs with desired ligands for targeted carriage to specific sites. Discussed is the role of QDs in antitumor therapy through drug delivery and gene delivery and the recently emerged photodynamic therapy (PDT). We also endeavor to critically address the major impediments in the clinical development of these multifunctional nanoplatforms, with a special focus on plausible advancements for the near future.

  8. A potentially dynamic lysosomal role for the endogenous TRPML proteins.

    Science.gov (United States)

    Zeevi, David A; Frumkin, Ayala; Offen-Glasner, Vered; Kogot-Levin, Aviram; Bach, Gideon

    2009-10-01

    Lysosomal storage disorders (LSDs) constitute a diverse group of inherited diseases that result from lysosomal storage of compounds occurring in direct consequence to deficiencies of proteins implicated in proper lysosomal function. Pathology in the LSD mucolipidosis type IV (MLIV), is characterized by lysosomal storage of lipids together with water-soluble materials in cells from every tissue and organ of affected patients. Mutations in the mucolipin 1 (TRPML1) protein cause MLIV and TRPML1 has also been shown to interact with two of its paralogous proteins, mucolipin 2 (TRPML2) and mucolipin 3 (TRPML3), in heterologous expression systems. Heterogeneous lysosomal storage is readily identified in electron micrographs of MLIV patient cells, suggesting that proper TRPML1 function is essential for the maintenance of lysosomal integrity. In order to investigate whether TRPML2 and TRPML3 also play a role in the maintenance of lysosomal integrity, we conducted gene-specific knockdown assays against these protein targets. Ultrastructural analysis revealed lysosomal inclusions in both TRPML2 and TRPML3 knockdown cells, suggestive of a common mechanism for these proteins, in parallel with TRPML1, in the regulation of lysosomal integrity. However, co-immunoprecipitation assays revealed that physical interactions between each of the endogenous TRPML proteins are quite limited. In addition, we found that all three endogenous proteins only partially co-localize with each other in lysosomal as well as extra-lysosomal compartments. This suggests that native TRPML2 and TRPML3 might participate with native TRPML1 in a dynamic form of lysosomal regulation. Given that depletion of TRPML2/3 led to lysosomal storage typical to an LSD, we propose that depletion of these proteins might also underlie novel LSD pathologies not described hitherto.

  9. Pathophysiology of hypophosphatasia and the potential role of asfotase alfa

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    Orimo H

    2016-05-01

    Full Text Available Hideo Orimo Division of Metabolism and Nutrition, Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan Abstract: Hypophosphatasia (HPP is an inherited systemic bone disease that is characterized by bone hypomineralization. HPP is classified into six forms according to the age of onset and severity as perinatal (lethal, perinatal benign, infantile, childhood, adult, and odontohypophosphatasia. The causative gene of the disease is the ALPL gene that encodes tissue-nonspecific alkaline phosphatase (TNAP. TNAP is expressed ubiquitously, and its physiological role is apparent in bone mineralization. A defect in bone mineralization can manifest in several ways, including rickets or osteomalacia in HPP patients. Patients with severe forms suffer from respiratory failure because of hypoplastic chest, which is the main cause of death. They sometimes present with seizures due to a defect in vitamin B6 metabolism resulting from the lack of alkaline phosphatase activity in neuronal cells, which is also lethal. Patients with a mild form of the disease exhibit rickets or osteomalacia and a functional defect of exercise. Odontohypophosphatasia shows only dental manifestations. To date, 302 mutations in the ALPL gene have been reported, mainly single-nucleotide substitutions, and the relationships between phenotype and genotype have been partially elucidated. An established treatment for HPP was not available until the recent development of enzyme replacement therapy. The first successful enzyme replacement therapy in model mice using a modified human TNAP protein (asfotase alfa was reported in 2008, and subsequently success in patients with severe form of the disease was reported in 2012. In 2015, asfotase alfa was approved in Japan in July, followed by in the EU and Canada in August, and then by the US Food and Drug Administration in the USA in October. It is expected that therapy with asfotase alfa will drastically change

  10. Pathophysiology of hypophosphatasia and the potential role of asfotase alfa

    Science.gov (United States)

    Orimo, Hideo

    2016-01-01

    Hypophosphatasia (HPP) is an inherited systemic bone disease that is characterized by bone hypomineralization. HPP is classified into six forms according to the age of onset and severity as perinatal (lethal), perinatal benign, infantile, childhood, adult, and odontohypophosphatasia. The causative gene of the disease is the ALPL gene that encodes tissue-nonspecific alkaline phosphatase (TNAP). TNAP is expressed ubiquitously, and its physiological role is apparent in bone mineralization. A defect in bone mineralization can manifest in several ways, including rickets or osteomalacia in HPP patients. Patients with severe forms suffer from respiratory failure because of hypoplastic chest, which is the main cause of death. They sometimes present with seizures due to a defect in vitamin B6 metabolism resulting from the lack of alkaline phosphatase activity in neuronal cells, which is also lethal. Patients with a mild form of the disease exhibit rickets or osteomalacia and a functional defect of exercise. Odontohypophosphatasia shows only dental manifestations. To date, 302 mutations in the ALPL gene have been reported, mainly single-nucleotide substitutions, and the relationships between phenotype and genotype have been partially elucidated. An established treatment for HPP was not available until the recent development of enzyme replacement therapy. The first successful enzyme replacement therapy in model mice using a modified human TNAP protein (asfotase alfa) was reported in 2008, and subsequently success in patients with severe form of the disease was reported in 2012. In 2015, asfotase alfa was approved in Japan in July, followed by in the EU and Canada in August, and then by the US Food and Drug Administration in the USA in October. It is expected that therapy with asfotase alfa will drastically change treatments and prognosis of HPP. PMID:27274262

  11. Potential role of rivaroxaban in patients with acute coronary syndrome

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    Fitchett DH

    2012-11-01

    Full Text Available David H FitchettDivision of Cardiology, Department of Medicine, St Michael's Hospital, University of Toronto, Toronto, Ontario, CanadaAbstract: Patients with acute coronary syndrome (ACS continue to be at risk for recurrent ischemic events, despite an early invasive strategy and the use of dual antiplatelet therapy. The anticoagulant pathway remains activated for a prolonged period after ACS and, consequently, has been a target for treatment. Early studies with warfarin indicated its benefit, but the risk of bleeding and the complexities of warfarin anticoagulation resulted in little use of this strategy. Rivaroxaban, apixaban, and dabigatran are new specific inhibitors of anticoagulant factors (Xa or IIa currently available for the prevention of thrombosis and/or thromboembolism. Thus far, studies with dabigatran and apixaban in ACS have shown no clinical benefit and bleeding has been increased. The ATLAS ACS 2-TIMI 51 trial observed the impact of rivaroxaban 2.5 mg and 5 mg twice daily in patients with recent ACS receiving current management (both early invasive strategy and dual antiplatelet therapy with aspirin and clopidogrel over a follow-up period of over 1 year. Rivaroxaban 2.5 mg twice daily reduced cardiovascular death, myocardial infarction, or stroke by 16%, and both cardiovascular and all-cause mortality by approximately 20%. Although major bleeding increased from 0.6% to 2.1% and intracranial hemorrhage from 0.2% to 0.6%, there was no increase in fatal bleeding. The role of rivaroxaban in the management of ACS is discussed in this review. The reduction in mortality is the main finding that could lead to the use of rivaroxaban in the management of ACS in high-risk individuals with a low bleeding risk.Keywords: cardiovascular death, myocardial infarction, stroke, anticoagulation, bleeding risk

  12. The potential role of MRI in veterinary clinical cardiology.

    Science.gov (United States)

    Gilbert, Stephen H; McConnell, Fraser J; Holden, Arun V; Sivananthan, Mohan U; Dukes-McEwan, Joanna

    2010-02-01

    Over the last decade, magnetic resonance imaging (MRI) has become established as a useful referral diagnostic method in veterinary medicine that is widely used in small animal brain and spinal diseases, aural, nasal and orbital disorders, planning soft tissue surgery, oncology and small animal and equine orthopaedics. The use of MRI in these disciplines has grown due to its unparalleled capability to image soft tissue structures. This has been exploited in human cardiology where, despite the inherent difficulties in imaging a moving, contractile structure, cardiac MRI (CMRI) has become the optimal technique for the morphological assessment and quantification of ventricular function. Both CMRI hardware and software systems have developed rapidly in the last 10 years but although several preliminary veterinary CMRI studies have been reported, the technique's growth has been limited and is currently used primarily in clinical research. A review of published studies is presented with a description of CMRI technology and the potential of CMRI is discussed along with some of the reasons for its limited usage.

  13. Potential roles for microbial endophytes in herbicide tolerance in plants.

    Science.gov (United States)

    Tétard-Jones, Catherine; Edwards, Robert

    2016-02-01

    Herbicide tolerance in crops and weeds is considered to be monotrophic, i.e. determined by the relative susceptibility of the physiological process targeted and the plant's ability to metabolise and detoxify the agrochemical. A growing body of evidence now suggests that endophytes, microbes that inhabit plant tissues and provide a range of growth, health and defence enhancements, can contribute to other types of abiotic and biotic stress tolerance. The current evidence for herbicide tolerance being bitrophic, with both free-living and plant-associated endophytes contributing to tolerance in the host plant, has been reviewed. We propose that endophytes can directly contribute to herbicide detoxification through their ability to metabolise xenobiotics. In addition, we explore the paradigm that microbes can 'prime' resistance mechanisms in plants such that they enhance herbicide tolerance by inducing the host's stress responses to withstand the downstream toxicity caused by herbicides. This latter mechanism has the potential to contribute to the growth of non-target-site-based herbicide resistance in weeds. Microbial endophytes already contribute to herbicide detoxification in planta, and there is now significant scope to extend these interactions using synthetic biology approaches to engineer new chemical tolerance traits into crops via microbial engineering.

  14. Active axial spondyloarthritis: potential role of certolizumab pegol

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    Ranatunga S

    2014-02-01

    Full Text Available Sriya Ranatunga, Anne V Miller Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL, USA Abstract: The axial spondyloarthropathies are a group of chronic inflammatory diseases that predominantly affect the axial joints. This group includes ankylosing spondylitis and nonradiographic axial spondyloarthropathy. While the pathogenesis of axial spondyloarthropathies is not clear, immunologically active tissues primarily include the entheses, ie, the areas where ligaments, tendons, and joint capsules attach to bone and to the annulus fibrosis at the vertebrae. One of the major mediators of the immune response in this group of diseases is tumor necrosis factor-alpha (TNFα. Blockade of TNFα results in reduced vascularity and inflammatory cell infiltration in the synovial tissues of affected joints. Certolizumab pegol (CZP is an Fc-free, PEGylated anti-TNFα monoclonal antibody. CZP has unique properties that differ from other available TNFα inhibitors by virtue of its lack of an Fc region, which minimizes potential Fc-mediated effects, and its PEGylation, which improves drug pharmacokinetics and bioavailability. It has been shown in clinical trials that CZP improves patient outcomes and reduces inflammation in the sacroiliac joints and spine in both ankylosing spondylitis and nonradiographic axial spondyloarthropathies. These data support CZP as a treatment option for axial spondyloarthropathies. Keywords: axial spondyloarthropathy, certolizumab pegol, anti-tumor necrosis factor-alpha, therapy

  15. The potential role of cannabinoids in epilepsy treatment.

    Science.gov (United States)

    De Caro, Carmen; Leo, Antonio; Citraro, Rita; De Sarro, Caterina; Russo, Roberto; Calignano, Antonio; Russo, Emilio

    2017-09-04

    Epilepsy is one of the world's oldest recognized and prevalent neurological diseases. It has a great negative impact on patients' quality of life (QOL) as a consequence of treatment resistant seizures in about 30% of patients together with drugs' side effects and comorbidities. Therefore, new drugs are needed and cannabinoids, above all cannabidiol, have recently gathered attention. Areas covered: This review summarizes the scientific data from human and animal studies on the major cannabinoids which have been of interest in the treatment of epilepsy, including drugs acting on the endocannabinoid system. Expert commentary: Despite the fact that cannabis has been used for many purposes over 4 millennia, the development of drugs based on cannabinoids has been very slow. Only recently, research has focused on their potential effects and CBD is the first treatment of this group with clinical evidence of efficacy in children with Dravet syndrome; moreover, other studies are currently ongoing to confirm its effectiveness in patients with epilepsy. On the other hand, it will be of interest to understand whether drugs acting on the endocannabinoid system will be able to reach the market and prove their known preclinical efficacy also in patients with epilepsy.

  16. The potential role of biofuels within the built environment

    Science.gov (United States)

    Lewis, C.

    1980-04-01

    The potential contribution of biofuels within both developed and developing nations is examined, particularly with respect to their utilization within the built environment. It is stressed that biomass, mainly in the forms of wood, animal dung and agricultural residues, is essentially a renewable resource and today accounts for approximately one-sixth of global fuel supplies. Examples of fuelwood consumption in European countries and in Africa are presented and the future of the bioenergy is considered, taking into account such main estimates as national energy density (energy consumed/ha of land area) and biomass productivity (net energy output/ha/year). Bioenergy production in low and high latitude countries, is also examined. The results of work on the blue-green Spirulina, an alga which contains 65-70% protein, and may yield about 200 cu m of biogas, containing 65-68% of CH4 at an energy content of 5.25 GI from 410 kg of its biomass are discussed.

  17. Salmonella-mediated cancer therapy: Roles and potential

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Vu Hong [Dept. of Experimental TherapeuticsBeckman Research Institute of City of Hope, Duarte (United States); Min, Jung Joon [Dept. of Nuclear MedicineChonnam National University Medical School, Gwangju (Korea, Republic of)

    2017-06-15

    The use of bacteria for cancer therapy, which was proposed many years ago, was not recognized as a potential therapeutic strategy until recently. Technological advances and updated knowledge have enabled the genetic engineering of bacteria for their safe and effective application in the treatment of cancer. The efficacy of radiotherapy depends mainly on tissue oxygen levels, and low oxygen concentrations in necrotic and hypoxic regions are a common cause of treatment failure. In addition, the distribution of a drug is important for the therapeutic effect of chemotherapy, and the poor vasculature in tumors impairs drug delivery, limiting the efficacy of a drug, especially in necrotic and hypoxic regions. Bacteria-mediated cancer therapy (BMCT) relies on facultative anaerobes that can survive in well or poorly oxygenated regions, and it therefore improves the therapeutic efficacy drug distribution throughout the tumor mass. Since the mid-1990s, the number of published bacterial therapy papers has increased rapidly, with a doubling time of 2.5 years in which the use of Salmonella increased significantly. BMCT is being reevaluated to overcome some of the drawbacks of conventional therapies. This review focuses on Salmonella-mediated cancer therapy as the most widely used type of BMCT.{sub 2}.

  18. Potential role of punicalagin against oxidative stress induced testicular damage

    Directory of Open Access Journals (Sweden)

    Faiza Rao

    2016-01-01

    Full Text Available Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98% on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU against oxidative stress-induced infertility. Results demonstrated that 9 mg kg−1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.

  19. Fetal Alcohol Spectrum Disorder: Potential Role of Endocannabinoids Signaling

    Directory of Open Access Journals (Sweden)

    Balapal S. Basavarajappa

    2015-10-01

    Full Text Available One of the unique features of prenatal alcohol exposure in humans is impaired cognitive and behavioral function resulting from damage to the central nervous system (CNS, which leads to a spectrum of impairments referred to as fetal alcohol spectrum disorder (FASD. Human FASD phenotypes can be reproduced in the rodent CNS following prenatal ethanol exposure. Several mechanisms are expected to contribute to the detrimental effects of prenatal alcohol exposure on the developing fetus, particularly in the developing CNS. These mechanisms may act simultaneously or consecutively and differ among a variety of cell types at specific developmental stages in particular brain regions. Studies have identified numerous potential mechanisms through which alcohol can act on the fetus. Among these mechanisms are increased oxidative stress, mitochondrial damage, interference with the activity of growth factors, glia cells, cell adhesion molecules, gene expression during CNS development and impaired function of signaling molecules involved in neuronal communication and circuit formation. These alcohol-induced deficits result in long-lasting abnormalities in neuronal plasticity and learning and memory and can explain many of the neurobehavioral abnormalities found in FASD. In this review, the author discusses the mechanisms that are associated with FASD and provides a current status on the endocannabinoid system in the development of FASD.

  20. Potential of Root Exudates from Wetland Plants and Their Potential Role for Denitrification and Allelopathic Interactions

    DEFF Research Database (Denmark)

    Zhai, Xu

    vary among different Phragmites haplotypes and consequently affect their invasion potential. The studies presented in this dissertation aimed at investigating the quantity and composition of the organic carbon released in root exudates from three common wetland species as affected by temperature...... wetlands. Furthermore, environmental factors such as temperature and light-regime affect the photosynthetic carbon fixation, which continuously influence the compositions and quantity of root exudates released into rhizosphere. Conversely, root exudates from invasive species might contain some phytotoxic...... and light-regime and how the root exudates potentially affect the nitrogen removal by denitrification in constructed wetlands. Also, the studies aimed at further elucidating the potential allelopathic interaction between the plants. The findings of the research suggest that the root exudates from wetland...

  1. Potential roles of noncoding RNAs in environmental epigenetic transgenerational inheritance.

    Science.gov (United States)

    Yan, Wei

    2014-12-01

    "Epigenetic transgenerational inheritance" (ETI) has been defined as germline (sperm or egg) transmission of epigenetic information between generations in the absence of direct exposures or genetic manipulations. Among reported cases of ETI in mammals, the majority are induced by environmental factors, including environmental toxicants [e.g. agricultural fungicide vinclozolin, plastic additive bisphenol A, pesticide methoxychlor, dioxin, di-(2-ethylhexyl) phthalate, dichlorodiphenyltrichloroethane, and hydrocarbons] and poor nutritional conditions. Although the ETI phenomenon is well established, the underlying mechanism remains elusive. Putative epimutations, including changes in DNA methylation and histone modification patterns, have been reported, but it remains unclear how these epimutations are formed in the first place, and how they are memorized in the germline and then get transmitted to subsequent generations. Based on recent advances in our understanding of regulatory noncoding RNAs (ncRNAs), I propose that ncRNAs are involved in ETI, during both the initial epimutation formation and the subsequent germline transmission of epimutations. ncRNAs can function at epigenetic levels by affecting DNA methylation and histone modifications, thereby changing gene transcriptional activities, which can lead to an altered mRNA transcriptome associated with a disease phenotype. Alternatively, novel or altered ncRNA expression can cause dysregulated post-transcriptional regulation, thus directly affecting the mRNA transcriptome and inducing a disease phenotype. Sperm-borne ncRNAs are potential mediators for epigenetic memory across generations, but they alone may not be sufficient for stable transmission of epimutations across generations. Overall, research on ncRNAs in the context of ETI is urgently needed to shed light on the underlying mechanism of ETI.

  2. Potential renovascular hypertension, space missions, and the role of magnesium

    Directory of Open Access Journals (Sweden)

    William J Rowe

    2009-11-01

    Full Text Available William J RoweFormer Assistant Clinical Professor of Medicine, Medical University of Ohio at Toledo, Keswick, VA, USAAbstract: Space flight (SF and dust inhalation in habitats cause hypertension whereas in SF (alone there is no consistent hypertension but reduced diurnal blood pressure (BP variation instead. Current pharmaceutical subcutaneous delivery systems are inadequate and there is impairment in the absorption, metabolism, excretion, and deterioration of some pharmaceuticals. Data obtained from the National Aeronautics and Space Administration through the Freedom of Information Act shows that Irwin returned from his 12-day Apollo 15 mission in 1971 and was administered a bicycle stress test. With just three minutes of exercise, his BP was >275/125 mm Hg (heart rate of only 130 beats per minute. There was no acute renal insult. Irwin’s apparent spontaneous remission is suggested to be related to the increase of a protective vasodilator, and his atrial natriuretic peptide (ANP reduced with SF because of reduced plasma volume. With invariable malabsorption and loss of bone/muscle storage sites, there are significant (P < 0.0001 reductions of magnesium (Mg required for ANP synthesis and release. Reductions of Mg and ANP can trigger pronounced angiotensin (200%, endothelin, and catecholamine elevations (clearly shown in recent years and vicious cycles between the latter and Mg deficits. There is proteinuria, elevated creatinine, and reduced renal concentrating ability with the potential for progressive inflammatory and oxidative stress-induced renal disease and hypertension with vicious cycles. After SF, animals show myocardial endothelial injuries and increased vascular resistance of extremities in humans. Even without dust, hypertension might eventually develop from renovascular hypertension during very long missions. Without sufficient endothelial protection from pharmaceuticals, a comprehensive gene research program should begin now

  3. The Potential Role(s) of Writing in Second Language Development

    Science.gov (United States)

    Williams, Jessica

    2012-01-01

    Writing is often seen as having a minor role in second language learning. This article explores recent research that suggests that writing can have a facilitative role in language development. In particular, it focuses on three features of writing: (1) its slower pace, and (2) the enduring record that it leaves, both of which can encourage…

  4. [Evolution of hyperplastic foci in the rat liver induced by diethylnitrosamine].

    Science.gov (United States)

    Gel'shteĭn, V I; Chipysheva, T A; Bannikov, G A

    1984-01-01

    The immunohistochemical localization of ligandin (L), A-protein (A) and alpha-fetoprotein (AFP) was studied in the liver of rats treated intraperitoneally with diethylnitrosamine (DENA). In early foci of altered cells there was a consecutive change in the content of antigens. The uniform content of L and A in these foci changed for the uniform content of only one marker. Late foci of altered hepatocytes were characterized by a heterogeneous distribution of the markers. 12-14 weeks after the treatment the neoplastic nodules with different antigenic phenotypes dependent on the morphological structure were detected. Cells in neoplastic nodules were uniform as to the marker content. Alpha-fetoprotein was unavailable in foci of altered cells and in neoplastic nodules either. It is concluded that evolution of most of foci follows the way of postnatal maturation similar to that in the normal liver and neoplastic nodules represent a side branch of differentiation blocked at different stages.

  5. Role of sodium tungstate as a potential antiplatelet agent

    Directory of Open Access Journals (Sweden)

    Fernández-Ruiz R

    2015-05-01

    slightly this response. In human blood, a dose-dependent effect was observed. At 200 µM, closure times in the PFA-100 were prolonged. On denuded vessels, %SC and thrombi formation (%T decreased with Na2O4W. Neither the aggregating response nor the viscoelastic clot properties were affected.Conclusion: Na2O4W decreases consistently the hemostatic capacity of platelets, inhibiting their adhesive and cohesive properties under flow conditions in mice and in human blood, resulting in smaller thrombi. Although Na2O4W may be acting on platelet PTP1B, other potential targets should not be disregarded. Keywords: sodium tungstate, protein tyrosine phosphatase 1B, platelet adhesion, antiplatelet agents

  6. Plague foci in Viet Nam: zoological and parasitological aspects.

    Science.gov (United States)

    Suntsov, V V; Huong, L T; Suntsova, N I; Gratz, N G

    1997-01-01

    Reported are the results of studies over the period 1989-94 on host-flea complexes in small mammals and their flea ectoparasites in and around a number of human settlements in Viet Nam in which human cases of plague had been found. Collections were also made in savanna and tropical forest areas within a 10-km radius of the settlements. The greatest numbers of small mammals, for the most part Rattus spp., and of the flea ectoparasite Xenopsylla cheopis were found in inhabited areas. X. cheopis was not found on any feral or sylvan mammal further than 0.6 km from settlements. A possible link between wild and commensal mammals may be provided by the flea Lentistivalius klossi, a specific parasite of squirrels and tree-shrews but also found in very small numbers on commensal rats. No zoonotic foci of plague were found in the immediate vicinity of the villages studied and it is most likely that plague persists in a commensal rat-X. cheopis cycle in and around human settlements in Viet Nam.

  7. Actin-binding proteins implicated in the formation of the punctate actin foci stimulated by the self-incompatibility response in Papaver.

    Science.gov (United States)

    Poulter, Natalie S; Staiger, Christopher J; Rappoport, Joshua Z; Franklin-Tong, Vernonica E

    2010-03-01

    The actin cytoskeleton is a key target for signaling networks and plays a central role in translating signals into cellular responses in eukaryotic cells. Self-incompatibility (SI) is an important mechanism responsible for preventing self-fertilization. The SI system of Papaver rhoeas pollen involves a Ca(2+)-dependent signaling network, including massive actin depolymerization as one of the earliest cellular responses, followed by the formation of large actin foci. However, no analysis of these structures, which appear to be aggregates of filamentous (F-)actin based on phalloidin staining, has been carried out to date. Here, we characterize and quantify the formation of F-actin foci in incompatible Papaver pollen tubes over time. The F-actin foci increase in size over time, and we provide evidence that their formation requires actin polymerization. Once formed, these SI-induced structures are unusually stable, being resistant to treatments with latrunculin B. Furthermore, their formation is associated with changes in the intracellular localization of two actin-binding proteins, cyclase-associated protein and actin-depolymerizing factor. Two other regulators of actin dynamics, profilin and fimbrin, do not associate with the F-actin foci. This study provides, to our knowledge, the first insights into the actin-binding proteins and mechanisms involved in the formation of these intriguing structures, which appear to be actively formed during the SI response.

  8. The p150 subunit of CAF-1 causes association of SUMO2/3 with the DNA replication foci

    Energy Technology Data Exchange (ETDEWEB)

    Uwada, Junsuke [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555 (Japan); Global COE (Centers of Excellence) Program, Global Initiative Center for Pulsed Power Engineering, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555 (Japan); Tanaka, Niina; Yamaguchi, Yutaro; Uchimura, Yasuhiro [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555 (Japan); Shibahara, Kei-ichi [Department of Integrated Genetics, National Institute of Genetics, Research Organization of Information and Systems, Mishima (Japan); Nakao, Mitsuyoshi [Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto (Japan); Saitoh, Hisato, E-mail: hisa@kumamoto-u.ac.jp [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555 (Japan); Global COE (Centers of Excellence) Program, Global Initiative Center for Pulsed Power Engineering, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555 (Japan)

    2010-01-01

    The small ubiquitin-related modifier 2/3 (SUMO2/3) can be post-translationally conjugated to a wide variety of proteins constituting chromatin, the platform for genetic and epigenetic regulation. Nevertheless, it is unclear how SUMO2/3 and SUMO2/3-modified proteins are delivered to the chromatin fibers. Here we report that the largest subunit of chromatin assembly factor 1 (CAF-1), human p150, interacts directly and preferentially with SUMO2/3. Amino acid residue of 98-105 in p150 is essential and sufficient for SUMO2/3 interaction. p150-SUMO2/3 interaction coincided with regions that replicate chromatin fibers, because accumulation of the proliferating cell nuclear antigen (PCNA), and incorporation of bromodeoxyuridine (BrdU) were detected at foci co-localized with both p150 and SUMO2/3 during the S-phase in a cell line expressing epitope-tagged p150. Although inhibition of SUMO2/3 expression had only a small effect on p150 deposition on the replication sites, depletion of p150 led to delocalization of SUMO2/3 from the replication foci. Furthermore, p150 mutants deficient in SUMO2/3 interaction, caused a major reduction of SUMO2/3 at the replication foci. Thus, our findings suggest an expanded role of p150 as a SUMO2/3-interacting factor, and raise the intriguing possibility that p150 plays a role in promoting delivery of SUMO2/3 or SUMO2/3-modified proteins (or both) on chromatin fibers during replication.

  9. Potential Role of Traditional Birth Attendants in Neonatal Healthcare in Rural Southern Nepal

    National Research Council Canada - National Science Library

    Falle, Tina Y; Mullany, Luke C; Thatte, Nandita; Khatry, Subarna K; LeClerq, Steven C; Darmstadt, Gary L; Katz, Joanne; Tielsch, James M

    2009-01-01

    The potential for traditional birth attendants (TBAs) to improve neonatal health outcomes has largely been overlooked during the current debate regarding the role of TBAs in improving maternal health...

  10. A phase IIa randomized, double-blind trial of erlotinib in inhibiting epidermal growth factor receptor signaling in aberrant crypt foci of the colorectum.

    Science.gov (United States)

    Gillen, Daniel L; Meyskens, Frank L; Morgan, Timothy R; Zell, Jason A; Carroll, Robert; Benya, Richard; Chen, Wen-Pin; Mo, Allen; Tucker, Chris; Bhattacharya, Asmita; Huang, Zhiliang; Arcilla, Myra; Wong, Vanessa; Chung, Jinah; Gonzalez, Rachel; Rodriguez, Luz Maria; Szabo, Eva; Rosenberg, Daniel W; Lipkin, Steven M

    2015-03-01

    Colorectal cancer progresses through multiple distinct stages that are potentially amenable to chemopreventative intervention. Epidermal growth factor receptor (EGFR) inhibitors are efficacious in advanced tumors including colorectal cancer. There is significant evidence that EGFR also plays important roles in colorectal cancer initiation, and that EGFR inhibitors block tumorigenesis. We performed a double-blind randomized clinical trial to test whether the EGFR inhibitor erlotinib given for up to 30 days had an acceptable safety and efficacy profile to reduce EGFR signaling biomarkers in colorectal aberrant crypt foci (ACF), a subset of which progress to colorectal cancer, and normal rectal tissue. A total of 45 patients were randomized to one of three erlotinib doses (25, 50, and 100 mg) with randomization stratified by nonsteroidal anti-inflammatory drug (NSAID) use. There were no unanticipated adverse events with erlotinib therapy. Erlotinib was detected in both normal rectal mucosa and ACFs. Colorectal ACF phosphorylated ERK (pERK), phosphorylated EGFR (pEGFR), and total EGFR signaling changes from baseline were modest and there was no dose response. Overall, this trial did not meet is primary efficacy endpoint. Colorectal EGFR signaling inhibition by erlotinib is therefore likely insufficient to merit further studies without additional prescreening stratification or potentially longer duration of use.

  11. Cohesin and the nucleolus constrain the mobility of spontaneous repair foci.

    Science.gov (United States)

    Dion, Vincent; Kalck, Véronique; Seeber, Andrew; Schleker, Thomas; Gasser, Susan M

    2013-11-01

    The regulation of chromatin mobility in response to DNA damage is important for homologous recombination in yeast. Anchorage reduces rates of recombination, whereas increased chromatin mobility correlates with more efficient homology search. Here we tracked the mobility and localization of spontaneous S-phase lesions bound by Rad52, and find that these foci have reduced movement, unlike enzymatically induced double-strand breaks. Moreover, spontaneous repair foci are positioned in the nuclear core, abutting the nucleolus. We show that cohesin and nucleolar integrity constrain the mobility of these foci, consistent with the notion that spontaneous, S-phase damage is preferentially repaired from the sister chromatid.

  12. The potential role of hydrogen energy in India and Western Europe

    NARCIS (Netherlands)

    van Ruijven, B.J.; Lakshmikanth, H.D.; van Vuuren, D.P.; de Vries, B.

    2008-01-01

    We used the TIMER energy model to explore the potential role of hydrogen in the energy systems of India and Western Europe, looking at the impacts on its main incentives: climate policy, energy security and urban air pollution. We found that hydrogen will not play a major role in both regions withou

  13. Media Impact on Fright Reactions and Belief in UFOs: The Potential Role of Mental Imagery.

    Science.gov (United States)

    Sparks, Glenn G.; And Others

    1995-01-01

    Explores the potential role of mental imagery for media effects in emotional responses to frightening mass media, and in the effects of the media on beliefs in UFOs. Finds that individual differences in vividness of mental imagery may play a crucial role in moderating both types of media impact. (SR)

  14. Azoxymethane-induced rat aberrant crypt foci: Relevance in studying chemoprevention of colon cancer

    Institute of Scientific and Technical Information of China (English)

    Jayadev Raju

    2008-01-01

    The pathogenesis of colon cancer involves sequential and multistep progression of epithelial cells initiated to a cancerous state with defined precancerous intermediaries.Aberrant crypt foci (ACF) represent the earliest identifiable intermediate precancerous lesions during colon carcinogenesis in both laboratory animals and humans.ACF are easily induced by colon-specific carcinogens in rodents and can be used to learn more about the process of colon carcinogenesis.For over two decades,since its first discovery,azoxymethane(AOM)-induced rodent ACF have served as surrogate biomarkers in the screening of various anticarcinogens and carcinogens.Several dietary constituents and phytochemicals have been tested for their colon cancer chemopreventive efficacy using the ACF system.There has been substantial effort in defining and refining ACF in terms of understanding their molecular make-up,and extensive research in this field is currently in progress.In chemoprevention studies,AOM-induced rat ACF have been very successful as biomarkers,and have provided several standardized analyses of data.There have been several studies that have reported that ACF data do not correlate to actual colon tumor outcome,however,and hence there has been an ambiguity about their role as biomarkers.The scope of this mini-review is to provide valuable insights and limitations of AOM-induced rat ACF as biomarkers in colon cancer chemoprevention studies.The role of the dynamics and biological heterogeneity of ACF is critical in understanding them as biomarkers in chemoprevention studies.

  15. Extracellular Vesicles: Role in Inflammatory Responses and Potential Uses in Vaccination in Cancer and Infectious Diseases

    Directory of Open Access Journals (Sweden)

    João Henrique Campos

    2015-01-01

    Full Text Available Almost all cells and organisms release membrane structures containing proteins, lipids, and nucleic acids called extracellular vesicles (EVs, which have a wide range of functions concerning intercellular communication and signaling events. Recently, the characterization and understanding of their biological role have become a main research area due to their potential role in vaccination, as biomarkers antigens, early diagnostic tools, and therapeutic applications. Here, we will overview the recent advances and studies of Evs shed by tumor cells, bacteria, parasites, and fungi, focusing on their inflammatory role and their potential use in vaccination and diagnostic of cancer and infectious diseases.

  16. mRNA decay proteins are targeted to poly(A+ RNA and dsRNA-containing cytoplasmic foci that resemble P-bodies in Entamoeba histolytica.

    Directory of Open Access Journals (Sweden)

    Itzel López-Rosas

    Full Text Available In higher eukaryotes, mRNA degradation and RNA-based gene silencing occur in cytoplasmic foci referred to as processing bodies (P-bodies. In protozoan parasites, the presence of P-bodies and their putative role in mRNA decay have yet to be comprehensively addressed. Identification of P-bodies might provide information on how mRNA degradation machineries evolved in lower eukaryotes. Here, we used immunofluorescence and confocal microscopy assays to investigate the cellular localization of mRNA degradation proteins in the human intestinal parasite Entamoeba histolytica and found evidence of the existence of P-bodies. Two mRNA decay factors, namely the EhXRN2 exoribonuclease and the EhDCP2 decapping enzyme, were localized in cytoplasmic foci in a pattern resembling P-body organization. Given that amoebic foci appear to be smaller and less rounded than those described in higher eukaryotes, we have named them "P-body-like structures". These foci contain additional mRNA degradation factors, including the EhCAF1 deadenylase and the EhAGO2-2 protein involved in RNA interference. Biochemical analysis revealed that EhCAF1 co-immunoprecipitated with EhXRN2 but not with EhDCP2 or EhAGO2-2, thus linking deadenylation to 5'-to-3' mRNA decay. The number of EhCAF1-containing foci significantly decreased after inhibition of transcription and translation with actinomycin D and cycloheximide, respectively. Furthermore, results of RNA-FISH assays showed that (i EhCAF1 colocalized with poly(A(+ RNA and (ii during silencing of the Ehpc4 gene by RNA interference, EhAGO2-2 colocalized with small interfering RNAs in cytoplasmic foci. Our observation of decapping, deadenylation and RNA interference proteins within P-body-like foci suggests that these structures have been conserved after originating in the early evolution of eukaryotic lineages. To the best of our knowledge, this is the first study to report on the localization of mRNA decay proteins within P

  17. Dynamics of Vector-Host Interactions in Avian Communities in Four Eastern Equine Encephalitis Virus Foci in the Northeastern U.S.

    Directory of Open Access Journals (Sweden)

    Goudarz Molaei

    2016-01-01

    empirically informed mathematical model for EEE virus transmission using Cs. melanura abundance and preferred and non-preferred avian hosts. To our knowledge this is the first mathematical model for EEE virus, a pathogen with many potential hosts, in the northeastern U.S. We measured strong feeding preferences for a number of avian species based on the proportion of mosquito blood meals identified from these bird species in relation to their observed frequencies. These included: American Robin, Tufted Titmouse, Common Grackle, Wood Thrush, Chipping Sparrow, Black-capped Chickadee, Northern Cardinal, and Warbling Vireo. We found that these bird species, most notably Wood Thrush, play a dominant role in supporting EEE virus amplification. It is also noteworthy that the competence of some of the aforementioned avian species for EEE virus has not been established. Our findings indicate that heterogeneity induced by mosquito host preference, is a key mediator of the epizootic transmission of vector-borne pathogens.Detailed knowledge of the vector-host interactions of mosquito populations in nature is essential for evaluating their vectorial capacity and for assessing the role of individual vertebrates as reservoir hosts involved in the maintenance and amplification of zoonotic agents of human diseases. Our study clarifies the host associations of Cs. melanura in four EEE virus foci in the northeastern U.S., identifies vector host preferences as the most important transmission parameter, and quantifies the contribution of preference-induced contact heterogeneity to enzootic transmission. Our study identifies Wood Thrush, American Robin and a few avian species that may serve as superspreaders of EEE virus. Our study elucidates spatiotemporal host species utilization by Cs. melanura in relation to avian host community. This research provides a basis to better understand the involvement of Cs. melanura and avian hosts in the transmission and ecology of EEE virus and the risk of human

  18. High levels of γ-H2AX foci and cell membrane oxidation in adolescents with type 1 diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Giovannini, Caterina [Unità di Genetica, Dipartimento di Biologia, Pisa University, Pisa (Italy); Piaggi, Simona [Sezione di Patologia Sperimentale, Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Pisa University, Pisa (Italy); Federico, Giovanni [Unità di Endocrinologia Pediatrica e Diabete, Dipartimento di Medicina Clinica e Sperimentale Pisa University, Pisa (Italy); Scarpato, Roberto, E-mail: roberto.scarpato@unipi.it [Unità di Genetica, Dipartimento di Biologia, Pisa University, Pisa (Italy)

    2014-12-15

    Highlights: • We aimed to detect signs of very early damage in peripheral cells of T1DM adolescents. • T1DM patients had high levels of oxidized cells and reduced expression of iNOS and NO. • Highly mutagenic lesions were markedly increased in the diabetic group, mainly in females. • The observed damage might increase the risk of cancer in the patients later in life. - Abstract: Oxidative stress caused by an excess of free radicals is implicated in the pathogenesis and development of type 1 diabetes mellitus (T1DM) and, in turn, it can lead to genome damage, especially in the form of DNA double-strand break (DSB). The DNA DSB is a potentially carcinogenic lesion for human cells. Thus, we aimed to evaluate whether the level of oxidative stress was increased in peripheral blood lymphocytes of a group of affected adolescents. In 35 T1DM adolescents and 19 healthy controls we assessed: (1) spontaneous and H{sub 2}O{sub 2}-induced oxidation of cell membrane using a fluorescence lipid probe; (2) spontaneous and LPS-induced expression of iNOS protein and indirect NO determination via cytofluorimetric analysis of O{sub 2}{sup −}; (3) immunofluorescent detection of the basal level of histone H2AX phosphorylation (γ-H2AX foci), a well-validated marker of DNA DSB. In T1DM, the frequencies of oxidized cells, both spontaneous and H{sub 2}O{sub 2}-induced (47.13 ± 0.02) were significantly higher than in controls (35.90 ± 0.03). Patients showed, in general, both a reduced iNOS expression and production of NO. Furthermore, the level of spontaneous nuclear damage, quantified as γ-H2AX foci, was markedly increased in T1DM adolescents (6.15 ± 1.08% of γ-H2AX{sup +} cells; 8.72 ± 2.14 γ-H2AXF/n; 9.26 ± 2.37 γ-H2AXF/np), especially in females. In the present study, we confirmed the role that oxidative stress plays in the disease damaging lipids of cell membrane and, most importantly, causing genomic damage in circulating white blood cells of affected adolescents

  19. β-HPV 5 and 8 E6 disrupt homology dependent double strand break repair by attenuating BRCA1 and BRCA2 expression and foci formation.

    Directory of Open Access Journals (Sweden)

    Nicholas A Wallace

    2015-03-01

    Full Text Available Recent work has explored a putative role for the E6 protein from some β-human papillomavirus genus (β-HPVs in the development of non-melanoma skin cancers, specifically β-HPV 5 and 8 E6. Because these viruses are not required for tumor maintenance, they are hypothesized to act as co-factors that enhance the mutagenic capacity of UV-exposure by disrupting the repair of the resulting DNA damage. Supporting this proposal, we have previously demonstrated that UV damage signaling is hindered by β-HPV 5 and 8 E6 resulting in an increase in both thymine dimers and UV-induced double strand breaks (DSBs. Here we show that β-HPV 5 and 8 E6 further disrupt the repair of these DSBs and provide a mechanism for this attenuation. By binding and destabilizing a histone acetyltransferase, p300, β-HPV 5 and 8 E6 reduce the enrichment of the transcription factor at the promoter of two genes critical to the homology dependent repair of DSBs (BRCA1 and BRCA2. The resulting diminished BRCA1/2 transcription not only leads to lower protein levels but also curtails the ability of these proteins to form repair foci at DSBs. Using a GFP-based reporter, we confirm that this reduced foci formation leads to significantly diminished homology dependent repair of DSBs. By deleting the p300 binding domain of β-HPV 8 E6, we demonstrate that the loss of robust repair is dependent on viral-mediated degradation of p300 and confirm this observation using a combination of p300 mutants that are β-HPV 8 E6 destabilization resistant and p300 knock-out cells. In conclusion, this work establishes an expanded ability of β-HPV 5 and 8 E6 to attenuate UV damage repair, thus adding further support to the hypothesis that β-HPV infections play a role in skin cancer development by increasing the oncogenic potential of UV exposure.

  20. Residual γH2AX foci as an indication of lethal DNA lesions

    Directory of Open Access Journals (Sweden)

    Banuelos C Adriana

    2010-01-01

    Full Text Available Abstract Background Evidence suggests that tumor cells exposed to some DNA damaging agents are more likely to die if they retain microscopically visible γH2AX foci that are known to mark sites of double-strand breaks. This appears to be true even after exposure to the alkylating agent MNNG that does not cause direct double-strand breaks but does produce γH2AX foci when damaged DNA undergoes replication. Methods To examine this predictive ability further, SiHa human cervical carcinoma cells were exposed to 8 DNA damaging drugs (camptothecin, cisplatin, doxorubicin, etoposide, hydrogen peroxide, MNNG, temozolomide, and tirapazamine and the fraction of cells that retained γH2AX foci 24 hours after a 30 or 60 min treatment was compared with the fraction of cells that lost clonogenicity. To determine if cells with residual repair foci are the cells that die, SiHa cervical cancer cells were stably transfected with a RAD51-GFP construct and live cell analysis was used to follow the fate of irradiated cells with RAD51-GFP foci. Results For all drugs regardless of their mechanism of interaction with DNA, close to a 1:1 correlation was observed between clonogenic surviving fraction and the fraction of cells that retained γH2AX foci 24 hours after treatment. Initial studies established that the fraction of cells that retained RAD51 foci after irradiation was similar to the fraction of cells that retained γH2AX foci and subsequently lost clonogenicity. Tracking individual irradiated live cells confirmed that SiHa cells with RAD51-GFP foci 24 hours after irradiation were more likely to die. Conclusion Retention of DNA damage-induced γH2AX foci appears to be indicative of lethal DNA damage so that it may be possible to predict tumor cell killing by a wide variety of DNA damaging agents simply by scoring the fraction of cells that retain γH2AX foci.

  1. Localized air foci in the lower thorax in the patients with pneumothorax: Skip pneumothoraces

    Energy Technology Data Exchange (ETDEWEB)

    Higuchi, Takeshi, E-mail: higuchi@hosp.niigata.niigata.jp [Department of Diagnostic Radiology, Niigata City General Hospital, 463-7 Chuo-ku, Shumoku, Niigata 950-1197 (Japan); Takahashi, Naoya, E-mail: nandtr@hosp.niigata.niigata.jp [Department of Diagnostic Radiology, Niigata City General Hospital, 463-7 Chuo-ku, Shumoku, Niigata 950-1197 (Japan); Kiguchi, Takao, E-mail: takakig@gmail.com [Department of Diagnostic Radiology, Niigata City General Hospital, 463-7 Chuo-ku, Shumoku, Niigata 950-1197 (Japan); Shiotani, Motoi, E-mail: Shiotani14@gmail.com [Department of Radiology, Niigata Cancer Center Hospital, 2-15-3 Chuo-ku, Kawagishicho, Niigata 951-8566 (Japan); Maeda, Haruo, E-mail: h-maeda@hosp.niigata.niigata.jp [Department of Diagnostic Radiology, Niigata City General Hospital, 463-7 Chuo-ku, Shumoku, Niigata 950-1197 (Japan)

    2013-08-15

    Purpose: To investigate the characteristics and imaging features of localized air foci in the lower thorax in patients with pneumothorax using thin-section multidetector computed tomography. Materials and methods: Of 10,547 consecutive CT examinations comprising the chest, the CT scans of 146 patients with ordinary pneumothoraces were identified and retrospectively evaluated. The study group included 110 male and 36 female patients (mean age, 50 years; range, 1–93 years). All examinations were performed at our institution between January 2009 and December 2009. Cause of pneumothorax was classified as traumatic or non-traumatic. Localized air foci in the lower thorax were defined as being localized air collections in the lower thorax that did not appear to be adjacent to the lung. If these criteria were met, the shape, size, location laterality, and number of foci were evaluated. Associations with trauma, sex, severity of the pneumothorax, and laterality were evaluated using the χ{sup 2} test. All P values <0.05 were considered significant. Results: Localized air foci in the lower thorax presented as slit-like or small ovoid air collections in the lowest part of the pleural space. These foci were observed in 79/146 (54.1%) patients. The traumatic pneumothoraces group showed a higher prevalence of these features than the non-traumatic group. Some foci that were situated in the anterior part mimicked the appearance of free intraperitoneal air. Conclusion: Patients with pneumothorax commonly had localized air foci in the lower thorax. Because such foci can mimic pneumoperitoneum, accurate recognition of them is required to avoid confusion with free intraperitoneal air, especially in traumatic cases.

  2. The role of litter beetles as potential reservoir for Salmonella enterica and thermophilic Campylobacter spp. between broiler flocks

    DEFF Research Database (Denmark)

    Skov, M.N.; Spencer, A.G.; Hald, Birthe

    2004-01-01

    We evaluated the role of beetles infesting broiler chicken rearing facilities as potential reservoirs for Salmonella enterica infections between successive broiler flocks. In addition, their role as potential reservoirs for thermophilic Campylobacter spp. was also investigated. Fourteen broiler h...

  3. Linking child maltreatment history with child abuse potential: Relative roles of maltreatment types

    Directory of Open Access Journals (Sweden)

    Mitkovic-Voncina Marija

    2014-01-01

    Full Text Available The independent roles of each childhood maltreatment type on child abuse potential in adults have been insufficiently explored and are inconsistent, with dissociation as one of the possible suggested mediators of intergenerational child abuse. We investigated these effects among 164 non-clinical adult parents, who filled in general questionnaires: Childhood Trauma Questionnaire (CTQ, Child Abuse Potential Inventory (CAPI and Dissociative Experience Scale (DES. Among all maltreatment types (emotional, physical and sexual abuse, emotional and physical neglect, emotional abuse was the only independent predictor in the regression model of child abuse potential. The relationship between emotional abuse history and child abuse potential was partially mediated by dissociation. The findings could speak in favor of the potentially unique detrimental role of emotional abuse in intergenerational maltreatment, with dissociation as one of the possible mechanisms.

  4. Biophysical regulation of Chlamydia pneumoniae-infected monocyte recruitment to atherosclerotic foci

    Science.gov (United States)

    Evani, Shankar J.; Ramasubramanian, Anand K.

    2016-01-01

    Chlamydia pneumoniae infection is implicated in atherosclerosis although the contributory mechanisms are poorly understood. We hypothesize that C. pneumoniae infection favors the recruitment of monocytes to atherosclerotic foci by altering monocyte biophysics. Primary, fresh human monocytes were infected with C. pneumoniae for 8 h, and the interactions between monocytes and E-selectin or aortic endothelium under flow were characterized by video microscopy and image analysis. The distribution of membrane lipid rafts and adhesion receptors were analyzed by imaging flow cytometry. Infected cells rolled on E-selectin and endothelial surfaces, and this rolling was slower, steady and uniform compared to uninfected cells. Infection decreases cholesterol levels, increases membrane fluidity, disrupts lipid rafts, and redistributes CD44, which is the primary mediator of rolling interactions. Together, these changes translate to higher firm adhesion of infected monocytes on endothelium, which is enhanced in the presence of LDL. Uninfected monocytes treated with LDL or left untreated were used as baseline control. Our results demonstrate that the membrane biophysical changes due to infection and hyperlipidemia are one of the key mechanisms by which C. pneumoniae can exacerbate atherosclerotic pathology. These findings provide a framework to characterize the role of ‘infectious burden’ in the development and progression of atherosclerosis.

  5. Seasonal Variation in Biting Rates of Simulium damnosum sensu lato, Vector of Onchocerca volvulus, in Two Sudanese Foci.

    Directory of Open Access Journals (Sweden)

    Isam M A Zarroug

    Full Text Available The abundance of onchocerciasis vectors affects the epidemiology of disease in Sudan, therefore, studies of vector dynamics are crucial for onchocerciasis control/elimination programs. This study aims to compare the relative abundance, monthly biting-rates (MBR and hourly-based distribution of onchocerciasis vectors in Abu-Hamed and Galabat foci. These seasonally-based factors can be used to structure vector control efforts to reduce fly-biting rates as a component of onchocerciasis elimination programs.A cross-sectional study was conducted in four endemic villages in Abu-Hamed and Galabat foci during two non-consecutive years (2007-2008 and 2009-2010. Both adults and aquatic stages of the potential onchocerciasis vector Simulium damnosum sensu lato were collected following standard procedures during wet and dry seasons. Adult flies were collected using human landing capture for 5 days/month. The data was recorded on handheld data collection sheets to calculate the relative abundance, MBR, and hourly-based distribution associated with climatic factors. The data analysis was carried out using ANOVA and Spearman rank correlation tests.Data on vector surveillance revealed higher relative abundance of S. damnosum s.l. in Abu- Hamed (39,934 flies than Galabat (8,202 flies. In Abu-Hamed, vector populations increased in January-April then declined in June-July until they disappeared in August-October. Highest black fly density and MBR were found in March 2007 (N = 9,444, MBR = 58,552.8 bites/person/month, and March 2010 (N = 2,603, MBR = 16,138.6 bites/person/month while none of flies were collected in August-October (MBR = 0 bites/person/month. In Galabat, vectors increased in September-December, then decreased in February-June. The highest vector density and MBR were recorded in September 2007 (N = 1,138, MBR = 6,828 bites/person/month and September 2010 (N = 1,163, MBR = 6,978 bites/person/month, whereas, none appeared in collection from April to

  6. Role of MicroRNAs in carcinogenesis that potential for biomarker of endometrial cancer

    OpenAIRE

    Widodo1); Djati, Muhammad Sasmito; Rifa'i, Muhaimin

    2016-01-01

    The non-invasive diagnostic tool for early detection of endometrial cancer still limited. The etiology of this disease is believed to be associated with disharmony hormone production. One predominant factor that regulate hormone production is microRNA (miRNAs). Some studies reported that miRNAs play a significant role in the process carcinogenesis. We have identified 12 of miRNAs that potentially have a role in controlling endometrial carcinogenesis pathways. Further analysis suggested that t...

  7. Zika virus causes supernumerary foci with centriolar proteins and impaired spindle positioning

    Science.gov (United States)

    Wolf, Benita; Diop, Fodé; Ferraris, Pauline; Wichit, Sineewanlaya; Busso, Coralie; Missé, Dorothée

    2017-01-01

    Zika virus (ZIKV) causes congenital microcephaly. Although ZIKV can impair cell cycle progression and provoke apoptosis, which probably contributes to disease aetiology through depletion of neural progenitor cells, additional cellular mechanisms may be important. Here, we investigated whether ZIKV infection alters centrosome number and spindle positioning, because such defects are thought to be at the root of inherited primary autosomal recessive microcephaly (MCPH). In addition to HeLa cells, in which centrosome number and spindle positioning can be well monitored, we analysed retinal epithelial cells (RPE-1), as well as brain-derived microglial (CHME-5) and neural progenitor (ReN) cells, using immunofluorescence. We established that ZIKV infection leads to supernumerary foci containing centriolar proteins that in some cases drive multipolar spindle assembly, as well as spindle positioning defects in HeLa, RPE-1 and CHME-5 cells, but not in ReN cells. We uncovered similar phenotypes in HeLa cells upon infection with dengue virus (DENV-2), another flavivirus that does not target brain cells and does not cause microcephaly. We conclude that infection with Flaviviridae can increase centrosome numbers and impair spindle positioning, thus potentially contributing to microcephaly in the case of Zika. PMID:28100662

  8. On the role of the Coulomb potential in strong field atomic ionization dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Tetchou Nganso, H.M. [Laboratoire de Physique Atomique, Moleculaire et Optique (PAMO), Universite Catholique de Louvain, 2 Chemin du Cyclotron, B-1348 Louvain-la-Neuve (Belgium)], E-mail: htetchou@yahoo.com; Giraud, S. [Ecole Normale Superieure de Cachan, Antenne de Bretagne, Avenue Robert Schuman, Campus de Ker Lann, F-35170 Bruz (France); Piraux, B. [Laboratoire de Physique Atomique, Moleculaire et Optique (PAMO), Universite Catholique de Louvain, 2 Chemin du Cyclotron, B-1348 Louvain-la-Neuve (Belgium); Popov, Yu.V. [Nuclear Physics Institute, Moscow State University, Moscow 119992 (Russian Federation); Kwato Njock, M.G. [Centre for Atomic Molecular Physics and Quantum Optics (CEPAMOQ), Faculty of Science, University of Douala, P.O. Box 8580 Douala (Cameroon)

    2007-10-15

    In this paper, we present a model aimed at exploring the role of the Coulomb potential in the mechanism of ionization of atomic hydrogen exposed to a strong low frequency pulsed laser field. Our approach is based on the solution of the time-dependent Schroedinger equation in momentum space. Although we are in a frequency and intensity regime where tunnelling is expected to dominate, our results indicate that the atomic structure associated to the Coulomb potential plays a significant role for low energy ejected electrons.

  9. Localized air foci in the lower thorax in the patients with pneumothorax: skip pneumothoraces.

    Science.gov (United States)

    Higuchi, Takeshi; Takahashi, Naoya; Kiguchi, Takao; Shiotani, Motoi; Maeda, Haruo

    2013-08-01

    To investigate the characteristics and imaging features of localized air foci in the lower thorax in patients with pneumothorax using thin-section multidetector computed tomography. Of 10,547 consecutive CT examinations comprising the chest, the CT scans of 146 patients with ordinary pneumothoraces were identified and retrospectively evaluated. The study group included 110 male and 36 female patients (mean age, 50 years; range, 1-93 years). All examinations were performed at our institution between January 2009 and December 2009. Cause of pneumothorax was classified as traumatic or non-traumatic. Localized air foci in the lower thorax were defined as being localized air collections in the lower thorax that did not appear to be adjacent to the lung. If these criteria were met, the shape, size, location laterality, and number of foci were evaluated. Associations with trauma, sex, severity of the pneumothorax, and laterality were evaluated using the χ(2) test. All P values thorax presented as slit-like or small ovoid air collections in the lowest part of the pleural space. These foci were observed in 79/146 (54.1%) patients. The traumatic pneumothoraces group showed a higher prevalence of these features than the non-traumatic group. Some foci that were situated in the anterior part mimicked the appearance of free intraperitoneal air. Patients with pneumothorax commonly had localized air foci in the lower thorax. Because such foci can mimic pneumoperitoneum, accurate recognition of them is required to avoid confusion with free intraperitoneal air, especially in traumatic cases. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Sense and Antisense DMPK RNA Foci Accumulate in DM1 Tissues during Development.

    Directory of Open Access Journals (Sweden)

    Lise Michel

    Full Text Available Myotonic dystrophy type 1 (DM1 is caused by an unstable expanded CTG repeat located within the DMPK gene 3'UTR. The nature, severity and age at onset of DM1 symptoms are very variable in patients. Different forms of the disease are described, among which the congenital form (CDM is the most severe. Molecular mechanisms of DM1 are well characterized for the adult form and involve accumulation of mutant DMPK RNA forming foci in the nucleus. These RNA foci sequester proteins from the MBNL family and deregulate CELF proteins. These proteins are involved in many cellular mechanisms such as alternative splicing, transcriptional, translational and post-translational regulation miRNA regulation as well as mRNA polyadenylation and localization. All these mechanisms can be impaired in DM1 because of the deregulation of CELF and MBNL functions. The mechanisms involved in CDM are not clearly described. In order to get insight into the mechanisms underlying CDM, we investigated if expanded RNA nuclear foci, one of the molecular hallmarks of DM1, could be detected in human DM1 fetal tissues, as well as in embryonic and neonatal tissues from transgenic mice carrying the human DMPK gene with an expanded CTG repeat. We observed very abundant RNA foci formed by sense DMPK RNA and, to a lesser extent, antisense DMPK RNA foci. Sense DMPK RNA foci clearly co-localized with MBNL1 and MBNL2 proteins. In addition, we studied DMPK sense and antisense expression during development in the transgenic mice. We found that DMPK sense and antisense transcripts are expressed from embryonic and fetal stages in heart, muscle and brain and are regulated during development. These results suggest that mechanisms underlying DM1 and CDM involved common players including toxic expanded RNA forming numerous nuclear foci at early stages during development.

  11. The Investigation of Drug Addiction Potential among Medical Students: Role of Subjective Components of Anger

    Directory of Open Access Journals (Sweden)

    A Agha Yusefi

    2016-02-01

    Full Text Available Objective: Given that drug addiction is not merely related to a specific individual or group, and few studies have investigated the role of anger in the development of drug addiction, this study was done to investigate the role of the components of anger in predicting addiction potential. Method: A descriptive-correlation research design was used for the conduct of this study. The number of 309 medical students in Kermanshah city was selected using stratified cluster sampling and completed Spielberger's State-Trait Anger Scale (STAS and Zargar’s addiction potential questionnaire. Results: The results showed that ate anger, trait anger, anger expression-out (AXO, anger expression-in (AXI, the overall index for the expression of anger were significantly associated with addiction potential. Similarly, anger control-out (ACO, anger control-in (ACI were correlated with addiction potential. In addition, the regression analysis results indicated that the components of state anger and anger expression-in (AXI together can predict 35% of changes related to addiction potential. Conclusion: State anger and anger expression-in (AXI as subjective components of anger have a significant role in predicting addiction potential among medical students. Anger management programs for medical students, as the most important segment of the society in the field of public health, are recommended to assign more credit to these two components.

  12. Do field-free electromagnetic potentials play a role in biology?

    Science.gov (United States)

    Szasz, A; Vincze, G; Andocs, G; Szasz, O

    2009-01-01

    All bio-systems are imperfect dielectrics. Their general properties however cannot be described by conventional simple electrodynamics; the system is more complex. A central question in our present paper is centered on a controversial debate of the possible effect of the zero fields (only potentials exist). We show that the identical use of the "field-free," "curl-free," and "force-free" terminologies is incorrect, there have definitely different meanings. It is shown that the effective electro-dynamical parameters that describe and modify living systems are the potentials and not the fields. We discuss how the potentials have a role in biological processes even in field-free cases.

  13. Role of COX-2 in the regulation of the metastatic potential of human breast tumor cells

    Directory of Open Access Journals (Sweden)

    M. A. Taipov

    2014-01-01

    Full Text Available The expression of СOX-2, VEGF, VEGFR-1, VEGFR-2, VEGFR-3, EGFR, endoglin (СD105, and IL-6 was analyzed in the human breast tumor cells having a varying metastatic potential. The role of these factors in the regulation of the metastatic potential of breast cancer cells, as well as that of COX-2 in the regulation of metastatic processes at the cellular level were examined. The potential capacity of human breast tumor cells to elaborate factors that stimulate tumor growth, angiogenesis, and metastasis was evaluated.

  14. Developing Effective Earthquake Risk Reduction Strategies: The Potential Role of Academic Institutions in Lebanon

    Science.gov (United States)

    Baytiyeh, Hoda

    2015-01-01

    Lebanon faces the risk of powerful earthquakes with potentially devastating effects. However, the Lebanese people in general have not yet recognized this risk, as current educational programs and government officials have failed to inform them about it. This article discusses the essential role that Lebanese institutions of higher education should…

  15. Futurism: Its Potential and Actual Role in Master of Business Administration (MBA) Education

    Science.gov (United States)

    Peterson, Robin T.

    2006-01-01

    In this article, the author highlights the potential role of "futurism" in master of business administration (MBA) curricula and the conceivable offerings of futurism to business planners. This article serves as a corollary to educators in MBA business education and concerns to the nature of futurism, the benefits of futurism to…

  16. Futurism: Its Potential and Actual Role in Master of Business Administration (MBA) Education

    Science.gov (United States)

    Peterson, Robin T.

    2006-01-01

    In this article, the author highlights the potential role of "futurism" in master of business administration (MBA) curricula and the conceivable offerings of futurism to business planners. This article serves as a corollary to educators in MBA business education and concerns to the nature of futurism, the benefits of futurism to managerial…

  17. Developing Effective Earthquake Risk Reduction Strategies: The Potential Role of Academic Institutions in Lebanon

    Science.gov (United States)

    Baytiyeh, Hoda

    2015-01-01

    Lebanon faces the risk of powerful earthquakes with potentially devastating effects. However, the Lebanese people in general have not yet recognized this risk, as current educational programs and government officials have failed to inform them about it. This article discusses the essential role that Lebanese institutions of higher education should…

  18. Indigenous Higher Education: The Role of Universities in Releasing the Potential

    Science.gov (United States)

    Andersen, Clair; Bunda, Tracey; Walter, Maggie

    2008-01-01

    The participation rate of Indigenous people in higher education is comparatively disparately low across all sectors. In this paper we examine the pivotal role of the university sector in addressing this inequity and releasing the potential for increased Indigenous enrolment, participation and completion in higher education. Indigenous higher…

  19. Spatial distribution of schistosomiasis foci on Itamaracá Island, Pernambuco, Brazil

    Directory of Open Access Journals (Sweden)

    CS Barbosa

    2004-08-01

    Full Text Available Acute cases of schistosomiasis have been found on the coastal area of Pernambuco, Brazil, due to environmental disturbances and disorderly occupation of the urban areas. This study identifies and spatially marks the main foci of the snail host species, Biomphalaria glabrata on Itamaracá Island. The chaotic occupation of the beach resorts has favoured the emergence of transmission foci, thus exposing residents and tourists to the risk of infection. A database covering five years of epidemiological investigation on snails infected by Schistosoma mansoni in the island was produced with information from the geographic positioning of the foci, number of snails collected, number of snails tested positive, and their infection rate. The spatial position of the foci were recorded through the Global Positioning System (GPS, and the geographical coordinates were imported by AutoCad. The software packages ArcView and Spring were used for data processing and spatial analysis. AutoCad 2000 was used to plot the pairs of coordinates obtained from GPS. Between 1998 and 2002 5009 snails, of which 12.2% were positive for S. mansoni, were collected in Forte Beach. A total of 27 foci and areas of environmental risk were identified and spatially analyzed allowing the identification of the areas exposed to varying degrees of risk.

  20. A rat liver foci promotion study with 50-Hz magnetic fields.

    Science.gov (United States)

    Rannug, A; Holmberg, B; Mild, K H

    1993-08-01

    To investigate the possible tumor-promoting effect of magnetic fields (MF), we have performed two liver foci bioassays in rats which were exposed to MF at four flux density levels (0.5 microT, 5 microT, 0.05 mT, and 0.5 mT). The MF were generated in exposure equipment consisting of copper coils surrounding racks with animal cages and giving homogenous horizontal 50-Hz magnetic fields. Rats previously submitted to partial hepatectomy and diethylnitrosamine treatment were exposed to MF for 12 weeks. Exposed and control rats were kept in separate rooms. As a positive control phenobarbital (PB) was administered for 12 weeks. The number, area, and volume of foci expressing gamma-glutamyl transpeptidase (GGT) and glutathione S-transferase (GST-p) were evaluated. The body weight gains and relative liver weights of MF-exposed rats were not different as compared to control rats. There was a slight increase in GGT-staining foci, but not in GST-p-staining foci, in the groups exposed to flux densities of 0.5 microT and 0.05 mT compared to the control group in the first experiment. The number of both GGT- and GST-p-staining foci in the livers of all MF-exposed groups were, however, within the control range when the results of the two experiments were considered together.

  1. Tall gastrodis tuber combined with antiepileptic drugs repairs abnormal perfusion foci in focal epilepsy

    Institute of Scientific and Technical Information of China (English)

    Weimin Wang; Zhenyu Fan; Yongqin Zhang; Yuxia Yang; Yaqing Liu; Xiaoli Dang; Wenjun Song; Yinping Wu; Jiang Ye

    2013-01-01

    One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 (34% of 86); the total number of abnormal perfusion foci decreased by 52 (36%) and changes in abnormal foci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy. Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.

  2. Formation of Subnuclear Foci Is a Unique Spatial Behavior of Mating MAPKs during Hyperosmotic Stress

    Directory of Open Access Journals (Sweden)

    Simon E. Vidal

    2013-02-01

    Full Text Available The assembly of signaling components and transcription factors in ordered subcellular structures is increasingly implicated as an important regulatory strategy for modulating the activity of cellular pathways. Here, we document the inducible formation of subnuclear foci formed by two mitogen-activated protein kinases (MAPKs in Saccharomyces cerevisiae upon hyperosmotic stress. Specifically, we demonstrate that activation of the hyperosmotic stress response pathway induces the mating pathway MAPK Fus3 and the filamentation pathway MAPK Kss1 to form foci in the nucleus that are organized by their shared downstream transcription factor Ste12. Foci formation of colocalized Ste12, Fus3, and Kss1 requires the kinase activity of the hyperosmotic response MAPK Hog1 and correlates with attenuated signaling in the mating pathway. Conversely, activation of the mating pathway prevents foci formation upon subsequent hyperosmotic stress. These results suggest that Hog1-mediated spatial localization of Fus3 and Ste12 into subnuclear foci could contribute to uncoupling the pheromone and osmolarity pathways, which share signaling components, under high-osmolarity conditions.

  3. Potential role of p53 mutation in chemical hepatocarcinogenesis of rats

    Institute of Scientific and Technical Information of China (English)

    Wei-Guo Deng; Yan Fu; Yu-Lin Li; Toshihiro Sugiyama

    2004-01-01

    AIM: Inactivation of p53 gene is one of the most frequent genetic alterations in carcinogenesis. The mutation status of p53 gene was analyzed, in order to understand the effect of p53 mutation on chemical hepatocarcinogenesis of rats.METHODS: During hepatocarcinogenesis of rats induced by 3′-methyl-4- dimethylaminoazobenzene (3′-Me-DAB),prehepatocarcinoma and hepatocarcinoma foci were collected by laser capture microdissection (LCMl), and quantitatively analyzed for levels of p53 mRNA by LightCyclerTM real-time RT-PCR and for mutations in p53 gene exons 5-8 by direct sequencing.RESULTS: Samples consisting of 44 precancerous foci and 24 cancerous foci were collected by LCMl. A quantitative analysis of p53 mRNA showed that p53 mRNA peaked at an early stage (week 6) in the prehepatocarcinoma lesion, more than ten times that of adjacent normal tissue, and gradually decreased from week 6 to week 24. The expression of p53 mRNA in adjacent normal tissue was significantly lower than that in prehepatocarcinoma. Similar to prehepatocarcinoma,p53 mRNA in cancer was markedly higher than that in adjacent normal tissue at week 12, and was closer to normal at week 24. Direct p53 gene sequencing showed that 35.3% (24/68) (9 precancer, 15 cancer) LCM samples exhibited point mutations, 20.5% of prehepatocarcinoma LCM samples presented missense mutations at exon 6/7 or/and 8, and was markedly lower than 62.5% of hepatocarcinoma ones (P<0.01). Mlutation of p53 gene formed the mutant hot spots at 5 codons. Positive immunostaining for p53 protein could be seen in prehepatocarcinoma and hepatocarcinoma foci at 24 weeks.CONCLUSION: p53 gene mutation is present in initial chemical hepatocarcinogenesis, and the mutation of p53 gene induced by 3′-Me-DAB is an important factor of hepatocarcinogenesis.

  4. The Opioid System in Temporal Lobe Epilepsy: Functional Role and Therapeutic Potential

    Directory of Open Access Journals (Sweden)

    Johannes Burtscher

    2017-08-01

    Full Text Available Temporal lobe epilepsy is considered to be one of the most common and severe forms of focal epilepsies. Patients often develop cognitive deficits and emotional blunting along the progression of the disease. The high incidence of resistance to antiepileptic drugs and a frequent lack of admissibility to surgery poses an unmet medical challenge. In the urgent quest of novel treatment strategies, neuropeptides are interesting candidates, however, their therapeutic potential has not yet been exploited. This review focuses on the functional role of the endogenous opioid system with respect to temporal lobe epilepsy, specifically in the hippocampus. The role of dynorphins and kappa opioid receptors (KOPr as modulators of neuronal excitability is well understood: both the reduced release of glutamate as well of postsynaptic hyperpolarization were shown in glutamatergic neurons. In line with this, low levels of dynorphin in humans and mice increase the risk of epilepsy development. The role of enkephalins is not understood so well. On one hand, some agonists of the delta opioid receptors (DOPr display pro-convulsant properties probably through inhibition of GABAergic interneurons. On the other hand, enkephalins play a neuro-protective role under hypoxic or anoxic conditions, most probably through positive effects on mitochondrial function. Despite the supposed absence of endorphins in the hippocampus, exogenous activation of the mu opioid receptors (MOPr induces pro-convulsant effects. Recently-expanded knowledge of the complex ways opioid receptors ligands elicit their effects (including biased agonism, mixed binding, and opioid receptor heteromers, opens up exciting new therapeutic potentials with regards to seizures and epilepsy. Potential adverse side effects of KOPr agonists may be minimized through functional selectivity. Preclinical data suggest a high potential of such compounds to control seizures, with a strong predictive validity toward human

  5. The Opioid System in Temporal Lobe Epilepsy: Functional Role and Therapeutic Potential.

    Science.gov (United States)

    Burtscher, Johannes; Schwarzer, Christoph

    2017-01-01

    Temporal lobe epilepsy is considered to be one of the most common and severe forms of focal epilepsies. Patients often develop cognitive deficits and emotional blunting along the progression of the disease. The high incidence of resistance to antiepileptic drugs and a frequent lack of admissibility to surgery poses an unmet medical challenge. In the urgent quest of novel treatment strategies, neuropeptides are interesting candidates, however, their therapeutic potential has not yet been exploited. This review focuses on the functional role of the endogenous opioid system with respect to temporal lobe epilepsy, specifically in the hippocampus. The role of dynorphins and kappa opioid receptors (KOPr) as modulators of neuronal excitability is well understood: both the reduced release of glutamate as well of postsynaptic hyperpolarization were shown in glutamatergic neurons. In line with this, low levels of dynorphin in humans and mice increase the risk of epilepsy development. The role of enkephalins is not understood so well. On one hand, some agonists of the delta opioid receptors (DOPr) display pro-convulsant properties probably through inhibition of GABAergic interneurons. On the other hand, enkephalins play a neuro-protective role under hypoxic or anoxic conditions, most probably through positive effects on mitochondrial function. Despite the supposed absence of endorphins in the hippocampus, exogenous activation of the mu opioid receptors (MOPr) induces pro-convulsant effects. Recently-expanded knowledge of the complex ways opioid receptors ligands elicit their effects (including biased agonism, mixed binding, and opioid receptor heteromers), opens up exciting new therapeutic potentials with regards to seizures and epilepsy. Potential adverse side effects of KOPr agonists may be minimized through functional selectivity. Preclinical data suggest a high potential of such compounds to control seizures, with a strong predictive validity toward human patients. The

  6. Carbohydrates in plant immunity and plant protection: roles and potential application as foliar sprays

    Directory of Open Access Journals (Sweden)

    Sophie eTrouvelot

    2014-11-01

    Full Text Available Increasing interest is devoted to carbohydrates for their roles in plant immunity. Some of them are elicitors of plant defenses whereas other ones act as signaling molecules in a manner similar to phytohormones. This review first describes the main classes of carbohydrates associated to plant immunity, their role and mode of action. More precisely, the state of the art about perception of PAMP, MAMP and DAMP type oligosaccharides is presented and examples of induced defense events are provided. A particular attention is paid to the structure / activity relationships of these compounds. The role of sugars as signaling molecules, especially in plant microbe interactions, is also presented. Secondly, the potentialities and limits of foliar sprays of carbohydrates to stimulate plant immunity for crop protection against diseases are discussed, with focus on the roles of the leaf cuticle and phyllosphere microflora.

  7. Potential role of transient receptor potential channel M5 in sensing putative pheromones in mouse olfactory sensory neurons.

    Science.gov (United States)

    Oshimoto, Arisa; Wakabayashi, Yoshihiro; Garske, Anna; Lopez, Roberto; Rolen, Shane; Flowers, Michael; Arevalo, Nicole; Restrepo, Diego

    2013-01-01

    Based on pharmacological studies of chemosensory transduction in transient receptor potential channel M5 (TRPM5) knockout mice it was hypothesized that this channel is involved in transduction for a subset of putative pheromones in mouse olfactory sensory neurons (OSNs). Yet, in the same study an electroolfactogram (EOG) in the mouse olfactory epithelium showed no significant difference in the responses to pheromones (and odors) between wild type and TRPM5 knockout mice. Here we show that the number of OSNs expressing TRPM5 is increased by unilateral naris occlusion. Importantly, EOG experiments show that mice lacking TRPM5 show a decreased response in the occluded epithelia to putative pheromones as opposed to wild type mice that show no change upon unilateral naris occlusion. This evidence indicates that under decreased olfactory sensory input TRPM5 plays a role in mediating putative pheromone transduction. Furthermore, we demonstrate that cyclic nucleotide gated channel A2 knockout (CNGA2-KO) mice that show substantially decreased or absent responses to odors and pheromones also have elevated levels of TRPM5 compared to wild type mice. Taken together, our evidence suggests that TRPM5 plays a role in mediating transduction for putative pheromones under conditions of reduced chemosensory input.

  8. A Review of Impact of Bam Earthquake on Cutaneous Leishmaniasis and Status: Epidemic of Old Foci, Emergence of New Foci and Changes in Features of the Disease

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Aflatoonian

    2016-01-01

    Full Text Available Background: Global findings indicate that incidence rate of cutaneous leishmaniasis (CL has significantly in­creased during the past decade, as documented in many countries. This review was aimed to evaluate the trend of CL cases in terms of demographic and clinical characteristics during a decade after the earthquake (2003–2012 com­pared to the corresponding period before the earthquake in Bam (1993–2003.Methods: Direct smear preparations along with different intrinsic methods were used for detection and identification of the causative agents.Results: Overall, 20999 cases of CL have occurred during the last 20 years (1993–2012, 6731 cases before and 14268 cases after the earthquake (P< 0.001.Conclusions: Following a major earthquake, several risk factors could activate epidemics of cutaneous leishmaniasis in old foci and induce emerging foci in new areas.

  9. Connecting biodiversity and potential functional role in modern euxinic environments by microbial metagenomics.

    Science.gov (United States)

    Llorens-Marès, Tomàs; Yooseph, Shibu; Goll, Johannes; Hoffman, Jeff; Vila-Costa, Maria; Borrego, Carles M; Dupont, Chris L; Casamayor, Emilio O

    2015-07-01

    Stratified sulfurous lakes are appropriate environments for studying the links between composition and functionality in microbial communities and are potentially modern analogs of anoxic conditions prevailing in the ancient ocean. We explored these aspects in the Lake Banyoles karstic area (NE Spain) through metagenomics and in silico reconstruction of carbon, nitrogen and sulfur metabolic pathways that were tightly coupled through a few bacterial groups. The potential for nitrogen fixation and denitrification was detected in both autotrophs and heterotrophs, with a major role for nitrogen and carbon fixations in Chlorobiaceae. Campylobacterales accounted for a large percentage of denitrification genes, while Gallionellales were putatively involved in denitrification, iron oxidation and carbon fixation and may have a major role in the biogeochemistry of the iron cycle. Bacteroidales were also abundant and showed potential for dissimilatory nitrate reduction to ammonium. The very low abundance of genes for nitrification, the minor presence of anammox genes, the high potential for nitrogen fixation and mineralization and the potential for chemotrophic CO2 fixation and CO oxidation all provide potential clues on the anoxic zones functioning. We observed higher gene abundance of ammonia-oxidizing bacteria than ammonia-oxidizing archaea that may have a geochemical and evolutionary link related to the dominance of Fe in these environments. Overall, these results offer a more detailed perspective on the microbial ecology of anoxic environments and may help to develop new geochemical proxies to infer biology and chemistry interactions in ancient ecosystems.

  10. Role of nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, S; Pettorossi, V E

    2000-01-01

    In rat brainstem slices, we investigated the role of nitric oxide in long-term potentiation induced in the ventral portion of the medial vestibular nuclei by high-frequency stimulation of the primary vestibular afferents. The nitric oxide scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide ] and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester were administered before and after induction of potentiation. Both drugs completely prevented long-term potentiation, whereas they did not impede the potentiation build-up, or affect the already established potentiation. These results demonstrate that the induction, but not the maintenance of vestibular long-term potentiation, depends on the synthesis and release into the extracellular medium of nitric oxide. In addition, we analysed the effect of the nitric oxide donor sodium nitroprusside on vestibular responses. Sodium nitroprusside induced long-term potentiation, as evidenced through the field potential enhancement and unit peak latency decrease. This potentiation was impeded by D, L-2-amino-5-phosphonopentanoic acid, and was reduced under blockade of synaptosomal platelet-activating factor receptors by ginkgolide B and group I metabotropic glutamate receptors by (R,S)-1-aminoindan-1, 5-dicarboxylic acid. When reduced, potentiation fully developed following the washout of antagonist, demonstrating an involvement of platelet-activating factor and group I metabotropic glutamate receptors in its full development. Potentiation induced by sodium nitroprusside was also associated with a decrease in the paired-pulse facilitation ratio, which persisted under ginkgolide B, indicating that nitric oxide increases glutamate release independently of platelet-activating factor-mediated presynaptic events. We suggest that nitric oxide, released after the activation of N-methyl-D-aspartate receptors, acts as a retrograde messenger leading to an enhancement of glutamate release to a

  11. High-resolution CT features of bleeding foci in patients with massive hemoptysis

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Keum Soo; Lee, Ki Nam; Jung, Won Jung; Kim, Jae Ic; Kang, Myong Jin; Park, Byeong Ho [Donga Univ. College of Medicine, Pusan (Korea, Republic of)

    2000-12-01

    To compare the high-resolution CT features of bleeding foci in patients with massive hemoptysis during embolization with those revealed by angiography. Between June 1997 and June 1999, we evaluated 25 patients who from among a total of 49 with arterial embolization due to massive hemoptysis underwent HRCT prior to embolization. We retrospectively analyzed medical records, and angiographic and HRCT findings. The time interval between HRCT and arterial embolization varied from two hours to six days. Angiography indicated that the bronchial, intercostal and internal mammary artery, and branches of the subclavian, were the foci of bleeding, and indicated the location of these in each pulmonary lobe. The HRCT findings were evaluated in terms of cavity, air-meniscus sign, bronchial dilatation, consolidation, ground-glass opacity, and fibrotic scar. We anlayzed the corresponding sites of HRCT and the angiographic findings of the foci of bleeding. In 24 of 25 patients, the foci of bleeding were angiographically confirmed, their presence being noted in 28 pulmonary lobes. HRCT findings corresponding to the bleeding foci revealed by angiography were the air-meniscus sign (8 of 10 lobes, 80.0%), cavity (7 of 9 lobes, 77.8%), bronchial dilatation (21 of 30 lobes, 70.0%), and fibrotic scar (1 of 23 lobes, 4.3%). The findings in areas of consolidation and/or ground-glass opacity only did not correspond, however. As compared with those revealed by angiography, the HRCT features of bleeding foci in patients with massive hemoptysis during embolization are in order of frequency, the air-meniscus sign, cavity, and bronchial dilatation.

  12. The potential roles of T-type Ca2+ channels in motor coordination

    Directory of Open Access Journals (Sweden)

    Young-Gyun ePark

    2013-10-01

    Full Text Available Specific behavioral patterns are expressed by complex combinations of muscle coordination. Tremors are simple behavioral patterns and are the focus of studies investigating motor coordination mechanisms in the brain. T-type Ca2+ channels mediate intrinsic neuronal oscillations and rhythmic burst spiking, and facilitate the generation of tremor rhythms in motor circuits. Despite substantial evidence that T-type Ca2+ channels mediate pathological tremors, their roles in physiological motor coordination and behavior remain unknown. Here, we review recent progress in understanding the roles that T-type Ca2+ channels play under pathological conditions, and discuss the potential relevance of these channels in mediating physiological motor coordination.

  13. Transient Receptor Potential Canonical Type 3 Channels - Their Evolving Role in Hypertension and Its Related Complications

    DEFF Research Database (Denmark)

    Wang, Peijian; Liu, Daoyan; Tepel, Martin

    2013-01-01

    , and cerebrovascular events. In this review, we summarize the role of TRPC3 channels in the cardiovascular system, we focus on their pathophysiogical role in hypertension and related target organ damages. We provide new insight into the involvement of TRPC3 channels in the development of hypertension and its related......ABSTRACT: Recent studies indicate that transient receptor potential canonical type 3 (TRPC3) channels contribute to the regulation of blood pressure, vascular and renal function. Several studies show that TRPC3 dysfunction is associated with hypertension, atherosclerosis, cardiac hypertrophy...

  14. The historical distribution of main malaria foci in Spain as related to water bodies.

    Science.gov (United States)

    Sousa, Arturo; García-Barrón, Leoncio; Vetter, Mark; Morales, Julia

    2014-08-06

    The possible connectivity between the spatial distribution of water bodies suitable for vectors of malaria and endemic malaria foci in Southern Europe is still not well known. Spain was one of the last countries in Western Europe to be declared free of malaria by the World Health Organization (WHO) in 1964. This study combines, by means of a spatial-temporal analysis, the historical data of patients and deceased with the distribution of water bodies where the disease-transmitting mosquitos proliferate. Therefore, data from historical archives with a Geographic Information System (GIS), using the Inverse Distance Weighted (IDW) interpolation method, was analyzed with the aim of identifying regional differences in the distribution of malaria in Spain. The reasons, why the risk of transmission is concentrated in specific regions, are related to worse socioeconomic conditions (Extremadura), the presence of another vector (Anopheles labranchiae) besides A. atroparvus (Levante) or large areas of water bodies in conditions to reproduce theses vectors (La Mancha and Western Andalusia). In the particular case of Western Andalusia, in 1913, the relatively high percentage of 4.73% of the surface, equal to 202362 ha, corresponds to wetlands and other unhealthy water bodies. These wetlands have been reduced as a result of desiccation policies and climate change such as the Little Ice Age and Global Climate Change. The comprehension of the main factors of these wetland changes in the past can help us interpret accurately the future risk of malaria re-emergence in temperate latitudes, since it reveals the crucial role of unhealthy water bodies on the distribution, endemicity and eradication of malaria in southern Europe.

  15. Spinocerebellar ataxia type 8 larger triplet expansion alters histone modification and induces RNA foci

    Directory of Open Access Journals (Sweden)

    Wu Yih-Ru

    2009-02-01

    Full Text Available Abstract Background Spinocerebellar ataxia type 8 (SCA8 involves the expression of an expanded CTG/CAG combined repeats (CR from opposite strands producing CUG expansion transcripts (ataxin 8 opposite strand, ATXN8OS and a polyglutamine expansion protein (ataxin 8, ATXN8. The pathogenesis of SCA8 is complex and the spectrum of clinical presentations is broad. Results Using stably induced cell models expressing 0, 23, 88 and 157 CR, we study the role of ATXN8OS transcripts in SCA8 pathogenesis. In the absence of doxycycline, the stable ATXN8OS CR cell lines exhibit low levels of ATXN8OS expression and a repeat length-related increase in staurosporine sensitivity and in the number of annexin positive cells. A repeat length-dependent repression of ATXN8OS expression was also notable. Addition of doxycycline leads to 25~50 times more ATXN8OS RNA expression with a repeat length-dependent increase in fold of ATXN8OS RNA induction. ChIP-PCR assay using anti-dimethyl-histone H3-K9 and anti-acetyl-histone H3-K14 antibodies revealed increased H3-K9 dimethylation and reduced H3-K14 acetylation around the ATXN8OS cDNA gene in 157 CR line. The repeat length-dependent increase in induction fold is probably due to the increased RNA stability as demonstrated by monitoring ATXN8OS RNA decay in cells treated with the transcriptional inhibitor, actinomycin D. In cells stably expressing ATXN8OS, RNA FISH experiments further revealed ribonuclear foci formation in cells carrying expanded 88 and 157 CR. Conclusion The present study demonstrates that the expanded CUG-repeat tracts are toxic to human cells and may affect ATXN8OS RNA expression and stability through epigenetic and post-transcriptional mechanisms.

  16. Estradiol-induced promotion of hepatocarcinogenesis in medaka: Relationship of foci of cellular alteration to neoplasia

    Energy Technology Data Exchange (ETDEWEB)

    Cooke, J.B.; Hinton, D.E. [Univ. of California, Davis, CA (United States)

    1995-12-31

    In some laboratory and field studies, female fish have higher prevalences of liver tumors than do males. The authors hypothesize gender and site-specific differences in prevalence are due to variable exposures of previously initiated fish to tumor modulating compounds. Estradiol, a growth promoter, increases incidences of hepatic tumors in carcinogen-treated rainbow trout and medaka (Oryzias latipes). Estradiol also increases incidences of hepatic foci of cellular alteration (FCA) in medaka. FCA are found in subadults of tumor-bearing feral populations. Lack of knowledge about the relationship of various phenotypes of FCA to eventual tumors, however, has prevented use of FCA as a biomarker. The authors examined fate and growth of liver FCA using a 2-step, initiation-promotion protocol. Three week old medaka were exposed to 200 ppm diethylnitrosamine (DEN) for 24 hr. and then fed 0.1 ppm 17-{beta}-estradiol (E2) continuously through sampling at weeks 4--26. Percent volume of FCA and morphometric characteristics of normal and focal hepatocytes, including numerical density and average hepatocyte volume were quantified using computer-assisted stereology. E2 increased percentage of liver occupied by DEN-initiated amphophilic, basophilic and eosinophilic FCA in both sexes. Focal parameters of young, DEN-initiated and estradiol-treated medaka were not reached until much later in fish given only DEN. Non-focal hepatocytes in estradiol-treated medaka were smaller and more numerous than in DEN-only counterparts. Morphometric analysis is quantitatively tracking the fate of specific phenotypes of FCA to determine their role in progression to cancer.

  17. The Historical Distribution of Main Malaria Foci in Spain as Related to Water Bodies

    Directory of Open Access Journals (Sweden)

    Arturo Sousa

    2014-08-01

    Full Text Available The possible connectivity between the spatial distribution of water bodies suitable for vectors of malaria and endemic malaria foci in Southern Europe is still not well known. Spain was one of the last countries in Western Europe to be declared free of malaria by the World Health Organization (WHO in 1964. This study combines, by means of a spatial-temporal analysis, the historical data of patients and deceased with the distribution of water bodies where the disease-transmitting mosquitos proliferate. Therefore, data from historical archives with a Geographic Information System (GIS, using the Inverse Distance Weighted (IDW interpolation method, was analyzed with the aim of identifying regional differences in the distribution of malaria in Spain. The reasons, why the risk of transmission is concentrated in specific regions, are related to worse socioeconomic conditions (Extremadura, the presence of another vector (Anopheles labranchiae besides A. atroparvus (Levante or large areas of water bodies in conditions to reproduce theses vectors (La Mancha and Western Andalusia. In the particular case of Western Andalusia, in 1913, the relatively high percentage of 4.73% of the surface, equal to 202362 ha, corresponds to wetlands and other unhealthy water bodies. These wetlands have been reduced as a result of desiccation policies and climate change such as the Little Ice Age and Global Climate Change. The comprehension of the main factors of these wetland changes in the past can help us interpret accurately the future risk of malaria re-emergence in temperate latitudes, since it reveals the crucial role of unhealthy water bodies on the distribution, endemicity and eradication of malaria in southern Europe.

  18. On the potential roles of ticks and migrating birds in the ecology of West Nile virus

    Directory of Open Access Journals (Sweden)

    Karl Hagman

    2014-01-01

    Full Text Available Background: Mosquitoes are the primary vectors of West Nile virus (WNV. Ticks have, however, been suggested to be potential reservoirs of WNV. To investigate their role in the spread of the virus, ticks, which had been collected from birds migrating northward from Africa to Europe, were analyzed for the potential presence of WNV RNA. Methods: On the Mediterranean islands of Capri and Antikythira, a total of 14,824 birds were captured and investigated from which 747 ticks were collected. Results and conclusions: Most of the identified ticks (93% were nymphs and larvae of Hyalomma marginatum sensu lato (s.l., most of which were or appear to be Hyalomma rufipes. Of these ticks, 729 were individually screened for WNV RNA. None of the ticks was found to be WNV positive. Thus, there was no evidence that H. marginatum s.l. ticks play a role in the spread of WNV from Africa to Europe.

  19. The role of the computer in science fair projects: Current status and potential

    Energy Technology Data Exchange (ETDEWEB)

    Trainor, M.S.

    1991-01-01

    The need for more students to enter the field of science is acute in the nation, and science fair projects provide a motivational mechanism to entice students into pursuing scientific careers. Computers play a major role in science today. Because computers are a major source of entertainment for our children, one would expect them to play a significant role in many science fair projects. This study investigated current and potential uses of computers in science fair projects and incorporated an informal case study of scientists, teachers, and students involved in science fair projects from a highly scientific community. Interviews, a survey, and observations were conducted. Results indicated that most projects either do not use or inadequately use computers and that a significant potential for more effective use of computers for science fair projects exists.

  20. MODEL OF GEOMEDIA CONTAINING DEFECTS: COLLECTIVE EFFECTS OF DEFECTS EVOLUTION DURING FORMATION OF POTENTIAL EARTHQUAKE FOCI

    Directory of Open Access Journals (Sweden)

    I. A. Panteleev

    2015-09-01

    Full Text Available This paper describes the statistical thermo-dynamical evolution of an ensemble of defects in the geomedium in the field of externally applied stresses. The authors introduce ‘tensor structural’ variables associated with two specific types of defects, fractures and localized shear faults (Fig. 1. Based on the procedure for averaging of the structural variables by statistical ensembles of defects, a self-consistency equation is developed; it determines the dependence of the macroscopic tensor of defects-induced strain on values of external stresses, the original pattern and interaction of defects. In the dimensionless case, the equation contains only the parameter of structural scaling, i.e. the ratio of specific structural scales, including the size of defects and an average distance between the defects.The self-consistency equation yields three typical responds of the geomedium containing defects to the increasing external stress (Fig. 2. The responses are determined from values of the structural scaling parameter. The concept of non-equilibrium free energy for a medium containing defects, given similar to the Ginzburg-Landau decomposition, allowed to construct evolutionary equations for the introduced parameters of order (deformation due to defects, and the structural scaling parameter and to explore their solutions (Fig. 3.It is shown that the first response corresponds to stable quasi-plastic deformation of the geomedium, which occurs in regularly located areas characterized by the absence of collective orientation effects. Reducing the structural scaling parameter leads to the second response characterized by the occurrence of an area of meta-stability in the behavior of the medium containing defects, when, at a certain critical stress, the orientation transition takes place in the ensemble of interacting defects, which is accompanied by an abrupt increase of deformation (Fig. 2. Under the given observation/averaging scale, this transition is manifested by localized cataclastic deformation (i.e. a set of weak earthquakes, which migrates in space at a velocity several orders of magnitude lower than the speed of sound, as a ‘slow’ deformation wave (Fig. 3. Further reduction of the structural scaling parameter leads to degeneracy of the orientation meta-stability and formation of localized dissipative defect structures in the medium. Once the critical stress is reached, such structures develop in the blow-up regime, i.e. the mode of avalanche-unstable growth of defects in the localized area that is shrinking eventually. At the scale of observation, this process is manifested as brittle fracturing that causes formation of a deformation zone, which size is proportional to the scale of observation, and corresponds to occurrence of a strong earthquake.On the basis of the proposed model showing the behavior of the geomedium containing defects in the field of external stresses, it is possible to describe main ways of stress relaxation in the rock massives – brittle large-scale destruction and cataclastic deformation as consequences of the collective behavior of defects, which is determined by the structural scaling parameter.Results of this study may prove useful for estimation of critical stresses and assessment of the geomedium status in seismically active regions and be viewed as model representations of the physical hypothesis about the uniform nature of deve­lopment of discontinuities/defects in a wide range of spatial scales. 

  1. Analysis of Lymphocytic DNA Damage in Early Multiple Sclerosis by Automated Gamma-H2AX and 53BP1 Foci Detection: A Case Control Study.

    Directory of Open Access Journals (Sweden)

    Ludwig Rasche

    previously frozen PBMCs of patients with than without CEL, γ-H2AX values of both groups overlapped and γ-H2AX did not correlate with the number or volume of CEL.γ-H2AX and 53BP1 foci do not seem to be promising diagnostic or disease activity biomarkers in patients with early MS. Lymphocytic DNA double-strand breaks are unlikely to play a major role in the pathophysiology of MS.

  2. Role of depth and location of minima of a double-well potential on vibrational resonance

    Energy Technology Data Exchange (ETDEWEB)

    Rajasekar, S [School of Physics, Bharathidasan University, Tiruchirapalli 620 024, Tamilnadu (India); Jeyakumari, S; Chinnathambi, V [Department of Physics, Sri KGS Arts College, Srivaikuntam 628 619, Tamilnadu (India); Sanjuan, M A F, E-mail: rajasekar@cnld.bdu.ac.i [Departamento de Fisica, Universidad Rey Juan Carlos, Tulipan s/n, 28933 Mostoles, Madrid (Spain)

    2010-11-19

    We report our investigation into the role of depth and location of minima of a double-well potential on vibrational resonance in both underdamped and overdamped Duffing oscillators. The systems are driven by both low- and high-frequency periodic forces. We obtain theoretical expressions for the amplitude g of the high-frequency force at which resonances occur. The depth and location of the minima of the potential wells have a distinct effect on vibrational resonance in the underdamped and overdamped cases. In the underdamped system at least one resonance and at most two resonances occur and the number of resonances can be altered by varying the depth and location of the minima of the potential wells. We show that in the overdamped system there is always one and only one resonance, and the value of g at which resonance occurs is independent of the depth of the wells, but varies linearly with the locations of the minima of the wells.

  3. Role of Family Resilience and Mindfulness in Addiction Potential of Students

    Directory of Open Access Journals (Sweden)

    S Jalili Nikoo

    2015-07-01

    Full Text Available Background & aim: family and individual factors are involved in addiction potential. The aim of this research was to investigate the role of family resiliency (family communication and problem solving, utilizing social and economic resources, maintaining a positive outlook, family connectedness, family spirituality, ability to make meaning of adversity and mindfulness in addiction potential of students. Method: the research method used in the present study was correlation. A number of 399 students from Yasuj University in 2012-13 academic years were selected through a multi- stage cluster sampling method and responded to the Iranian scale of addiction potential, family resiliency questionnaire, and short form of Freiburg mindfulness inventory. Collected data were analyzed using Pearson correlation coefficient and Simultaneous regression. Results: A negative and significant correlation was seen between family resiliency and its dimensions with addiction potential (P>0.01. Between mindfulness and addiction preparation, a significant and negative correlation was observed (P>0.01. The results of simultaneous regression analysis showed that family residency and mindfulness could significantly predict 13% of variance of addiction potential. Conclusion: The results of this study indicated the importance of family resilience and mindfulness as personal and family variables in preparing addiction. Therefore, the family resilience and mindfulness skills training could decrease the addiction potential among students.

  4. Effect of leaving chronic oral foci untreated on infectious complications during intensive chemotherapy

    NARCIS (Netherlands)

    Schuurhuis, J. M.; Span, L. F. R.; Stokman, M. A.; van Winkelhoff, A. J.; Vissink, A.; Spijkervet, F. K. L.

    2016-01-01

    Background: Leukaemic patients receiving intensive chemotherapy and patients undergoing autologous stem-cell transplantation (ASCT) are routinely screened for oral foci of infection to reduce infectious complications that could occur during therapy. In this prospective study we assessed the effect o

  5. Effect of leaving chronic oral foci untreated on infectious complications during intensive chemotherapy

    NARCIS (Netherlands)

    Schuurhuis, J M; Span, L. F. R.; Stokman, M A; van Winkelhoff, A J; Vissink, A; Spijkervet, F K L

    2016-01-01

    BACKGROUND: Leukaemic patients receiving intensive chemotherapy and patients undergoing autologous stem-cell transplantation (ASCT) are routinely screened for oral foci of infection to reduce infectious complications that could occur during therapy. In this prospective study we assessed the effect o

  6. Repair of abnormal perfusion foci in idiopathic epilepsy patients under long-term antiepileptic treatment

    Institute of Scientific and Technical Information of China (English)

    Weimin Wang; Siyu Zhao; Yaqing Liu

    2011-01-01

    Epileptic seizure control and the disappearance of epileptiform discharge are not indicative of the absence of abnormal perfusion foci.Perfusion abnormalities are a major cause of epileptic discharge, and the existence of abnormal perfusion foci implies possible relapse.Very little is known about perfusion abnormality repair in epilepsy.The present study selected 43 cases of idiopathic epilepsy under antiepileptic drug control for an average of 24 months.Comparisons between interictal single-photon emission CT (SPECT)images and long-term electroencephalogram (EEG) pre- and post-treatment showed that cases of normal SPECT increased by 48% (12/25) following treatment, with a total number of 15 reduced foci (36%, 15/41).Perfusion foci, i.e., region of interest, were altered following treatment.These changes included:normal to abnormal in 3 cases (7%, 3/43; 2 hyperperfusion and 1 hypoperfusion); abnormal to normal in 14 cases (32%, 14/43; 10 pre-treatment hypoperfusion and 4 hyperperfusion); abnormal to abnormal in 7 cases (16%, 7/43; hyperperfusion to hypoperfusion in 5 cases, hypoperfusion to hyperperfusion in 2 cases).Long-term EEG revealed in an increase in the number of normal cases by 20 (40%, 20/39), and there were 25 fewer cases with epileptiform discharges (66%, 25/38).These findings demonstrate that long-term control of anti-epileptic drugs partially repaired cerebral perfusion abnormalities and reduced epileptiform discharges in idiopathic epilepsy.

  7. Sandfly fauna of endemic leishmaniasis foci in Anzoátegui State, Venezuela.

    Science.gov (United States)

    González, R; Jorquera, A; De Sousa, L; Ledezma, E; Devera, R

    2002-01-01

    A census of the sandfly fauna was undertaken in 1993-98 in 5 endemic leishmaniasis foci situated at different altitudes in Anzoátegui State, Venezuela. From the 17 species of Lutzomyia identified, we believe that Lu. ovallesi, Lu. panamensis and Lu. gomezi are the probable vectors of cutaneous leishmaniasis, while Lu. evansi might transmit visceral leishmaniasis.

  8. Genetic micro-heterogeneity of Leishmania major in emerging foci of zoonotic cutaneous leishmaniasis in Tunisia.

    Science.gov (United States)

    Attia, Hanene; Sghaier, Rabiaa M; Gelanew, Tesfaye; Bali, Aymen; Schweynoch, Carola; Guerfali, Fatma Z; Mkannez, Ghada; Chlif, Sadok; Belhaj-Hamida, Nabil; Dellagi, Koussay; Schönian, Gabriele; Laouini, Dhafer

    2016-09-01

    Tunisia is endemic for zoonotic cutaneous leishmaniasis (ZCL), a parasitic disease caused by Leishmania (L.) major. ZCL displays a wide clinical polymorphism, with severe forms present more frequently in emerging foci where naive populations are dominant. In this study, we applied the multi-locus microsatellite typing (MLMT) using ten highly informative and discriminative markers to investigate the genetic structure of 35 Tunisian Leishmania (L.) major isolates collected from patients living in five different foci of Central Tunisia (two old and three emerging foci). Phylogenetic reconstructions based on genetic distances showed that nine of the ten tested loci were homogeneous in all isolates with homozygous alleles, whereas one locus (71AT) had a 58/64-bp bi-allelic profile with an allele linked to emerging foci. Promastigote-stage parasites with the 58-bp allele tend to be more resistant to in vitro complement lysis. These results, which stress the geographical dependence of the genetic micro-heterogeneity, may improve our understanding of the ZCL epidemiology and clinical outcome.

  9. S phase progression in human cells is dictated by the genetic continuity of DNA foci.

    Directory of Open Access Journals (Sweden)

    Apolinar Maya-Mendoza

    2010-04-01

    Full Text Available DNA synthesis must be performed with extreme precision to maintain genomic integrity. In mammalian cells, different genomic regions are replicated at defined times, perhaps to preserve epigenetic information and cell differentiation status. However, the molecular principles that define this S phase program are unknown. By analyzing replication foci within discrete chromosome territories during interphase, we show that foci which are active during consecutive intervals of S phase are maintained as spatially adjacent neighbors throughout the cell cycle. Using extended DNA fibers, we demonstrate that this spatial continuity of replication foci correlates with the genetic continuity of adjacent replicon clusters along chromosomes. Finally, we used bioinformatic tools to compare the structure of DNA foci with DNA domains that are seen to replicate during discrete time intervals of S phase using genome-wide strategies. Data presented show that a major mechanism of S phase progression involves the sequential synthesis of regions of the genome because of their genetic continuity along the chromosomal fiber.

  10. Cuticular hydrocarbons of Drosophila montana: geographic variation, sexual dimorphism and potential roles as pheromones.

    Science.gov (United States)

    Jennings, Jackson H; Etges, William J; Schmitt, Thomas; Hoikkala, Anneli

    2014-02-01

    Sexual selection within populations can play an important role in speciation when divergence in mating signals and their corresponding preferences occur along different coevolutionary trajectories in different populations. In insects, one potential target of sexual selection is the blend of cuticular hydrocarbons (CHCs), which often show intra- and interspecific variation, sexual dimorphism and may act as pheromones. In Drosophila montana, a cold-adapted, circumboreal member of the Drosophila virilis species group, flies from different populations have been found to show significant premating isolation as well as variation in male mating signal (song) and female preference. While the role of male courtship song in mate choice has been studied extensively, CHCs in this species have received little attention. In this study, we identified most of the CHCs found on the cuticle of D. montana and characterized population divergence and sexual dimorphism of CHC profiles among flies established from three natural populations - one European and two North American. We also studied their potential role as pheromones by analyzing CHCs of flies used in female-choice mating experiments. We report significant population×sex effects on CHC profiles, as well as significant relationships between some CHC principal components and particular mating behaviours, such as female attractiveness and male mating success, providing evidence that CHCs may play a role in mate choice in this species. The study also provides evidence for variation in the degree to which CHCs play a role in chemical communication among these populations, which may have an influence on the speciation process itself, and could be due to variation in interactions with other closely-related species that occur sympatrically with D. montana in some, but not other, parts of its distribution. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Potential role of Bacillus endospores in soil amended by olive mill wastewater.

    Science.gov (United States)

    Naclerio, Gino; Falasca, Antonio; Petrella, Emma; Nerone, Valentina; Cocco, Federica; Celico, Fulvio

    2010-01-01

    The main aim of this work was to know how spread is laccase activity in spores of Bacillus species isolated from a soil where Italian law allows olive mill wastewater (OMW) spreading, and to investigate the potential role of such autochthonous soil microorganisms in degradation of OMW phenols, and prevention of groundwater pollution. Laccase activity was detected for the first time in spores of wild-type Bacillus pumilus, B. cereus sensu lato, and B. amyloliquefaciens strains. Because B. pumilus, B. cereus sensu lato, and B. amyloliquefaciens, together with B. subtilis account for a total of 93% of Bacillus isolates at the study site, the nearly totality of Bacillus spores reveals laccase activity. Thus, taking also into consideration that Bacillus spores are more abundant (about 100-fold) than white-rot fungi (that possess a well known extracellular, radical-based ligninolytic enzyme system capable of degrading OMW phenols) in the studied soil, these spores may contribute to in-situ degradation of OMW phenols. This role is further emphasized by dilution of crude OMW during infiltration of rainwater through soil that allows to minimize the antibacterial activity of phenols. The widespread presence of Bacillus spores in soils indicates a potential detoxifying role of these spores in a broader context.

  12. Potential Role of Peptidylarginine Deiminase Enzymes and Protein Citrullination in Cancer Pathogenesis

    Directory of Open Access Journals (Sweden)

    Sunish Mohanan

    2012-01-01

    Full Text Available The peptidylarginine deiminases (PADs are a family of posttranslational modification enzymes that catalyze the conversion of positively charged protein-bound arginine and methylarginine residues to the uncharged, nonstandard amino acid citrulline. This enzymatic activity is referred to as citrullination or, alternatively, deimination. Citrullination can significantly affect biochemical pathways by altering the structure and function of target proteins. Five mammalian PAD family members (PADs 1–4 and 6 have been described and show tissue-specific distribution. Recent reviews on PADs have focused on their role in autoimmune diseases. Here, we will discuss the potential role of PADs in tumor progression and tumor-associated inflammation. In the context of cancer, increasing clinical evidence suggests that PAD4 (and possibly PAD2 has important roles in tumor progression. The link between PADs and cancer is strengthened by recent findings showing that treatment of cell lines and mice with PAD inhibitors significantly suppresses tumor growth and, interestingly, inflammatory symptoms. At the molecular level, transcription factors, coregulators, and histones are functional targets for citrullination by PADs, and citrullination of these targets can affect gene expression in multiple tumor cell lines. Next generation isozyme-specific PAD inhibitors may have therapeutic potential to regulate both the inflammatory tumor microenvironment and tumor cell growth.

  13. Roles of plant Metal Tolerance Proteins (MTP in metal storage and potential use in biofortification strategies.

    Directory of Open Access Journals (Sweden)

    Felipe Klein Ricachenevsky

    2013-05-01

    Full Text Available Zinc (Zn is an essential micronutrient for plants, playing catalytic or structural roles in enzymes, transcription factors, ribosomes and membranes. In humans, Zn deficiency is the second most common mineral nutritional disorder, affecting around 30% of the world’s population. People living in poverty usually have their diets based on milled cereals, which contain low Zn concentrations. Biofortification of crops is an attractive cost-effective solution for low mineral dietary intake. In order to increase the amounts of bioavailable Zn in crop edible portions, it is necessary to understand how plants take up, distribute and store Zn within their tissues, as well as to characterize potential candidate genes for biotechnological manipulation. The Metal Tolerance Proteins (MTP were described as metal efflux transporters from the cytoplasm, transporting mainly Zn2+ but also Mn2+, Fe2+, Cd2+, Co2+ and Ni2+. Substrate specificity appears to be conserved in phylogenetically related proteins. MTPs characterized so far in plants have a role in general Zn homeostasis and tolerance to Zn excess; in tolerance to excess Mn and also in the response to Fe deficiency. More recently, the first MTPs in crop species have been functionally characterized. In Zn hyperaccumulator plants, the MTP1 protein is related to hypertolerance to elevated Zn concentrations. . Here, we review the current knowledge on this protein family, as well as biochemical functions and physiological roles of MTP transporters in Zn hyperaccumulators and non-accumulators. The potential applications of MTP transporters in biofortification efforts are discussed.

  14. The potential role of stereolithography in the study of facial aging.

    Science.gov (United States)

    Pessa, J E

    2001-02-01

    The potential role of high-resolution stereolithography for the study of facial aging was evaluated. Stereolithography has been used extensively in the engineering sciences to create model replicas prior to full production. More recently, stereolithography has found a role in the preoperative planning of complex dentofacial anomalies. Previous work has suggested that continued differential growth of the maxilla may occur throughout life. To further evaluate this finding, computed tomography scans were collected from younger (mean, 20.2 years) and older (mean, 58.8 years) individuals (N = 20). Both men and women were included. An exact replica of the facial skeleton was made for each subject by the process of laser polymerization. The angles of the maxillary wall and piriform aperture, defined by specific points, were measured relative to sella-nasion. Height, width, and depth changes were also evaluated. Findings show that angular changes occurred with age. The mean angle of the maxilla relative to sella-nasion decreased from 69 degrees to 56.8 degrees with age (P =.015). The mean angle of the piriform likewise decreased from 65.1 degrees to 55.7 degrees (P =.019). This angular change with age suggests that differential growth may continue throughout life. This work highlights the potential role of 3-dimensional modeling for future research in the field of facial aging. Curve and contour analysis are 2 additional areas in which stereolithography may yield valuable insights into the mechanisms of facial growth.

  15. Chemico-osmosis in geologic membranes: Role of membrane potential gradient

    Science.gov (United States)

    Cheng, Guanchu; Jim Hendry, M.

    2014-09-01

    Chemico-osmosis is conventionally regarded to occur in the positive direction, i.e., from low to high concentration reservoirs. However, experiments have shown that chemico-osmosis in clay membranes can occur in the opposite direction, i.e., from high to low concentration reservoirs. Conceptual interpretations of this negative osmosis suggest that the diffused electrolytes exert “drag” on water molecules, thus driving the entire solution toward the low concentration reservoir. This paper proposes a quantitative interpretation of this phenomenon considering the role of the induced membrane potential gradient. To this end, a model, which involves the expansion of pore-scale electrokinetics to continuum-scale chemico-osmosis behaviors, is developed for quantification of this membrane potential gradient. The numerical investigation based on the model shows that the membrane potential gradient (1) is caused by the requirement of electroneutrality in the solutions on either side of the membrane; (2) is directly proportional to the difference in effective diffusivity for cations and anions; and (3) contributes to retarding cation migration, enhancing anion migration, and driving the solution flux from low to high concentration reservoirs. These three observations thus suggest that a likely cause of negative osmosis is a decreasing tendency for the solution flux from low to high concentration reservoirs caused by a decreasing membrane potential gradient. Using these findings, previous experiments are discussed and interpreted with success from the electrodynamic perspective of the membrane potential gradient.

  16. The Role of Academic Burnout, Resilience, and Perceived Stress in Predicting Students\\\\\\' Addiction Potential

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    mojtaba salmabadi

    2015-06-01

    Full Text Available Objective: This study aimed at determining the role of academic burnout, resilience, and perceived stress in predicting students' addiction potential. Method: In this correlational study, the number of 200 high school students in of South Khorasan province was selected as the participants through random cluster sampling and they responded to the three pertinent questionnaires, namely resilience scale, academic burnout scale, perceived stress scale, and addiction potential scale. Results: The results showed that academic burnout, perceived stress, and resilience were positively correlated with addiction potential. Similarly, there was a significant positive relationship between academic burnout and perceived stress. Conclusion: Dimensions of burnout (emotional exhaustion, apathy, impotency, dimensions of perceived stress (negative emotional responses and coping ability level, and resilience could predict 20% of addiction potential. Among these dimensions, only coping ability level and resilience were significantly effective in predicting addiction potential therefore, educational authorities are recommended to pay more attention to the prevention and treatment of addiction in students towards having a healthy society.

  17. Mitigation potential and cost in tropical forestry - relative role for agroforestry

    Energy Technology Data Exchange (ETDEWEB)

    Makundi, Willy R.; Sathaye, Jayant A.

    2004-01-01

    This paper summarizes studies of carbon mitigation potential (MP) and costs of forestry options in seven developing countries with a focus on the role of agroforestry. A common methodological approach known as comprehensive mitigation assessment process (COMAP) was used in each study to estimate the potential and costs between 2000 and 2030. The approach requires the projection of baseline and mitigation land-use scenarios derived from the demand for forest products and forestland for other uses such as agriculture and pasture. By using data on estimated carbon sequestration, emission avoidance, costs and benefits, the model enables one to estimate cost effectiveness indicators based on monetary benefit per t C, as well as estimates of total mitigation costs and potential when the activities are implemented at equilibrium level. The results show that about half the MP of 6.9 Gt C (an average of 223 Mt C per year) between 2000 and 2030 in the seven countries could be achieved at a negative cost, and the other half at costs not exceeding $100 per t C. Negative cost indicates that non-carbon revenue is sufficient to offset direct costs of about half of the options. The agroforestry options analyzed bear a significant proportion of the potential at medium to low cost per t C when compared to other options. The role of agroforestry in these countries varied between 6% and 21% of the MP, though the options are much more cost effective than most due to the low wage or opportunity cost of rural labor. Agroforestry options are attractive due to the large number of people and potential area currently engaged in agriculture, but they pose unique challenges for carbon and cost accounting due to the dispersed nature of agricultural activities in the tropics, as well as specific difficulties arising from requirements for monitoring, verification, leakage assessment and the establishment of credible baselines.

  18. Potential primary roles of glial cells in the mechanisms of psychiatric disorders.

    Science.gov (United States)

    Yamamuro, Kazuhiko; Kimoto, Sohei; Rosen, Kenneth M; Kishimoto, Toshifumi; Makinodan, Manabu

    2015-01-01

    While neurons have long been considered the major player in multiple brain functions such as perception, emotion, and memory, glial cells have been relegated to a far lesser position, acting as merely a "glue" to support neurons. Multiple lines of recent evidence, however, have revealed that glial cells such as oligodendrocytes, astrocytes, and microglia, substantially impact on neuronal function and activities and are significantly involved in the underlying pathobiology of psychiatric disorders. Indeed, a growing body of evidence indicates that glial cells interact extensively with neurons both chemically (e.g., through neurotransmitters, neurotrophic factors, and cytokines) and physically (e.g., through gap junctions), supporting a role for these cells as likely significant modifiers not only of neural function in brain development but also disease pathobiology. Since questions have lingered as to whether glial dysfunction plays a primary role in the biology of neuropsychiatric disorders or a role related solely to their support of neuronal physiology in these diseases, informative and predictive animal models have been developed over the last decade. In this article, we review recent findings uncovered using glia-specific genetically modified mice with which we can evaluate both the causation of glia dysfunction and its potential role in neuropsychiatric disorders such as autism and schizophrenia.

  19. [Novel adipokines: their potential role in the pathogenesis of obesity and metabolic disorders].

    Science.gov (United States)

    Korek, Emilia; Krauss, Hanna

    2015-01-02

    Since identification in 1994 of leptin, a hormone produced by adipocytes, adipose tissue has become the subject of intensive research. These studies contributed to the discovery that adipocytes have the ability to synthesize and secrete biologically active substances called "adipokines". Adipokines include a variety of cytokines, peptide hormones and enzymes that play a role in a wide variety of biological functions. For example, they are involved in the regulation of appetite, energy homeostasis, vascular hemostasis, blood pressure, inflammatory and immune processes and play a role in the metabolism of carbohydrates and fats. In obese patients, the secretion of adipokines is frequently abnormal. These changes may predispose to the development of insulin resistance, hypertension and inflammation. Therefore, adipokines are the subject of ongoing clinical trials. The family of adipokines is increasing by the newly discovered peptides. This paper presents the current state of knowledge about retinol binding protein 4 (RBP-4), fasting-induced adipose factor/angiopoietin-like protein 4 (FIAF/ANGPTL4), fibroblast growth factor-21 (FGF21), dipeptidyl peptidase-4 (DPP-4), irisin and their potential role in the pathogenesis of metabolic disorders associated with obesity. The knowledge of the role of newly discovered adipokines may help in the treatment of metabolic syndrome.

  20. Potential role of Demodex mites and bacteria in the induction of rosacea.

    Science.gov (United States)

    Jarmuda, Stanislaw; O'Reilly, Niamh; Zaba, Ryszard; Jakubowicz, Oliwia; Szkaradkiewicz, Andrzej; Kavanagh, Kevin

    2012-11-01

    Rosacea is a common dermatological condition that predominantly affects the central regions of the face. Rosacea affects up to 3 % of the world's population and a number of subtypes are recognized. Rosacea can be treated with a variety of antibiotics (e.g. tetracycline or metronidazole) yet no role for bacteria or microbes in its aetiology has been conclusively established. The density of Demodex mites in the skin of rosacea patients is higher than in controls, suggesting a possible role for these mites in the induction of this condition. In addition, Bacillus oleronius, known to be sensitive to the antibiotics used to treat rosacea, has been isolated from a Demodex mite from a patient with papulopustular rosacea and a potential role for this bacterium in the induction of rosacea has been proposed. Staphylococcus epidermidis has been isolated predominantly from the pustules of rosacea patients but not from unaffected skin and may be transported around the face by Demodex mites. These findings raise the possibility that rosacea is fundamentally a bacterial disease resulting from the over-proliferation of Demodex mites living in skin damaged as a result of adverse weathering, age or the production of sebum with an altered fatty acid content. This review surveys the literature relating to the role of Demodex mites and their associated bacteria in the induction and persistence of rosacea and highlights possible therapeutic options.

  1. Reductive detoxification of acrolein as a potential role for aldehyde reductase (AKR1A) in mammals.

    Science.gov (United States)

    Kurahashi, Toshihiro; Kwon, Myoungsu; Homma, Takujiro; Saito, Yuka; Lee, Jaeyong; Takahashi, Motoko; Yamada, Ken-Ichi; Miyata, Satoshi; Fujii, Junichi

    2014-09-12

    Aldehyde reductase (AKR1A), a member of the aldo-keto reductase superfamily, suppresses diabetic complications via a reduction in metabolic intermediates; it also plays a role in ascorbic acid biosynthesis in mice. Because primates cannot synthesize ascorbic acid, a principle role of AKR1A appears to be the reductive detoxification of aldehydes. In this study, we isolated and immortalized mouse embryonic fibroblasts (MEFs) from wild-type (WT) and human Akr1a-transgenic (Tg) mice and used them to investigate the potential roles of AKR1A under culture conditions. Tg MEFs showed higher methylglyoxal- and acrolein-reducing activities than WT MEFs and also were more resistant to cytotoxicity. Enzymatic analyses of purified rat AKR1A showed that the efficiency of the acrolein reduction was about 20% that of glyceraldehyde. Ascorbic acid levels were quite low in the MEFs, and while the administration of ascorbic acid to the cells increased the intracellular levels of ascorbic acid, it had no affect on the resistance to acrolein. Endoplasmic reticulum stress and protein carbonylation induced by acrolein treatment were less evident in Tg MEFs than in WT MEFs. These data collectively indicate that one of the principle roles of AKR1A in primates is the reductive detoxification of aldehydes, notably acrolein, and protection from its detrimental effects.

  2. Survivin: Potential role in diagnosis, prognosis and targeted therapy of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Ting-Ting Wang; Xiao-Ping Qian; Bao-Rui Liu

    2007-01-01

    Survivin is a protein that is highly expressed in a vast number of malignancies, but is minimally expressed in normal tissues. It plays a role as an inhibitor of cell death in cancer cells, thus facilitating the growth of these cells.Tn the case of gastric cancer, survivin is over-expressed in tumor cells and plays a role in the carcinogenesis process. Several studies on gastric cancer have indicated that there is a relationship between survivin expression and the ultimate behavior of the carcinoma. Since the expression pattern of survivin is selective to cancer cells,it has been described as an "ideal target" for cancer therapy. Currently, several pre-clinical and clinical trials are on-going to investigate the effects of interfering with survivin function in cancer cells as a biologic therapy. Survivin is a potentially significant protein in the diagnosis, prognosis and treatment of gastric tumors.

  3. The potential role of IGF-I receptor mRNA in rats with diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    匡洪宇; 邹伟; 刘丹; 史榕荇; 程丽华; 殷慧清; 刘晓民

    2003-01-01

    Objective To evaluate the potential role of insulin-like growth factor-1 receptor mRNA(IGF-IR mRNA) in the onset and development of retinopathy in diabetic rats.Methods A diabetic model was duplicated in Wistar rats. The early changes in the retina were examined using light and transmission electron microscopy. Expression of IGF-IR mRNA was analyzed using in situ hybridization.Results Weak expression of IGF-IR mRNA(5%) was found in retinas of normal rats, but was significantly increased (15% and 18%) in the retinas of diabetic rats after 3 and 6 months of diabetes (P<0.01). In situ hybridization and morphological study demonstrated that there was a positive correlation between IGF-IR mRNA expression and retinal changes at various stages.Conclusion Increased IGF-IR mRNA might play an important role in the onset and development of diabetic retinopathy.

  4. The potential role of vitamin D for prevention and treatment of tuberculosis and infectious diseases.

    Science.gov (United States)

    Dini, Catia; Bianchi, Antonio

    2012-01-01

    Vitamin D deficiency (VDD) is a common condition among several populations in the world. VDD is associated with higher incidence of immune system disorders and faster progression of some infectious diseases. Vitamin D is known to be of physiological importance, it is considered an essential micronutrient for the bone health and plays a beneficial role in the prevention and/or treatment of a number of chronic diseases. Vitamin D has a complex action on the immune system. Evidence that vitamin D protects against tuberculosis has been supported by in vitro, epidemiological and some preliminary clinical studies. Vitamin D has a potential effect on HIV (human immunodeficiency virus) and plays a crucial role in the defence against respiratory infections. Vitamin D supplementation could be a low-cost, practical method to protect groups of people with high incidence of those diseases. Public health education should stress the need for adequate dietary intake of vitamin D in those vulnerable groups.

  5. Potential role of a cognitive rehabilitation program following left temporal lobe epilepsy surgery

    Directory of Open Access Journals (Sweden)

    Camila de Vasconcelos Geraldi

    Full Text Available ABSTRACT Research into memory and epilepsy has focused on measuring problems and exploring causes with limited attention directed at the role of neuropsychological rehabilitation in alleviating post-operative memory difficulties. Objectives To assess the effects of a memory rehabilitation program in patients with left temporal lobe epilepsy following surgery. Methods Twenty-four patients agreed to participate and 18 completed the study; nine received memory rehabilitation while nine had no input and were designated as controls. Verbal learning efficiency, naming abilities, memory subjective ratings, ecological activity measures and a language fMRI paradigm were used as outcome measures. Results Improved verbal learning and naming test performance, increase in memory strategy use and improved self-perception were observed following the rehabilitation. Changes in fMRI activation patterns were seen in the rehabilitation group over the long term. Conclusion The findings support the potential role of a cognitive rehabilitation program following left temporal lobe surgery.

  6. Current concepts in the pathophysiology of fibromyalgia: the potential role of oxidative stress and nitric oxide.

    Science.gov (United States)

    Ozgocmen, Salih; Ozyurt, Huseyin; Sogut, Sadik; Akyol, Omer

    2006-05-01

    Fibromyalgia (FM) is a common chronic pain syndrome with an unknown etiology. Recent years added new information to our understanding of FM pathophysiology. Researches on genetics, biogenic amines, neurotransmitters, hypothalamic-pituitary-adrenal axis hormones, oxidative stress, and mechanisms of pain modulation, central sensitization, and autonomic functions in FM revealed various abnormalities indicating that multiple factors and mechanisms are involved in the pathogenesis of FM. Oxidative stress and nitric oxide may play an important role in FM pathophysiology, however it is still not clear whether oxidative stress abnormalities documented in FM are the cause or the effect. This should encourage further researches evaluating the potential role of oxidative stress and nitric oxide in the pathophysiology of FM and the efficacy of antioxidant treatments (omega-3 and -6 fatty acids, vitamins and others) in double blind and placebo controlled trials. These future researches will enhance our understanding of the complex pathophysiology of this disorder.

  7. Th9 lymphocytes: A recent history from IL-9 to its potential role in rheumatic diseases.

    Science.gov (United States)

    Rojas-Zuleta, Wilmer Gerardo; Vásquez, Gloria

    2016-07-01

    Various subtypes of effector T cells have been described up to date, and each one has its specific immunological function and a defined cytokine secretion profile. Th9 lymphocytes, recently described, are characterized by a high IL-9 expression. Their differentiation requires the integration of IL-4 and TGF-β signaling pathways and the coordinated participation of multiple transcription factors. Their role has been mainly found in immunity against parasites and in allergic inflammatory processes. Nevertheless, they have been implicated in processes as autoimmunity, cancer and recently in rheumatic diseases. The objective of this review is to describe the discovery of this cellular subtype, its differentiation, expression regulation and its potential role in rheumatic diseases.

  8. The potential key seed-dispersing role of the arboreal marsupial Dromiciops gliroides

    Science.gov (United States)

    Amico, Guillermo C.; Rodríguez-Cabal, Mariano A.; Aizen, Marcelo A.

    2009-01-01

    Marsupial seed dispersal is a rare phenomenon, although it may be ecologically significant in southern South America. The marsupial Dromiciops gliroides is endemic to the northern part of the temperate forest of South America. Here we describe the food habits and examine the potential role of D. gliroides as a seed disperser. We evaluated the diet of this marsupial in its natural habitat and in captivity. Dromiciops gliroides is omnivorous showing high consumption of a diversity of fruits. In captivity, D. gliroides consumed fruits from 80% of 22 native plant species we examined. Experiments conducted with fruits from two common understory shrubs show that seed passage through the digestive tract of D. gliroides enhances germination. Our results suggest that this species may have an important role as a seed disperser in the temperate forest of South America, which might offset a scarcity of frugivorous bird species.

  9. Exercise-induced muscle damage and the potential protective role of estrogen.

    Science.gov (United States)

    Kendall, Becky; Eston, Roger

    2002-01-01

    Exercise-induced muscle damage is a well documented phenomenon that often follows unaccustomed and sustained metabolically demanding activities. This is a well researched, but poorly understood area, including the actual mechanisms involved in the muscle damage and repair cycle. An integrated model of muscle damage has been proposed by Armstrong and is generally accepted. A more recent aspect of exercise-induced muscle damage to be investigated is the potential of estrogen to have a protective effect against skeletal muscle damage. Estrogen has been demonstrated to have a potent antioxidant capacity that plays a protective role in cardiac muscle, but whether this antioxidant capacity has the ability to protect skeletal muscle is not fully understood. In both human and rat studies, females have been shown to have lower creatine kinase (CK) activity following both eccentric and sustained exercise compared with males. As CK is often used as an indirect marker of muscle damage, it has been suggested that female muscle may sustain less damage. However, these findings may be more indicative of the membrane stabilising effect of estrogen as some studies have shown no histological differences in male and female muscle following a damaging protocol. More recently, investigations into the potential effect of estrogen on muscle damage have explored the possible role that estrogen may play in the inflammatory response following muscle damage. In light of these studies, it may be suggested that if estrogen inhibits the vital inflammatory response process associated with the muscle damage and repair cycle, it has a negative role in restoring normal muscle function after muscle damage has occurred. This review is presented in two sections: firstly, the processes involved in the muscle damage and repair cycle are reviewed; and secondly, the possible effects that estrogen has upon these processes and muscle damage in general is discussed. The muscle damage and repair cycle is

  10. The role of the exchange in the embedding electrostatic potential for the fragment molecular orbital method.

    Science.gov (United States)

    Fedorov, Dmitri G; Kitaura, Kazuo

    2009-11-01

    We have examined the role of the exchange in describing the electrostatic potential in the fragment molecular orbital method and showed that it should be included in the total Fock matrix to obtain an accurate one-electron spectrum; however, adding it to the Fock matrices of individual fragments and pairs leads to very large errors. For the error analysis we have used the virial theorem; numerical tests have been performed for solvated phenol at the Hartree-Fock level with the 6-31G( *) and 6-311G( * *) basis sets.

  11. The potential role of cell phones in dissemination of bacteria in a healthcare sett

    Directory of Open Access Journals (Sweden)

    Mateusz P. Kister

    2016-04-01

    Full Text Available The mobile phone is an indispensible accessory, both from a social and a professional point of view, which is being used in a variety of environments, including those with high bacteria levels. Medical personnel, patients or even people simply passing by the healthcare facilities, having and using their mobile phones are likely to transmit bacteria, thus it might be suspected that mobile phones are to some extent a link in the cross-contamination. The purpose of this work was to collect information concerning the potential role of cell phones in a dissemination of bacteria based on available research data.

  12. The Potential Role of Kallistatin in the Development of Abdominal Aortic Aneurysm.

    Science.gov (United States)

    Li, Jiaze; Krishna, Smriti Murali; Golledge, Jonathan

    2016-08-11

    Abdominal aortic aneurysm (AAA) is a vascular condition that causes permanent dilation of the abdominal aorta, which can lead to death due to aortic rupture. The only treatment for AAA is surgical repair, and there is no current drug treatment for AAA. Aortic inflammation, vascular smooth muscle cell apoptosis, angiogenesis, oxidative stress and vascular remodeling are implicated in AAA pathogenesis. Kallistatin is a serine proteinase inhibitor, which has been shown to have a variety of functions, potentially relevant in AAA pathogenesis. Kallistatin has been reported to have inhibitory effects on tumor necrosis factor alpha (TNF-α) signaling induced oxidative stress and apoptosis. Kallistatin also inhibits vascular endothelial growth factor (VEGF) and Wnt canonical signaling, which promote inflammation, angiogenesis, and vascular remodeling in various pre-clinical experimental models. This review explores the potential protective role of kallistatin in AAA pathogenesis.

  13. The Potential Role of Kallistatin in the Development of Abdominal Aortic Aneurysm

    Directory of Open Access Journals (Sweden)

    Jiaze Li

    2016-08-01

    Full Text Available Abdominal aortic aneurysm (AAA is a vascular condition that causes permanent dilation of the abdominal aorta, which can lead to death due to aortic rupture. The only treatment for AAA is surgical repair, and there is no current drug treatment for AAA. Aortic inflammation, vascular smooth muscle cell apoptosis, angiogenesis, oxidative stress and vascular remodeling are implicated in AAA pathogenesis. Kallistatin is a serine proteinase inhibitor, which has been shown to have a variety of functions, potentially relevant in AAA pathogenesis. Kallistatin has been reported to have inhibitory effects on tumor necrosis factor alpha (TNF-α signaling induced oxidative stress and apoptosis. Kallistatin also inhibits vascular endothelial growth factor (VEGF and Wnt canonical signaling, which promote inflammation, angiogenesis, and vascular remodeling in various pre-clinical experimental models. This review explores the potential protective role of kallistatin in AAA pathogenesis.

  14. Molecular markers in prostate cancer.Part II:potential roles in management

    Institute of Scientific and Technical Information of China (English)

    Sachin Agrawal; Krishnaji P.Patil; William D.Dunsmuir

    2009-01-01

    Predicting treatment responses in advanced prostate cancer (PCa) currently centres on prostate-specific antigen (PSA) kinetics and on being able to visualize measurable changes in imaging modalities.New molecular markers have emerged as potential diagnostic and prognostic indicators;these were summarized in Part I of this review in the Asian Journal of Andrology.A number of molecular markers are now being used to enhance PCa imaging and staging.However,management options for advanced and hormone-resistant PCa (HRPC) are limited and additional therapeutic options are needed.Molecular markers have been proposed as potential therapeutic targets using gene therapy and immunomodulation.Additionally,markers identified in early PCa and precursor lesions may offer novel targets for chemoprevention and vaccine development.This review summarizes the current advances regarding the roles of these markers in the management of PCa.

  15. The Role and Potential Therapeutic Application of Myeloid-Derived Suppressor Cells in Allo- and Autoimmunity

    Directory of Open Access Journals (Sweden)

    Qi Zhang

    2015-01-01

    Full Text Available Myeloid-derived suppressor cells (MDSCs are a heterogeneous population of cells that consists of myeloid progenitor cells and immature myeloid cells. They have been identified as a cell population that may affect the activation of CD4+ and CD8+ T-cells to regulate the immune response negatively, which makes them attractive targets for the treatment of transplantation and autoimmune diseases. Several studies have suggested the potential suppressive effect of MDSCs on allo- and autoimmune responses. Conversely, MDSCs have also been found at various stages of differentiation, accumulating during pathological situations, not only during tumor development but also in a variety of inflammatory immune responses, bone marrow transplantation, and some autoimmune diseases. These findings appear to be contradictory. In this review, we summarize the roles of MDSCs in different transplantation and autoimmune diseases models as well as the potential to target these cells for therapeutic benefit.

  16. Potential Role of Olive Oil Phenolic Compounds in the Prevention of Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Jose Rodríguez-Morató

    2015-03-01

    Full Text Available Adherence to the Mediterranean Diet (MD has been associated with a reduced incidence of neurodegenerative diseases and better cognitive performance. Virgin olive oil, the main source of lipids in the MD, is rich in minor phenolic components, particularly hydroxytyrosol (HT. HT potent antioxidant and anti-inflammatory actions have attracted researchers’ attention and may contribute to neuroprotective effects credited to MD. In this review HT bioavailability and pharmacokinetics are presented prior to discussing health beneficial effects. In vitro and in vivo neuroprotective effects together with its multiple mechanisms of action are reviewed. Other microconstituents of olive oil are also considered due to their potential neuroprotective effects (oleocanthal, triterpenic acids. Finally, we discuss the potential role of HT as a therapeutic tool in the prevention of neurodegenerative diseases.

  17. THE ROLE OF THE INNOVATION POTENTIAL IN THE MANAGEMENT SYSTEM OF ECONOMIC SECURITY OF ENTERPRISES

    Directory of Open Access Journals (Sweden)

    Y. P. Anisimov

    2015-01-01

    Full Text Available The article explores the theoretical foundations of innovative potential of the enterprise and its role for sustainable development and economic security. The urgency of the problem of sustainable development innovative capacity, low level of theoretical and practical elaboration, poor methodological and conceptual basis for the development of economic security, increasing competitiveness and strengthening market situation of enterprises, determined the choice of the research topic. Scientific awareness of the key problems of the economy determined the significance of the research topic, the relevance of which is determined by the need for new theoretical concepts, methodological developments and practical recommendations on the role of innovation potential in the management system of economic security of enterprises. The system of economic security management is the basis of the successful functioning and development of enterprises. In market conditions, the economic security of organizations is directly outside-the implementation of innovations into the production process, which is an effective means of increasing competitiveness, improving the quality of products. The innovative capacity of enterprises consists of a unique ability to increase such components as material and investment, information, personnel that will help the organization to achieve new strategic goals. It should be noted that not all products are offered by organizations on the existing market, generates potential, but only one that is potentially profitable. That is, the products created on the basis of innovative technologies, from-while a high quality and should demand amongst consumers. Economic security policy is a system of views, different measures, methods of solutions, specific actions in the area of economic security, which determine the conditions for achieving business goals. Thus, the implemented security policy allocates the organization to carry out economic

  18. Structural basis for bitter taste receptor activation and its potential role in targeting diabetes

    Directory of Open Access Journals (Sweden)

    Ravinder Abrol

    2015-03-01

    Full Text Available Background: Taste receptors are G protein-coupled receptors that, besides being present in the taste buds, have also been shown to be present in the gastrointestinal (GI system, respiratory system, and brain, though their function at these locations is not well understood. Objective: To understand the nutrient mediated release of gut peptides like GLP-1 from enteroendocrine L-cells of the GI system, we focused on a bitter taste receptor TAS2R38 (based on animal models to investigate the structural basis of its potential role in the release of gut peptides. Methods: The atomic-level structure of bitter taste receptor TAS2R38 was predicted using GEnSeMBLE, a first-principle based GPCR structure prediction method. These structures were obtained for the dominant taster haplotype (PAV as well as for the nontaster haplotype (AVI of the receptor. The known ligands phenylthiocarbamide (PTC and 6-n-propylthiouracil (PTU were docked to these structures to provide a structural basis for the taster and nontaster haplotypes. Results: Docking of known ligands PTU and PTC to taster and nontaster haplotypes of the bitter taste receptor showed a backbone hydrogen bond to residue 262 in taster but not in nontaster haplotype, suggesting a potential mode of action of these molecules in the activation of the bitter taste receptor. Conclusion: These results, combined with the ability of PTC to release gut peptides from in vitro models of the enteroendocrine L-cells, suggest a potential structural basis for TAS2R38 activation that can lead to the release of those peptides. This release has a therapeutic benefit for type 2 diabetes and implies a role for bitter tasting (but safe natural compounds targeting TAS2R38 as potential drug candidates for curing type 2 diabetes.

  19. Role and potential of renewable energy and energy efficiency for global energy supply

    Energy Technology Data Exchange (ETDEWEB)

    Krewitt, Wolfram; Nienhaus, Kristina [German Aerospace Center e.V. (DLR), Stuttgart (Germany); Klessmann, Corinna; Capone, Carolin; Stricker, Eva [Ecofys Germany GmbH, Berlin (Germany); Graus, Wina; Hoogwijk, Monique [Ecofys Netherlands BV, Utrecht (Netherlands); Supersberger, Nikolaus; Winterfeld, Uta von; Samadi, Sascha [Wuppertal Institute for Climate, Environment and Energy GmbH, Wuppertal (Germany)

    2009-12-15

    The analysis of different global energy scenarios in part I of the report confirms that the exploitation of energy efficiency potentials and the use of renewable energies play a key role in reaching global CO2 reduction targets. An assessment on the basis of a broad literature research in part II shows that the technical potentials of renewable energy technologies are a multiple of today's global final energy consumption. The analysis of cost estimates for renewable electricity generation technologies and even long term cost projections across the key studies in part III demonstrates that assumptions are in reasonable agreement. In part IV it is shown that by implementing technical potentials for energy efficiency improvements in demand and supply sectors by 2050 can be limited to 48% of primary energy supply in IEA's ''Energy Technology Perspectives'' baseline scenario. It was found that a large potential for cost-effective measures exists, equivalent to around 55-60% of energy savings of all included efficiency measures (part V). The results of the analysis on behavioural changes in part VI show that behavioural dimensions are not sufficiently included in energy scenarios. Accordingly major research challenges are revealed. (orig.)

  20. Role of the potential landscape on the single-file diffusion through channels

    Energy Technology Data Exchange (ETDEWEB)

    Goldt, S. D.; Terentjev, E. M. [Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE (United Kingdom)

    2014-12-14

    Transport of colloid particles through narrow channels is ubiquitous in cell biology as well as becoming increasingly important for microfluidic applications or targeted drug delivery. Membrane channels in cells are useful models for artificial designs because of their high efficiency, selectivity, and robustness to external fluctuations. Here, we model the passive channels that let cargo simply diffuse through them, affected by a potential profile along the way. Passive transporters achieve high levels of efficiency and specificity from binding interactions with the cargo inside the channel. This however leads to a paradox: why should channels which are so narrow that they are blocked by their cargo evolve to have binding regions for their cargo if that will effectively block them? Using Brownian dynamics simulations, we show that different potentials, notably symmetric, increase the flux through narrow passive channels – and investigate how shape and depth of potentials influence the flux. We find that there exist optimal depths for certain potential shapes and that it is most efficient to apply a small force over an extended region of the channel. On the other hand, having several spatially discrete binding pockets will not alter the flux significantly. We also explore the role of many-particle effects arising from pairwise particle interactions with their neighbours and demonstrate that the relative changes in flux can be accounted for by the kinetics of the absorption reaction at the end of the channel.

  1. Spatial prediction and analysis of Himalayan marmot plague natural epidemic foci in China based on HJ-1 satellite data

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Plague,caused by the gram-negative bacterium Yersinia pestis,is a serious and rapidly progressing illness in humans that can be fatal if not treated effectively.The Qinghai-Tibet Plateau is the largest area of natural Himalayan marmot(Marmota himalayana) plague foci in China and covers more than 630000 km2.Akesai County in Gansu Province is a part of this natural focus of plague and was chosen as a study area.Our study used an ecological niche modeling(ENM) approach to predict the potential distribution of the Himalayan marmot.Environment and Disaster Monitor Satellite(HJ-1) data was used to investigate environment factors that affect plague host animal activity.Host animal point data from active surveillance was combined with environmental variables from the HJ-1 satellite and other databases,and the models of the potential distribution of Himalayan marmot were produced with the Genetic Algorithm for Rule-Set Production(GARP).The probability of marmot presence was divided into 0-5%,5%-20%,20%-40%,40%-80%,and 80%-100% subgroups.Areas with 80%-100% probability exhibited the greatest potential for the presence of Himalayan marmot.According to the predicted potential distribution of Himalayan marmot in the study area,active surveillance of plague hosts and plague control and prevention could be more efficient.

  2. Increased glycation of hemoglobin in chronic renal failure: [corrected] potential role of oxidative stress.

    Science.gov (United States)

    Selvaraj, Nambiar; Bobby, Zachariah; Sridhar, Magadi Gopalakrishna

    2008-04-01

    Among the various mechanisms proposed, the process of non-enzymatic glycation of proteins is believed to play an important role in the pathogenesis of chronic complications associated with renal failure. The two traditional factors found to modulate the early glycation of proteins are the prevailing concentration of glucose and half life of the protein. Among the various proteins that are known to undergo nonenzymatic glycation in vivo, hemoglobin has been the most thoroughly investigated. Determination of glycated hemoglobin in diabetic patients is currently acknowledged as the most reliable indicator for assessment of retrospective glycemic control and the planning of clinical management. The clinical utility of glycated hemoglobin measurements, however, in renal failure is controversial, given the numerous earlier studies showing no correlation between glycated hemoglobin and other indicators of blood glucose control in uremic subjects. With few exceptions, previous studies have suggested that the concentration of glycated hemoglobin was increased in uremic patients. There is documented evidence that increased glycated hemoglobin levels are found in certain non-diabetic states. So it stands to reason that hyperglycemia, although clearly being the culprit in diabetes, does not provide the complete answer to the etiology of increased early glycated products in non-diabetic conditions including chronic renal failure. This article reviews available evidence supporting increased glycation of hemoglobin in patients with chronic renal failure. Potential mechanisms for this increase are examined with special emphasis on the potential role of oxidative stress.

  3. Lipidomics: potential role in risk prediction and therapeutic monitoring for diabetes and cardiovascular disease.

    Science.gov (United States)

    Meikle, Peter J; Wong, Gerard; Barlow, Christopher K; Kingwell, Bronwyn A

    2014-07-01

    Lipidomics has developed rapidly over the past decade to the point where clinical application may soon be possible. Developments including high throughput technologies enable the simultaneous quantification of several hundred lipid species, thereby providing a global assessment of lipid metabolism. Given the key role of lipids in the pathophysiology of diabetes and cardiovascular disease, lipidomics has the potential to: i) Significantly improve prediction of future disease risk, ii) Inform on mechanisms of disease pathogenesis, iii) Identify patient groups responsive to particular therapies and iv) More closely monitor response to therapy. Lipidomic analyses of both whole plasma and lipoprotein subfractions are integral to the current initiative to understand the relationships between lipoprotein composition and function and how these are affected by disease and treatment. This approach will not only aid in appropriate targeting of existing lipid lowering therapies such as statins and fibrates, but will be important in unravelling the controversies surrounding HDL-based therapies which have failed in clinical trials to date. The ultimate utility of lipidomics to clinical practice will depend firstly on the ability of risk prediction models incorporating lipidomic parameters to significantly improve upon conventional clinical risk markers in predicting future disease risk. Secondly, for widespread application, lipidomic-based measurements must be practical and accessible through standard pathology laboratories. This review will cover developments in lipidomics including methodology, bioinformatics/statistics, insights into disease pathophysiology, the effect of therapeutic interventions, the role of large clinical outcome trials in validating lipidomic approaches to patient management and potential applications in clinical practice.

  4. Role of TRPM7 in Cancer: Potential as Molecular Biomarker and Therapeutic Target

    Directory of Open Access Journals (Sweden)

    Nelson S. Yee

    2017-04-01

    Full Text Available The transient receptor potential melastatin-subfamily member 7 (TRPM7 is a ubiquitously expressed ion channel with intrinsic kinase activity. Molecular and electrophysiological analyses of the structure and activity of TRPM7 have revealed functional coupling of its channel and kinase activity. Studies have indicated the important roles of TRPM7 channel-kinase in fundamental cellular processes, physiological responses, and embryonic development. Accumulating evidence has shown that TRPM7 is aberrantly expressed and/or activated in human diseases including cancer. TRPM7 plays a variety of functional roles in cancer cells including survival, cell cycle progression, proliferation, growth, migration, invasion, and epithelial-mesenchymal transition (EMT. Data from a study using mouse xenograft of human cancer show that TRPM7 is required for tumor growth and metastasis. The aberrant expression of TRPM7 and its genetic mutations/polymorphisms have been identified in various types of carcinoma. Chemical modulators of TRPM7 channel produced inhibition of proliferation, growth, migration, invasion, invadosome formation, and markers of EMT in cancer cells. Taken together, these studies suggest the potential value of exploiting TRPM7 channel-kinase as a molecular biomarker and therapeutic target in human malignancies.

  5. Potential role of traditional birth attendants in neonatal healthcare in rural southern Nepal.

    Science.gov (United States)

    Falle, Tina Y; Mullany, Luke C; Thatte, Nandita; Khatry, Subarna K; LeClerq, Steven C; Darmstadt, Gary L; Katz, Joanne; Tielsch, James M

    2009-02-01

    The potential for traditional birth attendants (TBAs) to improve neonatal health outcomes has largely been overlooked during the current debate regarding the role of TBAs in improving maternal health. Randomly-selected TBAs (n=93) were interviewed to gain a more thorough understanding of their knowledge, attitudes, and practices regarding maternal and newborn care. Practices, such as using a clean cord-cutting instrument (89%) and hand-washing before delivery (74%), were common. Other beneficial practices, such as thermal care, were low. Trained TBAs were more likely to wash hands with soap before delivery, use a clean delivery-kit, and advise feeding colostrum. Although mustard oil massage was a universal practice, 52% of the TBAs indicated their willingness to consider alternative oils. Low-cost, evidence-based interventions for improving neonatal outcomes might be implemented by TBAs in this setting where most births take place in the home and neonatal mortality risk is high. Continuing efforts to define the role of TBAs may benefit from an emphasis on their potential as active promoters of essential newborn care.

  6. Potential Role of Pet Cats As a Sentinel Species for Human Exposure to Flame Retardants

    Directory of Open Access Journals (Sweden)

    Luis A. Henríquez-Hernández

    2017-05-01

    Full Text Available Flame retardants are a wide group of chemicals used by the industry to avoid combustion of materials. These substances are commonly found in plastics, electronic equipment, fabrics, and in many other everyday articles. Subsequently, ubiquitous environmental contamination by these common chemical is frequently reported. In the present study, we have evaluated the level of exposure to polychlorinated biphenyls (PCBs, brominated diphenyl ethers (BDEs, and organophosphorous flame retardants (OPFRs in pet cats through the analysis of their serum. We also analyzed the level exposure to such chemicals in a series of 20 cat owners, trying to disclose the role of pet cats as sentinel species of human exposure to FRs. Our results showed that PCBs, banned 40 years ago, showed the lowest levels of exposure, followed by BDEs—banned recently. Congeners PCB-138 and PCB-180 were detected in ≥50% of the series, while BDE-47 was detected in near 90% of the pet cats. On the other hand, the highest levels were that of OPFRs, whose pattern of detection was similar to that observed in humans, thus suggesting a potential role of cats as a sentinel species for human exposure to these currently used FRs. Six out of 11 OPFRs determined [2-ethylhexyldiphenyl phosphate, tributylphosphate, triisobutylphosphate, triphenylphosphate, tris (2-chloroethyl phosphate, and tris (2-chloroisopropyl phosphate] were detected in 100% of the samples. It will be interesting to perform future studied aimed to elucidating the potential toxicological effects of these highly detected chemicals both, in cats and humans.

  7. Nup153 and Nup50 promote recruitment of 53BP1 to DNA repair foci by antagonizing BRCA1-dependent events.

    Science.gov (United States)

    Mackay, Douglas R; Howa, Amanda C; Werner, Theresa L; Ullman, Katharine S

    2017-10-01

    DNA double-strand breaks are typically repaired through either the high-fidelity process of homologous recombination (HR), in which BRCA1 plays a key role, or the more error-prone process of non-homologous end joining (NHEJ), which relies on 53BP1. The balance between NHEJ and HR depends, in part, on whether 53BP1 predominates in binding to damage sites, where it protects the DNA ends from resection. The nucleoporin Nup153 has been implicated in the DNA damage response, attributed to a role in promoting nuclear import of 53BP1. Here, we define a distinct requirement for Nup153 in 53BP1 intranuclear targeting to damage foci and report that Nup153 likely facilitates the role of another nucleoporin, Nup50, in 53BP1 targeting. The requirement for Nup153 and Nup50 in promoting 53BP1 recruitment to damage foci induced by either etoposide or olaparib is abrogated in cells deficient for BRCA1 or its partner BARD1, but not in cells deficient for BRCA2. Together, our results further highlight the antagonistic relationship between 53BP1 and BRCA1, and place Nup153 and Nup50 in a molecular pathway that regulates 53BP1 function by counteracting BRCA1-mediated events. © 2017. Published by The Company of Biologists Ltd.

  8. Anaerobic fungi (phylum Neocallimastigomycota): advances in understanding their taxonomy, life cycle, ecology, role and biotechnological potential.

    Science.gov (United States)

    Gruninger, Robert J; Puniya, Anil K; Callaghan, Tony M; Edwards, Joan E; Youssef, Noha; Dagar, Sumit S; Fliegerova, Katerina; Griffith, Gareth W; Forster, Robert; Tsang, Adrian; McAllister, Tim; Elshahed, Mostafa S

    2014-10-01

    Anaerobic fungi (phylum Neocallimastigomycota) inhabit the gastrointestinal tract of mammalian herbivores, where they play an important role in the degradation of plant material. The Neocallimastigomycota represent the earliest diverging lineage of the zoosporic fungi; however, understanding of the relationships of the different taxa (both genera and species) within this phylum is in need of revision. Issues exist with the current approaches used for their identification and classification, and recent evidence suggests the presence of several novel taxa (potential candidate genera) that remain to be characterised. The life cycle and role of anaerobic fungi has been well characterised in the rumen, but not elsewhere in the ruminant alimentary tract. Greater understanding of the 'resistant' phase(s) of their life cycle is needed, as is study of their role and significance in other herbivores. Biotechnological application of anaerobic fungi, and their highly active cellulolytic and hemi-cellulolytic enzymes, has been a rapidly increasing area of research and development in the last decade. The move towards understanding of anaerobic fungi using -omics based (genomic, transcriptomic and proteomic) approaches is starting to yield valuable insights into the unique cellular processes, evolutionary history, metabolic capabilities and adaptations that exist within the Neocallimastigomycota.

  9. SPO11-Independent DNA Repair Foci and Their Role in Meiotic Silencing

    NARCIS (Netherlands)

    F. Carofiglio (Fabrizia); A. Inagaki (Akiko); S.I. de Vries (Sanne); E. Wassenaar (Evelyne); S. Schoenmakers (Sam); C.E. Vermeulen (Cindy); W.A. van Cappellen (Gert); E. Sleddens-Linkels (Esther); J.A. Grootegoed (Anton); H.P.J. te Riele (Hein); B. de Massy (Bernard); W.M. Baarends (Willy)

    2013-01-01

    textabstractIn mammalian meiotic prophase, the initial steps in repair of SPO11-induced DNA double-strand breaks (DSBs) are required to obtain stable homologous chromosome pairing and synapsis. The X and Y chromosomes pair and synapse only in the short pseudo-autosomal regions. The rest of the chrom

  10. Morphological heterogeneity of the simultaneous ipsilateral invasive tumor foci in breast carcinoma: a retrospective study of 418 cases of carcinomas.

    Science.gov (United States)

    Boros, Monica; Marian, Cristina; Moldovan, Cosmin; Stolnicu, Simona

    2012-10-15

    The aim of this paper was to assess whether the morphological appearance (i.e. histological tumor type and histological grade) of simultaneous invasive breast carcinoma foci is heterogeneous, since it is known that adjuvant therapy is established according to these parameters. Patients with simultaneous breast tumors in which only the features of the largest neoplastic focus are reported could thus be undertreated. A retrospective study of 418 cases of breast carcinomas was conducted over a 3-year period. The histological tumor types and histological grades of multifocal/multicentric carcinomas in each tumor focus were compared, and mismatches among foci were recorded. Ninety-one of the 418 cases reviewed had multiple carcinomas (21.77%). A comparison between multiple synchronous tumor foci revealed that their histological type was different in 12.08% of the cases. Mismatches among foci were also observed in 9.89% of the cases when evaluating the histological grade, and 5 out of 9 additional tumor foci with a different grade from the largest (index) tumor (55.55%) displayed a higher grade compared to the index tumor. Since the histological tumor type and histological grade of the individual foci may vary considerably within the same tumor and the additional foci may be of higher grade than the index tumor, we believe that reporting morphologic parameters with more unfavorable characteristics in addition to the parameters of the index tumor is imperative.

  11. Potential Role of Metabolic Intervention in the Management of Advanced Differentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Sri Harsha Tella

    2017-07-01

    Full Text Available Well-differentiated thyroid carcinoma (DTC is the most common endocrine malignancy that has an excellent prognosis with a 5-year survival rate of about 98%. However, approximately 50% of the patients with DTC who present with distant metastases (advanced DTC die from the disease within 5 years of initial diagnosis even after getting the appropriate therapy. Apart from recent advancements in chemotherapy agents, the potential role of metabolic interventions, including the use of metformin, ketogenic diet, and high-dose vitamin C in the management of advanced cancers have been investigated as a less toxic co-adjuvant therapies. The role of vitamin C has been of interest again after a preclinical mice study showed that high-dose vitamin C is selectively lethal to KRAS and BRAF mutant colorectal cancer cells by targeting the glutathione pathway. This raises the possibility of utilizing high-doses of vitamin C in the treatment of aDTC where KRAS and BRAF mutations are common. Similarly, alteration of cellular metabolism by low-carbohydrate ketogenic diets can be an important therapeutic strategy to selectively kill cancer cells that mainly survive on glycolysis. Among the potential adjuvant therapies proposed in this paper, metformin is the only agent that has shown benefit in human model of aDTC, the others have shown benefit but in preclinical/animal studies only and need to be further evaluated in large clinical trials. In conclusion, in addition to concurrent chemotherapy options, these metabolic interventions may have a great potential as co-adjuvant therapy in the management of aDTC.

  12. Potential role of CXCL10 in the induction of cell injury and mitochondrial dysfunction.

    Science.gov (United States)

    Singh, Lipi; Arora, Sunil Kumar; Bakshi, Dapinder K; Majumdar, Siddarth; Wig, Jai Dev

    2010-06-01

    Chemokines have been known to play a critical role in pathogenesis of chronic pancreatitis and acinar cell death. However, the role played by one of the CXC chemokines: CXCL10 in regulation of acinar cell death has remained unexplored. Hence, this study was designed to assess the role of CXCL10 promoting apoptosis in ex vivo cultured acinar cells. Primary human pancreatic acinar cell cultures were established and exposed to varying doses of CXCL10 for different time intervals. Apoptotic induction was evaluated by both qualitative as well as quantitative analyses. Various mediators of apoptosis were also studied by Western blotting, membrane potential (Psim) and ATP depletion in acinar cells. Analysis of apoptosis via DNA ladder and cell death detection - ELISA demonstrated that CXCL10 induced 3.9-fold apoptosis when administrated at an optimal dose of 0.1 mug of recombinant CXCL10 for 8 h. Quantitative analysis using FACS and dual staining by PI-annexin showed increased apoptosis (48.98 and 53.78% respectively). The involvement of upstream apoptotic regulators like pJNK, p38 and Bax was established on the basis of their increased expression of CXCL10. The change of Psim by 50% was observed in the presence of CXCL10 in treated acinar cells along with enhanced expression of Cytochrome C, apaf-1 and caspase 9/3 activation. In addition, ATP depletion was also noticed in CXCL10 stimulated acinar cells. CXCL10 induces cell death in human cultured pancreatic cells leading to apoptosis and DNA fragmentation via CXCR3 signalling. These signalling mechanisms may play an important role in parenchymal cell loss and injury in pancreatitis.

  13. The potential role of omega-3 fatty acids supplements in increasing athletic performance

    Directory of Open Access Journals (Sweden)

    Șerban GLIGOR

    2017-03-01

    Full Text Available Polyunsaturated omega-3 and omega-6 fatty acids are essential fatty acids that cannot be produced by the body itself and therefore must be provided through nutrition. Omega-6 and particularly omega-3 fatty acids have important roles in the organism, contributing to the maintenance and promotion of health. The optimal proportion of omega-6/omega-3 fatty acids is 2:1, or even better 1:1. They are involved in normal growth and development, play a role in the prevention of coronary and cardiovascular diseases, of diabetes mellitus, of arterial hypertension, arthritis and cancer. Omega-3 fatty acids mainly have an anti-inflammatory effect, but also act as hypolipidemic and antithrombotic agents. A potential role of omega-3 fatty acids is that of increasing physical performance. Their role in the physical activity refers on one side to the global health of athletes and on the other side to their anti-inflammatory effect, as high intensity physical exercise induces increased free-radical production and microtraumas, with the induction of an inflammatory status. The anti-inflammatory effect of these fatty acids manifests through an increased production of endogenous antioxidant enzymes, through decreasing the production of prostaglandins metabolites, decreasing the production of leukotriene B4, etc. They are also effective on reducing muscle pain post eccentric exercise and on decreasing the severity of bronchoconstriction induced by exercise, as well as improving pulmonary function variables. In conclusion it seems that supplementing diets with omega-3 fatty acids, apart from having benefic effects on health and on the prevention and management of certain affections, proves to be a beneficial for physical activity and athletic performance.

  14. Culturable microorganisms associated with Sishen iron ore and their potential roles in biobeneficiation.

    Science.gov (United States)

    Adeleke, Rasheed; Cloete, T E; Khasa, D P

    2012-03-01

    With one of the largest iron ore deposits in the world, South Africa is recognised to be among the top ten biggest exporters of iron ore. Increasing demand and consumption of this mineral triggered search for processing technologies, which can be utilised to "purify" the low-grade iron ore minerals that contain high levels of unwanted potassium (K) and phosphorus (P). This study investigated a potential biological method that can be further developed for the full biobeneficiation of low-grade iron ore minerals. Twenty-three bacterial strains that belong to Proteobacteria, Firmicutes, Bacteroidetes and Actinobateria were isolated from the iron ore minerals and identified with sequence homology and phylogenetic methods. The abilities of these isolates to lower the pH of the growth medium and solubilisation of tricalcium phosphate were used to screen them as potential mineral solubilisers. Eight isolates were successfully screened with this method and utilised in shake flask experiments using iron ore minerals as sources of K and P. The shake flask experiments revealed that all eight isolates have potentials to produce organic acids that aided the solubilisation of the iron ore minerals. In addition, all eight isolates produced high concentrations of gluconic acid followed by relatively lower concentrations of acetic, citric and propanoic acid. Scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) analyses also indicated extracellular polymeric substances could play a role in mineral solubilisation.

  15. Solar Wind Sputtering of Lunar Surface Materials: Role and Some Possible Implications of Potential Sputtering

    Science.gov (United States)

    Barghouty, A. F.; Adams, J. H., Jr.; Meyer, F.; Reinhold, c.

    2010-01-01

    Solar-wind induced sputtering of the lunar surface includes, in principle, both kinetic and potential sputtering. The role of the latter mechanism, however, in many focused studies has not been properly ascertained due partly to lack of data but can also be attributed to the assertion that the contribution of solar-wind heavy ions to the total sputtering is quite low due to their low number density compared to solar-wind protons. Limited laboratory measurements show marked enhancements in the sputter yields of slow-moving, highly-charged ions impacting oxides. Lunar surface sputtering yields are important as they affect, e.g., estimates of the compositional changes in the lunar surface, its erosion rate, as well as its contribution to the exosphere as well as estimates of hydrogen and water contents. Since the typical range of solar-wind ions at 1 keV/amu is comparable to the thickness of the amorphous rim found on lunar soil grains, i.e. few 10s nm, lunar simulant samples JSC-1A AGGL are specifically enhanced to have such rims in addition to the other known characteristics of the actual lunar soil particles. However, most, if not all laboratory studies of potential sputtering were carried out in single crystal targets, quite different from the rim s amorphous structure. The effect of this structural difference on the extent of potential sputtering has not, to our knowledge, been investigated to date.

  16. Simulation of symmetric nuclei and the role of Pauli potential in binding energies

    Energy Technology Data Exchange (ETDEWEB)

    M. Angeles Perez-Garcia, K. Tsushima, A. Valcarce

    2009-05-01

    It is shown that the use of a density dependent effective Pauli potential together with a nucleon-nucleon interaction potential plays a crucial role to reproduce not only the binding energies but also the matter root mean square radii of medium mass range spin-isospin saturated nuclei. This study is performed with a semiclassical Monte Carlo many-body simulation within the context of a simplified nucleon-nucleon interaction to focus on the effect of the genuine correlations due to the fermionic nature of nucleons. The procedure obtained is rather robust and it does not depend on the detailed features of the nucleon-nucleon interaction. For nuclei below saturation the density dependence may be represented in terms either of the nucleon number, $A$, or the associated Fermi momenta. When testing the simulation procedure for idealized "infinite" symmetric nuclear matter within the corresponding range of densities, it turns out that finite size effects affect the Pauli potential strength parametrization in systems up to about 120 particles while remaining approximately stable for larger systems.

  17. Bladder Cancer and Urothelial Impairment: The Role of TRPV1 as Potential Drug Target

    Directory of Open Access Journals (Sweden)

    Francesco Mistretta

    2014-01-01

    Full Text Available Urothelium, in addition to its primary function of barrier, is now understood to act as a complex system of cell communication that exhibits specialized sensory properties in the regulation of physiological or pathological stimuli. Furthermore, it has been hypothesized that bladder inflammation and neoplastic cell growth, the two most representative pathological conditions of the lower urinary tract, may arise from a primary defective urothelial lining. Transient receptor potential vanilloid channel 1 (TRPV1, a receptor widely distributed in lower urinary tract structures and involved in the physiological micturition reflex, was described to have a pathophysiological role in inflammatory conditions and in the genesis and development of urothelial cancer. In our opinion new compounds, such as curcumin, the major component of turmeric Curcuma longa, reported to potentiate the effects of the chemotherapeutic agents used in the management of recurrent urothelial cancer in vitro and also identified as one of several compounds to own the vanillyl structure required to work like a TRPV1 agonist, could be thought as complementary in the clinical management of both the recurrences and the inflammatory effects caused by the endoscopic resection or intravesical chemotherapy administration or could be combined with adjuvant agents to potentiate their antitumoral effect.

  18. Predicting the vulnerability of great apes to disease: the role of superspreaders and their potential vaccination.

    Science.gov (United States)

    Carne, Charlotte; Semple, Stuart; Morrogh-Bernard, Helen; Zuberbühler, Klaus; Lehmann, Julia

    2013-01-01

    Disease is a major concern for the conservation of great apes, and one that is likely to become increasingly relevant as deforestation and the rise of ecotourism bring humans and apes into ever closer proximity. Consequently, it is imperative that preventative measures are explored to ensure that future epidemics do not wipe out the remaining populations of these animals. In this paper, social network analysis was used to investigate vulnerability to disease in a population of wild orang-utans and a community of wild chimpanzees. Potential 'superspreaders' of disease--individuals with disproportionately central positions in the community or population--were identified, and the efficacy of vaccinating these individuals assessed using simulations. Three resident female orang-utans were identified as potential superspreaders, and females and unflanged males were predicted to be more influential in disease spread than flanged males. By contrast, no superspreaders were identified in the chimpanzee network, although males were significantly more central than females. In both species, simulating the vaccination of the most central individuals in the network caused a greater reduction in potential disease pathways than removing random individuals, but this effect was considerably more pronounced for orang-utans. This suggests that targeted vaccinations would have a greater impact on reducing disease spread among orang-utans than chimpanzees. Overall, these results have important implications for orang-utan and chimpanzee conservation and highlight the role that certain individuals may play in the spread of disease and its prevention by vaccination.

  19. Aberrant Crypt Foci: The Case for Inclusion as a Biomarker for Colon Cancer

    OpenAIRE

    Jay Morris; Michael J. Wargovich; Brown, Vondina R.

    2010-01-01

    Aberrant crypt foci (ACF) are one of the earliest histopathological manifestations of colon cancer. In this review, we critically present the molecular, cellular, histopathological, and chemopreventive evidence that ACF are relevant biomarkers for colon cancer. The laboratory and clinical evidence are highly suggestive that ACF are in the pathway leading to colon cancer, but not all ACF will do so. The possible fate and outcome of ACF in the progression toward colon cancer may be dependent on...

  20. Sanation of carious and periapical foci in young athletes with impairment of cardiovascular adaptation

    Directory of Open Access Journals (Sweden)

    I. I. Belyaev

    2014-01-01

    Full Text Available The aim of this study was to evaluate the impact of sanation of oral cavity in young athletes on the course of adaptation of the cardiovascular system to the condition of sports activities. According to the research results, it was revealed that the optimal period for sanation of periapical odontogenic foci in athletes with clinical signs of impairment (dysfunction of cardiovascular system adaptation to exercise stress was a preparatory training period, while carious lesion sanation required preparatory or postcompetition periods.

  1. Rapid identification of paragonimiasis foci by lay informants in Lao People's Democratic Republic.

    Directory of Open Access Journals (Sweden)

    Peter Odermatt

    Full Text Available BACKGROUND: Paragonimiasis is a food-borne trematodiasis leading to lung disease. Worldwide, an estimated 21 million people are infected. Foci of ongoing transmission remain often unnoticed. We evaluated a simple questionnaire approach using lay-informants at the village level to identify paragonimiasis foci and suspected paragonimiasis cases. METHODOLOGY/PRINCIPAL FINDINGS: The study was carried out in an endemic area of Lao People's Democratic Republic. Leaders of 49 remote villages in northern Vientiane Province were asked to notify suspected paragonimiasis patients using a four-item questionnaire sent through administrative channels: persons responding positively for having chronic cough (more than 3 weeks and/or blood in sputum with or without fever. We validated the village leaders' reports in ten representative villages with a door-to-door survey. We examined three sputa of suspected patients for the presence of Paragonimus eggs and acid fast bacilli. 91.8% of village leaders participated and notified a total of 220 suspected patients; 76.2% were eventually confirmed; an additional 138 suspected cases were found in the survey. Sensitivity of village leaders' notice for "chronic cough" and "blood in sputum" was 100%; "blood in sputum" alone reached a sensitivity of 85.7%. SIGNIFICANCE: Our approach led to the identification of three previously unknown foci of transmission. A rapid and simple lay-informant questionnaire approach is a promising low-cost community diagnostic tool of paragonimiasis control programs.

  2. Evaluation of three-dimensional distribution of foci of diffuse lung diseases with computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Niwa, Masamitsu [Nagoya City Univ. (Japan). Medical School

    1998-11-01

    Three-dimensional distribution of foci of diffuse lung disease was evaluated by CT image, and it was examined whether each lung disease could be diagnosed by different distribution. Subjects were 120 cases (idiopathic interstitial pneumonia 15 cases, sarcoidosis 23 cases, miliary tuberculosis 10 cases, diffuse panbronchiolitis 7 cases, chronic pulmonary emphysema 6 cases, pulmonary metastasis 9 cases, SLE 6 cases, PSS 8 cases, dermatomyositis (DM) 6 cases, RA 7 cases, SjS 9 cases and others 14 cases). CT image was obtained from apex to base of lung with 10 mm gapless. The image was divided into three parts in both head-tail direction and back-front direction, and two parts in cortex medulla direction, and the ratio of foci to whole in each part was evaluated in five phases, and the part with the highest ratio was determined as the predominant side. In idiopathic interstitial pneumonia, sarcoidosis, miliary tuberculosis, diffuse panbronchiolitis, chronic pulmonary emphysema, pulmonary metastasis, PSS and DM, the predominant side was confirmed, respectively, and usefulness of differential diagnosis was recognized. Constant distribution wasn't recognized in SLE, RA and SjS, because the state of disease was not always same in the foci of these diseases. (K.H.)

  3. Enhancing effects of mustard oil on preneoplastic hepatic foci development in Wistar rats.

    Science.gov (United States)

    Shukla, Yogeshwer; Arora, Annu

    2003-02-01

    Dietary habits are known to be the major contributory factor in the development of cancer. Mustard oil, which is extensively used in India and elsewhere as a flying and cooking medium, is reported to induce an inflammatory response. The development of altered hepatic foci is an early carcinogenic change in rat liver in diethylnitrosamine (DEN)-induced hepatocarcinogenesis. In the present study, the development of preneoplastic lesions was observed following administration of mustard oil (0.5 mL/day for 8 weeks) in DEN-initiated and partially hepatomized Wistar rats. A significant decrease in the relative and absolute liver weight of mustard oil-exposed rats was recorded. The results revealed a significant increase in the number and area of placental glutathione-S-transferase (GST-P) and gamma-glutamyl transpeptidase (GGT)-positive foci in mustard oil-administered animals. The GST-P- and GGT-positive foci were more prominent in the animals given boiled (up to 300 degrees C for 3 hours) mustard oil in comparison to the animals given fresh mustard oil. These results indicate the possible tumourigenic risk associated with mustard oil consumption.

  4. pH, redox potential and local biofilm potential microenvironments within Geobacter sulfurreducens biofilms and their roles in electron transfer.

    Science.gov (United States)

    Babauta, Jerome T; Nguyen, Hung Duc; Harrington, Timothy D; Renslow, Ryan; Beyenal, Haluk

    2012-10-01

    The limitation of pH inside electrode-respiring biofilms is a well-known concept. However, little is known about how pH and redox potential are affected by increasing current inside biofilms respiring on electrodes. Quantifying the variations in pH and redox potential with increasing current is needed to determine how electron transfer is tied to proton transfer within the biofilm. In this research, we quantified pH and redox potential variations in electrode-respiring Geobacter sulfurreducens biofilms as a function of respiration rates, measured as current. We also characterized pH and redox potential at the counter electrode. We concluded that (1) pH continued to decrease in the biofilm through different growth phases, showing that the pH is not always a limiting factor in a biofilm and (2) decreasing pH and increasing redox potential at the biofilm electrode were associated only with the biofilm, demonstrating that G. sulfurreducens biofilms respire in a unique internal environment. Redox potential inside the biofilm was also compared to the local biofilm potential measured by a graphite microelectrode, where the tip of the microelectrode was allowed to acclimatize inside the biofilm. Copyright © 2012 Wiley Periodicals, Inc.

  5. Molecular Evidence of a Trypanosoma brucei gambiense Sylvatic Cycle in the Human African Trypanosomiasis Foci of Equatorial Guinea

    Directory of Open Access Journals (Sweden)

    Carlos eCordon-Obras

    2015-07-01

    Full Text Available Gambiense trypanosomiasis is considered an anthroponotic disease. Consequently, control programs are generally aimed at stopping transmission of Trypanosoma brucei gambiense (T. b. gambiense by detecting and treating human cases. However, the persistence of numerous foci despite efforts to eliminate this disease questions this strategy as unique tool to pursue the eradication. The role of animals as a reservoir of T. b. gambiense is still controversial, but could partly explain maintenance of the infection at hypo-endemic levels. In the present study, we evaluated the presence of T. b. gambiense in wild animals in Equatorial Guinea. The infection rate ranged from 0.8% in the insular focus of Luba to more than 12% in Mbini, a focus with a constant trickle of human cases. The parasite was detected in a wide range of animal species including four species never described previously as putative reservoirs. Our study comes to reinforce the hypothesis that animals may play a role in the persistence of T. b. gambiense transmission, being particularly relevant in low transmission settings. Under these conditions the integration of sustained vector control and medical interventions should be considered to achieve the elimination of Gambiense trypanosomiasis.

  6. AFSC/RACE/EcoFOCI - Ichthyoplankton data collected in support of FOCI assessment surveys and ecosystem observations in the Bering, Beaufort, and Chukchi Seas and the Gulf of Alaska 1972 to Present

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The dataset contains records of fish eggs and larvae collected during FOCI assessment surveys. Records include all data pertinent to identify where specimens were...

  7. Radioiodine therapy of benign non-toxic goitre. Potential role of recombinant human TSH

    DEFF Research Database (Denmark)

    Fast, S; Bonnema, S J; Hegedüs, L

    2011-01-01

    This review provides an update on recombinant human TSH (rh-TSH) augmented radioiodine (¹³¹I) therapy and outlines its potential role in the treatment of symptomatic benign multinodular non-toxic goitre. In some countries, ¹³¹I has been used for three decades to reduce the size of nodular goitres......-56% amplification of goitre reduction at one-year post radioiodine compared to conventional (without rh-TSH) ¹³¹I therapy. Although patient satisfaction is not improved at one-year, this approach facilitates tracheal decompression and is particularly promising in large goitres. The majority of multinodular non......-toxic goitre patients may not require amplified goitre reduction. But as an alternative strategy, rh-TSH allows up to 80% reduction of the therapeutic ¹³¹I activity while still achieving goitre reduction comparable to that of conventional ¹³¹I therapy and maintaining high patient satisfaction. The dose...

  8. Potential role of high mobility group box 1 in viral infectious diseases.

    Science.gov (United States)

    Wang, Haichao; Ward, Mary F; Fan, Xue-Gong; Sama, Andrew E; Li, Wei

    2006-01-01

    A nuclear protein, high mobility group box 1 (HMGB1), is released passively by necrotic cells and actively by macrophages/monocytes in response to exogenous and endogenous inflammatory stimuli. After binding to the receptor for advanced glycation end products (RAGE), or Toll-like receptor 4 (TLR4), HMGB1 activates macrophages/monocytes to express proinflammatory cytokines, chemokines, and adhesion molecules. Pharmacological suppression of its activities or release is protective against lethal endotoxemia and sepsis, establishing HMGB1 as a critical mediator of lethal systemic inflammation. In light of observations that many viruses (e.g., West Nile virus, Salmon anemia virus) can induce passive HMGB1 release, we propose a potential pathogenic role of HMGB1 in viral infectious diseases.

  9. Alpha-Synuclein Stimulation of Astrocytes: Potential Role for Neuroinflammation and Neuroprotection

    Directory of Open Access Journals (Sweden)

    He-Jin Lee

    2010-01-01

    Full Text Available Selective loss of neurons, abnormal protein deposition and neuroinflammation are the common pathological features of neurodegenerative diseases, and these features are closely related to one another. In Parkinson's disease, abnormal aggregation and deposition of α-synuclein is known as a critical event in pathogenesis of the disease, as well as in other related neurodegenerative disorders, such as dementia with Lewy bodies and multiple system atrophy. Increasing evidence suggests that α-synuclein aggregates can activate glial cells to induce neuroinflammation. However, how an inflammatory microenvironment is established and maintained by this protein remains unknown. Findings from our recent study suggest that neuronal α-synuclein can be directly transferred to astrocytes through sequential exocytosis and endocytosis and induce inflammatory responses from astrocytes. Here we discuss potential roles of astrocytes in a cascade of events leading to α-synuclein-induced neuroinflammation.

  10. The potential role of natural tumor promoters in marine turtle fibropapillomatosis

    Science.gov (United States)

    Landsberg, J.H.; Balazs, G.H.; Steidinger, K.A.; Baden, D.G.; Work, T.M.; Russel, D.J.

    1999-01-01

    Fibropapillomatosis (FP) in green turtles Chelonia mydas is a debilitating, neoplastic disease that has reached worldwide epizootic levels. The etiology of FP is unknown but has been linked to oncogenic viruses. Toxic benthic dinoflagellates (Prorocentrum spp.) are not typically considered tumorigenic agents, yet they have a worldwide distribution and produce a tumor promoter, okadaic acid (OA). Prorocentrum spp. are epiphytic on macroalgae and seagrasses that are normal components of green turtle diets. Here we show that green turtles in the Hawaiian Islands consume Prorocentrum and that high-risk FP areas are associated with areas where P. lima and P. concavum are both highly prevalent and abundant. The presence of presumptive OA in the tissues of Hawaiian green turtles further suggests exposure and a potential role for this tumor promoter in the etiology of FP.

  11. Potential Role of (-)-epigallocatechin-3-gallate (EGCG) in the Secondary Prevention of Alzheimer Disease.

    Science.gov (United States)

    Xicota, Laura; Rodríguez-Morató, Jose; Dierssen, Mara; de la Torre, Rafael

    2015-08-25

    Medical advances in the last decades have increased the average life expectancy, but also the incidence and prevalence of age-associated neurodegenerative diseases. Alzheimer disease (AD) is one of the most common neurodegenerative diseases and the most prevalent type of dementia. A plethora of different mechanisms contribute to AD, among which oxidative stress plays a key role in its development and progression. So far, there are no pharmacological treatments available and the current medications are mainly symptomatic. In the last years, dietary polyphenols have gained research attention due to their interesting biological activities, and more specifically their antioxidant properties. (-)-epigallocatechin-3-gallate (EGCG) is a natural flavanol that has been extensively studied regarding its potential effects in AD. In this review we present the current in vitro and in vivo experimentation regarding the use of EGCG in AD. We also review the complex mechanisms of action of EGCG, not only limited to its antioxidant activity, which may explain its beneficial health effects.

  12. Cardiovascular Disease and Psychiatric Comorbidity: The Potential Role of Perseverative Cognition

    Directory of Open Access Journals (Sweden)

    Britta A. Larsen

    2009-01-01

    Full Text Available The high comorbidity between psychiatric disorders and cardiovascular disease has received increasing attention, yet little is known about the processes linking the two. One plausible contributing mechanism is the tendency of those with psychiatric disorders to ruminate on stressful events. This phenomenon, sometimes called perseverative cognition, can extend the psychological and physiological effects of stress, which could contribute to cardiovascular disease etiology. In this paper, we discuss the potential role of perseverative cognition in mediating the relationship between psychiatric illness and cardiovascular disease. Rumination can delay physiological recovery from acute stress, which in turn has been found to predict future cardiovascular health. This delayed recovery could act as a mechanism in the longitudinal link between worry and cardiovascular health. The cognitive inflexibility that characterizes mood and anxiety disorders may then contribute to disease not by producing greater reactivity, but instead through extending activation, increasing the risks for cardiovascular damage.

  13. Potential role of anticonvulsants in the treatment of obsessive-compulsive and related disorders.

    Science.gov (United States)

    Wang, Hee Ryung; Woo, Young Sup; Bahk, Won-Myong

    2014-10-01

    We reviewed the extant literature to evaluate the current evidence regarding the efficacy and safety of anticonvulsants in the treatment of obsessive-compulsive and related disorders. Relevant literature was accessed using the Cochrane database, embase and PubMed on 29 October 2013. Prospective studies examining the efficacy of anticonvulsants in obsessive-compulsive and related disorders were included. Case reports, case series, and retrospective studies were excluded. A total of 10 studies were included in this review. The studies of obsessive-compulsive disorder, except for two negative studies, showed favorable efficacy results of anticonvulsants. In one study on body dysmorphic disorder, levetiracetam showed favorable efficacy. In two lamotrigine studies for pathologic skin-picking, the efficacy findings were inconsistent. In one trichotillomania study, topiramate had reduced hair-pulling symptoms. Despite limited evidence, our review suggests that anticonvulsants have a potential role in the treatment of obsessive-compulsive and related disorders.

  14. Anaesthesia for electroconvulsive therapy: An overview with an update on its role in potentiating electroconvulsive therapy

    Directory of Open Access Journals (Sweden)

    Pavan Kumar Kadiyala

    2017-01-01

    Full Text Available Despite advances in pharmacotherapy, electroconvulsive therapy (ECT remains a mainstay treatment option in psychiatry since its introduction in 1930s. It can be used primarily in severe illnesses when there is an urgent need for treatment or secondarily after failure or intolerance to pharmacotherapy. The 'unmodified' technique of ECT was practised initially, with a high incidence of musculoskeletal complications. Several modifications including general anaesthesia and muscle relaxation are used to increase the safety and patient acceptability of ECT. Various anaesthetic techniques including medications are considered to provide adequate therapeutic seizure, simultaneously controlling seizure-induced haemodynamic changes and side effects. A brief review of literature on choice of these anaesthetic techniques is discussed. This article is intended to reinforce the knowledge of clinicians, who may have limited exposure to ECT procedure. Importance is given to the recent updates on the role of induction agents in potentiating therapeutic response to ECT in psychiatric disorders.

  15. CAM use in dermatology. Is there a potential role for honey, green tea, and vitamin C?

    Science.gov (United States)

    Barbosa, Naiara S; Kalaaji, Amer N

    2014-02-01

    Complementary and alternative medicine (CAM) is a group of non-traditional medical practices that includes natural products, manipulations, and mind and body medicine. CAM use has grown and become popular among patients. In dermatology, honey, green tea, and vitamin C have been used as topical treatments for a variety of diseases. We performed a systematic review to explore the cutaneous effects of each of these three products. Honey's unique antibacterial, anti-inflammatory, and antioxidant properties were shown to contribute to wound healing, especially in ulcers and burns. Green tea, among many health benefits, demonstrated protection from ultraviolet-induced events, such as photoimmunosuppression and skin cancer growth. Vitamin C, known for its antioxidant properties and key role in collagen production, has been shown to produce positive effects on skin hyperpigmentation and aging. Future large well-designed clinical trials are needed in order to further investigate the potential of these agents as dermatological therapies.

  16. The potential role of inhibitor of differentiation-3 in human adipose tissue remodeling and metabolic health

    DEFF Research Database (Denmark)

    Svendstrup, Mathilde; Vestergaard, Henrik

    2014-01-01

    in the tissue. Regulation of angiogenesis in SAT and VAT in response to diet is therefore crucial for the metabolic outcome in obesity. Knowledge about the underlying genetic mechanisms determining metabolic health in obesity is very limited. We aimed to review the literature of the inhibitor of differentiation......-3 (ID3) gene in relation to adipose tissue and angiogenesis in humans in order to determine whether ID3 could be involved in the regulation of adipose tissue expansion and metabolic health in human obesity. We find evidence that ID3 is involved in regulatory mechanisms in adipose tissue...... literature suggest ID3 to play a potential role in the underlying regulatory mechanisms of metabolic health in human obesity. The literature is still sparse and further studies focusing on human ID3 in relation to the nature of obesity are warranted....

  17. The Potential Role of Non-Traditional Donors' Aid in Africa

    DEFF Research Database (Denmark)

    Kragelund, Peter

    The fast growth of big economies like China and India has resulted in a new-found interest in the economic and political consequences for the developed economies. However, the global rise of emerging economies also affects the potentials of South-South collaboration. Emerging economies invest...... and trade with partners in the South, and they use development assistance to facilitate these economic flows. This paper examines the consequences for Africa as well as for the traditional donors of the reemergence of the following four important non-traditional donors to Africa: China, India, Brazil...... and South Africa. Although the total size of the development assistance from these donors is still small in comparison to the traditional donors’ aid, its role is growing rapidly. So far, the ‘Western’, in particular the American, perception of these donors has been that of rogue donors supporting African...

  18. The role of streptokinase as a virulence determinant of Streptococcus pyogenes--potential for therapeutic targeting.

    Science.gov (United States)

    McArthur, Jason D; Cook, Simon M; Venturini, Carola; Walker, Mark J

    2012-03-01

    Streptococcus pyogenes is a major human pathogen responsible for numerous diseases ranging from uncomplicated skin and throat infections to severe, life threatening invasive disease such as necrotising fasciitis and streptococcal toxic shock syndrome. These severe invasive infections progress rapidly and produce high rates of morbidity and mortality despite the implementation of aggressive treatment plans. The activation of plasminogen and the acquisition of plasmin activity at the bacterial cell surface is critical for the invasive pathogenesis of this organism. To facilitate this process, S. pyogenes secrete streptokinase, a potent plasminogen activating protein. Here, we describe the role of streptokinase in invasive pathogenesis and discuss some potentially useful strategies for disruption of streptokinase mediated plasminogen activation which could be employed to treat severe invasive S. pyogenes infections.

  19. Ginseng on Cancer: Potential Role in Modulating Inflammation-Mediated Angiogenesis.

    Science.gov (United States)

    Dai, Daisy; Zhang, Chun-Feng; Williams, Stephanie; Yuan, Chun-Su; Wang, Chong-Zhi

    2017-01-01

    Angiogenesis is a regulated process integral to many physiological and pathological situations, including carcinogenesis and tumor growth. The majority of the angiogenic processes are related to inflammation. The interplay is not only important in the case of pathogen entry but also influential in chronic inflammatory diseases, tumor growth and tissue regeneration. Modulating the interaction between inflammation and angiogenesis could be an important target for cancer treatment and wound healing alike. Ginseng has a wide range of pharmacological effects, including anti-inflammatory and angiogenesis-modulating activities. This paper presents the recent research progresses on the inhibition of angiogenesis by ginseng and its active constituents, with a particular focus on processes mediated by inflammation. The modulatory role of ginseng compounds in inflammation-mediated angiogenesis involving hypoxia and microRNAs are also discussed. With the potential to modulate the angiogenesis at the transcriptional, translational and protein signaling level via various different mechanisms, ginseng could prove to be effective in cancer therapeutics.

  20. Contributing to the early detection of Rett syndrome: the potential role of auditory Gestalt perception.

    Science.gov (United States)

    Marschik, Peter B; Einspieler, Christa; Sigafoos, Jeff

    2012-01-01

    To assess whether there are qualitatively deviant characteristics in the early vocalizations of children with Rett syndrome, we had 400 native Austrian-German speakers listen to audio recordings of vocalizations from typically developing girls and girls with Rett syndrome. The audio recordings were rated as (a) inconspicuous, (b) conspicuous or (c) not able to decide between (a) and (b). The results showed that participants were accurate in differentiating the vocalizations of typically developing children compared to children with Rett syndrome. However, the accuracy for rating verbal behaviors was dependent on the type of vocalization with greater accuracy for canonical babbling compared to cooing vocalizations. The results suggest a potential role for the use of rating child vocalizations for early detection of Rett syndrome. This is important because clinical criteria related to speech and language development remain important for early identification of Rett syndrome.

  1. The Role of Education in Transforming the Potential Social Skills of College Students

    Directory of Open Access Journals (Sweden)

    Kuwi Hoi New

    2012-12-01

    Full Text Available This study advances “transformation” as the role of education in changing individual lives, and offers it as central to a theoretical framework that enables one to understand college education and the development of students in institutions of higher learning. Using a qualitative analytical approach, with in-depth field interviews, this research proposes a model that clarifies the process by which students are transformed into fully potential individuals as a consequence of their college experience. Education transforms both societies and people in a particular direction by shaping and reshaping their patterns of thoughts, means of problem solving and ways of life. This will then contribute to further individual and social transformation. This study finds that the process of education enables significant changes in students by contributing to the social skills that transform their identity and ultimately their society.

  2. The potential role and limitations of echocardiography in acute respiratory distress syndrome.

    Science.gov (United States)

    Lazzeri, Chiara; Cianchi, Giovanni; Bonizzoli, Manuela; Batacchi, Stefano; Peris, Adriano; Gensini, Gian Franco

    2016-04-01

    Bedside use of Doppler echocardiography is being featured as a promising, clinically useful tool in assessing the pulmonary circulation in patients with acute respiratory distress syndrome (ARDS). The present review is aimed at summarizing the available evidence obtained with echocardiography on right ventricle (RV) function and pulmonary circulation in ARDS and to highlight the potential of this technique in clinical practice (only articles in English language were considered). According to the available evidence on echocardiographic findings, the following conclusions can be drawn: (a) echocardiography (transthoracic and transesophageal) has a growing role in the management ARDS patients mainly because of the strict interactions between the lung (and ventilation) and the RV and pulmonary circulation; (b) there may be a continuum of alterations in RV size and function and pulmonary circulation which may end in the development of acute cor pulmonale, probably paralleling ARDS disease severity; and (c) the detection of acute cor pulmonale should prompt intensivists to tailor their ventilatory strategy to the individual patient depending on the echocardiography findings. Bearing in mind the clinical role and growing importance of echocardiography in ARDS and the available evidence on this topic, we present a flow chart including the parameters to be measured and the timing of echo exams in ARDS patients. Despite the important progress that echocardiography has gained in the evaluation of patients with ARDS, several open questions remain and echocardiography still appears to be underused in these patients. A more systematic use of echocardiography (mainly through shared protocols) in ARDS could help intensivists to tailor the optimal treatment in individual patients as well as highlighting the limits and potential of this methodology in patients with ALI.

  3. Potential role for peptidylarginine deiminase 2 (PAD2 in citrullination of canine mammary epithelial cell histones.

    Directory of Open Access Journals (Sweden)

    Brian D Cherrington

    Full Text Available Peptidylarginine Deiminases (PADs convert arginine residues on substrate proteins to citrulline. Previous reports have documented that PAD2 expression and activity varies across the estrous cycle in the rodent uterus and pituitary gland, however, the expression and function of PAD2 in mammary tissue has not been previously reported. To gain more insight into potential reproductive roles for PAD2, in this study we evaluated PAD2 expression and localization throughout the estrous cycle in canine mammary tissue and then identified possible PAD2 enzymatic targets. Immunohistochemical and immunofluorescence analysis found PAD2 expression is low in anestrus, limited to a distinct, yet sparse, subset of epithelial cells within ductal alveoli during estrus/early diestrus, and encompasses the entire epithelium of the mammary duct in late diestrus. At the subcellular level, PAD2 is expressed in the cytoplasm, and to a lesser extent, the nucleus of these epithelial cells. Surprisingly, stimulation of canine mammary tumor cells (CMT25 shows that EGF, but not estrogen or progesterone, upregulates PAD2 transcription and translation suggesting EGF regulation of PAD2 and possibly citrullination in vivo. To identify potential PAD2 targets, anti-pan citrulline western blots were performed and results showed that citrullination activity is limited to diestrus with histones appearing to represent major enzymatic targets. Use of site-specific anti-citrullinated histone antibodies found that the N-terminus of histone H3, but not H4, appears to be the primary target of PAD activity in mammary epithelium. This observation supports the hypothesis that PAD2 may play a regulatory role in the expression of lactation related genes via histone citrullination during diestrus.

  4. Smoker Identity and Its Potential Role in Young Adults’ Smoking Behavior: A Meta-Ethnography

    Science.gov (United States)

    2015-01-01

    Objective: Identity is an important influence on behavior. To identify potential targets for smoking cessation interventions in young adults, we synthesized findings from qualitative studies on smoker identity and potential influences on smoking and smoking cessation. Methods: A systematic search of 4 electronic databases up to September 19, 2013, was conducted to identify qualitative studies on smoker identity in smokers and ex-smokers aged 16–34. Key concepts were extracted from individual studies and synthesized into higher-order interpretations by following the principles of meta-ethnography. Results: Seventeen relevant papers were identified. At the highest level of interpretation, we identified 4 types of findings: (a) contributory factors to identity, (b) identity in relation to smoking, (c) contextual and temporal patterning, and (d) behavior in relation to smoking. Contributory factors included the desire to establish aspirational individual and social identities, enact a smoker identity appropriate to the momentary social context, and alter personal nonsmoking rules when consuming alcohol. Smoker identity was multifaceted and incorporated individuals’ defensive rationalizations, and both positive and negative feelings attached to it. Smoker identities took time to develop, were subject to change, and were context dependent. Identity was found to play a role in quit attempts. Conclusions: Qualitative research into the identity of young adult smokers has established it as a multifaceted phenomenon serving important functions but also involving conflict and defensive rationalizations. It develops over time and contextual factors influence its expression. The nature of a smoker’s identity can play an important role in smoking cessation. PMID:25622078

  5. Scytonemin Plays a Potential Role in Stabilizing the Exopolysaccharidic Matrix in Terrestrial Cyanobacteria.

    Science.gov (United States)

    Gao, Xiang

    2017-02-01

    Cyanobacteria are photosynthetic oxygen-evolving prokaryotes that are distributed in diverse habitats. They synthesize the ultraviolet (UV)-screening pigments, scytonemin (SCY) and mycosporine-like amino acids (MAAs), located in the exopolysaccharide (EPS) matrix. Multiple roles for both pigments have gradually been recognized, such as sunscreen ability, antioxidant activity, and heat dissipation from absorbed UV radiation. In this study, a filamentous terrestrial cyanobacterium Nostoc flagelliforme was used to evaluate the potential stabilizing role of SCY on the EPS matrix. SCY (∼3.7 %) was partially removed from N. flagelliforme filaments by rinsing with 100 % acetone for 5 s. The physiological damage to cells resulting from this treatment, in terms of photosystem II activity parameter Fv/Fm, was repaired after culturing the sample for 40 h. The physiologically recovered sample was further desiccated by natural or rapid drying and then allowed to recovery for 24 h. Compared with the normal sample, a relatively slower Fv/Fm recovery was observed in the SCY-partially removed sample, suggesting that the decreased SCY concentration in the EPS matrix caused cells to suffer further damage upon desiccation. In addition, the SCY-partially removed sample could allow the release of MAAs (∼25 %) from the EPS matrix, while the normal sample did not. Therefore, damage caused by drying of the former resulted from at least the reduction of structural stability of the EPS matrix as well as the loss of partial antioxidant compounds. Considering that an approximately 4 % loss of SCY led to this significant effect, the structurally stabilizing potential of SCY on the EPS matrix is crucial for terrestrial cyanobacteria survival in complex environments.

  6. Potential Role of Selenoenzymes and Antioxidant Metabolism in relation to Autism Etiology and Pathology

    Directory of Open Access Journals (Sweden)

    Laura J. Raymond

    2014-01-01

    Full Text Available Autism and autism spectrum disorders (ASDs are behaviorally defined, but the biochemical pathogenesis of the underlying disease process remains uncharacterized. Studies indicate that antioxidant status is diminished in autistic subjects, suggesting its pathology is associated with augmented production of oxidative species and/or compromised antioxidant metabolism. This suggests ASD may result from defects in the metabolism of cellular antioxidants which maintain intracellular redox status by quenching reactive oxygen species (ROS. Selenium-dependent enzymes (selenoenzymes are important in maintaining intercellular reducing conditions, particularly in the brain. Selenoenzymes are a family of ~25 genetically unique proteins, several of which have roles in preventing and reversing oxidative damage in brain and endocrine tissues. Since the brain’s high rate of oxygen consumption is accompanied by high ROS production, selenoenzyme activities are particularly important in this tissue. Because selenoenzymes can be irreversibly inhibited by many electrophiles, exposure to these organic and inorganic agents can diminish selenoenzyme-dependent antioxidant functions. This can impair brain development, particularly via the adverse influence of oxidative stress on epigenetic regulation. Here we review the physiological roles of selenoproteins in relation to potential biochemical mechanisms of ASD etiology and pathology.

  7. The Double Role of p53 in Cancer and Autoimmunity and Its Potential as Therapeutic Target.

    Science.gov (United States)

    Fierabracci, Alessandra; Pellegrino, Marsha

    2016-11-25

    p53 is a sequence-specific short-lived transcription factor expressed at low concentrations in various tissues while it is upregulated in damaged, tumoral or inflamed tissue. In normally proliferating cells, p53 protein levels and function are tightly controlled by main regulators, i.e., MDM2 (mouse double minute 2) and MDM4 proteins. p53 plays an important role due to its ability to mediate tumor suppression. In addition to its importance as a tumor suppressor, p53 coordinates diverse cellular responses to stress and damage and plays an emerging role in various physiological processes, including fertility, cell metabolism, mitochondrial respiration, autophagy, cell adhesion, stem cell maintenance and development. Interestingly, it has been recently implicated in the suppression of autoimmune and inflammatory diseases in both mice and humans. In this review based on current knowledge on the functional properties of p53 and its regulatory pathways, we discuss the potential utility of p53 reactivation from a therapeutic perspective in oncology and chronic inflammatory disorders leading to autoimmunity.

  8. The potential protective role of Physalis peruviana L. fruit in cadmium-induced hepatotoxicity and nephrotoxicity.

    Science.gov (United States)

    Dkhil, Mohamed A; Al-Quraishy, Saleh; Diab, Marwa M S; Othman, Mohamed S; Aref, Ahmed M; Abdel Moneim, Ahmed E

    2014-12-01

    This study aimed to investigate the potential protective role of Physalis peruviana L. (family Solanaceae) against cadmium-induced hepatorenal toxicity in Wistar rats. Herein, cadmium chloride (CdCl2) (6.5 mg/kg bwt/day) was intraperitoneally injected for 5 days, and methanolic extract of physalis (MEPh) was pre-administered to a group of Cd-treated rats by an oral administration at a daily dose of 200 mg/kg bwt for 5 days. The findings revealed that CdCl2 injection induced significant decreases in kidney weight and kidney index. Cadmium intoxication increased the activities of liver enzymes and the bilirubin level, in addition to the levels of uric acid, urea and creatinine were increased in the serum. The pre-administration of MEPh alleviated hepatorenal toxicity in Cd-treated rats. Physalis was noted to play a good hepatorenal protective role, reducing lipid peroxidation, nitric oxide, and enhancing enzymatic activities and non-enzymatic antioxidant molecule, glutathione, in hepatic and renal tissues of Cd-treated rats. Moreover, physalis treatment was able to reverse the histopathological changes in liver and kidney tissues and also increased the expression of Bcl-2 protein in liver and kidney of rats. Overall, the results showed that MEPh can induce antioxidant and anti-apoptotic effects and also exerts beneficial effects for the treatment of Cd-induced hepatorenal toxicity.

  9. Potential Role of Dipeptidyl Peptidase IV in the Pathophysiology of Heart Failure

    Directory of Open Access Journals (Sweden)

    Thiago A. Salles

    2015-02-01

    Full Text Available Dipeptidyl peptidase IV (DPPIV is a widely expressed multifunctional serine peptidase that exists as a membrane-anchored cell surface protein or in a soluble form in the plasma and other body fluids. Numerous substrates are cleaved at the penultimate amino acid by DPPIV, including glucagon-like peptide-1 (GLP-1, brain natriuretic peptide (BNP and stromal cell-derived factor-1 (SDF-α, all of which play important roles in the cardiovascular system. In this regard, recent reports have documented that circulating DPPIV activity correlates with poorer cardiovascular outcomes in human and experimental heart failure (HF. Moreover, emerging evidence indicates that DPPIV inhibitors exert cardioprotective and renoprotective actions in a variety of experimental models of cardiac dysfunction. On the other hand, conflicting results have been found when translating these promising findings from preclinical animal models to clinical therapy. In this review, we discuss how DPPIV might be involved in the cardio-renal axis in HF. In addition, the potential role for DPPIV inhibitors in ameliorating heart disease is revised, focusing on the effects of the main DPPIV substrates on cardiac remodeling and renal handling of salt and water.

  10. In vitro interactions of extracellular histones with LDL suggest a potential pro-atherogenic role.

    Directory of Open Access Journals (Sweden)

    Alan D Pemberton

    Full Text Available BACKGROUND: Nuclear histones have previously been shown to aggregate LDL in vitro, suggestive of a possible pro-atherogenic role. Recent studies indicate that histones are released during acute inflammation, and therefore might interact with circulating lipoproteins in vivo. In view of the associative link between inflammation and cardiovascular disease, the behaviour of histones was investigated using in vitro models of LDL retention and foam cell formation. METHODOLOGY/PRINCIPAL FINDINGS: Heparin agarose beads were used as a model of a matrix rich in sulphated glycosaminoglycans, to which histones bind strongly. Histone-modified beads were observed to pull down more LDL from solution than untreated beads, indicating that histones can function as bridging molecules, enhancing LDL retention. Furthermore, addition of heparin inhibited histone-induced aggregation of LDL. To model foam cell formation, murine RAW 264.7 macrophages were incubated for 24 h in the presence of LDL, histones, LDL plus histones or vehicle control. Cells incubated with LDL in the presence of histones accumulated significantly more intracellular lipid than with LDL or histone alone. CONCLUSIONS/SIGNIFICANCE: These results are consistent with a potential pro-atherogenic role for extracellular histones, which should be investigated further.

  11. Verification of a Fissile Material Cut-off Treaty (FMCT): The Potential Role of the IAEA

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Jin Ho [Korea Institute of Nuclear Nonproliferation and Control, Daejeon (Korea, Republic of)

    2016-05-15

    The objective of a future verification of a FMCT(Fissile Material Cut-off Treaty) is to deter and detect non-compliance with treaty obligations in a timely and non-discriminatory manner with regard to banning the production of fissile material for nuclear weapons or other nuclear devices. Since the International Atomic Energy Agency (IAEA) has already established the IAEA safeguards as a verification system mainly for Non -Nuclear Weapon States (NNWSs), it is expected that the IAEA's experience and expertise in this field will make a significant contribution to setting up a future treaty's verification regime. This paper is designed to explore the potential role of the IAEA in verifying the future treaty by analyzing verification abilities of the Agency in terms of treaty verification and expected challenges. Furthermore, the concept of multilateral verification that could be facilitated by the IAEA will be examined as a measure of providing a credible assurance of compliance with a future treaty. In this circumstance, it is necessary for the IAEA to be prepared for playing a leading role in FMCT verifications as a form of multilateral verification by taking advantage of its existing verification concepts, methods, and tools. Also, several challenges that the Agency faces today need to be overcome, including dealing with sensitive and proliferative information, attribution of fissile materials, lack of verification experience in military fuel cycle facilities, and different attitude and culture towards verification between NWSs and NNWSs.

  12. The Role of Reactive Oxygen Species and Autophagy in Periodontitis and Their Potential Linkage

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    Chengcheng Liu

    2017-06-01

    Full Text Available Periodontitis is a chronic inflammatory disease that causes damage to periodontal tissues, which include the gingiva, periodontal ligament, and alveolar bone. The major cause of periodontal tissue destruction is an inappropriate host response to microorganisms and their products. Specifically, a homeostatic imbalance between reactive oxygen species (ROS and antioxidant defense systems has been implicated in the pathogenesis of periodontitis. Elevated levels of ROS acting as intracellular signal transducers result in autophagy, which plays a dual role in periodontitis by promoting cell death or blocking apoptosis in infected cells. Autophagy can also regulate ROS generation and scavenging. Investigations are ongoing to elucidate the crosstalk mechanisms between ROS and autophagy. Here, we review the physiological and pathological roles of ROS and autophagy in periodontal tissues. The redox-sensitive pathways related to autophagy, such as mTORC1, Beclin 1, and the Atg12-Atg5 complex, are explored in depth to provide a comprehensive overview of the crosstalk between ROS and autophagy. Based on the current evidence, we suggest that a potential linkage between ROS and autophagy is involved in the pathogenesis of periodontitis.

  13. Potential role and therapeutic interests of myo-inositol in metabolic diseases.

    Science.gov (United States)

    Croze, Marine L; Soulage, Christophe O

    2013-10-01

    Several inositol isomers and in particular myo-inositol (MI) and D-chiro-inositol (DCI), were shown to possess insulin-mimetic properties and to be efficient in lowering post-prandial blood glucose. In addition, abnormalities in inositol metabolism are associated with insulin resistance and with long term microvascular complications of diabetes, supporting a role of inositol or its derivatives in glucose metabolism. The aim of this review is to focus on the potential benefits of a dietary supplement of myo-inositol, by far the most common inositol isomer in foodstuffs, in human disorders associated with insulin resistance (polycystic ovary syndrome, gestational diabetes mellitus or metabolic syndrome) or in prevention or treatment of some diabetic complications (neuropathy, nephropathy, cataract). The relevance of such a nutritional strategy will be discussed for each context on the basis of the clinical and/or animal studies. The dietary sources of myo-inositol and its metabolism from its dietary uptake to its renal excretion will be also covered in this review. Finally, the actual insights into inositol insulin-sensitizing effects will be addressed and in particular the possible role of inositol glycans as insulin second messengers.

  14. Review: Eicosanoids in preterm labor and delivery: Potential roles of exosomes in eicosanoid functions.

    Science.gov (United States)

    Peiris, H N; Vaswani, K; Almughlliq, F; Koh, Y Q; Mitchell, M D

    2016-12-09

    Preterm delivery is a major obstetric health problem contributing to poor neonatal outcome including low birth weight, respiratory distress syndrome, gastrointestinal, immunologic, central nervous system, hearing, and vision problems. Worldwide, approximately 15 million babies are born prematurely each year. The critical question which remains is how to identify women destined to deliver preterm from those who will achieve a term delivery. Prostaglandins, in all mammals are important in the parturient process. Increased intrauterine prostaglandin production is associated with labor and in fact prostaglandin E2 (PGE2) or analogs are widely used clinically for cervical ripening and labor induction. Measurements of circulating eicosanoids have been problematic because of the rapid and major clearance by the lungs and then kidneys resulting in very low concentrations in plasma. Moreover, since eicosanoids are produced by all mammalian tissues, the sources of the measured eicosanoids are unknown. Our understanding of how cells communicate has undergone a paradigm shift with the recognition of the role of exosomes in intercellular signaling. Recent publications have identified enzymes and products of arachidonic acid metabolism (eicosanoids) within exosomes. This review will explore the potential roles of exosomes in eicosanoid functions that are critical in preterm labor and delivery.

  15. Potential Role of Dipeptidyl Peptidase IV in the Pathophysiology of Heart Failure

    Science.gov (United States)

    Salles, Thiago A.; dos Santos, Leonardo; Barauna, Valério G.; Girardi, Adriana C. C.

    2015-01-01

    Dipeptidyl peptidase IV (DPPIV) is a widely expressed multifunctional serine peptidase that exists as a membrane-anchored cell surface protein or in a soluble form in the plasma and other body fluids. Numerous substrates are cleaved at the penultimate amino acid by DPPIV, including glucagon-like peptide-1 (GLP-1), brain natriuretic peptide (BNP) and stromal cell-derived factor-1 (SDF-α), all of which play important roles in the cardiovascular system. In this regard, recent reports have documented that circulating DPPIV activity correlates with poorer cardiovascular outcomes in human and experimental heart failure (HF). Moreover, emerging evidence indicates that DPPIV inhibitors exert cardioprotective and renoprotective actions in a variety of experimental models of cardiac dysfunction. On the other hand, conflicting results have been found when translating these promising findings from preclinical animal models to clinical therapy. In this review, we discuss how DPPIV might be involved in the cardio-renal axis in HF. In addition, the potential role for DPPIV inhibitors in ameliorating heart disease is revised, focusing on the effects of the main DPPIV substrates on cardiac remodeling and renal handling of salt and water. PMID:25690036

  16. Bovine mastitis disease/pathogenicity: evidence of the potential role of microbial biofilms.

    Science.gov (United States)

    Gomes, Fernanda; Saavedra, Maria José; Henriques, Mariana

    2016-04-01

    Bovine mastitis (BM) is a disease with high incidence worldwide and one of the most relevant bovine pathologies and the most costly to the dairy industry. BM is an inflammation of the udder and represents one of the most difficult veterinary diseases to control. Biofilm formation is considered a selective advantage for pathogens causing mastitis, facilitating bacterial persistence in the udder. In fact, recently some authors drew attention to the biofilm formation ability presented by several mastitis causing pathogens and to its possible relation with recurrent mastitis infections and with the increased resistance to antimicrobial agents and host immune defence system. Actually, up to now, several researchers reported the potential role of cells in this mode of growth in the previous facts mentioned. As a consequence of the presence of biofilms, the infection here focused is more difficult to treat and eradicate, making this problem a more relevant pressing issue. Thus, we believe that a deeper knowledge of these structures in mastitis can help to determine the best control strategy to be used in veterinary practice in order to reduce losses in the dairy industry and to ensure milk safety and quality. The aim of this paper was to review the existing research and consequently to provide an overview of the role of biofilms in BM infections. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Cytomegalovirus: its potential role in the development of cutaneous T-cell lymphoma.

    Science.gov (United States)

    Ballanger, F; Bressollette, C; Volteau, C; Planche, L; Dreno, B

    2009-06-01

    To investigate the potential role of CMV in cutaneous T-cell lymphoma (CTCL), we studied cytomegalovirus (CMV) seroprevalence in parapsoriasis (PP), mycosis fungoides (MF) and Sézary syndrome (SS) compared with healthy control patients. In cases where CMV seropositivity was observed, CMV PCR analyses were performed on skin biopsies. CMV seroprevalence was 37.1% in the control group, 50.68% in the PP + MF + SS group (P = 0.08), 56.2% in the MF + SS group (P = 0.07), 40% in the PP group (P = 0.9), 66.67% in the MF group (P = 0.009), 42.86% in the SS group (P = 0.9). CMV PCR in initial skin biopsies were all negative. However, PCR CMV was positive in two SS skin biopsies realized at an advanced stage. Our results show that latent CMV infection may play a role in the susceptibility of MF in predisposed subjects by inducing T-cell proliferation and resistance to apoptosis. Concerning SS, an immunosuppressive state may be responsible for CMV reactivation that in turn may interfere with evolution of the disease.

  18. Potential role of Shh-Gli1-BMI1 signaling pathway nexus in glioma chemoresistance.

    Science.gov (United States)

    Shahi, M H; Farheen, S; Mariyath, M P M; Castresana, J S

    2016-11-01

    Chemoresistance is a common hurdle for the proper treatment of gliomas. The role of Shh-Gli1 signaling in glioma progression has been reported. However, its role in glioma chemoresistance has not been well studied yet. In this work, we found that Shh-Gli1 signaling regulates the expression of one stem cell marker, BMI1 (B cell-specific Moloney murine leukemia virus), in glioma. Interestingly, we also demonstrated high expression of MRP1 (multi-drug resistance protein 1) in glioma. MRP1 expression was decreased by BMI1 siRNA and Shh-Gli1 cell signaling specific inhibitor GANT61 in our experiments. GANT61 very efficiently inhibited cell colony growth in glioma cell lines, compared to temozolomide. Moreover, a synergic effect of GANT61 and temozolomide drastically decreased the LD50 of temozolomide in the cell colony experiments. Therefore, our results suggest that there is a potential nexus of Shh-Gli1-BMI1 cell signaling to regulate MRP1 and to promote chemoresistance in glioma. Henceforth, our study opens the possibility of facing new targets, Gli1 and BMI1, for the effective treatment of glioma suppression of chemoresistance with adjuvant therapy of GANT61 and temozolomide.

  19. Caspase-14 Expression Impairs Retinal Pigment Epithelium Barrier Function: Potential Role in Diabetic Macular Edema

    Directory of Open Access Journals (Sweden)

    Selina Beasley

    2014-01-01

    Full Text Available We recently showed that caspase-14 is a novel molecule in retina with potential role in accelerated vascular cell death during diabetic retinopathy (DR. Here, we evaluated whether caspase-14 is implicated in retinal pigment epithelial cells (RPE dysfunction under hyperglycemia. The impact of high glucose (HG, 30 mM D-glucose on caspase-14 expression in human RPE (ARPE-19 cells was tested, which showed significant increase in caspase-14 expression compared with normal glucose (5 mM D-glucose + 25 mM L-glucose. We also evaluated the impact of modulating caspase-14 expression on RPE cells barrier function, phagocytosis, and activation of other caspases using ARPE-19 cells transfected with caspase-14 plasmid or caspase-14 siRNA. We used FITC-dextran flux assay and electric cell substrate impedance sensing (ECIS to test the changes in RPE cell barrier function. Similar to HG, caspase-14 expression in ARPE-19 cells increased FITC-dextran leakage through the confluent monolayer and decreased the transcellular electrical resistance (TER. These effects of HG were prevented by caspase-14 knockdown. Furthermore, caspase-14 knockdown prevented the HG-induced activation of caspase-1 and caspase-9, the only activated caspases by HG. Phagocytic activity was unaffected by caspase-14 expression. Our results suggest that caspase-14 contributes to RPE cell barrier disruption under hyperglycemic conditions and thus plays a role in the development of diabetic macular edema.

  20. Potential roles of self-reactive T cells in autoimmunity: lessons from cancer immunology.

    Science.gov (United States)

    Andersen, Mads Hald

    2014-12-01

    The immune system is a complex arrangement of cells and molecules that preserve the integrity of the organism by eliminating all elements judged to be dangerous. Several regulatory mechanisms function to terminate immune responses to antigens, return the immune system to a basal state after the antigen has been cleared, and maintain unresponsiveness, or tolerance, to self-antigens. In recent years, reports have described T cell responses to several proteins involved in regulating the immune system, particularly under malignant conditions. The present review highlights specific T cells that recognize proteins involved in three, well-defined immunosuppressive mechanisms: (1) inhibitory T cell pathways (i.e., PD-L1), (2) regulatory T cells (i.e., Foxp3(+)), and (3) metabolic enzymes, like indoleamine-2,3-dioxygenase. Cytotoxic T cells can eliminate regulatory cells, thereby suppressing and/or delaying local immune suppression; conversely, regulatory CD4(+) and non-cytotoxic CD8(+) T cells enhance target-mediated immune suppression. The apparent lack of tolerance against endogenous proteins expressed by regulatory cells is intriguing, because it suggests that self-reactive T cells play a general role of fine-tuning the immune system. Thus, T cell responses may be generally used to maintain the homeostasis of the immune system. Further exploration is warranted to investigate the potential role of auto-reactive T cells under different physiological and/or pathological conditions.

  1. The potential role of vitamin D for prevention and treatment of tuberculosis and infectious diseases

    Directory of Open Access Journals (Sweden)

    Catia Dini

    2012-01-01

    Full Text Available INTRODUCTION: Vitamin D deficiency (VDD is a common condition among several populations in the world. VDD is associated with higher incidence of immune system disorders and faster progression of some infectious diseases. Vitamin D is known to be of physiological importance, it is considered an essential micronutrient for the bone health and plays a beneficial role in the prevention and/or treatment of a number of chronic diseases. Vitamin D has a complex action on the immune system. RESULTS: Evidence that vitamin D protects against tuberculosis has been supported by in vitro, epidemiological and some preliminary clinical studies. Vitamin D has a potential effect on HIV (human immunodeficiency virus and plays a crucial role in the defence against respiratory infections. CONCLUSIONS: Vitamin D supplementation could be a low-cost, practical method to protect groups of people with high incidence of those diseases. Public health education should stress the need for adequate dietary intake of vitamin D in those vulnerable groups.

  2. Novel and potential physiological roles of vacuolar-type H+-ATPase in marine organisms.

    Science.gov (United States)

    Tresguerres, Martin

    2016-07-15

    The vacuolar-type H(+)-ATPase (VHA) is a multi-subunit enzyme that uses the energy from ATP hydrolysis to transport H(+) across biological membranes. VHA plays a universal role in essential cellular functions, such as the acidification of lysosomes and endosomes. In addition, the VHA-generated H(+)-motive force can drive the transport of diverse molecules across cell membranes and epithelia for specialized physiological functions. Here, I discuss diverse physiological functions of VHA in marine animals, focusing on recent discoveries about base secretion in shark gills, potential bone dissolution by Osedax bone-eating worms and its participation in a carbon-concentrating mechanism that promotes coral photosynthesis. Because VHA is evolutionarily conserved among eukaryotes, it is likely to play many other essential physiological roles in diverse marine organisms. Elucidating and characterizing basic VHA-dependent mechanisms could help to determine species responses to environmental stress, including (but not limited to) that resulting from climate change. © 2016. Published by The Company of Biologists Ltd.

  3. The development of psychotic disorders in adolescence: a potential role for hormones.

    Science.gov (United States)

    Trotman, Hanan D; Holtzman, Carrie W; Ryan, Arthur T; Shapiro, Daniel I; MacDonald, Allison N; Goulding, Sandra M; Brasfield, Joy L; Walker, Elaine F

    2013-07-01

    This article is part of a Special Issue "Puberty and Adolescence". The notion that adolescence is characterized by dramatic changes in behavior, and often by emotional upheaval, is widespread and longstanding in popular western culture. In recent decades, this notion has gained increasing support from empirical research showing that the peri- and post-pubertal developmental stages are associated with a significant rise in the rate of psychiatric symptoms and syndromes. As a result, interest in adolescent development has burgeoned among researchers focused on the origins of schizophrenia and other psychotic disorders. Two factors have fueled this trend: 1) increasing evidence from longitudinal research that adolescence is the modal period for the emergence of "prodromal" manifestations, or precursors of psychotic symptoms, and 2) the rapidly accumulating scientific findings on brain structural and functional changes occurring during adolescence and young adulthood. Further, gonadal and adrenal hormones are beginning to play a more prominent role in conceptualizations of adolescent brain development, as well as in the origins of psychiatric symptoms during this period (Walker and Bollini, 2002; Walker et al., 2008). In this paper, we begin by providing an overview of the nature and course of psychotic disorders during adolescence/young adulthood. We then turn to the role of hormones in modulating normal brain development, and the potential role they might play in the abnormal brain changes that characterize youth at clinical high-risk (CHR) for psychosis. The activational and organizational effects of hormones are explored, with a focus on how hormone-induced changes might be linked with neuropathological processes in the emergence of psychosis. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Breast cancer associated a2 isoform vacuolar ATPase immunomodulates neutrophils: potential role in tumor progression.

    Science.gov (United States)

    Ibrahim, Safaa A; Katara, Gajendra K; Kulshrestha, Arpita; Jaiswal, Mukesh K; Amin, Magdy A; Beaman, Kenneth D

    2015-10-20

    In invasive breast cancer, tumor associated neutrophils (TAN) represent a significant portion of the tumor mass and are associated with increased angiogenesis and metastasis. Identifying the regulatory factors that control TAN behavior will help in developing ideal immunotherapies. Vacuolar ATPases (V-ATPases), multi-subunit proton pumps, are highly expressed in metastatic breast cancer cells. A cleaved peptide from a2 isoform V-ATPase (a2NTD) has immunomodulatory role in tumor microenvironment. Here, we report for the first time the role of V-ATPase in neutrophils modulation. In invasive breast cancer cells, a2NTD was detected and a2V was highly expressed on the surface. Immunohistochemical analysis of invasive breast cancer tissues revealed that increased neutrophil recruitment and blood vessel density correlated with increased a2NTD levels. In order to determine the direct regulatory role of a2NTD on neutrophils, recombinant a2NTD was used for the treatment of neutrophils isolated from the peripheral blood of healthy volunteers. Neutrophils treated with a2NTD (a2Neuɸ) showed increased secretion of IL-1RA, IL-10, CCL-2 and IL-6 that are important mediators in cancer related inflammation. Moreover, a2Neuɸ exhibited an increased production of protumorigenic factors including IL-8, matrix metaloprotinase-9 and vascular endothelial growth factor. Further, functional characterization of a2Neuɸ revealed that a2Neuɸ derived products induce in vitro angiogenesis as well as increase the invasiveness of breast cancer cells. This study establishes the modulatory effect of breast cancer associated a2V on neutrophils, by the action of a2NTD, which has a positive impact on tumor progression, supporting that a2V can be a potential selective target for breast cancer therapy.

  5. Potential for small-scale, decentralized energy sources and the Federal role in their development

    Energy Technology Data Exchange (ETDEWEB)

    Hayes, D.

    1978-02-01

    The idea that the solution to our energy problems is to be found in an expanded role for small-scale, decentralized energy sources, particularly solar energy, has gained considerable attention and increasing respectability in recent years. One of the most articulate spokesmen for this point of view is Denis Hayes. Mr. Hayes explained his perspective on the energy problem to an invited audience of about 85 professionals and students in the energy policy field. This paper is an edited version of Mr. Hayes' presentation. In his presentation, Mr. Hayes discussed the prospects for fossil and nuclear energy, stressing the potential limitations on coal use due to the problem of CO/sub 2/ and the greenhouse effect, and highlighting the hazards of the plutonium economy. He described the role conservation can play in dealing with the energy problem, but declared that conservation alone is not enough. There is still a need, he indicated, to replace declining energy sources with some alternative. In his view, the most promising alternative is solar energy, and Mr. Hayes discussed the various ways in which it can be utilized. The presentation concluded with a number of suggestions regarding Federal actions and policy initiatives that Mr. Hayes feels are needed to encourage solar energy development. These ideas served as the focus for the question and answer session which followed the presentation. Questions dealt with many issues, including priorities in solar R and D, the role of the Federal government vis a vis the private sector, the timing of solar energy implementation, and the strategy and tactics of the solar movement.

  6. The potential role of regucalcin in kidney cell regulation: Involvement in renal failure (Review).

    Science.gov (United States)

    Yamaguchi, Masayoshi

    2015-11-01

    The kidneys play a physiologic role in the regulation of urine formation and nutrient reabsorption in the proximal tubule epithelial cells. Kidney development has been shown to be regulated through calcium (Ca2+) signaling processes that are present through numerous steps of tubulogenesis and nephron induction during embryonic development of the kidneys. Ca2+-binding proteins, such as calbindin-D28k and regucalcin are important proteins that are commonly used as biomarkers in pronephric tubules, and the ureteric bud and metanephric mesenchyme. Previous research on regucalcin focused on Ca2+ sensors that are involved in renal organogenesis and the link between Ca2+-dependent signals and polycystins. Moreover, regucalcin has been highlighted to play a multifunctional role in kidney cell regulation. The regucalcin gene, which is localized on the X chromosome, is regulated through various transcription factors. Regucalcin has been found to regulate intracellular Ca2+ homeostasis in kidney proximal tubule epithelial cells. Regucalcin has been demonstrated to regulate the activity of various enzymes that are involved in intracellular signaling pathways. It has been noted that regucalcin suppresses DNA synthesis and regulates the gene expression of various proteins related to mineral transport, transcription factors, cell proliferation and apoptosis. The overexpression of regucalcin has been shown to exert suppressive effects on cell proliferation and apoptotic cell death, which are stimulated by various stimulatory factors. Moreover, regucalcin gene expression was found to to be involved in various pathophysiological states, including renal failure. This review discusses recent findings concerning the potential role of regucalcin as a regulatory protein in the kidney proximal tubule epithelial cells.

  7. Potential role for PADI-mediated histone citrullination in preimplantation development

    Directory of Open Access Journals (Sweden)

    Kan Rui

    2012-06-01

    Full Text Available Abstract Background The peptidylarginine deiminases (PADIs convert positively charged arginine residues to neutrally charged citrulline on protein substrates in a process that is known as citrullination or deimination. Previous reports have documented roles for histone citrullination in chromatin remodeling and gene regulation in several tissue types, however, a potential role for histone citrullination in chromatin-based activities during early embryogenesis has not been investigated. Results In the present study, we tested by laser scanning confocal indirect immunofluorescence microscopy whether specific arginine residues on the histone H3 and H4 N-terminal tails (H4R3, H3R2 + 8 + 17, and H3R26 were citrullinated in mouse oocytes and preimplantation embryos. Results showed that all of the tested residues were deiminated with each site showing a unique localization pattern during early development. Given these findings, we next tested whether inhibition of PADI activity using the PADI-specific inhibitor, Cl-amidine, may affect embryonic development. We found that treatment of pronuclear stage zygotes with Cl-amidine reduces both histone H3 and H4 tail citrullination and also potently blocks early cleavage divisions in vitro. Additionally, we found that the Cl-amidine treatment reduces acetylation at histone H3K9, H3K18, and H4K5 while having no apparent effect on the repressive histone H3K9 dimethylation modification. Lastly, we found that treatment of zygotes with trichostatin A (TSA to induce hyperacetylation also resulted in an increase in histone citrullination at H3R2 + 8 + 17. Conclusions Given the observed effects of Cl-amidine on embryonic development and the well documented correlation between histone acetylation and transcriptional activation, our findings suggest that histone citrullination may play an important role in facilitating gene expression in early embryos by creating a chromatin environment that is

  8. The potential role of serotonergic mechanisms in the spinal oxytocin-induced antinociception.

    Science.gov (United States)

    Godínez-Chaparro, Beatriz; Martínez-Lorenzana, Guadalupe; Rodríguez-Jiménez, Javier; Manzano-García, Alfredo; Rojas-Piloni, Gerardo; Condés-Lara, Miguel; González-Hernández, Abimael

    2016-12-01

    The role of oxytocin (OXT) in pain modulation has been suggested. Indeed, hypothalamic paraventricular nuclei (PVN) electrical stimuli reduce the nociceptive neuronal activity (i.e., neuronal discharge associated with activation of Aδ- and C-fibers) of the spinal dorsal horn wide dynamic range (WDR) cells and nociceptive behavior. Furthermore, raphe magnus nuclei lesion reduces the PVN-induced antinociception, suggesting a functional interaction between the OXT and the serotoninergic system. The present study investigated in Wistar rats the potential role of spinal serotonergic mechanisms in the OXT- and PVN-induced antinociception. In long-term secondary mechanical allodynia and hyperalgesia induced by formalin or extracellular unitary recordings of the WDR cells we evaluated the role of 5-hydroxytryptamine (5-HT) effect on the OXT-induced antinociception. All drugs were given intrathecally (i.t.). OXT (1×10(-5)-1×10(-4)nmol) or 5-HT (1×10(-3)-1×10(-1)nmol) prevented the formalin-induced sensitization, an effect mimicked by PVN stimulation. Moreover, administration of OXT (1×10(-5)nmol) plus 5-HT (1×10(-3)nmol) at ineffective doses, produced antinociception. This effect was antagonized by: (i) d(CH2)5[Tyr(Me)(2),Thr(4),Tyr-NH2(9)]OVT (oxytocin receptor antagonist; 2×10(-2)nmol); or (ii) methiothepin (a non-specific 5-HT1/2/5/6/7 receptor antagonist; 80nmol). Similar results were obtained with PVN stimulation plus 5-HT (5×10(-5)nmol). In WDR cell recordings, the PVN-induced antinociception was enhanced by i.t. 5-HT and partly blocked when the spinal cord was pre-treated with methiothepin (80nmol). Taken together, these results suggest that serotonergic mechanisms at the spinal cord level are partly involved in the OXT-induced antinociception.

  9. Neurosteroids in the fetus and neonate: potential protective role in compromised pregnancies.

    Science.gov (United States)

    Hirst, Jonathan J; Palliser, Hannah K; Yates, Della M; Yawno, Tamara; Walker, David W

    2008-01-01

    Complications during pregnancy and birth asphyxia lead to brain injury, with devastating consequences for the neonate. In this paper we present evidence that the steroid environment during pregnancy and at birth aids in protecting the fetus and neonate from asphyxia-induced injury. Earlier studies show that the placental progesterone production has a role in the synthesis and release of neuroactive steroids or their precursors into the fetal circulation. Placental precursor support leads to remarkably high concentrations of allopregnanolone in the fetal brain and to a dramatic decline with the loss of the placenta at birth. These elevated concentrations influence the distinct behavioral states displayed by the late gestation fetus and exert a suppressive effect that maintains sleep-like behavioral states that are present for much of fetal life. This suppression reduces CNS excitability and suppresses excitotoxicity. With the availability of adequate precursors, mechanisms within the fetal brain ultimately control neurosteroid levels. These mechanisms respond to episodes of acute hypoxia by increasing expression of 5alpha-reductase and P450scc enzymes and allopregnanolone synthesis in the brain. This allopregnanolone response, and potentially that of other neurosteroids including 5alpha-tetrahydrodeoxycorticosterone (TH-DOC), reduces hippocampal cell death following acute asphyxia and suggests that stimulation of neurosteroid production may protect the fetal brain. Importantly, inhibition of neurosteroid synthesis in the fetal brain increases the basal cell death suggesting a role in controlling developmental processes late in gestation. Synthesis of neurosteroid precursors in the fetal adrenal such as deoxycorticosterone (DOC), and their conversion to active neurosteroids in the fetal brain may also have a role in neuroprotection. This suggests that the adrenal glands provide precursor DOC for neurosteroid synthesis after birth and this may lead to a switch from

  10. Review: MicroRNAs in assisted reproduction and their potential role in IVF failure.

    Science.gov (United States)

    Siristatidis, Charalampos; Vogiatzi, Paraskevi; Brachnis, Nikos; Liassidou, Aspasia; Iliodromiti, Zoe; Bettocchi, Stefano; Chrelias, Charalampos

    2015-01-01

    MicroRNAs (miRNAs) have recently emerged as important regulators of gene expression stability. In the endometrium, miRNAs are involved in the dynamic changes associated with the menstrual cycle, implicated in implantation and in reproductive disorders. We performed a review in an attempt to assess the potential biological pathways linking altered miRNAs profiles with in vitro fertilisation (IVF) failure. Crucially, as miRNAs appear to have a significant role in the course of reproduction, they are excellent research candidates with the potential to enable a better understanding over the underlying molecular activities that prevent implantation and further progression of the embryo. Further steps include in-depth pathway mapping of the implantation process and the characterization of the respective miRNAs and associated links. The efficiency of any intervention should determine whether miRNA profiling could possibly be adopted in routine practice to substantially improve the diagnostic accuracy and, in parallel, the directed treatment of the next-generation IVF.

  11. G protein coupled receptor 18: A potential role for endocannabinoid signaling in metabolic dysfunction.

    Science.gov (United States)

    Rajaraman, Gayathri; Simcocks, Anna; Hryciw, Deanne H; Hutchinson, Dana S; McAinch, Andrew J

    2016-01-01

    Endocannabinoids are products of dietary fatty acids that are modulated by an alteration in food intake levels. Overweight and obese individuals have substantially higher circulating levels of the arachidonic acid derived endocannabinoids, anandamide and 2-arachidonoyl glycerol, and show an altered pattern of cannabinoid receptor expression. These cannabinoid receptors are part of a large family of G protein coupled receptors (GPCRs). GPCRs are major therapeutic targets for various diseases within the cardiovascular, neurological, gastrointestinal, and endocrine systems, as well as metabolic disorders such as obesity and type 2 diabetes mellitus. Obesity is considered a state of chronic low-grade inflammation elicited by an immunological response. Interestingly, the newly deorphanized GPCR (GPR18), which is considered to be a putative cannabinoid receptor, is proposed to have an immunological function. In this review, the current scientific knowledge on GPR18 is explored including its localization, signaling pathways, and pharmacology. Importantly, the involvement of nutritional factors and potential dietary regulation of GPR18 and its (patho)physiological roles are described. Further research on this receptor and its regulation will enable a better understanding of the complex mechanisms of GPR18 and its potential as a novel therapeutic target for treating metabolic disorders.

  12. Role of Transient Receptor Potential Vanilloid 1 in Inflammation and Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Fumio Tsuji

    2012-08-01

    Full Text Available Transient receptor potential vanilloid 1 (TRPV1, a non-selective cation channel, is a receptor activated by high temperatures and chemical agonists such as the vanilloids and protons. Because of these properties, TRPV1 has emerged as a polymodal nocisensor of nociceptive afferent neurons. TRPV1 is thought to be a central transducer of hyperalgesia and a prime target for controlling pain pharmacologically because it is a point where many proalgesic pathways converge and it is upregulated and sensitized by inflammation and injury. However, whether TRPV1 agonists promote or inhibit inflammation remains unclear. We recently demonstrated that SA13353 (1-[2-(1-adamantylethyl]-1-pentyl-3-[3-(4-pyridylpropyl]urea, a novel TRPV1 agonist, inhibits tumor necrosis factor-a production by the activation of capsaicin-sensitive afferent neurons and reduces the severity of symptoms in kidney injury, lung inflammation, arthritis, and encephalomyelitis. These results suggest that TRPV1 agonists may act as anti-inflammatories in certain inflammatory and autoimmune conditions in vivo. Given the potential deleterious effects of inhibiting the population of channels with a protective function, caution should be taken in the use of potent TRPV1 antagonists as a general strategy to treat inflammation. Further studies are required to clarify the role of TRPV1 and neuropeptides, which are released because of TRPV1 activation in inflammation and autoimmune diseases.

  13. The human milk microbiota: origin and potential roles in health and disease.

    Science.gov (United States)

    Fernández, Leónides; Langa, Susana; Martín, Virginia; Maldonado, Antonio; Jiménez, Esther; Martín, Rocío; Rodríguez, Juan M

    2013-03-01

    Human milk has been traditionally considered sterile; however, recent studies have shown that it represents a continuous supply of commensal, mutualistic and/or potentially probiotic bacteria to the infant gut. Culture-dependent and -independent techniques have revealed the dominance of staphylococci, streptococci, lactic acid bacteria and bifidobacteria in this biological fluid, and their role on the colonization of the infant gut. These bacteria could protect the infant against infections and contribute to the maturation of the immune system, among other functions. Different studies suggest that some bacteria present in the maternal gut could reach the mammary gland during late pregnancy and lactation through a mechanism involving gut monocytes. Thus, modulation of maternal gut microbiota during pregnancy and lactation could have a direct effect on infant health. On the other hand, mammary dysbiosis may lead to mastitis, a condition that represents the first medical cause for undesired weaning. Selected strains isolated from breast milk can be good candidates for use as probiotics. In this review, their potential uses for the treatment of mastitis and to inhibit mother-to-infant transfer of HIV are discussed.

  14. Curcumin and treatment of melanoma: The potential role of microRNAs.

    Science.gov (United States)

    Lelli, Diana; Pedone, Claudio; Sahebkar, Amirhosssein

    2017-04-01

    Melanoma is the most aggressive type of skin cancer and is characterized by poor prognosis in its advanced stages because treatments are poorly effective and burdened with severe adverse effects. MicroRNAs (miRNAs) are small non-coding RNAs that are implicated in several cellular processes; they are categorized as oncogenic and tumor suppressor miRNAs. Several miRNAs are implicated in the pathogenesis and progression of melanoma, such as the tumor suppressor miR-let7b that targets cyclin D and regulates cell cycle. Curcumin is a natural compound derived from Curcuma longa L. (turmeric) with anti-cancer properties, documented also in melanoma, and is well tolerated in humans. Pharmacological activity of curcumin is mediated by modulation of several pathways, such as JAK-2/STAT3, thus inhibiting melanoma cell migration and invasion and enhancing apoptosis of these cells. The low oral bioavailability of curcumin has led to the development of curcumin analogues, such as EF24, with greater anti-tumor efficacy and metabolic stability. Potential anti-cancer activity of curcumin and its analogues is also mediated by modulation of miRNAs such as miR21, that is implicated in cell cycle regulation and apoptosis through down-regulation of PTEN and PDCD4 proteins. Curcumin has a potential role in the treatment of melanoma, though further studies are necessary to explore its clinical efficacy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Potential role for ET-2 acting through ETA receptors in experimental colitis in mice.

    Science.gov (United States)

    Claudino, R F; Leite, D F; Bento, A F; Chichorro, J G; Calixto, J B; Rae, G A

    2017-02-01

    This study attempted to clarify the roles of endothelins and mechanisms associated with ETA/ETB receptors in mouse models of colitis. Colitis was induced by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS, 1.5 mg/animal) or dextran sulfate sodium (DSS, 3%). After colitis establishment, mice received Atrasentan (ETA receptor antagonist, 10 mg/kg), A-192621 (ETB receptor antagonist, 20 mg/kg) or Dexamethasone (1 mg/kg) and several inflammatory parameters were assessed, as well as mRNA levels for ET-1, ET-2 and ET receptors. Atrasentan treatment ameliorates TNBS- and DSS-induced colitis. In the TNBS model was observed reduction in macroscopic and microscopic score, colon weight, neutrophil influx, IL-1β, MIP-2 and keratinocyte chemoattractant (KC) levels, inhibition of adhesion molecules expression and restoration of IL-10 levels. However, A192621 treatment did not modify any parameter. ET-1 and ET-2 mRNA was decreased 24 h, but ET-2 mRNA was markedly increased at 48 h after TNBS. ET-2 was able to potentiate LPS-induced KC production in vitro. ETA and ETB receptors mRNA were increased at 24, 48 and 72 h after colitis induction. Atrasentan treatment was effective in reducing the severity of colitis in DSS- and TNBS-treated mice, suggesting that ETA receptors might be a potential target for inflammatory bowel diseases.

  16. The microbiota-gut-brain axis and its potential therapeutic role in autism spectrum disorder.

    Science.gov (United States)

    Li, Q; Zhou, J-M

    2016-06-02

    Autism spectrum disorder (ASD) is a series of neurodevelopmental disorders that are characterized by deficits in both social and cognitive functions. Although the exact etiology and pathology of ASD remain unclear, a disorder of the microbiota-gut-brain axis is emerging as a prominent factor in the generation of autistic behaviors. Clinical studies have shown that gastrointestinal symptoms and compositional changes in the gut microbiota frequently accompany cerebral disorders in patients with ASD. A disturbance in the gut microbiota, which is usually induced by a bacterial infection or chronic antibiotic exposure, has been implicated as a potential contributor to ASD. The bidirectional microbiota-gut-brain axis acts mainly through neuroendocrine, neuroimmune, and autonomic nervous mechanisms. Application of modulators of the microbiota-gut-brain axis, such as probiotics, helminthes and certain special diets, may be a promising strategy for the treatment of ASD. This review mainly discusses the salient observations of the disruptions of the microbiota-gut-brain axis in the pathogenesis of ASD and reveals its potential therapeutic role in autistic deficits.

  17. The role of Notch in the cardiovascular system: potential adverse effects of investigational Notch inhibitors

    Directory of Open Access Journals (Sweden)

    Paola eRizzo

    2015-01-01

    Full Text Available Targeting the Notch pathway is a new promising therapeutic approach for cancer patients. Inhibition of Notch is effective in the oncology setting because it causes a reduction of highly proliferative tumor cells and it inhibits survival of cancer stem cells which are considered responsible for tumor recurrence and metastasis. Additionally, since Delta- like ligand 4 (Dll4- activated Notch signalling is a major modulator of angiogenesis, anti-Dll4 agents are being investigated to reduce vascularization of the tumor. Notch plays a major role in the heart during the development and, after birth, in response to cardiac damage. Therefore, agents used to inhibit Notch in the tumors (gamma secretase inhibitors and anti-Dll4 agents could potentially affect myocardial repair. The past experience with trastuzumab and other tyrosine kinase inhibitors used for cancer therapy demonstrates that the possible cardiotoxicity of agents targeting shared pathways between cancer and heart and the vasculature should be considered. To date, Notch inhibition in cancer patients has resulted only in mild gastrointestinal toxicity. Little is known about the potential long term cardiotoxicity associated to Notch inhibition in cancer patients. In this review we will focus on mechanisms through which inhibition of Notch signalling could lead to cardiomyocytes and endothelial dysfunctions. These adverse effects could contrast with the benefits of therapeutic responses in cancer cells during times of increased cardiac stress and/or in the presence of cardiovascular risk factor

  18. Potential Molecular Targeted Therapeutics: Role of PI3-K/Akt/mTOR Inhibition in Cancer.

    Science.gov (United States)

    Sokolowski, Kevin M; Koprowski, Steven; Kunnimalaiyaan, Selvi; Balamurugan, Mariappan; Gamblin, T Clark; Kunnimalaiyaan, Muthusamy

    2016-01-01

    Primary liver cancer is one of the most commonly occurring cancers worldwide. Hepatocellular carcinoma (HCC) represents the majority of primary liver cancer and is the 3rd most common cause of cancer-related deaths globally. Survival rates of patients with HCC are dependent upon early detection as concomitant liver dysfunction and advanced disease limits traditional therapeutic options such as resection or ablation. Unfortunately, at the time of diagnosis, most patients are not eligible for curative surgery and have a five-year relative survival rate less than 20%, leading to systemic therapy as the only option. Currently, sorafenib is the only approved systemic therapy; however, it has a limited survival advantage and low efficacy prompting alternative strategies. The inception of sorafenib for HCC systemic therapy and the understanding involved of cancer therapy have led to an enhanced focus of the PI3-k/Akt/mTOR pathway as a potential area of targeting including pan and isoform-specific PI3-K inhibitors, Akt blockade, and mTOR suppression. The multitude, expanding roles, and varying clinical trials of these inhibitors have led to an increase in knowledge and availability for current and future studies. In this review, we provide a review of the literature with the aim to focus on potential targets for HCC therapies as well as an in depth focus on Akt inhibition.

  19. Special Issue: The Potential Role for Community Monitoring in MRV and in Benefit Sharing in REDD+

    Directory of Open Access Journals (Sweden)

    Arturo Balderas Torres

    2015-01-01

    Full Text Available Since the early design of activities to reduce emissions from deforestation and forest degradation in developing countries (REDD+ under the United Nations Framework Convention on Climate Change (UNFCCC, the need to engage local communities and indigenous groups in monitoring and reporting has been recognized. REDD+ has advanced under the UNFCCC negotiations, but most countries still need to define formally what the role of communities in their national monitoring systems will be. Previous research and experiences have shown that local communities can effectively contribute in the monitoring of natural resources. This editorial introduces a Special Issue of Forests which discusses the implications of and potential for including community based monitoring (CBM in monitoring and benefit-sharing systems in REDD+. It outlines the main points of the nine contributions to the Special Issue which cover a wide geographical area and report on projects and research which engages more than 150 communities from eight different countries from Africa, Asia and Latin America. The editorial summarizes how the articles and reports build further understanding of the potential of CBM to contribute to the implementation, monitoring and distribution of benefits in REDD+. It also discusses the results of an on-going opinion survey on issues related to CBM and its relation to benefit sharing, which indicates that there is still disagreement on a number of key elements.

  20. Potential role of Cyr61 induced degeneration of human Muller cells in diabetic retinopathy.

    Directory of Open Access Journals (Sweden)

    Fen Zhou

    Full Text Available The degeneration of Müller cells has been recognized to involve in the pathogenesis of diabetic retinopathy. However, the mechanism is not yet clear. This study is to explore the potential role of Cyr61, a secreted signaling protein in extracellular matrix, in inducing human Müller cell degeneration in diabetic retinopathy (DR. Twenty patients with proliferative diabetic retinopathy (PDR and twelve non-diabetic patients were recruited for this study. Vitreous fluid was collected during vitrectomy surgery for Cyr61 ELISA. Human Müller cell line MIO-M1 were cultured to be subconfluent, and then treated with glucose (0-20 mM or Cyr61 (0-300 ng/ml. Cyr61 expression induced by increasing concentrations of glucose was evaluated by RT-qPCR and Western blot. Effects of Cyr61 on Müller cells viability, migration and apoptosis were observed by MTT assay, Transwell assay, and TUNEL assay. Vitreous Cyr61 levels were observed to be 8-fold higher in patients with PDR (3576.92 ± 1574.58 pg/mL, compared with non-diabetic controls (436.14 ± 130.69 pg/mL. Interestingly, the active PDR group was significantly higher than the quiescent PDR group (P<0.01. In retinal Müller cells culture, high glucose significantly and dose-dependently elevated Cyr61 expression at both mRNA and protein levels. Cyr61 at high concentrations dose-dependently inhibited the viability and migration of Müller cells. TUNEL assay further revealed that high concentration of Cyr61 significantly promoted the cell apoptosis. In conclusion, these findings demonstrated for the first time that the expression of Cyr61 was elevated by high glucose in Müller cells, and Cyr61 inhibited cell viability and migration while induced apoptosis, suggesting the potential role of Cyr61 in Müller cell degeneration. The elevated Cyr61 levels in vitreous fluid of PDR patients further support its role in diabetic retinopathy (DR.

  1. AFSC/RACE/EcoFOCI: 2010 BEST and BSIERP Study 1WE10/WE10-08

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Ecosystem & Fisheries-Oceanography Coordinated Investigations (Eco-FOCI) is an effort by National Oceanic and Atmospheric Administration (NOAA) and associated...

  2. Emerging Insights on Brazilian Pepper Tree (Schinus terebinthifolius) Invasion: The Potential Role of Soil Microorganisms

    Science.gov (United States)

    Dawkins, Karim; Esiobu, Nwadiuto

    2016-01-01

    Invasive plant species constitute a major ecological and economic problem worldwide, often distorting trophic levels and ecosystem balance. Numerous studies implicate factors ranging from environmental plasticity, competition for nutrient and space, and allelopathy in the success of invasive species in general. The Brazilian Pepper tree (BP) was introduced to the United States in the 1800s and has since become a category one invasive plant in Florida. It has aggressively spread to about 3000 km2 of terrestrial surface, fueled in part by the prevalence of the hybrid genotypes and environmental perturbations. It displays some of the well-established invasive mechanisms but there is a serious dearth of knowledge on the plant–microbe–soil interactions and whether the rhizobiome plays any roles in the displacement of native flora and the range expansion of BP. Several control measures, including chemical, mechanical, and biological antagonism have been used with limited success while restoration of natives in soils from which BP was removed has proved problematic partly due to a poorly understood phenomenon described as the “BP legacy effect.” Emerging evidence suggests that allelopathy, selective recruitment of beneficial soil microbes, disruption of microbial community structure and alteration of nutrient cycling, exhibited by many other invasive plant species may also be involved in the case of BP. This brief review discusses the well-established BP invasion mechanisms and highlights the current understanding of the molecular, below-ground processes. It also points out the gaps in studies on the potential role of microbial interactions in the success of BP invasion. These hitherto poorly studied mechanisms could further explain the aggressive spread of BP and could potentially contribute significantly to effective control measures and enable appropriate strategies for restoring native plants. The review advocates for the use of cutting-edge techniques in

  3. Vanadium: a review of its potential role in the fight against diabetes.

    Science.gov (United States)

    Badmaev, V; Prakash, S; Majeed, M

    1999-06-01

    The potential role of vanadium in human health is described as a building material of bones and teeth. However, another very interesting and promising application for vanadium in human health emerges from recent studies that evaluated the role of vanadium in the management of diabetes. Vanadium is present in a variety of foods that we commonly eat. Skim milk, lobster, vegetable oils, many vegetables, grains and cereals are rich source of vanadium (>1 ppm). Fruits, meats, fish, butter, cheese, and beverages are relatively poor sources of vanadium. The daily dietary intake in humans has been estimated to vary from 10 microg to 2 mg of elemental vanadium, depending on the environmental sources of this mineral in the air, water, and food of the particular region tested. In animals, vanadium has been shown essential (1-10 microg vanadium per gram of diet). There is only circumstantial evidence that vanadium is essential for humans. However, in doses ranging from 0.083 mmol/d to 0.42 mmol/d, vanadium has shown therapeutic potential in clinical studies with patients of both insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM) type. Although vanadium has a significant biological potential, it has a poor therapeutic index, and attempts have been made to reduce the dose of vanadium required for therapeutic effectiveness. Organic forms of vanadium, as opposed to the inorganic sulfate salt of vanadium, are recognized as safer, more absorbable, and able to deliver a therapeutic effect up to 50% greater than the inorganic forms. The goal is to provide vanadium with better gastrointestinal absorption, and in a form that is best able to produce the desired biological effects. As a result, numerous organic complexes of vanadium have been developed including bis(maltolato)oxovanadium (BMOV), bis(cysteinamide N-octyl)oxovanadium known as Naglivan, bis(pyrrolidine-N-carbodithioato)oxovanadium, vanadyl-cysteine methyl ester, and bis

  4. The potential role of stethoscopes as a source of nosocomial infection

    Directory of Open Access Journals (Sweden)

    Neetu Gupta

    2014-01-01

    Full Text Available Background: Infectious diseases can be transmitted in various ways . Indirect transmission or vehicle-borne transmission of infection can occur through various agents like instruments, utensils, water, or food. In hospital settings, transmission of infection through contaminated medical devices is always a possibility. Stethoscope is the symbol of health professionals. However, the diaphragm and bells of the stethoscopes have been shown to harbor pathogenic and nonpathogenic microorganisms. Aims: 1 To determine the degree of contamination of stethoscopes used by clinicians and nurses. 2 To identify various microbes from such contaminated stethoscopes and to assess their role as potential pathogens. 3 To determine the effectiveness of 70% ethanol as a disinfecting agent. Materials and Methods: Stethoscopes of 50 healthcare workers from different departments were included in the study. Bacteriological cultures of the samples were done on blood agar and MacConkey agar plates. Organisms were identified by conventional phenotypic methods. Antibiotic sensitivity test (ABST of the microorganisms was performed by Kirby-Bauer disk diffusion method. Results: Average number of colonies on each stethoscope was 30 . Pathogenic microorganisms including Staphylococcus aureus, Acinetobacter species, Citrobacter species, Pseudomonas stutzeri, Bacillus species, and Aspergillus fumigatus were identified. Among the potential pathogenic organisms, coagulase-negative staphylococci were isolated. Numbers of colonies were highest among the stethoscopes sampled from surgery ward and Medical Intensive Care Unit MICU. Conclusion: Stethoscopes harbor potential pathogens capable of surviving on their surfaces. Despite their best intentions, health professionals can act as a vector for transmission of disease. Disinfecting procedures may be necessary between consecutive patients. Attention to simple preventive strategies can reduce the disease transmission rate.

  5. Role of the transient receptor potential vanilloid 1 in inflammation and sepsis

    Directory of Open Access Journals (Sweden)

    Devesa I

    2011-05-01

    Full Text Available Isabel Devesa1, Rosa Planells-Cases2, Gregorio Fernández-Ballester1, José Manuel González-Ros1, Antonio Ferrer-Montiel1, Asia Fernández-Carvajal11Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Alicante; 2Centro de Investigación Príncipe Felipe, Valencia, SpainAbstract: The transient receptor potential vanilloid 1 (TRPV1 is a thermoreceptor that responds to noxious temperatures, as well as to chemical agonists, such as vanilloids and protons. In addition, its channel activity is notably potentiated by proinflammatory mediators released upon tissue damage. The TRPV1 contribution to sensory neuron sensitization by proalgesic agents has signaled this receptor as a prime target for analgesic and anti-inflammatory drug intervention. However, TRPV1 antagonists have notably failed in clinical and preclinical studies because of their unwanted side effects. Recent reports have unveiled previously unrecognized anti-inflammatory and protective functions of TRPV1 in several diseases. For instance, this channel has been suggested to play an anti-inflammatory role in sepsis. Therefore, the use of potent TRPV1 antagonists as a general strategy to treat inflammation must be cautiously considered, given the deleterious effects that may arise from inhibiting the population of channels that have a protective function. The use of TRPV1 antagonists may be limited to treating those pathologies where enhanced receptor activity contributes to the inflamed state. Alternatively, therapeutic paradigms, such as reduction of inflammatory-mediated increase of receptor expression in the cell surface, may be a better strategy to prevent abrogation of the TRPV1 subpopulation involved in anti-inflammatory and protective processes.Keywords: transient receptor potential, nociceptor, capsaicin, pain, ion channel, analgesia

  6. [Helicobacter pylori morphological forms and their potential role in the transmission of infection].

    Science.gov (United States)

    Rudnicka, Karolina; Graczykowski, Maciej; Tenderenda, Michał; Chmiela, Magdalena

    2014-03-04

    More than 50% of the world's population is infected with Helicobacter pylori (H. pylori) - a Gram negative bacterium, which persists in the human stomach and duodenum, causing gastric or duodenal ulcers and gastric cancer. The majority of H. pylori cells demonstrate rod-shape morphology occurring in two subtypes: spiral and S-shaped. Both are isolated from mucus layer biopsy specimens of the stomach or from short-term cultures. However, results obtained from electron microscopy revealed that H. pylori long-term cultures not only consist of classic, spiral shaped bacteria, but also contain alternative forms of coccoid cells. Further investigations showed that coccoid forms of H. pylori may be divided into two types: viable but non-culturable coccus (VBnC) and a degenerative form, coccoid stage which is probably the effect of bacterial cell death. Transformation from spiral to coccoid form is induced under stress conditions, such as the presence of antibiotics. But still there is no evidence for reversion from the coccoid state to the viable and infectious spiral form. Besides the planktonic form, H. pylori also forms homo-, and heterogenic biofilms, which may constitute a potential environmental reservoir of this bacterium. The antigenic repertoire and the immunomodulatory and infectious properties of different H. pylori forms differ greatly. The variation in those properties suggests that morphological forms of H. pylori are potentially involved in the transmission of the infection. This review presents recent findings on the variability, antigenicity and infectious properties of H. pylori morphological forms and their potential role in the transmission of the infection.

  7. Helicobacter pylori morphological forms and their potential role in the transmission of infection

    Directory of Open Access Journals (Sweden)

    Karolina Rudnicka,

    2014-03-01

    Full Text Available More than 50% of the world’s population is infected with Helicobacter pylori (H. pylori – a Gram negative bacterium, which persists in the human stomach and duodenum, causing gastric or duodenal ulcers and gastric cancer. The majority of H. pylori cells demonstrate rod-shape morphology occurring in two subtypes: spiral and S-shaped. Both are isolated from mucus layer biopsy specimens of the stomach or from short-term cultures. However, results obtained from electron microscopy revealed that H. pylori long-term cultures not only consist of classic, spiral shaped bacteria, but also contain alternative forms of coccoid cells. Further investigations showed that coccoid forms of H. pylori may be divided into two types: viable but non-culturable coccus (VBnC and a degenerative form, coccoid stage which is probably the effect of bacterial cell death. Transformation from spiral to coccoid form is induced under stress conditions, such as the presence of antibiotics. But still there is no evidence for reversion from the coccoid state to the viable and infectious spiral form. Besides the planktonic form, H. pylori also forms homo-, and heterogenic biofilms, which may constitute a potential environmental reservoir of this bacterium. The antigenic repertoire and the immunomodulatory and infectious properties of different H. pylori forms differ greatly. The variation in those properties suggests that morphological forms of H. pylori are potentially involved in the transmission of the infection. This review presents recent findings on the variability, antigenicity and infectious properties of H. pylori morphological forms and their potential role in the transmission of the infection.

  8. Imaging Features that Discriminate between Foci Induced by High-and Low-LET Radiation in Human Fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Costes, Sylvain V.; Boissiere, Arnaud; Ravani, Shraddha; Romano,Raquel; Parvin, Bahram; Barcellos-Hoff, Mary Helen

    2006-10-08

    In this study, we investigated the formation ofradiation-induced foci in normal human fibroblasts exposed to X rays or130 keV/mum nitrogen ions using antibodies to phosphorylated proteinkinase ataxia telangiectasia mutated (ATMp) and histone H2AX(gamma-H2AX). High-content automatic image analysis was used to quantifythe immunofluorescence of radiation-induced foci. The size ofradiation-induced foci increased for both proteins over a 2-h periodafter nitrogen-ion irradiation, while the size of radiation-induced focidid not change after exposure to low-LET radiation. The number ofradiation-induced ATMp foci showed a more rapid rise and greaterfrequency after X-ray exposure and was resolved more rapidly such thatthe frequency of radiation-induced foci decreased by 90 percent comparedto 60 percent after exposure to high-LET radiation 2 h after 30 cGy. Incontrast, the kinetics of radiation-induced gamma-H2AX focus formationwas similar for high- and low-LET radiation in that it reached a plateauearly and remained constant for up to 2 h. High-resolution 3D images ofradiation-induced gamma-H2AX foci and dosimetry computation suggest thatmultiple double-strand breaks from nitrogen ions are encompassed withinlarge nuclear domains of 4.4 Mbp. Our work shows that the size andfrequency of radiation-induced foci vary as a function of radiationquality, dose, time and protein target. Thus, even though double-strandbreaks and radiation-induced foci are correlated, the dynamic nature ofboth contradicts their accepted equivalence for low doses of differentradiation qualities.

  9. p53 binding protein 1 foci as a biomarker of DNA double strand breaks induced by ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ng, C.K.M.; Wong, M.Y.P.; Lam, R.K.K.; Ho, J.P.Y. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Chiu, S.K. [Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Yu, K.N., E-mail: peter.yu@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); State Key Laboratory in Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong)

    2011-12-21

    Foci of p53 binding protein 1 (53 BP1) have been used as a biomarker of DNA double-strand breaks (DSBs) in cells induced by ionizing radiations. 53 BP1 was shown to relocalize into foci shortly after irradiation, with the number of foci closely paralleling the number of DNA DSBs. However, consensus on criteria in terms of the numbers of 53 BP1 foci to define cells damaged by direct irradiation or by bystander signals has not been reached, which is partly due to the presence of 53 BP1 also in normal cells. The objective of the present work was to study the changes in the distribution of cells with different numbers of 53 BP1 foci in a cell population after low-dose ionizing irradiation (<0.1 Gy) provided by alpha particles, with a view to propose feasible criteria for defining cells damaged by direct irradiation or by bystander signals. It was proposed that the change in the percentage of cells with 1-3 foci should be used for such purposes. The underlying reasons were discussed.

  10. Exploring the Potential of Role Play in Higher Education: Development of a Typology and Teacher Guidelines

    Science.gov (United States)

    Rao, Deepa; Stupans, Ieva

    2012-01-01

    Role-play, in which learners act out roles in case scenarios, appears to be used across a broad range of discipline areas to address learning across the cognitive, psychomotor and affective domains. This paper describes the development of a prospective typology of role-play learning opportunities derived from role-play scenarios used at one large…

  11. Educational and Professional Potential of Personnel: Essence and Role in Formation of Investment Attractiveness of a Company

    OpenAIRE

    Skrynkovskyy Ruslan M.

    2013-01-01

    The article reveals the essence of educational and professional potential of personnel and investment attractiveness of a company. It provides a model of formation of investment attractiveness of a company. It establishes the role of educational and professional potential of personnel in formation of investment attractiveness of a company. It provides a mathematical description of influence of educational and professional potential of personnel on investment attractiveness of a company.В стат...

  12. Action potential processing in a detailed Purkinje cell model reveals a critical role for axonal compartmentalization

    Directory of Open Access Journals (Sweden)

    Stefano eMasoli

    2015-02-01

    Full Text Available The Purkinje cell (PC is among the most complex neurons in the brain and plays a critical role for cerebellar functioning. PCs operate as fast pacemakers modulated by synaptic inputs but can switch from simple spikes to complex bursts and, in some conditions, show bistability. In contrast to original works emphasizing dendritic Ca-dependent mechanisms, recent experiments have supported a primary role for axonal Na-dependent processing, which could effectively regulate spike generation and transmission to deep cerebellar nuclei (DCN. In order to account for the numerous ionic mechanisms involved (at present including Nav1.6, Cav2.1, Cav3.1, Cav3.2, Cav3.3, Kv1.1, Kv1.5, Kv3.3, Kv3.4, Kv4.3, KCa1.1, KCa2.2, KCa3.1, Kir2.x, HCN1, we have elaborated a multicompartmental model incorporating available knowledge on localization and gating of PC ionic channels. The axon, including initial segment (AIS and Ranvier nodes (RNs, proved critical to obtain appropriate pacemaking and firing frequency modulation. Simple spikes initiated in the AIS and protracted discharges were stabilized in the soma through Na-dependent mechanisms, while somato-dendritic Ca channels contributed to sustain pacemaking and to generate complex bursting at high discharge regimes. Bistability occurred only following Na and Ca channel down-regulation. In addition, specific properties in RNs K currents were required to limit spike transmission frequency along the axon. The model showed how organized electroresponsive functions could emerge from the molecular complexity of PCs and showed that the axon is fundamental to complement ionic channel compartmentalization enabling action potential processing and transmission of specific spike patterns to DCN.

  13. A critical role for the transient receptor potential channel type 6 in human platelet activation.

    Directory of Open Access Journals (Sweden)

    Hari Priya Vemana

    Full Text Available While calcium signaling is known to play vital roles in platelet function, the mechanisms underlying its receptor-operated calcium entry component (ROCE remain poorly understood. It has been proposed, but never proven in platelets, that the canonical transient receptor potential channel-6 (TRPC6 mediates ROCE. Nonetheless, we have previously shown that the mouse TRPC6 regulates hemostasis, thrombogenesis by regulating platelet aggregation. In the present studies, we used a pharmacological approach to characterize the role of TRPC6 in human platelet biology. Thus, interestingly, we observed that a TRPC6 inhibitor exerted significant inhibitory effects on human platelet aggregation in a thromboxane receptor (TPR-selective manner; no additional inhibition was observed in the presence of the calcium chelator BAPTA. This inhibitor also significantly inhibited human platelet secretion (dense and alpha granules, integrin IIb-IIIa, Akt and ERK phosphorylation, again, in a TPR-selective manner; no effects were observed in response to ADP receptor stimulation. Furthermore, there was a causal relationship between these inhibitory effects, and the capacity of the TRPC6 inhibitor to abrogate elevation in intracellular calcium, that was again found to be TPR-specific. This effect was not found to be due to antagonism of TPR, as the TRPC6 inhibitor did not displace the radiolabeled antagonist [3H]SQ29,548 from its binding sites. Finally, our studies also revealed that TRPC6 regulates human clot retraction, as well as physiological hemostasis and thrombus formation, in mice. Taken together, our findings demonstrate, for the first time, that TRPC6 directly regulates TPR-dependent ROCE and platelet function. Moreover, these data highlight TRPC6 as a novel promising therapeutic strategy for managing thrombotic disorders.

  14. POTENTIAL CLUSTERS IN BANAT AND THEIR ROLE IN REGIONAL ECONOMIC DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Ramona IŞFĂNESCU

    2010-06-01

    Full Text Available The interest in the study of clusters and their role in the economic development of certain regions has constantly grown in the past years. This interest has also been emphasized by the emergence of successful clusters in many regions; these are clusters that have visibly and they have determined the increase in competitiveness of those particular regions. Clusters are geographic gatherings of firms and institutions, connected to each other and specialized in certain fields of activity. In Romania, due to the low cooperation level among enterprises we cannot say that proper clusters exists, but just some “spatial gatherings” of firms activating in certain domains, connected by the need of using certain natural resources and the existence of a specialized workforce in that particular domain. Natural “clusters” can be identified by means of quantitative analyses, these indicating the possibility to identify certain spatial assemblies of firms in a certain economic sector. Starting from these quantitative analyses, for Banat region have been identified some important spatial gatherings of firms activating in certain domains which could represent potential clusters in this area. As clusters function on the principle of cooperation among enterprises, a strong point of the region is the presence of foreign investors which promoted the model of enterprise cooperation through sub-contracting local enterprises. Among these, we mention the Italian investors which brought to Banat, especially to Timiş County the Italian cluster model. Are there in Banat premises for the emergence of clusters? Which are the fields of activity in which these clusters can emerge? What role will these clusters play in the economic development of the region? These are just some of the questions that we aim answering to through this study.

  15. Beef tallow increases apoptosis and decreases aberrant crypt foci formation relative to soybean oil in rat colon.

    Science.gov (United States)

    Khil, Jinmo; Gallaher, Daniel D

    2004-01-01

    Although epidemiological studies have implicated red meat as increasing colon cancer risk, animal studies have generally not been supportive of such an effect. This study examined red meat components, such as beef protein and tallow, on markers of colon cancer risk. Rats administered dimethylhydrazine were fed either casein or beef protein as the protein source and soybean oil or tallow as the fat source in a 2 2 factorial design for 9 wk. There were fewer preneoplastic lesions [aberrant crypt foci (ACF)] and a greater apoptotic labeling index (P tallow compared with soybean oil. Fecal bile acid concentrations were significantly lower in rats fed tallow compared with soybean oil. There were no significant differences in mucosal cell proliferation. No significant effects were found due to protein source or to interactions between fat and protein sources for ACF, cell proliferation labeling indexes, or bile acid concentrations. However, there was a significant protein by fat source interaction for the apoptotic labeling index. The decreased number of ACF, decreased fecal bile acid concentration, and increased mucosal apoptosis with tallow consumption are not consistent with a role for this fat in increasing risk of colon cancer.

  16. Resilience of invaded riparian landscapes: the potential role of soil-stored seed banks.

    Science.gov (United States)

    Tererai, Farai; Gaertner, Mirijam; Jacobs, Shayne M; Richardson, David M

    2015-01-01

    We investigated the potential role of soil-stored seed banks in driving vegetation recovery under varying intensities of invasion by the alien tree Eucalyptus camaldulensis along the Berg River in South Africa's Western Cape Province. We asked: How do richness, diversity, and composition of soil-stored seed banks vary with invasion intensity? What is the difference between the seed banks and above-ground vegetation with respect to species richness, diversity, composition, and structure? To what extent do soil-stored seed banks provide reliable sources for restoring native plant communities? Through a seedling-emergence approach, we compared seedling density, richness, and diversity in plots under varying Eucalyptus cover. Seed bank characteristics were also compared with those of the above-ground vegetation. Except in terms of diversity and density, the richness and composition of native species varied significantly among invasion conditions. Despite the paucity of native tree and shrub species in the seed bank, it was more diverse than extant vegetation. Some species occurred exclusively either in the seed bank or in the above-ground vegetation. Although this ecosystem has been degraded by several agents, including Eucalyptus invasion, soil-stored seed banks still offer modest potential for driving regeneration of native plant communities, but secondary invasions need to be managed carefully. Remnant populations of native plants in the above-ground vegetation remaining after E. camaldulensis clearing provide a more promising propagule source for rapid regeneration. Further work is needed to elucidate possible effects of invasion on successional pathways following E. camaldulensis removal and the effects of hydrochory on seed bank dynamics.

  17. The potential role of infectious agents and pelvic inflammatory disease in ovarian carcinogenesis.

    Science.gov (United States)

    Ingerslev, Kasper; Hogdall, Estrid; Schnack, Tine Henrichsen; Skovrider-Ruminski, Wojciech; Hogdall, Claus; Blaakaer, Jan

    2017-01-01

    The etiological cause of ovarian cancer is poorly understood. It has been theorized that bacterial or viral infection as well as pelvic inflammatory disease could play a role in ovarian carcinogenesis. To review the literature on studies examining the association between ovarian cancer and bacterial or viral infection or pelvic inflammatory disease. Database search through MEDLINE, applying the medical subject headings: "Ovarian neoplasms", AND "Chlamydia infections", "Neisseria gonorrhoeae", "Mycoplasma genitalium", "Papillomaviridae", or "pelvic inflammatory disease". Corresponding searches were performed in EMBASE, and Web of Science. The literature search identified 935 articles of which 40 were eligible for inclusion in this review. Seven studies examined the association between bacterial infection and ovarian cancer. A single study found a significant association between chlamydial infection and ovarian cancer, while another study identified Mycoplasma genitalium in a large proportion of ovarian cancer cases. The remaining studies found no association. Human papillomavirus detection rates varied from 0 to 67% and were generally higher in the Asian studies than in studies from Western countries. Cytomegalovirus was the only other virus to be detected and was found in 50% of cases in a case-control study. The association between ovarian cancer and pelvic inflammatory disease was examined in seven epidemiological studies, two of which, reported a statistically significant association. Data indicate a potential association between pelvic inflammatory disease and ovarian cancer. An association between ovarian cancer and high-risk human papillomavirus genotypes may exist in Asia, whereas an association in Western countries seems unlikely due to the low reported prevalence. Potential carcinogenic bacteria were found, but results were inconsistent, and further research is warranted.

  18. Potential role for PAD2 in gene regulation in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Brian D Cherrington

    Full Text Available The peptidylarginine deiminase (PAD family of enzymes post-translationally convert positively charged arginine residues in substrate proteins to the neutral, non-standard residue citrulline. PAD family members 1, 2, 3, and 6 have previously been localized to the cell cytoplasm and, thus, their potential to regulate gene activity has not been described. We recently demonstrated that PAD2 is expressed in the canine mammary gland epithelium and that levels of histone citrullination in this tissue correlate with PAD2 expression. Given these observations, we decided to test whether PAD2 might localize to the nuclear compartment of the human mammary epithelium and regulate gene activity in these cells. Here we show, for the first time, that PAD2 is specifically expressed in human mammary gland epithelial cells and that a portion of PAD2 associates with chromatin in MCF-7 breast cancer cells. We investigated a potential nuclear function for PAD2 by microarray, qPCR, and chromatin immunoprecipitation analysis. Results show that the expression of a unique subset of genes is disregulated following depletion of PAD2 from MCF-7 cells. Further, ChIP analysis of two of the most highly up- and down-regulated genes (PTN and MAGEA12, respectively found that PAD2 binds directly to these gene promoters and that the likely mechanism by which PAD2 regulates expression of these genes is via citrullination of arginine residues 2-8-17 on histone H3 tails. Thus, our findings define a novel role for PAD2 in gene expression in human mammary epithelial cells.

  19. Potential pathogenic role of aggregative-adhering Corynebacterium diphtheriae of different clonal groups in endocarditis.

    Science.gov (United States)

    Hirata Jr, R; Pereira, G A; Filardy, A A; Gomes, D L R; Damasco, P V; Rosa, A C P; Nagao, P E; Pimenta, F P; Mattos-Guaraldi, A L

    2008-11-01

    Invasive diseases caused by Corynebacterium diphtheriae have been described increasingly. Several reports indicate the destructive feature of endocarditis attributable to nontoxigenic strains. However, few reports have dealt with the pathogenicity of invasive strains. The present investigation demonstrates a phenotypic trait that may be used to identify potentially invasive strains. The study also draws attention to clinical and microbiological aspects observed in 5 cases of endocarditis due to C. diphtheriae that occurred outside Europe. Four cases occurred in female school-age children (7-14 years) treated at different hospitals in Rio de Janeiro, Brazil. All patients developed other complications including septicemia, renal failure and/or arthritis. Surgical treatment was performed on 2 patients for valve replacement. Lethality was observed in 40% of the cases. Microorganisms isolated from 5 blood samples and identified as C. diphtheriae subsp mitis (N = 4) and C. diphtheriae subsp gravis (N = 1) displayed an aggregative adherence pattern to HEp-2 cells and identical one-dimensional SDS-PAGE protein profiles. Aggregative-adhering invasive strains of C. diphtheriae showed 5 distinct RAPD profiles. Despite the clonal diversity, all 5 C. diphtheriae invasive isolates seemed to display special bacterial adhesive properties that may favor blood-barrier disruption and systemic dissemination of bacteria. In conclusion, blood isolates from patients with endocarditis exhibited a unique adhering pattern, suggesting a pathogenic role of aggregative-adhering C. diphtheriae of different clones in endocarditis. Accordingly, the aggregative-adherence pattern may be used as an indication of some invasive potential of C. diphtheriae strains.

  20. Potential pathogenic role of aggregative- adhering Corynebacterium diphtheriae of different clonal groups in endocarditis

    Directory of Open Access Journals (Sweden)

    R. Hirata Jr.

    2008-11-01

    Full Text Available Invasive diseases caused by Corynebacterium diphtheriae have been described increasingly. Several reports indicate the destructive feature of endocarditis attributable to nontoxigenic strains. However, few reports have dealt with the pathogenicity of invasive strains. The present investigation demonstrates a phenotypic trait that may be used to identify potentially invasive strains. The study also draws attention to clinical and microbiological aspects observed in 5 cases of endocarditis due to C. diphtheriae that occurred outside Europe. Four cases occurred in female school-age children (7-14 years treated at different hospitals in Rio de Janeiro, Brazil. All patients developed other complications including septicemia, renal failure and/or arthritis. Surgical treatment was performed on 2 patients for valve replacement. Lethality was observed in 40% of the cases. Microorganisms isolated from 5 blood samples and identified as C. diphtheriae subsp mitis (N = 4 and C. diphtheriae subsp gravis (N = 1 displayed an aggregative adherence pattern to HEp-2 cells and identical one-dimensional SDS-PAGE protein profiles. Aggregative-adhering invasive strains of C. diphtheriae showed 5 distinct RAPD profiles. Despite the clonal diversity, all 5 C. diphtheriae invasive isolates seemed to display special bacterial adhesive properties that may favor blood-barrier disruption and systemic dissemination of bacteria. In conclusion, blood isolates from patients with endocarditis exhibited a unique adhering pattern, suggesting a pathogenic role of aggregative-adhering C. diphtheriae of different clones in endocarditis. Accordingly, the aggregative-adherence pattern may be used as an indication of some invasive potential of C. diphtheriae strains.

  1. A novel technique using three-dimensionally documented biopsy mapping allows precise re-visiting of prostate cancer foci with serial surveillance of cell cycle progression gene panel.

    Science.gov (United States)

    Ukimura, Osamu; Gross, Mitchell E; de Castro Abreu, Andre Luis; Azhar, Raed A; Matsugasumi, Toru; Ushijima, So; Kanazawa, Motohiro; Aron, Manju; Gill, Inderbir S

    2015-06-01

    Conventional systematic biopsy has the shortcoming of sampling error and reveals "no evidence of cancer" with a rate of >50% on active surveillance (AS). The objective of this study is to report our initial experience of applying a 3D-documented biopsy-mapping technology to precisely re-visit geographically documented low-risk prostate cancer and to perform serial analysis of cell-cycle-progression (CCP) gene-panel. Over a period of 40 months (1/2010-4/2013), the 3D-biopsy-mapping technique, in which the spatial location of biopsy-trajectory was digitally recorded (Koelis), was carried out. A pair of diagnostic (1st-look) and surveillance (2nd-look) biopsy were performed per subject (n = 25), with median interval of 12 months. The documented biopsy-trajectory was used as a target to guide the re-visiting biopsy from the documented cancer focus, as well as the targeted field-biopsy from the un-sampled prostatic field adjacent to negative diagnostic biopsies. The accuracy of re-visiting biopsy and biopsy-derived CCP signatures were evaluated in the pair of the serial biopsy-cores. The 1st-look-biopsy revealed a total of 43 cancer lesions (1.7 per patient). The accuracy of re-visiting cancer was 86% (37/43) per lesion, 76% (65/86) per core, and 80% (20/25) per patient. This technology also provided an opportunity for 3D-targeted field-biopsy in order to potentially minimize sampling errors. The CCP gene-panel of the 1st-look (-0.59) versus 2nd-look (-0.37) samples had no significant difference (P = 0.4); which suggested consistency in the molecular signature of the known cancer foci during the short-time interval of median 12 months. Any change in CCP of the same cancer foci would be likely due to change in sampling location from the less to more significant portion in the cancer foci rather than true molecular progression. The study limitations include a small number of the patients. The 3D-documented biopsy-mapping technology achieved an encouraging re

  2. Modulation of neuroinflammation: The role and therapeutic potential of transient receptor potential vanilloid 1 in neuro-immune axis.

    Science.gov (United States)

    Kong, Wei-Lin; Peng, Yuan-Yuan; Peng, Bi-Wen

    2017-03-22

    Transient receptor potential vanilloid type 1 channel (TRPV1), as a ligand-gated non-selective cation channel, has recently been demonstrated to have wide expression in the neuro-immune axis, where its multiple functions occur through regulation of both neuronal and non-neuronal activities. Growing evidence has suggested that TRPV1 is functionally expressed in glial cells, especially in the microglia and astrocytes. Glial cells perform immunological functions in response to pathophysiological challenges through pro-inflammatory or anti-inflammatory cytokines and chemokines in which TRPV1 is involved. Sustaining inflammation might mediate a positive feedback loop of neuroinflammation and exacerbate neurological disorders. Accumulating evidence has suggested that TRPV1 is closely related to immune responses and might be recognized as a molecular switch in the neuroinflammation of a majority of seizures and neurodegenerative diseases. In this review, we evidenced that inflammation modulates the expression and activity of TRPV1 in the central nervous system (CNS) and TRPV1 exerts reciprocal actions over neuroinflammatory processes. Together, the literature supports the hypothesis that TRPV1 may represent potential therapeutic targets in the neuro-immune axis.

  3. Mapping and assessment of epileptogenic foci using frequency-entropy templates

    Science.gov (United States)

    Ben-Jacob, Eshel; Doron, Itai; Gazit, Tomer; Rephaeli, Eden; Sagher, Oren; Towle, Vernon L.

    2007-11-01

    Much effort has been devoted to developing analysis methods of subdural electroencephalogram and depth electrode recordings of epileptic patients being evaluated for surgical resection. The general approach is to investigate the brain activity at different locations as recorded by the different electrodes in an attempt to localize the epileptogenic focus or foci. Currently, most of the methods are based on the notion that epileptogenic brain activity is associated with changes in synchronization and in complexity. Here we present a method that is based on the temporal dynamics combined with the spectral distribution of energy in terms of frequency-entropy (FE) templates. The FE templates are based upon maximum information partitioning into a set of frequency bands. The FE template is calculated by wavelet packet decomposition followed by an application of the best basis algorithm minimizing the entropy cost function. A comparison between two FE templates is performed by a special quantitative similarity measure according to the overlap in the partitioning into frequency bands and weighted by the bands’ entropy. For localization of the epileptogenic foci, the templates of each electrode during the interictal period are compared with a representative template evaluated from the ensemble of all electrodes during the ictal period. We suggest associating the locations that reveal high template similarity to the ictal template with the epileptogenic foci. To test the method and the underlying assumptions, we perform retrospective analysis of the recorded brain activity, from both grid and depth electrodes, from 11 patients suffering from medically intractable epilepsy. Application of the ictal-interictal FE template similarity analysis revealed regions in the epileptic brain in which the interictal characteristics are highly similar to those of the ictal period. To asses the foci we compared the interictal templates of the different electrodes to each other, forming

  4. Assembly and function of DNA double-strand break repair foci in mammalian cells

    DEFF Research Database (Denmark)

    Bekker-Jensen, Simon; Mailand, Niels

    2010-01-01

    phosphorylation, ubiquitylation, SUMOylation, and acetylation. Over the last decade, insight into the identity of proteins residing in IRIF and the molecular underpinnings of their retention at these structures has been vastly expanded. Despite such advances, however, our understanding of the biological relevance...... of such DNA repair foci still remains limited. In this review, we focus on recent discoveries on the mechanisms that govern the formation of IRIF, and discuss the implications of such findings in light of our understanding of the physiological importance of these structures....

  5. Why should I share my knowledge? A multiple foci of commitment perspective

    DEFF Research Database (Denmark)

    Swart, Juani; Kinnie, Nicholas; van Rossenberg, Yvonne Gerarda Theodora;

    2014-01-01

    Knowledge-intensive firms need to leverage their individual knowledge assets via knowledge sharing to create collective knowledge resources. This process is, however, in the control of the knowledge worker. We explore this personal and emotive quality of knowledge sharing by asking: ‘How does emp...... of the interrelationship between (a) the types and foci of commitment and (b) bidirectional knowledge sharing.......Knowledge-intensive firms need to leverage their individual knowledge assets via knowledge sharing to create collective knowledge resources. This process is, however, in the control of the knowledge worker. We explore this personal and emotive quality of knowledge sharing by asking: ‘How does...

  6. Giardia Colonizes and Encysts in High-Density Foci in the Murine Small Intestine

    Science.gov (United States)

    Barash, N. R.; Nosala, C.; Pham, J. K.; McInally, S. G.; Gourguechon, S.; McCarthy-Sinclair, B.

    2017-01-01

    ABSTRACT Giardia lamblia is a highly prevalent yet understudied protistan parasite causing significant diarrheal disease worldwide. Hosts ingest Giardia cysts from contaminated sources. In the gastrointestinal tract, cysts excyst to become motile trophozoites, colonizing and attaching to the gut epithelium. Trophozoites later differentiate into infectious cysts that are excreted and contaminate the environment. Due to the limited accessibility of the gut, the temporospatial dynamics of giardiasis in the host are largely inferred from laboratory culture and thus may not mirror Giardia physiology in the host. Here, we have developed bioluminescent imaging (BLI) to directly interrogate and quantify the in vivo temporospatial dynamics of Giardia infection, thereby providing an improved murine model to evaluate anti-Giardia drugs. Using BLI, we determined that parasites primarily colonize the proximal small intestine nonuniformly in high-density foci. By imaging encystation-specific bioreporters, we show that encystation initiates shortly after inoculation and continues throughout the duration of infection. Encystation also initiates in high-density foci in the proximal small intestine, and high density contributes to the initiation of encystation in laboratory culture. We suggest that these high-density in vivo foci of colonizing and encysting Giardia likely result in localized disruption to the epithelium. This more accurate visualization of giardiasis redefines the dynamics of the in vivo Giardia life cycle, paving the way for future mechanistic studies of density-dependent parasitic processes in the host. IMPORTANCE Giardia is a single-celled parasite causing significant diarrheal disease in several hundred million people worldwide. Due to limited access to the site of infection in the gastrointestinal tract, our understanding of the dynamics of Giardia infections in the host has remained limited and largely inferred from laboratory culture. To better understand

  7. Multiparametric MR imaging of prostate cancer foci: assessing the detectability and localizability of Gleason 7 peripheral zone cancers based on image contrasts

    Science.gov (United States)

    Gibson, Eli; Gaed, Mena; Hrinivich, Thomas; Gómez, José A.; Moussa, Madeleine; Romagnoli, Cesare; Mandel, Jonathan; Bastian-Jordan, Matthew; Cool, Derek W.; Ghoul, Suha; Pautler, Stephen E.; Chin, Joseph L.; Crukley, Cathie; Bauman, Glenn S.; Fenster, Aaron; Ward, Aaron D.

    2014-03-01

    Purpose: Multiparametric magnetic resonance imaging (MPMRI) supports detection and staging of prostate cancer, but the image characteristics needed for tumor boundary delineation to support focal therapy have not been widely investigated. We quantified the detectability (image contrast between tumor and non-cancerous contralateral tissue) and the localizability (image contrast between tumor and non-cancerous neighboring tissue) of Gleason score 7 (GS7) peripheral zone (PZ) tumors on MPMRI using tumor contours mapped from histology using accurate 2D-3D registration. Methods: MPMRI [comprising T2-weighted (T2W), dynamic-contrast-enhanced (DCE), apparent diffusion coefficient (ADC) and contrast transfer coefficient images] and post-prostatectomy digitized histology images were acquired for 6 subjects. Histology contouring and grading (approved by a genitourinary pathologist) identified 7 GS7 PZ tumors. Contours were mapped to MPMRI images using semi-automated registration algorithms (combined target registration error: 2 mm). For each focus, three measurements of mean +/- standard deviation of image intensity were taken on each image: tumor tissue (mT+/-sT), non-cancerous PZ tissue Results: T2W images showed the strongest detectability, although detectability |D|>=1 was observed on either ADC or DCE images, or both, for all foci. Localizability on all modalities was variable; however, ADC images showed localizability |L|>=1 for 3 foci. Conclusions: Delineation of GS7 PZ tumors on individual MPMRI images faces challenges; however, images may contain complementary information, suggesting a role for fusion of information across MPMRI images for delineation.

  8. 乳腺钙化在乳腺疾病诊断中的价值%Diagnostic value of the calcified foci in mammography for breast diseases

    Institute of Scientific and Technical Information of China (English)

    莫任光; 苏佳娜; 郭晓婷

    2012-01-01

    目的 探讨乳腺钥靶X线中钙化的影像特点在乳腺疾病中的临床意义.方法 对我院100例手术及病理证实有钙化的乳腺疾病进行分析.结果 100例乳腺钙化中,良性病变39例,乳腺癌61例.结论 乳腺钙化是乳腺疾病重要X线征象,特别是钙化形态在乳腺癌诊断中具有重要意义.%Objective To study the diagnostic value of the calcified foci in mammography for the benign and malignant breast disease.Methods In 100 female individuals,calcifications had been found in mammography and confirmed by surgery or biopsy.The characteristics of the morphology and distribution were analyzed retrospectively.Results 61 out of 100 cases with calcified foci were breast cancers,occupying 61.0%,while the left 39 cases were benign.Conclusion Calcifications in mammography are very valuable,especially the shape of the calcifications plays an important role in differential diagnosis for benign and malignant breast diseases.

  9. Regulation and regulatory role of WNT signaling in potentiating FSH action during bovine dominant follicle selection.

    Directory of Open Access Journals (Sweden)

    P S P Gupta

    Full Text Available Follicular development occurs in wave like patterns in monotocous species such as cattle and humans and is regulated by a complex interaction of gonadotropins with local intrafollicular regulatory molecules. To further elucidate potential mechanisms controlling dominant follicle selection, granulosa cell RNA harvested from F1 (largest and F2 (second largest follicles isolated at predeviation (PD and onset of diameter deviation (OD stages of the first follicular wave was subjected to preliminary RNA transcriptome analysis. Expression of numerous WNT system components was observed. Hence experiments were performed to test the hypothesis that WNT signaling modulates FSH action on granulosa cells during follicular waves. Abundance of mRNA for WNT pathway members was evaluated in granulosa cells harvested from follicles at emergence (EM, PD, OD and early dominance (ED stages of the first follicular wave. In F1 follicles, abundance of CTNNB1 and DVL1 mRNAs was higher and AXIN2 mRNA was lower at ED versus EM stages and DVL1 and FZD6 mRNAs were higher and AXIN2 mRNA was lower in F1 versus F2 follicle at the ED stage. Bovine granulosa cells were treated in vitro with increasing doses of the WNT inhibitor IWR-1+/- maximal stimulatory dose of FSH. IWR-1 treatment blocked the FSH-induced increase in granulosa cell numbers and reduced the FSH-induced increase in estradiol. Granulosa cells were also cultured in the presence or absence of FSH +/- IWR-1 and hormonal regulation of mRNA for WNT pathway members and known FSH targets determined. FSH treatment increased CYP19A1, CCND2, CTNNB1, AXIN2 and FZD6 mRNAs and the stimulatory effect on CYP19A1 mRNA was reduced by IWR-1. In contrast, FSH reduced CARTPT mRNA and IWR-1 partially reversed the inhibitory effect of FSH. Results support temporal and hormonal regulation and a potential role for WNT signaling in potentiating FSH action during dominant follicle selection.

  10. The Role of Tau in Neurodegenerative Diseases and Its Potential as a Therapeutic Target

    Directory of Open Access Journals (Sweden)

    Michael S. Wolfe

    2012-01-01

    Full Text Available The abnormal deposition of proteins in and around neurons is a common pathological feature of many neurodegenerative diseases. Among these pathological proteins, the microtubule-associated protein tau forms intraneuronal filaments in a spectrum of neurological disorders. The discovery that dominant mutations in the MAPT gene encoding tau are associated with familial frontotemporal dementia strongly supports abnormal tau protein as directly involved in disease pathogenesis. This and other evidence suggest that tau is a worthwhile target for the prevention or treatment of tau-associated neurodegenerative diseases, collectively called tauopathies. However, it is critical to understand the normal biological roles of tau, the specific molecular events that induce tau to become neurotoxic, the biochemical nature of pathogenic tau, the means by which pathogenic tau exerts neurotoxicity, and how tau pathology propagates. Based on known differences between normal and abnormal tau, a number of approaches have been taken toward the discovery of potential therapeutics. Key questions still remain open, such as the nature of the connection between the amyloid-β protein of Alzheimer’s disease and tau pathology. Answers to these questions should help better understand the nature of tauopathies and may also reveal new therapeutic targets and strategies.

  11. Potential role of antioxidant food supplements, preservatives and colorants in the pathogenesis of allergy and asthma.

    Science.gov (United States)

    Zaknun, Daniela; Schroecksnadel, Sebastian; Kurz, Katharina; Fuchs, Dietmar

    2012-01-01

    A significant increase in the incidence of allergy and asthma has been observed during the past decades. The background of this phenomenon has not been well explained, but changes in lifestyle and habits are heavily discussed as contributing factors. Among these is a too clean environment, which may predispose individuals to increased sensitivity to allergic responses. Also the increase in dietary supplements including preservatives and colorants may contribute to this. In vitro, we and others have shown in freshly isolated human peripheral blood mononuclear cells that antioxidant compounds like vitamins C and E as well as food preservatives and colorants exert significant suppressive effects on the Th1 immune activation cascade. The effects observed may be based on the interaction of antioxidant compounds with proinflammatory cascades involving important signal transduction elements such as nuclear factor-κB. Although only obtained in vitro, these results show an anti-inflammatory property of compounds which could shift the Th1-Th2-type immune balance towards Th2-type immunity. This review article discusses the potential role of increased use of antioxidant food supplements as well as preservatives and colorants in the increase in allergy and asthma in the Western world.

  12. Therapeutic potential and biological role of endogenous antioxidant enzymes in multiple sclerosis pathology.

    Science.gov (United States)

    Schreibelt, Gerty; van Horssen, Jack; van Rossum, Saskia; Dijkstra, Christine D; Drukarch, Benjamin; de Vries, Helga E

    2007-12-01

    Reactive oxygen species contribute to the formation and persistence of multiple sclerosis (MS) lesions by acting on distinct pathological processes. To counteract the detrimental effects of ROS the central nervous system is endowed with a protective mechanism consisting of enzymatic and non-enzymatic antioxidants. Expression of most antioxidant enzymes is regulated through the transcription factor nuclear factor-E2-related factor (Nrf2) and antioxidant response elements (ARE) in the genes encoding enzymatic antioxidants and is induced by oxidative stress. In brain tissue of MS patients, enhanced expression of Nrf2/ARE-regulated antioxidants is suggestive of the occurrence of oxidative stress in these lesions. Antioxidant therapy may therefore represent an attractive treatment of MS. Several studies have shown that antioxidant therapy is beneficial in vitro and in vivo in animal models for MS. However, the use of exogenous antioxidants for MS treatment has drawbacks, as large amounts of antioxidants are required to achieve functional antioxidant levels in the central nervous system. Therefore, the induction of endogenous antioxidant enzymes by activators of the Nrf2/ARE pathway may be an interesting approach to obtain sufficient levels of antioxidants to interfere with pathological processes underlying MS lesion formation. In this review we summarize and discuss the biological role, regulation and potential therapeutic effects of endogenous antioxidant enzymes in MS. We propose that antioxidants may inhibit the development and progression of MS lesions and may therefore represent an attractive therapeutic target for the treatment of MS and other oxidative stress-related neurological diseases.

  13. Potential Role of Carvedilol in the Cardiac Immune Response Induced by Experimental Infection with Trypanosoma cruzi

    Directory of Open Access Journals (Sweden)

    Aline Luciano Horta

    2017-01-01

    Full Text Available Trypanosoma cruzi causes a cardiac infection characterized by an inflammatory imbalance that could become the inciting factor of the illness. To this end, we evaluated the role of carvedilol, a beta-blocker with potential immunomodulatory properties, on the immune response in C57BL/6 mice infected with VL-10 strain of T. cruzi in the acute phase. Animals (n=40 were grouped: (i not infected, (ii infected, (iii infected + carvedilol, and (iv not infected + carvedilol. We analyzed parameters related to parasitemia, plasma levels of TNF, IL-10, and CCL2, and cardiac histopathology after the administration of carvedilol for 30 days. We did not observe differences in the maximum peaks of parasitemia in the day of their detection among the groups. The plasma TNF was elevated at 60 days of infection in mice treated or not with carvedilol. However, we observed a decreased CCL2 level and increased IL-10 levels in those infected animals treated with carvedilol, which impacted the reduction of the inflammatory infiltration in cardiac tissue. For this experimental model, carvedilol therapy was not able to alter the levels of circulating parasites but modulates the pattern of CCL2 and IL-10 mediators when the VL10 strain of T. cruzi was used in C57BL6 mice.

  14. A Potential Profibrogenic Role of Biliary Epithelium-Derived Cardiotrophin-1 in Pediatric Cholestatic Liver Disease.

    Science.gov (United States)

    Hua, Xiangwei; Shan, Yuhua; Li, Dawei; Xu, Dongwei; Zhang, Jiang; Yang, Taihua; Han, Longzhi; Shen, Conghuan; Xia, Yun; Chen, Qimin; Ma, Xiong; Zhang, Jianjun; Xia, Qiang

    2015-08-01

    As a cytokine of the interleukin-6 family, cardiotrophin-1 (CT-1) has been shown to be an important endogenous protector in liver injury. Our study aimed to investigate the role of CT-1 in liver fibrosis in pediatric cholestatic liver disease (PCLD). CT-1 mRNA and protein expression levels were upregulated in PCLD liver biopsy tissues compared with controls. Immunohistochemistry and confocal microscopy of liver sections showed that CT-1 was predominantly expressed by biliary epithelium cells. Serum CT-1 was elevated significantly in the children with PCLD compared with controls. Serum CT-1 levels exhibited a moderate positive correlation with the Scheuer stage of hepatic fibrosis and serum TB levels and a weak correlation with serum ALP levels. In vitro analysis indicated that LX-2 cells preconditioned with CT-1 exhibited significant increments in proliferation and accumulation of extracellular matrix components, while also positively regulating the STAT3 and p38MAPK pathways. In conclusion, biliary epithelium-derived CT-1 may exert a profibrogenic potential in PCLD.

  15. Protein-protein interactions: principles, techniques, and their potential role in new drug development.

    Science.gov (United States)

    Khan, Shagufta H; Ahmad, Faizan; Ahmad, Nihal; Flynn, Daniel C; Kumar, Raj

    2011-06-01

    A vast network of genes is inter-linked through protein-protein interactions and is critical component of almost every biological process under physiological conditions. Any disruption of the biologically essential network leads to pathological conditions resulting into related diseases. Therefore, proper understanding of biological functions warrants a comprehensive knowledge of protein-protein interactions and the molecular mechanisms that govern such processes. The importance of protein-protein interaction process is highlighted by the fact that a number of powerful techniques/methods have been developed to understand how such interactions take place under various physiological and pathological conditions. Many of the key protein-protein interactions are known to participate in disease-associated signaling pathways, and represent novel targets for therapeutic intervention. Thus, controlling protein-protein interactions offers a rich dividend for the discovery of new drug targets. Availability of various tools to study and the knowledge of human genome have put us in a unique position to understand highly complex biological network, and the mechanisms involved therein. In this review article, we have summarized protein-protein interaction networks, techniques/methods of their binding/kinetic parameters, and the role of these interactions in the development of potential tools for drug designing.

  16. Contrast sensitivity, ocular blood flow and their potential role in assessing ischaemic retinal disease.

    Science.gov (United States)

    Shoshani, Yochai Z; Harris, Alon; Rusia, Deepam; Spaeth, George L; Siesky, Brent; Pollack, Ayala; Wirostko, Barbara

    2011-08-01

    To examine the definition, evaluation methodology, association to ocular blood flow and potential clinical value of contrast sensitivity (CS) testing in clinical and research settings, focusing in patients with ischemic retinal disease. A review of the medical literature focusing on CS and ocular blood flow in ischemic retinal disease. CS may be more sensitive than other methods at detecting subtle defects or improvements in primarily central retinal ganglion cell function early on in a disease process. CS testing attempts to provide spatial detection differences which are not directly assessed with standard visual acuity chart testing. Analyzing all studies that have assessed both CS change and ocular blood flow, it is apparent that both choroidal circulation and retinal circulation may have an important role in influencing CS. The concept that CS is directly influenced by ocular blood flow is supported by reviewing the studies involving both. Although the studies in the literature have not established a direct cause and effect relationship per se, the literature review makes it logical to assume that changes in retinal and choroidal blood flow influence CS. This raises the possibility that a subjective visual characteristic, specifically CS, may be able to be evaluated more objectively by studying blood flow. It appears appropriate to study the relationship between blood flow and CS more extensively to develop improved ways of measuring various aspects of blood flow to the eye and to best quantify early changes in visual function. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

  17. Aversive startle potentiation and fear pathology: Mediating role of threat sensitivity and moderating impact of depression.

    Science.gov (United States)

    Yancey, James R; Vaidyanathan, Uma; Patrick, Christopher J

    2015-11-01

    Enhanced startle reactivity during exposure to unpleasant cues (aversive startle potentiation; ASP) appears in the RDoC matrix as a physiological index of acute threat response. Increased ASP has been linked to focal fear disorders and to scale measures of dispositional fearfulness (i.e., threat sensitivity; THT+). However, some studies have reported reduced ASP for fear pathology accompanied by major depressive disorder (MDD) or pervasive distress. The current study evaluated whether (a) THT+ as indexed by reported dispositional fearfulness mediates the relationship between fear disorders (when unaccompanied by depression) and ASP, and (b) depression moderates relations of THT+ and fear disorders with ASP. Fear disorder participants without MDD showed enhanced ASP whereas those with MDD (or other distress conditions) showed evidence of reduced ASP. Continuous THT+ scores also predicted ASP, and this association: (a) was likewise moderated by depression/distress, and (b) accounted for the relationship between ASP and fear pathology without MDD. These findings point to a role for the RDoC construct of acute threat, operationalized dispositionally, in enhanced ASP shown by individuals with fear pathology unaccompanied by distress pathology. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. A potential role for Helicobacter pylori heat shock protein 60 in gastric tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chen-Si [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (China); He, Pei-Juin [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); Tsai, Nu-Man [School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Li, Chi-Han; Yang, Shang-Chih; Hsu, Wei-Tung [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); Wu, Ming-Shiang [Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Wu, Chang-Jer [Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan (China); Cheng, Tain-Lu [Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Liao, Kuang-Wen, E-mail: kitchhen@yahoo.com.tw [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China)

    2010-02-05

    Helicobacter pylori has been found to promote the malignant process leading to gastric cancer. Heat shock protein 60 of H. pylori (HpHSP60) was previously been identified as a potent immunogene. This study investigates the role of HpHSP60 in gastric cancer carcinogenesis. The effect of HpHSP60 on cell proliferation, anti-death activity, angiogenesis and cell migration were explored. The results showed that HpHSP60 enhanced migration by gastric cancer cells and promoted tube formation by umbilical vein endothelial cells (HUVECs); however, HpHSP60 did not increase cell proliferation nor was this protein able to rescue gastric cancer cells from death. Moreover, the results also indicated HpHSP60 had different effects on AGS gastric cancer cells or THP-1 monocytic cells in terms of their expression of pro-inflammatory cytokines, which are known to be important to cancer development. We propose that HpHSP60 may trigger the initiation of carcinogenesis by inducing pro-inflammatory cytokine release and by promoting angiogenesis and metastasis. Thus, this extracellular pathogen-derived HSP60 is potentially a vigorous virulence factor that can act as a carcinogen during gastric tumorigenesis.

  19. Presence and potential role of thermophilic bacteria in temperate terrestrial environments

    Science.gov (United States)

    Portillo, M. C.; Santana, M.; Gonzalez, J. M.

    2012-01-01

    Organic sulfur and nitrogen are major reservoirs of these elements in terrestrial systems, although their cycling remains to be fully understood. Both sulfur and nitrogen mineralization are directly related to microbial metabolism. Mesophiles and thermophiles were isolated from temperate environments. Thermophilic isolates were classified within the Firmicutes, belonging to the Geobacillus, Brevibacillus, and Ureibacillus genera, and showed optimum growth temperatures between 50°C and 60°C. Sulfate and ammonium produced were higher during growth of thermophiles both for isolated strains and natural bacterial assemblages. They were positively related to organic nutrient load. Temperature also affected the release of sulfate and ammonium by thermophiles. Quantitative, real-time reverse-transcription polymerase chain reaction on environmental samples indicated that the examined thermophilic Firmicutes represented up to 3.4% of the total bacterial community RNA. Temperature measurements during summer days showed values above 40°C for more than 10 h a day in soils from southern Spain. These results support a potential role of thermophilic bacteria in temperate terrestrial environments by mineralizing organic sulfur and nitrogen ruled by the existence and length of warm periods.

  20. Potential Role of Carvedilol in the Cardiac Immune Response Induced by Experimental Infection with Trypanosoma cruzi

    Science.gov (United States)

    Horta, Aline Luciano; Leite, Ana Luisa Junqueira; Paula Costa, G.

    2017-01-01

    Trypanosoma cruzi causes a cardiac infection characterized by an inflammatory imbalance that could become the inciting factor of the illness. To this end, we evaluated the role of carvedilol, a beta-blocker with potential immunomodulatory properties, on the immune response in C57BL/6 mice infected with VL-10 strain of T. cruzi in the acute phase. Animals (n = 40) were grouped: (i) not infected, (ii) infected, (iii) infected + carvedilol, and (iv) not infected + carvedilol. We analyzed parameters related to parasitemia, plasma levels of TNF, IL-10, and CCL2, and cardiac histopathology after the administration of carvedilol for 30 days. We did not observe differences in the maximum peaks of parasitemia in the day of their detection among the groups. The plasma TNF was elevated at 60 days of infection in mice treated or not with carvedilol. However, we observed a decreased CCL2 level and increased IL-10 levels in those infected animals treated with carvedilol, which impacted the reduction of the inflammatory infiltration in cardiac tissue. For this experimental model, carvedilol therapy was not able to alter the levels of circulating parasites but modulates the pattern of CCL2 and IL-10 mediators when the VL10 strain of T. cruzi was used in C57BL6 mice.

  1. Vitamin D: new roles and therapeutic potential in inflammatory bowel disease.

    LENUS (Irish Health Repository)

    Raftery, Tara

    2012-11-01

    Inflammatory bowel disease (IBD) encompasses 2 independent but related entities: ulcerative colitis (UC) and Crohn\\'s disease. Crohn\\'s disease is characterised by transmural patchy inflammation which can involve any portion of the gastrointestinal tract. UC is characterised by superficial inflammation that begins in the rectum and extends proximally along the colon. In Europe, approximately 2.2 million people have a diagnosis of IBD. The aetiology of IBD is unknown, however, immune, environmental and genetic factors are thought to be involved. Individuals with IBD are at risk of developing osteoporosis. In line with this, there are clear guidelines that recommend vitamin D supplementation for IBD patients to prevent bone disease, especially when undergoing steroid treatment. Despite an established role for vitamin D in IBD, deficiency is common. More novel effects of vitamin D beyond bone are emerging. It is now well established that vitamin D is an important regulator of the immune system which may have implications for the development, severity and management of immune related disorders such as IBD. The efficacy of vitamin D as an immune modulator in IBD remains to be proven. This review aims to evaluate the evidence implicating vitamin D deficiency in IBD pathogenesis, to examine vitamin D\\'s anti-inflammatory mechanisms and to explore its therapeutic potential, optimal serum levels and dietary intakes which may support immune function in this disease.

  2. Rats' urinary metabolomes reveal the potential roles of functional foods and exercise in obesity management.

    Science.gov (United States)

    Farag, Mohamed A; Ammar, N M; Kholeif, T E; Metwally, N S; El-Sheikh, N M; Wessjohann, Ludger A; Abdel-Hamid, A Z

    2017-03-22

    The complexity of the metabolic changes in obese individuals still presents a challenge for the understanding of obesity-related metabolic disruptions and for obesity management. In this study, a gas chromatography mass spectrometry (GC-MS) based metabolomics approach targeting urine metabolism has been applied to assess the potential roles of functional foods and exercise for obesity management in rats. Male albino rats diagnosed as obese via histopathology and biochemical assays were administered functional foods in common use for obesity management including pomegranate, grapefruit, and red cabbage juice extracts in parallel with swimming exercise. Urine samples were collected from these rats, and likewise from healthy control animals, for metabolite analysis using (GC-MS) coupled to multivariate data analysis. The results revealed a significant elevation in oxalate and phosphate levels in obese rat urine concurrent with lower lactate levels as compared to the control group. Furthermore, and to pinpoint the bioactive agents in the administered functional foods, ultra performance liquid chromatography (UPLC) coupled to high resolution time-of-flight mass spectrometry (TOF-MS) was employed for secondary metabolite profiling. The different phenolic classes found in the examined functional foods, viz. ellagitannins in pomegranate, flavanones in grapefruit and flavonols in red cabbage, are likely to mediate their anti-obesity effects. The results indicate that these functional foods and exercise were quite effective in reverting obesity-related metabolic disruptions back to normal status, as revealed by orthogonal partial least squares-discriminant analysis (OPLS-DA).

  3. Tropically adapted cattle of Africa: perspectives on potential role of copy number variations.

    Science.gov (United States)

    Wang, M D; Dzama, K; Rees, D J G; Muchadeyi, F C

    2016-04-01

    Africa is host to diverse and locally adapted cattle breeds that are expected to survive the harsh and extreme tropical environments associated with diseases and parasite infections, heat stress and episodes of feed and water scarcity. Genomic copy number variations (CNVs) are considered to be primary role players in cattle breed formation and adaptation where isolation and genetic drift together with subsequent mutations have created an enormous diversity of local populations. CNVs are modifications in DNA structure comprising deletions, duplications and insertions that are >1 kb in size. Despite attracting much attention, the frequency and pattern of bovine CNV events, especially in African cattle breeds, are for the most part largely unknown. Characterization of genetic variation in the indigenous cattle of Africa will be a vital step toward dissecting the molecular mechanisms underlying phenotypic variation and local adaptation. This review therefore aims to describe the current knowledge regarding bovine CNVs and the implications and potentials they encompass for dissecting genetic adaptation and the genotypic skeleton of tropical African cattle populations.

  4. [The Potential Role of an Academic Society for Oncology Specialists to Promote Cancer Education in Schools].

    Science.gov (United States)

    Nishiyama, Masahiko

    2015-08-01

    Cancer mortality in Japan is forecasted to become high; thus, learning about cancer, cancer prevention, and cancer treatment will be indispensable for the Japanese. Recognition of the increasing rates of cancer has initiated a discussion regarding the introduction of cancer education into the regular educational curriculum for the younger generation. The importance of cancer education is noww idely recognized, and the 2nd Basic Plan to Promote Cancer Control Programs is directed at early initiation of education. The Ministry of Education, Culture, Sports, Science and Technology is nowreview ing the detailed plan, with an intention to draw a conclusion by the end of the 2016 business year. However, ongoing debates have revealed that there are many obstacles in the way of this practice. Much effort should be directed at solving these issues in the most realistic way. This paper reviews potential actions by oncology specialists, and attempts to clarify the possible role of an academic society for oncology specialists in the development of cancer education systems at school.

  5. Determining the role of phonology in silent reading using event-related brain potentials.

    Science.gov (United States)

    Newman, Randy Lynn; Connolly, John F

    2004-09-01

    The goal of the present study was to delineate phonology's role in silent reading using event-related brain potential (ERP) techniques. Terminal endings of high cloze sentences were manipulated in four conditions in which the terminal word was: (1) the high cloze ending and thus orthographically, phonologically and semantically congruent (e.g., The gambler had a streak of bad luck.); (2) a pseudohomophone that was orthographically incongruent, but was phonologically congruent to the anticipated ending (e.g., The ship disappeared into the thick phog [fog].); (3) a word that was orthographically, phonologically and semantically incongruent to expectations (e.g., The dog chased the cat up the Queen [tree].); or (4) a nonword and consequently orthographically, phonologically and semantically incongruent to expectations (e.g., The gas station is about two miles down the bole [road].). A N270 was elicited by orthographically incongruent words and nonwords (conditions 2, 3 and 4), likely reflecting violations of orthographic form expectations, while the presence of the N400 to semantically incongruent words and nonwords (conditions 3 and 4) reflected violations of semantic expectations. The relative absence of the N400 response to pseudohomophones (condition 3) indicates that integrating word meaning with sentential context is influenced by the phonological representation of the presented letter string. The implication of these results for theories of word recognition is discussed.

  6. Interactive role of trauma cytokines and erythropoietin and their therapeutic potential for acute and chronic wounds.

    Science.gov (United States)

    Bader, Augustinus; Lorenz, Katrin; Richter, Anja; Scheffler, Katja; Kern, Larissa; Ebert, Sabine; Giri, Shibashish; Behrens, Maria; Dornseifer, Ulf; Macchiarini, Paolo; Machens, Hans-Günther

    2011-02-01

    If controllable, stem cell activation following injury has the therapeutic potential for supporting regeneration in acute or chronic wounds. Human dermally-derived stem cells (FmSCs) were exposed to the cytokines interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) in the presence of erythropoietin (EPO). Cells were cultured under ischemic conditions and phenotypically characterized using flow cytometry. Topical EPO application was performed in three independent clinical wound healing attempts. The FmSCs expressed the receptor for EPO. EPO had a strong inhibitory effect on FmSC growth in the absence of IL-6 and TNF-α. With IL-6, the EPO effects were reversed to that of growth stimulation. TNF-α had the strongest stimulatory effect. In contrast, IL-1β had an inhibitory effect. Topically applied EPO considerably enhanced wound healing and improved wound conditions of acute and chronic wounds. Site specificity of stem cell activation is mediated by IL-6 and TNF-α. In trauma, EPO ceases its inhibitory role and reverts to a clinically relevant boosting function. EPO may be an important therapeutic tool for the topical treatment of acute and chronic wounds.

  7. The role of S100B protein as a potential marker in affective disorders.

    Science.gov (United States)

    Rajewska-Rager, Aleksandra; Pawlaczyk, Magdalena

    2016-01-01

    Both recurrent depressive disorders and affective bipolar disorders are characterized by the changes in glial tissue. S100B protein is a calcium-binding molecule, mainly secreted by glial cells, which, depending on its concentration, has a trophic or toxic effect on neuronal cells. In the recent years, due to the postulated glial hypothesis of affective disorders and the ideas concerning brain neuroplasticity, there has been a growing interest in S100B protein and its role in affective disorders. The aim of this study was to review the available subject literature from the recent years. This article presents a review of studies from the last years based on the literature available in PubMed/MEDLINE database. In the previous studies conducted in patients with mood disorders it has been shown that the increased S100B protein serum level occurs both in patients with depression and with mania compared to the patients from control group. The studies were mainly conducted on adult population; there are no studies on children and adolescents with bipolar affective disorder so far. The majority of studies indicated the more important association between the increased S100B protein levels and the occurrence of a depressive episode as well as the regulation of S100B protein level during the effective pharmacological treatment, which can be a potential marker of the efficacy of treatment.

  8. Carbon Turnover during Effluent Application to the Land: A Potential Role for Vegetation?

    Directory of Open Access Journals (Sweden)

    Vasileios A. Tzanakakis

    2015-01-01

    Full Text Available This work investigates the effect of plant species (Eucalyptus camaldulensis vs. Arundo donax on carbon (C turnover during wastewater application to the land. The study was carried out in 40-liter pots under field conditions and plant species were treated either with pre-treated municipal wastewater or freshwater. Plant species had a strong effect on soil organic matter with pots planted with E. camaldulensis showing greater values than pots planted with A. donax. In accordance, greater respiration rates were measured in E. camaldulensis pots compared to those planted with A. donax. The respiration rate followed a decreasing trend with the progress of the season for both species. These findings suggest differences in soil microbial community composition and/or activity in the rhizosphere of plant species. Minor effects of plant species or effluent were observed in dissolved organic carbon, protein, and hexoses content. In conclusion, the results of the present study reveal an important role of plant species on C cycling in terrestrial environments with potential implications on the sequestration of C and release of nutrients and pollutants.

  9. The potential role of regenerative medicine in the management of traumatic patients

    Directory of Open Access Journals (Sweden)

    Mahmoudreza Moradi

    2015-01-01

    Full Text Available Abstract: Traumatic injury represents the most common cause of death in ages 1 to 44 years and a significant proportion of patients treated in hospital emergency wards each year. Unfortunately, for patients who survive their injuries, survival is not equal to complete recovery. Many traumatic injuries are difficult to treat with conventional therapy and result in permanent disability. In such situations, regenerative medicine has the potential to play an important role in recovery of function. Regenerative medicine is a field that seeks to maintain or restore function with the development of biological substitutes for diseased or damaged tissues. Several regenerative approaches are currently under investigation, with a few achieving clinical application. For example, engineered skin has gained FDA approval, and more than 20 tissue engineered skin substitutes are now commercially available. Other organ systems with promising animal models and small human series include the central and peripheral nervous systems, the musculoskeletal system, the respiratory and genitourinary tracts, and others. This paper will be a clinically oriented review of the regenerative approaches currently under investigation of special interest to those caring for traumatic patients.

  10. Potential role of metabolomics in diagnosis and surveillance of gastric cancer.

    Science.gov (United States)

    Chan, Angela W; Gill, Richdeep S; Schiller, Daniel; Sawyer, Michael B

    2014-09-28

    Gastric cancer is one of the deadliest cancers worldwide, and is especially prevalent in Asian countries. With such high morbidity and mortality, early diagnosis is essential to achieving curative intent treatment and long term survival. Metabolomics is a new field of study that analyzes metabolites from biofluids and tissue samples. While metabolomics is still in its infancy, there are numerous potential applications in oncology, specifically early diagnosis. Only a few studies in the literature have examined metabolomics' role in gastric cancer. Various fatty acid, carbohydrate, nucleic acid, and amino acid metabolites have been identified that distinguish gastric cancer from normal tissue and benign gastric disease. However, findings from these few studies are at times conflicting. Most studies demonstrate some relationship of cancer cells to the Warburg Effect, in that glycolysis predominates with conversion of pyruvate to lactate. This is one of the most consistent findings across the literature. There is less consistency in metabolomic signature with respect to nucleic acids, lipids and amino acids. In spite of this, metabolomics holds some promise for cancer surveillance but further studies are necessary to achieve consistency and validation before it can be widely employed as a clinical tool.

  11. Diet, Food Intake of Phrynocephalus frontalis (Agamidae) and Its Potential Role in Desert Habitat

    Institute of Scientific and Technical Information of China (English)

    Chunwang LI; Xue LIAN; Songhua TANG; Junhuai BI; and Zhigang JIANG

    2013-01-01

    We examined the dietary diversity and food intake of Phrynocephalus frontalis, compared the difference of insect diversity in the natural habitats with different lizard densities, and discussed the potential role of this lizard in the desert ecosystem. The results show that:(1) arthropodans of the orders Coleoptera, Hymenoptera and Hemiptera were major dietary components of P. frontalis;(2) coleoptera larvae always formed the predominant component of lizard diets;(3) dietary diversities of P. frontalis were not significantly different between summer and autumn or between the two sexes;(4) the similarity in trophic niches between seasons was 0.756, whereas the similarity in trophic niches between sexes was 0.994;(5) stomach content weight of lizards varied signiifcantly among different seasons, but there was no signiifcant difference in stomach content weight between sexes;(6) insect diversity differed signiifcantly among the groups of the habitat with different degrees of lizard density, and the habitat with moderate lizards density had the highest insect diversity. We infer that P. frontalis prey mainly on insects and change their diet and food intake with season;males and females consumed similar preys in types and weights. As an important predator, P. frontalis could affect the insect community in the arid ecosystem of Hunshandak Desert on the Mongolian Plateau.

  12. A potential oncogenic role of the commonly observed E2F5 overexpression in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yuzhu Jiang; Seon-Hee Yim; Hai-Dong Xu; Seung-Hyun Jung; So Young Yang; Hae-Jin Hu; Chan-Kwon Jung; Yeun-Jun Chung

    2011-01-01

    AIM: To explore the expression pattern of E2F5 in primary hepatocellular carcinomas (HCCs) and elucidate the roles of E2F5 in hepatocarcinogenesis. METHODS: E2F5 expression was analyzed in 120 primary HCCs and 29 normal liver tissues by immunohistochemistry analysis. E2F5-small interfering RNA was transfected into HepG2, an E2F5-overexpressed HCC cell line. After E2F5 knockdown, cell growth capacity and migrating potential were examined. RESULTS: E2F5 was significantly overexpressed in primary HCCs compared with normal liver tissues (P = 0.008). The E2F5-silenced cells showed significantly reduced proliferation (P = 0.004). On the colony formation and soft agar assays, the number of colonies was significantly reduced in E2F5-silenced cells (P = 0.004 and P = 0.009, respectively). E2F5 knockdown resulted in the accumulation of G0/G1 phase cells and a reduction of S phase cells. The number of migrating/invading cells was also reduced after E2F5 knockdown (P = 0.021). CONCLUSION: To our knowledge, this is the first evidence that E2F5 is commonly overexpressed in primary HCC and that E2F5 knockdown significantly repressed the growth of HCC cells.

  13. Potential Role of the Last Half Repeat in TAL Effectors Revealed by a Molecular Simulation Study

    Directory of Open Access Journals (Sweden)

    Hua Wan

    2016-01-01

    Full Text Available TAL effectors (TALEs contain a modular DNA-binding domain that is composed of tandem repeats. In all naturally occurring TALEs, the end of tandem repeats is invariantly a truncated half repeat. To investigate the potential role of the last half repeat in TALEs, we performed comparative molecular dynamics simulations for the crystal structure of DNA-bound TALE AvrBs3 lacking the last half repeat and its modeled structure having the last half repeat. The structural stability analysis indicates that the modeled system is more stable than the nonmodeled system. Based on the principle component analysis, it is found that the AvrBs3 increases its structural compactness in the presence of the last half repeat. The comparison of DNA groove parameters of the two systems implies that the last half repeat also causes the change of DNA major groove binding efficiency. The following calculation of hydrogen bond reveals that, by stabilizing the phosphate binding with DNA at the C-terminus, the last half repeat helps to adopt a compact conformation at the protein-DNA interface. It further mediates more contacts between TAL repeats and DNA nucleotide bases. Finally, we suggest that the last half repeat is required for the high-efficient recognition of DNA by TALE.

  14. Potential Role of the Last Half Repeat in TAL Effectors Revealed by a Molecular Simulation Study

    Science.gov (United States)

    Wan, Hua; Chang, Shan; Hu, Jian-ping; Tian, Xu-hong

    2016-01-01

    TAL effectors (TALEs) contain a modular DNA-binding domain that is composed of tandem repeats. In all naturally occurring TALEs, the end of tandem repeats is invariantly a truncated half repeat. To investigate the potential role of the last half repeat in TALEs, we performed comparative molecular dynamics simulations for the crystal structure of DNA-bound TALE AvrBs3 lacking the last half repeat and its modeled structure having the last half repeat. The structural stability analysis indicates that the modeled system is more stable than the nonmodeled system. Based on the principle component analysis, it is found that the AvrBs3 increases its structural compactness in the presence of the last half repeat. The comparison of DNA groove parameters of the two systems implies that the last half repeat also causes the change of DNA major groove binding efficiency. The following calculation of hydrogen bond reveals that, by stabilizing the phosphate binding with DNA at the C-terminus, the last half repeat helps to adopt a compact conformation at the protein-DNA interface. It further mediates more contacts between TAL repeats and DNA nucleotide bases. Finally, we suggest that the last half repeat is required for the high-efficient recognition of DNA by TALE. PMID:27803930

  15. The Role of Strigolactones and Their Potential Cross-talk under Hostile Ecological Conditions in Plants

    Science.gov (United States)

    Mishra, Sonal; Upadhyay, Swati; Shukla, Rakesh K.

    2017-01-01

    The changing environment always questions the survival mechanism of life on earth. The plant being special in the sense of their sessile habit need to face many of these environmental fluctuations as they have a lesser escape option. To counter these adverse conditions, plants have developed efficient sensing, signaling, and response mechanism. Among them the role of phytohormones in the management of hostile ecological situations is remarkable. The strigolactone, a newly emerged plant hormone has been identified with many functions such as growth stimulant of parasitic plants, plant architecture determinant, arbuscular mycorrhiza symbiosis promoter, and also in many other developmental and environmental cues. Despite of their immense developmental potential, the strigolactone research in the last few years has also established their significance in adverse environmental condition. In the current review, its significance under drought, salinity, nutrient starvation, temperature, and pathogenic assail has been discussed. This review also opens the research prospects of strigolactone to better manage the crop loss under hostile ecological conditions. PMID:28119634

  16. The Role of Canonical Transient Receptor Potential Channels in Seizure and Excitotoxicity

    Directory of Open Access Journals (Sweden)

    Fang Zheng

    2014-04-01

    Full Text Available Canonical transient receptor potential (TRPC channels are a family of polymodal cation channels with some degree of Ca2+ permeability. Although initially thought to be channels mediating store-operated Ca2+ influx, TRPC channels can be activated by stimulation of Gq-coupled G-protein coupled receptors, or by an increase in intracellular free Ca2+ concentration. Thus, activation of TRPC channels could be a common downstream event of many signaling pathways that contribute to seizure and excitotoxicity, such as N-methyl-D-aspartate (NMDA receptor-mediated Ca2+ influx, or metabotropic glutamate receptor activation. Recent studies with genetic ablation of various TRPC family members have demonstrated that TRPC channels, in particular heteromeric TRPC1/4 channels and homomeric TRPC5 channels, play a critical role in both pilocarpine-induced acute seizures and neuronal cell death. However, exact underlying mechanisms remain to be fully elucidated, and selective TRPC modulators and antibodies with better specificity are urgently needed for future research.

  17. The role of event-related brain potentials in assessing central auditory processing.

    Science.gov (United States)

    Alain, Claude; Tremblay, Kelly

    2007-01-01

    The perception of complex acoustic signals such as speech and music depends on the interaction between peripheral and central auditory processing. As information travels from the cochlea to primary and associative auditory cortices, the incoming sound is subjected to increasingly more detailed and refined analysis. These various levels of analyses are thought to include low-level automatic processes that detect, discriminate and group sounds that are similar in physical attributes such as frequency, intensity, and location as well as higher-level schema-driven processes that reflect listeners' experience and knowledge of the auditory environment. In this review, we describe studies that have used event-related brain potentials in investigating the processing of complex acoustic signals (e.g., speech, music). In particular, we examine the role of hearing loss on the neural representation of sound and how cognitive factors and learning can help compensate for perceptual difficulties. The notion of auditory scene analysis is used as a conceptual framework for interpreting and studying the perception of sound.

  18. Role and therapeutic potential of G-protein coupled receptors in breast cancer progression and metastases.

    Science.gov (United States)

    Singh, Anukriti; Nunes, Jessica J; Ateeq, Bushra

    2015-09-15

    G-protein-coupled receptors (GPCRs) comprise a large family of cell-surface receptors, which have recently emerged as key players in tumorigenesis, angiogenesis and metastasis. In this review, we discussed our current understanding of the many roles played by GPCRs in general, and particularly Angiotensin II type I receptor (AGTR1), a member of the seven-transmembrane-spanning G-protein coupled receptor superfamily, and its significance in breast cancer progression and metastasis. We have also discussed different strategies for targeting AGTR1, and its ligand Angiotension II (Ang II), which might unravel unique opportunities for breast cancer prevention and treatment. For example, AGTR1 blockers (ARBs) which are already in clinical use for treating hypertension, merit further investigation as a therapeutic strategy for AGTR1-positive cancer patients and may have the potential to prevent Ang II-AGTR1 signalling mediated cancer pathogenesis and metastases. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Role of oxidative stress & transient receptor potential in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Protiti Bose

    2015-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD affect millions of people worldwide and is known to be one of the leading causes of death. The highly sensitive airways protect themselves from irritants by cough and sneeze which propel endogenous and exogenous substances to minimize airway noxious effects. One noxious effect of these substances is activation of peripheral sensory nerve endings of nociceptor neurons innervating these airways lining thus transmitting dangerous signals from the environment to the central nervous system (CNS. Nociceptor neurons include transient receptor potential (TRP ion channels, especially the vanilloid and ankyrin subfamilies, TRPV1/A1 which can be activated by noxious chemical challenges in models of airways disease. As oxidative stress may activate airways sensory neurons and contribute to COPD exacerbations we sought to review the role that TRP channel activation by oxidative signals may have on airway responses. i0 t would be prudent to target the TRP channels with antagonists and lower systemic oxidative stress with agents that can modulate TRP expression and boost the endogenous levels of antioxidants for treatment and management of COPD.

  20. Anemia in Chronic Obstructive Pulmonary Disease and the Potential Role of Iron Deficiency.

    Science.gov (United States)

    Vasquez, Amber; Logomarsino, John V

    2016-01-01

    The purpose of this review is to evaluate the role of anemia on patient outcomes in chronic obstructive pulmonary disease (COPD), the potential contribution that low iron stores may play in this process, and possible treatment considerations. A review of research studies found that anemia is associated with declining functional outcomes, increased health care utilization and costs, and increased mortality in COPD. Associations exist between reduced iron intake and progression of COPD and in reduction of iron status with declining lung function. Currently data are limited on the effects of either treating anemia or utilizing iron supplementation in anemic COPD patients. If iron supplementation might therefore reverse some of the declines that patients experience, then routine screening and treatment may turn out to be an effective, simple and inexpensive intervention. Iron supplementation models utilized in other inflammatory-related disease states were reviewed as a possible starting point to evaluate treatment options in COPD. Future research can be directed to establish best practice standards for the use of iron supplementation in COPD.

  1. Quinolinic acid selectively induces apoptosis of human astrocytes: potential role in AIDS dementia complex

    Directory of Open Access Journals (Sweden)

    Wang Lily

    2005-07-01

    Full Text Available Abstract There is evidence that the kynurenine pathway (KP and particularly one of its end products, quinolinic acid (QUIN play a role in the pathogenesis of several major neuroinflammatory diseases, and more particularly AIDS dementia complex (ADC. We hypothesized that QUIN may be involved in astrocyte apoptosis because: 1 apoptotic astrocytes have been observed in the brains of ADC patients, 2 ADC patients have elevated cerebrospinal fluid QUIN concentrations, and 3 QUIN can induce astrocyte death. Primary cultures of human fetal astrocytes were treated with three pathophysiological concentrations of QUIN. Numeration of apoptotic cells was assessed using double immunocytochemistry for expression of active caspase 3 and for nucleus condensation. We found that treatment of human astrocytes with QUIN induced morphological (cell body shrinking and biochemical changes (nucleus condensation and over-expression of active caspase 3 of apoptosis. After 24 hours of treatment with QUIN 500 nM and 1200 nM respectively 10 and 14% of astrocytes were undergoing apoptosis. This would be expected to lead to a relative lack of trophic support factors with consequent neuronal dysfunction and possibly death. Astroglial apoptosis induced by QUIN provides another potential mechanism for the neurotoxicity of QUIN during ADC.

  2. Cellular and Molecular Pathology of Age-Related Macular Degeneration: Potential Role for Proteoglycans

    Directory of Open Access Journals (Sweden)

    Othman Al Gwairi

    2016-01-01

    Full Text Available Age-related macular degeneration (AMD is a retinal disease evident after the age of 50 that damages the macula in the centre of retina. It leads to a loss of central vision with retained peripheral vision but eventual blindness occurs in many cases. The initiation site of AMD development is Bruch’s membrane (BM where multiple changes occur including the deposition of plasma derived lipids, accumulation of extracellular debris, changes in cell morphology, and viability and the formation of drusen. AMD manifests as early and late stage; the latter involves cell proliferation and neovascularization in wet AMD. Current therapies target the later hyperproliferative and invasive wet stage whilst none target early developmental stages of AMD. In the lipid deposition disease atherosclerosis modified proteoglycans bind and retain apolipoproteins in the artery wall. Chemically modified trapped lipids are immunogenic and can initiate a chronic inflammatory process manifesting as atherosclerotic plaques and subsequent artery blockages, heart attacks, or strokes. As plasma derived lipoprotein deposits are found in BM in early AMD, it is possible that they arise by a similar process within the macula. In this review we consider aspects of the pathological processes underlying AMD with a focus on the potential role of modifications to secreted proteoglycans being a cause and therefore a target for the treatment of early AMD.

  3. Cellular and Molecular Pathology of Age-Related Macular Degeneration: Potential Role for Proteoglycans.

    Science.gov (United States)

    Al Gwairi, Othman; Thach, Lyna; Zheng, Wenhua; Osman, Narin; Little, Peter J

    2016-01-01

    Age-related macular degeneration (AMD) is a retinal disease evident after the age of 50 that damages the macula in the centre of retina. It leads to a loss of central vision with retained peripheral vision but eventual blindness occurs in many cases. The initiation site of AMD development is Bruch's membrane (BM) where multiple changes occur including the deposition of plasma derived lipids, accumulation of extracellular debris, changes in cell morphology, and viability and the formation of drusen. AMD manifests as early and late stage; the latter involves cell proliferation and neovascularization in wet AMD. Current therapies target the later hyperproliferative and invasive wet stage whilst none target early developmental stages of AMD. In the lipid deposition disease atherosclerosis modified proteoglycans bind and retain apolipoproteins in the artery wall. Chemically modified trapped lipids are immunogenic and can initiate a chronic inflammatory process manifesting as atherosclerotic plaques and subsequent artery blockages, heart attacks, or strokes. As plasma derived lipoprotein deposits are found in BM in early AMD, it is possible that they arise by a similar process within the macula. In this review we consider aspects of the pathological processes underlying AMD with a focus on the potential role of modifications to secreted proteoglycans being a cause and therefore a target for the treatment of early AMD.

  4. Diabetes and Kidney Disease in American Indians: Potential Role of Sugar-Sweetened Beverages.

    Science.gov (United States)

    Yracheta, Joseph M; Lanaspa, Miguel A; Le, MyPhuong T; Abdelmalak, Manal F; Alfonso, Javier; Sánchez-Lozada, Laura G; Johnson, Richard J

    2015-06-01

    Since the early 20th century, a marked increase in obesity, diabetes, and chronic kidney disease has occurred in the American Indian population, especially the Pima Indians of the Southwest. Here, we review the current epidemic and attempt to identify remediable causes. A search was performed using PubMed and the search terms American Indian and obesity, American Indian and diabetes, American Indian and chronic kidney disease, and American Indian and sugar or fructose, Native American, Alaska Native, First Nations, Aboriginal, Amerind, and Amerindian for American Indian for articles linking American Indians with diabetes, obesity, chronic kidney disease, and sugar; additional references were identified in these publications traced to 1900 and articles were reviewed if they were directly discussing these topics. Multiple factors are involved in the increased risk for diabetes and kidney disease in the American Indian population, including poverty, overnutrition, poor health care, high intake of sugar, and genetic mechanisms. Genetic factors may be especially important in the Pima, as historical records suggest that this group was predisposed to obesity before exposure to Western culture and diet. Exposure to sugar-sweetened beverages may also be involved in the increased risk for chronic kidney disease. In these small populations in severe health crisis, we recommend further studies to investigate the role of excess added sugar, especially sugar-sweetened beverages, as a potentially remediable risk factor.

  5. Medication calculation: the potential role of digital game-based learning in nurse education.

    Science.gov (United States)

    Foss, Brynjar; Mordt Ba, Petter; Oftedal, Bjørg F; Løkken, Atle

    2013-12-01

    Medication dose calculation is one of several medication-related activities that are conducted by nurses daily. However, medication calculation skills appear to be an area of global concern, possibly because of low numeracy skills, test anxiety, low self-confidence, and low self-efficacy among student nurses. Various didactic strategies have been developed for student nurses who still lack basic mathematical competence. However, we suggest that the critical nature of these skills demands the investigation of alternative and/or supplementary didactic approaches to improve medication calculation skills and to reduce failure rates. Digital game-based learning is a possible solution because of the following reasons. First, mathematical drills may improve medication calculation skills. Second, games are known to be useful during nursing education. Finally, mathematical drill games appear to improve the attitudes of students toward mathematics. The aim of this article was to discuss common challenges of medication calculation skills in nurse education, and we highlight the potential role of digital game-based learning in this area.

  6. Fabrication of microscale medical devices by two-photon polymerization with multiple foci via a spatial light modulator.

    Science.gov (United States)

    Gittard, Shaun D; Nguyen, Alexander; Obata, Kotaro; Koroleva, Anastasia; Narayan, Roger J; Chichkov, Boris N

    2011-11-01

    Two-photon polymerization is an appealing technique for producing microscale devices due to its flexibility in producing structures with a wide range of geometries as well as its compatibility with materials suitable for biomedical applications. The greatest limiting factor in widespread use of two-photon polymerization is the slow fabrication times associated with line-by-line, high-resolution structuring. In this study, a recently developed technology was used to produce microstructures by two-photon polymerization with multiple foci, which significantly reduces the production time. Computer generated hologram pattern technology was used to generate multiple laser beams in controlled positions from a single laser. These multiple beams were then used to simultaneously produce multiple microstructures by two-photon polymerization. Arrays of micro-Venus structures, tissue engineering scaffolds, and microneedle arrays were produced by multifocus two-photon polymerization. To our knowledge, this work is the first demonstration of multifocus two-photon polymerization technology for production of a functional medical device. Multibeam fabrication has the potential to greatly improve the efficiency of two-photon polymerization production of microscale devices such as tissue engineering scaffolds and microneedle arrays.

  7. The Exploration of Role Induction as a Potential Method for Improving Men's Perceptions of Career Counseling

    Science.gov (United States)

    Kantamneni, Neeta; Christianson, Heidi Fowell; Smothers, Melissa Kraemer; Wester, Stephen R.

    2011-01-01

    The authors explored the influence of role induction on men's perceptions of career counseling and attitudes toward seeking professional help. Two separate role inductions were presented to 268 male college students; the first discussed holistic career counseling, and the second integrated a discussion of male gender role socialization. Results…

  8. An ImageJ-based algorithm for a semi-automated method for microscopic image enhancement and DNA repair foci counting

    Energy Technology Data Exchange (ETDEWEB)

    Klokov, D., E-mail: dmitry.klokov@cnl.ca [Canadian Nuclear Laboratories, Chalk River, Ontario (Canada); Suppiah, R. [Queen' s Univ., Dept. of Biomedical and Molecular Sciences, Kingston, Ontario (Canada)

    2015-06-15

    Proper evaluation of the health risks of low-dose ionizing radiation exposure heavily relies on the ability to accurately measure very low levels of DNA damage in cells. One of the most sensitive methods for measuring DNA damage levels is the quantification of DNA repair foci that consist of macromolecular aggregates of DNA repair proteins, such as γH2AX and 53BP1, forming around individual DNA double-strand breaks. They can be quantified using immunofluorescence microscopy and are widely used as markers of DNA double-strand breaks. However this quantification, if performed manually, may be very tedious and prone to inter-individual bias. Low-dose radiation studies are especially sensitive to this potential bias due to a very low magnitude of the effects anticipated. Therefore, we designed and validated an algorithm for the semi-automated processing of microscopic images and quantification of DNA repair foci. The algorithm uses ImageJ, a freely available image analysis software that is customizable to individual cellular properties or experimental conditions. We validated the algorithm using immunolabeled 53BP1 and γH2AX in normal human fibroblast AG01522 cells under both normal and irradiated conditions. This method is easy to learn, can be used by nontrained personnel, and can help avoiding discrepancies in inter-laboratory comparison studies examining the effects of low-dose radiation. (author)

  9. The Potential Role of HMGB1 Release in Peritoneal Dialysis-Related Peritonitis

    Science.gov (United States)

    Li, Huiyang; Xiong, Liping; Zhou, Yi; Fan, Jinjin; Yu, Xueqing; Mao, Haiping

    2013-01-01

    High mobility group box 1 (HMGB1), a DNA-binding nuclear protein, has been implicated as an endogenous danger signal in the pathogenesis of infection diseases. However, the potential role and source of HMGB1 in the peritoneal dialysis (PD) effluence of patients with peritonitis are unknown. First, to evaluate HMDB1 levels in peritoneal dialysis effluence (PDE), a total of 61 PD patients were enrolled in this study, including 42 patients with peritonitis and 19 without peritonitis. Demographic characteristics, symptoms, physical examination findings and laboratory parameters were recorded. HMGB1 levels in PDE were determined by Western blot and ELISA. The concentrations of TNF-α and IL-6 in PDE were quantified by ELISA. By animal model, inhibition of HMGB1 with glycyrrhizin was performed to determine the effects of HMGB1 in LPS-induced mice peritonitis. In vitro, a human peritoneal mesothelial cell line (HMrSV5) was stimulated with lipopolysaccharide (LPS), HMGB1 extracellular content in the culture media and intracellular distribution in various cellular fractions were analyzed by Western blot or immunofluorescence. The results showed that the levels of HMGB1 in PDE were higher in patients with peritonitis than those in controls, and gradually declined during the period of effective antibiotic treatments. Furthermore, the levels of HMGB1 in PDE were positively correlated with white blood cells (WBCs) count, TNF-α and IL-6 levels. However, pretreatment with glycyrrhizin attenuated LPS-induced acute peritoneal inflammation and dysfunction in mice. In cultured HMrSV5 cells, LPS actively induced HMGB1 nuclear-cytoplasmic translocation and release in a time and dose-dependent fashion. Moreover, cytosolic HMGB1 was located in lysosomes and secreted via a lysosome-mediated secretory pathway following LPS stimulation. Our study demonstrates that elevated HMGB1 levels in PDE during PD-related peritonitis, at least partially, from peritoneal mesothelial cells, which may be

  10. Increasing access to modern contraceptives: the potential role of community solidarity through altruistic contributions

    Directory of Open Access Journals (Sweden)

    Onwujekwe Obinna E

    2012-07-01

    Full Text Available Abstract Background There is an urgent need for universal access to modern contraceptives in Nigeria, to facilitate the achievement of the Millennium Development Goals and other national goals. This study provides information on the potential role of community solidarity in increasing access to contraceptives for the most-poor people through exploration of the role of altruism by determining level of altruistic willingness to pay (WTP for modern contraceptives across different geographic contexts in Nigeria. Methods It was a cross-sectional national survey which took place in six states spread across the six-geopolitical zones of the country. In each state, an urban and a rural area were selected for the study, giving a total of 6 urban and 6 rural sites. A pre-tested interviewer-administered questionnaire was used to collect information from at least 720 randomly selected householders from each state. The targeted respondent in a household was a female primary care giver of child bearing age (usually the wives, or in her absence, another female household member of child bearing age. A scenario on altruistic WTP was presented before the value was elicited using a binary with open-ended follow-up question format. Test of validity of elicited altruistic WTP was undertaken using Tobit regression. Findings More than 50 % of the respondents across all the states were willing to contribute some money so that the very poor would be provided with modern contraceptives. The average amount of money that people were willing to contribute annually was 650 Naira (US$4.5. Mean altruistic WTP differed across SES quintiles and urban-rural divide (p  Conclusion There is room for community solidarity to ensure that the very poor benefit from modern contraceptives and assure universal coverage with modern contraceptives. The factors that determine altruistic WTP should be harnessed to ensure that altruistic contributions are actually made. The challenge will

  11. The potential role of HMGB1 release in peritoneal dialysis-related peritonitis.

    Directory of Open Access Journals (Sweden)

    Shirong Cao

    Full Text Available High mobility group box 1 (HMGB1, a DNA-binding nuclear protein, has been implicated as an endogenous danger signal in the pathogenesis of infection diseases. However, the potential role and source of HMGB1 in the peritoneal dialysis (PD effluence of patients with peritonitis are unknown. First, to evaluate HMDB1 levels in peritoneal dialysis effluence (PDE, a total of 61 PD patients were enrolled in this study, including 42 patients with peritonitis and 19 without peritonitis. Demographic characteristics, symptoms, physical examination findings and laboratory parameters were recorded. HMGB1 levels in PDE were determined by Western blot and ELISA. The concentrations of TNF-α and IL-6 in PDE were quantified by ELISA. By animal model, inhibition of HMGB1 with glycyrrhizin was performed to determine the effects of HMGB1 in LPS-induced mice peritonitis. In vitro, a human peritoneal mesothelial cell line (HMrSV5 was stimulated with lipopolysaccharide (LPS, HMGB1 extracellular content in the culture media and intracellular distribution in various cellular fractions were analyzed by Western blot or immunofluorescence. The results showed that the levels of HMGB1 in PDE were higher in patients with peritonitis than those in controls, and gradually declined during the period of effective antibiotic treatments. Furthermore, the levels of HMGB1 in PDE were positively correlated with white blood cells (WBCs count, TNF-α and IL-6 levels. However, pretreatment with glycyrrhizin attenuated LPS-induced acute peritoneal inflammation and dysfunction in mice. In cultured HMrSV5 cells, LPS actively induced HMGB1 nuclear-cytoplasmic translocation and release in a time and dose-dependent fashion. Moreover, cytosolic HMGB1 was located in lysosomes and secreted via a lysosome-mediated secretory pathway following LPS stimulation. Our study demonstrates that elevated HMGB1 levels in PDE during PD-related peritonitis, at least partially, from peritoneal mesothelial cells

  12. Apoptotic potential role of Agave palmeri and Tulbaghia violacea extracts in cervical cancer cells.

    Science.gov (United States)

    Mthembu, Nonkululeko N; Motadi, Lesetja Raymond

    2014-09-01

    Cervical cancer, a gynaecological malignant disorder, is a common cause of death in females in Sub-Saharan Africa, striking nearly half a million of lives each year worldwide. Currently, more than 50 % of all modern drugs in clinical use are of natural products, many of which have an ability to control cancer cells (Madhuri and Pandey, Curr Sci 96:779-783, 2009; Richter, Traditional medicines and traditional healers in South Africa, 2003). In South Africa, plants used to treat cancer are rare even though majority of our population continue to put their trust in traditional medicine. In this study we aimed to screen Agave palmeri (AG) and Tulbaghia violacea (TV) for potential role in inducing cell death in cervical cancer cell lines HeLa and ME-180, and in normal human fibroblast cell line KMST-6 cell lines. To achieve this, AG and TV crude extracts were utilized to screen for apoptosis induction, inhibition of cell proliferation followed by elucidation of the role of Bax, Bcl-2, p53, Rb, RBBP and Mdm2 genes in cervical cancer. In brief, plant leaves and roots were collected, crushed and methanolic extracts obtained. Different concentrations of the stock extracts were used to treat cancer cells and measure cell death using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay and flow cytometry. Western blot was applied to measure gene expression at protein level using RBBP6, p53, Mdm2, Rb, Bax, Bcl-2 and β-actin mouse monoclonal primary antibodies (IgG) and goat anti mouse coupled with horseradish peroxidase secondary antibody from Santa Cruz Biotechnology and real time-PCR was used for mRNA expression level. Plant extracts of AG and TV were time (24 h) and dose (50, 100, 150 μg/ml) dependent in their induction of cell death with an IC50 ~ 150 μg/ml. A further mixed respond by several genes was observed following treatment with the two plant extracts where RBBP6 was seen to be spliced in cancer cells while Bax was induced and Bcl-2 was

  13. Enhancing the care navigation model: potential roles for health sciences librarians.

    Science.gov (United States)

    Huber, Jeffrey T; Shapiro, Robert M; Burke, Heather J; Palmer, Aaron

    2014-01-01

    This study analyzed the overlap between roles and activities that health care navigators perform and competencies identified by the Medical Library Association’s (MLA’s) educational policy statement.Roles and activities that health care navigators perform were gleaned from published literature. Once common roles and activities that health care navigators perform were identified, MLA competencies were mapped against those roles and activities to identify areas of overlap. The greatest extent of correspondence occurred in patient empowerment and support. Further research is warranted to determine the extent to which health sciences librarians might assume responsibility for roles and activities that health care navigators perform

  14. A potential role for intragenic miRNAs on their hosts' interactome

    Directory of Open Access Journals (Sweden)

    Kuo Winston P

    2010-10-01

    Full Text Available Abstract Background miRNAs are small, non-coding RNA molecules that mainly act as negative regulators of target gene messages. Due to their regulatory functions, they have lately been implicated in several diseases, including malignancies. Roughly half of known miRNA genes are located within previously annotated protein-coding regions ("intragenic miRNAs". Although a role of intragenic miRNAs as negative feedback regulators has been speculated, to the best of our knowledge there have been no conclusive large-scale studies investigating the relationship between intragenic miRNAs and host genes and their pathways. Results miRNA-containing host genes were three times longer, contained more introns and had longer 5' introns compared to a randomly sampled gene cohort. These results are consistent with the observation that more than 60% of intronic miRNAs are found within the first five 5' introns. Host gene 3'-untranslated regions (3'-UTRs were 40% longer and contained significantly more adenylate/uridylate-rich elements (AREs compared to a randomly sampled gene cohort. Coincidentally, recent literature suggests that several components of the miRNA biogenesis pathway are required for the rapid decay of mRNAs containing AREs. A high-confidence set of predicted mRNA targets of intragenic miRNAs also shared many of these features with the host genes. Approximately 20% of intragenic miRNAs were predicted to target their host mRNA transcript. Further, KEGG pathway analysis demonstrated that 22 of the 74 pathways in which host genes were associated showed significant overrepresentation of proteins encoded by the mRNA targets of associated intragenic miRNAs. Conclusions Our findings suggest that both host genes and intragenic miRNA targets may potentially be subject to multiple layers of regulation. Tight regulatory control of these genes is likely critical for cellular homeostasis and absence of disease. To this end, we examined the potential for negative

  15. The ability of two cooked food mutagens to induce aberrant crypt foci in mice

    DEFF Research Database (Denmark)

    Kristiansen, E.; Meyer, Otto A.; Thorup, I.

    1997-01-01

    The aberrant crypt foci assay has been used extensively to study different compounds for chemopreventive action, but almost all investigations have used initiators not normally found in the diet, In the present study two food-borne initiators, 2-amino-3-methyl-imidazo [4,5-f]quinoline (IQ) and 2......-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) were used, To simulate the human exposure further, we chose a feeding regimen with continuous low IQ- and PhIP-doses, Throughout the study female mice were given diets with or without 0.03% IQ or 0.03% PhIP, Two additional groups were given...... azoxymethane (AOM) (5 mg/kg body weight) and 1,2-dimethylhydrazine dihydrochloride (DMH-2HCI) (20 mg/kg body weight), respectively, one dose a week for two weeks, Animals were killed after four and 10 weeks, After four weeks only the mice dosed with IQ and PhIP had aberrant crypt foci, A much higher number...

  16. The Performance of Ictal Brain SPECT for Localizing Epileptogenic Foci in Temporal Lobe epilepsies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Sil; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Koh, Chang Soon; Chang, Kee Hyun; Lee, Sang Kun; Chung, Chun Kee [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1995-06-15

    Anterior temporal lobectomy has become a widely used respective surgery in patients with medically intractable temporal lobe epilepsies. Prerequisites of this resection include the accurate localization of the epileptogenic focus and the determination that the proposed resection would not result in unacceptable postoperative memory or language deficits. The purpose of this study was to evaluate the performance of ictal SPECT compared to MRI findings for localization of epileptogenic foci in this group of patients. 11 patients who had been anterior temporal oral lobectomy were evaluated with ictal {sup 99m}Tc-HMPAO SPECT and MRI. MRI showed 8/11(73%) concordant lesion to the side of surgery and ictal SPECT also showed 8/11(73%) concordant hyperperfusion. In 3 cases with incorrect or nonlocalizing findings of MRI, ictal SPECT showed concordant hyperperfusion. In 2 cases confirmed by pre-resectional invasive EEG, MRI showed bilateral and contralateral lesion but ictal SPECT showed concordant hyperperfusion. 3 delayed injection of ictal SPECT showed discordant hyperperfusion. Thus, ictal SPECT was a useful method for localizing epileptogenic foci in temporal lobe epilepsies and appeared complementay to MRI.

  17. Identification of preneoplastic lesions as mucin-depleted foci in patients with sporadic colorectal cancer.

    Science.gov (United States)

    Sakai, Eiji; Morioka, Takamitsu; Yamada, Eiji; Ohkubo, Hidenori; Higurashi, Takuma; Hosono, Kunihiro; Endo, Hiroki; Takahashi, Hirokazu; Takamatsu, Reika; Cui, Changxu; Shiozawa, Manabu; Akaike, Makoto; Samura, Hironori; Nishimaki, Tadashi; Nakajima, Atsushi; Yoshimi, Naoki

    2012-01-01

    In experimental models, mucin-depleted foci (MDF), formed by dysplastic crypts devoid of mucin production have been recognized to be correlated with colorectal carcinogenesis and to serve as preneoplastic lesions of colorectal cancer (CRC). In humans, there is only one report of identification of MDF in patients with familial adenomatous polyposis and CRC; however, the histological characteristics of human MDF are not discussed extensively in the report. In the present study, colonic samples from 53 patients with sporadic CRC were stained with Alcian blue and examined for the presence of MDF. Subsequently, the samples were examined for the presence of aberrant crypt foci (ACF) by methylene blue staining. We classified MDF into two categories: flat-MDF and protruded-MDF (having the characteristics of both ACF and MDF). We found a total of 354, 41 and 19 colonic mucosal lesions with a mean multiplicity of 44, 38.9 and 66.9 crypts (ACF, flat-MDF and protruded-MDF, respectively). The density of MDF was 0.0082 lesions/cm(2) . The ACF identified in sporadic CRC patients corresponded to hyperplastic or non-dysplasic lesions. However, MDF identified in these patients corresponded to low-grade dysplasia. In addition, we found that Paneth cell metaplasia and inflammatory cell infiltration were specific histological features of MDF. These histological characteristics are reported to be associated with the development of CRC. Therefore, our results indicate that MDF might represent preneoplastic lesions in human colorectal carcinogenesis. © 2011 Japanese Cancer Association.

  18. An improved classification of foci for carcinogenicity testing by statistical descriptors.

    Science.gov (United States)

    Callegaro, Giulia; Stefanini, Federico Mattia; Colacci, Annamaria; Vaccari, Monica; Urani, Chiara

    2015-10-01

    Carcinogenesis is a multi-step process involving genetic alterations and non-genotoxic mechanisms. The in vitro cell transformation assay (CTA) is a promising tool for both genotoxic and non-genotoxic carcinogenesis. CTA relies on the ability of cells (e.g. BALB/c 3T3 mouse embryo fibroblasts) to develop a transformed phenotype after the treatment with suspected carcinogens. The classification of the transformed phenotype is based on coded morphological features, which are scored under a light microscope by trained experts. This procedure is time-consuming and somewhat prone to subjectivity. Herewith we provide a promising approach based on image analysis to support the scoring of malignant foci in BALB/c 3T3 CTA. The image analysis system is a quantitative approach, based on measuring features of malignant foci: dimension, multilayered growth, and invasivity into the surrounding monolayer of non-transformed cells. A logistic regression model was developed to estimate the probability for each focus to be transformed as a function of three statistical image descriptors. The estimated sensitivity of the derived classifier (untransformed against Type III) was 0.9, with an Area Under the Curve (AUC) value equal to 0.90 under the Receiver Operating Characteristics (ROC) curve.

  19. THE ROLE OF THE COMMERCIAL BANKS' CAPITAL IN REALIZATION OF INVESTMENT POTENTIAL OF BANKING SYSTEM OF UKRAINE

    Directory of Open Access Journals (Sweden)

    I. Lyutiy

    2015-03-01

    Full Text Available The article studies modern trends in investment corporate lending in Ukraine and the ultimate role of banking system in context of capital investments funding in Ukraine. The impact of structure and dynamics of commercial banks’ financial resources on realization of investment potential of Ukrainian banking system is analyzed. The role of banks’ capital adequacy as a precondition for expansion of investment corporate lending is determined.

  20. The current and potential role of satellite remote sensing in the campaign against malaria

    Science.gov (United States)

    Kazansky, Yaniv; Wood, Danielle; Sutherlun, Jacob

    2016-04-01

    Malaria and other vector borne diseases claim lives and cause illness, especially in less developed countries. Although well understood methods, such as spraying and insecticidal nets, are identified as effective deterrents to malaria transmission by mosquitoes, the nations that have the greatest burden from the disease also struggle to deploy such measures sufficiently. More targeted and up to date information is needed to identify which regions of malaria-endemic countries are most likely to be at risk of malaria in the near future. This will allow national governments, local officials and public health workers to deploy protective equipment and personnel where they are most needed. This paper explores the role of environmental data generated via satellite remote sensing as an ingredient to a Malaria Early Warning System. Data from remote sensing satellites can cover broad geographical areas frequently and consistently. Much of the relevant data may be accessed by malaria-endemic countries at minimal cost via international data sharing polices. While previous research studies have demonstrated the potential to assign malaria risk to a geographic region based on indicators from satellites and other sources, there is still a need to deploy such tools in a broader and more operational manner to inform decision making on malaria management. This paper describes current research on the use of satellite-based environmental data to predict malaria risk and examines the barriers and opportunities for implementing Malaria Early Warning Systems enabled by satellite remote sensing. A Systems Architecture Framework analyses the components of a Malaria Early Warning System and highlights the need for effective coordination across public and private sector organizations.

  1. Breastfeeding may improve nocturnal sleep and reduce infantile colic: potential role of breast milk melatonin.

    Science.gov (United States)

    Cohen Engler, Anat; Hadash, Amir; Shehadeh, Naim; Pillar, Giora

    2012-04-01

    Melatonin is secreted during the night in adults but not in infants. It has a hypnotic effect as well as a relaxing effect on the smooth muscle of the gastrointestinal tract. It is plausible that breast milk, which consists of melatonin, may have an effect on improving infants' sleep and reducing infantile colic. Our first goal was to assess the differences in the prevalence and severity of infantile colic and nocturnal sleep between breast-fed infants and supplement-fed infants. The second was to characterize the profile of melatonin secretion in human breast milk compared to artificial formulas. Ninety-four mothers of healthy 2 to 4-month-old infants filled a questionnaire regarding irritability/potential infantile colic and sleep characteristics. For the second part, we measured melatonin levels in breast milk of five women every 2 h during 24 h and in three samples of commonly used artificial formulas. Exclusively breast-fed infants had a significantly lower incidence of colic attacks (p = 0.04), lower severity of irritability attacks (p = 0.03), and a trend for longer nocturnal sleep duration (p = 0.06). Melatonin in human milk showed a clear circadian curve and was unmeasurable in all artificial milks. Exclusive breastfeeding is associated with reduced irritability/colic and a tendency toward longer nocturnal sleep. Breast milk (nocturnal) consists of substantial melatonin levels, whereas artificial formulas do not. We speculate that melatonin which is supplied to the infant via breast milk plays a role in improving sleep and reducing colic in breast-fed infants compared to formula-fed ones.

  2. Intermolecular DNA ligation activity of eukaryotic toposiomerase II: Potential roles in nucleic acid recombination

    Energy Technology Data Exchange (ETDEWEB)

    Gale, K.C.R.

    1992-01-01

    Single-stranded [phi]X174 (+) strand DNA was used as a model substrate for topoisomerase II to determine whether double-stranded DNA cleavage observed in vitro reflects the in vivo intermediate in the enzyme's catalytic cycle and to investigate potential mechanisms for topoisomerase II-mediated DNA recombination. As found previously for topoisomerase II-mediated cleavage of double-stranded DNA, the enzyme was covalently linked to the 5[prime]-termini of cleaved [phi]X174 molecules. Optimal reaction conditions were similar for the two substrates. In contrast to results with double-stranded molecules, single-stranded DNA cleavage increased with time, was not reversible, and did not require the presence of SDS. Cleavage products generated in the absence of protein denaturant contained free 3[prime]-OH DNA termini. These results strongly suggest that the covalent topoisomerase II-cleaved DNA complex observed in vitro is the active intermediate in the enzyme's catalytic code. Topoisomerase II is capable of joining cleaved [phi]X174 (+) strand DNA to duplex oligonucleotide acceptor molecules by an intermolecular ligation reaction. Intermolecular DNA ligation proceeded in a time and oligonucleotide concentration dependent fashion. The covalent linkage is between the 5[prime]-phosphate of [phi]X174 (+) strand DNA and the 3[prime]-OH of oligonucleotide acceptor molecules. The reaction was dependent on the presence of a divalent cation, was inhibited by salt, and was not affected by the presence of ATP. The enzyme was capable of ligating [phi]X174 (+) strand DNA to double-stranded oligonucleotides that contained 5[prime]-overhang, 3[prime]-overhang, or blunt ends. Single-stranded, nicked, or gapped oligonucleotides could also be used as acceptor molecules. These results demonstrate that the type II enzyme has an intrinsic ability to mediate illegitimate DNA recombination in vitro and suggests possible roles for topoisomerase II in nucleic acid recombination in vivo.

  3. Biological roles and therapeutic potential of hydroxy-carboxylic acid receptors

    Directory of Open Access Journals (Sweden)

    Kashan eAhmed

    2011-10-01

    Full Text Available In the recent past, deorphanization studies have described intermediates of energy metabolism to activate G protein-coupled receptors (GPCRs and to thereby regulate metabolic functions. GPR81, GPR109A and GPR109B, formerly known as the nicotinic acid receptor family, are encoded by clustered genes and share a high degree of sequence homology. Recently, hydroxy-carboxylic acids were identified as endogenous ligands of GPR81, GPR109A and GPR109B, and therefore these receptors have been placed into a novel receptor family of hydroxy-carboxylic acid (HCA receptors. The HCA1 receptor (GPR81 is activated by the glycolytic metabolite 2-hydroxy-propionic acid (lactate, the HCA2 receptor is activated by the ketone body 3-hydroxy-butyric acid and the HCA3 receptor (GPR109B is a receptor for the β-oxidation intermediate 3-hydroxy-octanoic acid. While HCA1 and HCA2 receptors are present in most mammalian species, the HCA3 receptor is exclusively found in humans and higher primates. HCA receptors are expressed in adipose tissue and mediate anti-lipolytic effects in adipocytes through Gi-type G-protein-dependent inhibition of adenylyl cyclase. HCA2 and HCA3 inhibit lipolysis during conditions of increased β-oxidation such as prolonged fasting, whereas HCA1 mediates the anti-lipolytic effects of insulin in the fed state. As HCA2 is a receptor for the established anti-dyslipidemic drug nicotinic acid, HCA1 and HCA3 also represent promising drug targets and several synthetic ligands for HCA receptors have been developed. In this article, we will summarize the deorphanization and pharmacological characterization of HCA receptors. Moreover, we will discuss recent progress in elucidating the physiological and pathophysiological role to further evaluate the therapeutic potential of the HCA receptor family for the treatment of metabolic disease.

  4. Potential role for snoRNAs in PKR activation during metabolic stress

    Science.gov (United States)

    Youssef, Osama A.; Safran, Sarah A.; Nix, David A.; Hotamisligil, Gökhan S.; Bass, Brenda L.

    2015-01-01

    Protein kinase RNA-activated (PKR) has long been known to be activated by viral double-stranded RNA (dsRNA) as part of the mammalian immune response. However, in mice PKR is also activated by metabolic stress in the absence of viral infection, and this requires a functional kinase domain, as well as a functional dsRNA-binding domain. The endogenous cellular RNA that potentially leads to PKR activation during metabolic stress is unknown. We investigated this question using mouse embryonic fibroblast cells expressing wild-type PKR (PKRWT) or PKR with a point mutation in each dsRNA-binding motif (PKRRM). Using this system, we identified endogenous RNA that interacts with PKR after induction of metabolic stress by palmitic acid (PA) treatment. Specifically, RIP-Seq analyses showed that the majority of enriched RNAs that interacted with WT PKR (≥twofold, false discovery rate ≤ 5%) were small nucleolar RNAs (snoRNAs). Immunoprecipitation of PKR in extracts of UV–cross-linked cells, followed by RT-qPCR, confirmed that snoRNAs were enriched in PKRWT samples after PA treatment, but not in the PKRRM samples. We also demonstrated that a subset of identified snoRNAs bind and activate PKR in vitro; the presence of a 5′-triphosphate enhanced PKR activity compared with the activity with a 5′-monophosphate, for some, but not all, snoRNAs. Finally, we demonstrated PKR activation in cells upon snoRNA transfection, supporting our hypothesis that endogenous snoRNAs can activate PKR. Our results suggest an unprecedented and unexpected model whereby snoRNAs play a role in the activation of PKR under metabolic stress. PMID:25848059

  5. A Numerical Modelling Study on the Potential Role of Tsunamis in the Biblical Exodus

    Directory of Open Access Journals (Sweden)

    José M. Abril

    2015-07-01

    Full Text Available The reliability of the narrative of the Biblical Exodus has been subject of heated debate for decades. Recent archaeological studies seem to provide new insight of the exodus path, and although with a still controversial chronology, the effects of the Minoan Santorini eruption have been proposed as a likely explanation of the biblical plagues. Particularly, it has been suggested that flooding by the associated tsunamis could explain the first plague and the sea parting. Recent modelling studies have shown that Santorini’s tsunami effects were negligible in the eastern Nile Delta, but the released tectonic stress could have triggered local tsunamigenic sources in sequence. This paper is aimed to a quantitative assessment of the potential role of tsunamis in the biblical parting of the sea. Several “best case” scenarios are tested through the application of a numerical model for tsunami propagation that has been previously validated. The former paleogeographic conditions of the eastern Nile Delta have been implemented based upon recent geological studies; and several feasible local sources for tsunamis are proposed. Tsunamis triggered by submarine landslides of 10–30 km3 could have severely impacted the northern Sinai and southern Levantine coasts but with weak effects in the eastern Nile Delta coastline. The lack of noticeable flooding in this area under the most favorable conditions for tsunamis, along with the time sequence of water elevations, make difficult to accept them as a plausible and literally explanation of the first plague and of the drowning of the Egyptian army in the surroundings of the former Shi-Hor Lagoon.

  6. The Potential Role of Hemopexin and Heme Oxygenase-1 Inducer in a Model of Sepsis

    Directory of Open Access Journals (Sweden)

    Passainte S. Hassaan

    2015-01-01

    Full Text Available Background and Aims. Sepsis can evoke disseminated intravascular coagulation, resulting in multiple organ failure and death. Heme oxygenase-1 (HO-1 and hemopexin (HPx can mediate cytoprotective mechanisms against these deleterious effects. This study aims to determine a role for HO-1 and HPx in coagulopathy induced by septic inflammation and define whether they can enhance the production of anti-inflammatory cytokine IL-10. Materials and Methods. 48 healthy male albino rats were divided equally into 4 groups: control group: animals subjected to laparotomy and bowel manipulation; CLP group: severe sepsis induced by cecal ligation puncture (CLP; CLP + hemin group: animals received single intraperitoneal injection of hemin (50 µmol/kg 12 h before sepsis induction; CLP + HPx group: animals received single HPx dose (150 µg/rat, i.v. 30 min before sepsis induction. Survival rates were calculated. Prothrombin time (PT, activated partial thromboplastin time (APTT, and activated protein C (APC, liver HO-1, serum, and liver IL-10 levels were measured, 48 hrs after sepsis induction. Liver and lung were excised for histopathological examination. Results. Hemin and HPx administration upregulated liver HO-1 and IL-10. They prolonged PT, PTT and increased APC. They reduced the inflammatory infiltrate and thrombosis in liver and lung parenchyma. However, hemin was superior in controlling coagulopathy and HO-1 production, while HPx was more potent stimulant of IL-10 expression. Conclusions. Hemin and HPx have a potential beneficial effect in severe sepsis regarding coagulopathy and inflammation.

  7. Multi-functional roles of chitosan as a potential protective agent against obesity.

    Directory of Open Access Journals (Sweden)

    Ann M Walsh

    Full Text Available Chitosan, a natural polysaccharide comprising copolymers of glucosamine and N-acetylglucosamine, has been shown to have anti-obesity properties. Two experiments (Exp. 1 and Exp. 2 were performed to determine the role of chitosan on dietary intake, body weight gain, and fat deposition in a pig model, as well as identifying potential mechanisms underlying the anti-obesity effect of chitosan. In Exp. 1, the nutrient digestibility experiment, 16 pigs (n = 4/treatment were randomly allocated to one of four dietary treatments as follows: 1 basal diet; 2 basal diet plus 300 ppm chitosan; 3 basal diet plus 600 ppm chitosan; 4 basal diet plus 1200 ppm chitosan. The main observation was that crude fat digestibility was lower in the 1200 ppm chitosan group when compared with the control group (P<0.05. In Exp. 2, a total of 80 pigs (n = 20/treatment were offered identical dietary treatments to that offered to animals in Exp. 1. Blood samples were collected on day 0, day 35 and at the end of the experiment (day 57. Animals offered diets containing 1200 ppm chitosan had a lower daily dietary intake (P<0.001 and body weight gain (P<0.001 from day 35 to 57 when compared with all the other treatment groups. Animals offered diets containing 1200 ppm chitosan had a significantly lower final body weight (P<0.01 when compared with all the other treatment groups. The decreased dietary intake observed in the 1200 ppm chitosan group was associated with increased serum leptin concentrations (P<0.001 and a decrease in serum C-reactive protein (CRP concentrations (P<0.05. In conclusion, the results of this study highlight novel endocrine mechanisms involving the modulation of serum leptin and CRP concentrations by which chitosan exhibits anti-obesity properties in vivo.

  8. Assessment of the Potential Role of Streptomyces in Cave Moonmilk Formation

    Directory of Open Access Journals (Sweden)

    Marta Maciejewska

    2017-06-01

    Full Text Available Moonmilk is a karstic speleothem mainly composed of fine calcium carbonate crystals (CaCO3 with different textures ranging from pasty to hard, in which the contribution of biotic rock-building processes is presumed to involve indigenous microorganisms. The real microbial input in the genesis of moonmilk is difficult to assess leading to controversial hypotheses explaining the origins and the mechanisms (biotic vs. abiotic involved. In this work, we undertook a comprehensive approach in order to assess the potential role of filamentous bacteria, particularly a collection of moonmilk-originating Streptomyces, in the genesis of this speleothem. Scanning electron microscopy (SEM confirmed that indigenous filamentous bacteria could indeed participate in moonmilk development by serving as nucleation sites for CaCO3 deposition. The metabolic activities involved in CaCO3 transformation were furthermore assessed in vitro among the collection of moonmilk Streptomyces, which revealed that peptides/amino acids ammonification, and to a lesser extend ureolysis, could be privileged metabolic pathways participating in carbonate precipitation by increasing the pH of the bacterial environment. Additionally, in silico search for the genes involved in biomineralization processes including ureolysis, dissimilatory nitrate reduction to ammonia, active calcium ion transport, and reversible hydration of CO2 allowed to identify genetic predispositions for carbonate precipitation in Streptomyces. Finally, their biomineralization abilities were confirmed by environmental SEM, which allowed to visualize the formation of abundant mineral deposits under laboratory conditions. Overall, our study provides novel evidences that filamentous Actinobacteria could be key protagonists in the genesis of moonmilk through a wide spectrum of biomineralization processes.

  9. 3,4,5-Trichloroaniline nephrotoxicity in vitro: potential role of free radicals and renal biotransformation.

    Science.gov (United States)

    Racine, Christopher; Ward, Dakota; Anestis, Dianne K; Ferguson, Travis; Preston, Deborah; Rankin, Gary O

    2014-11-13

    Chloroanilines are widely used in the manufacture of drugs, pesticides and industrial intermediates. Among the trichloroanilines, 3,4,5-trichloroaniline (TCA) is the most potent nephrotoxicant in vivo. The purpose of this study was to examine the nephrotoxic potential of TCA in vitro and to determine if renal biotransformation and/or free radicals contributed to TCA cytotoxicity using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the animal model. IRCC (~4 million cells/mL; 3 mL) were incubated with TCA (0, 0.1, 0.25, 0.5 or 1.0 mM) for 60-120 min. In some experiments, IRCC were pretreated with an antioxidant or a cytochrome P450 (CYP), flavin monooxygenase (FMO), cyclooxygenase or peroxidase inhibitor prior to incubation with dimethyl sulfoxide (control) or TCA (0.5 mM) for 120 min. At 60 min, TCA did not induce cytotoxicity, but induced cytotoxicity as early as 90 min with 0.5 mM or higher TCA and at 120 min with 0.1 mM or higher TCA, as evidenced by increased lactate dehydrogenase (LDH) release. Pretreatment with the CYP inhibitor piperonyl butoxide, the cyclooxygenase inhibitor indomethacin or the peroxidase inhibitor mercaptosuccinate attenuated TCA cytotoxicity, while pretreatment with FMO inhibitors or the CYP inhibitor metyrapone had no effect on TCA nephrotoxicity. Pretreatment with an antioxidant (α-tocopherol, glutathione, ascorbate or N-acetyl-L-cysteine) also reduced or completely blocked TCA cytotoxicity. These results indicate that TCA is directly nephrotoxic to IRCC in a time and concentration dependent manner. Bioactivation of TCA to toxic metabolites by CYP, cyclooxygenase and/or peroxidase contributes to the mechanism of TCA nephrotoxicity. Lastly, free radicals play a role in TCA cytotoxicity, although the exact nature of the origin of these radicals remains to be determined.

  10. Trypanosoma vivax, T. congolense "forest type" and T. simiae: prevalence in domestic animals of sleeping sickness foci of Cameroon.

    Science.gov (United States)

    Nimpaye, H; Njiokou, F; Njine, T; Njitchouang, G R; Cuny, G; Herder, S; Asonganyi, T; Simo, G

    2011-05-01

    In order to better understand the epidemiology of Human and Animal trypanosomiasis that occur together in sleeping sickness foci, a study of prevalences of animal parasites (Trypanosoma vivax, T. congolense "forest type", and T. simiae) infections was conducted on domestic animals to complete the previous work carried on T. brucei gambiense prevalence using the same animal sample. 875 domestic animals, including 307 pigs, 264 goats, 267 sheep and 37 dogs were sampled in the sleeping sickness foci of Bipindi, Campo, Doumé and Fontem in Cameroon. The polymerase chain reaction (PCR) based method was used to identify these trypanosome species. A total of 237 (27.08%) domestic animals were infected by at least one trypanosome species. The prevalence of T. vivax, T. congolense "forest type" and T. simiae were 20.91%, 11.42% and 0.34% respectively. The prevalences of 7 vivax and T. congolense "forest type" differed significantly between the animal species and between the foci (p < 0.0001); however, these two trypanosomes were found in all animal species as well as in all the foci subjected to the study. The high prevalences of 7 vivax and T congolense "forest type" in Bipindi and Fontem-Center indicate their intense transmission in these foci.

  11. Imaging and clinical characteristics of children with multiple foci of microsusceptibility changes in the brain on susceptibility-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Niwa, Tetsu [Kanagawa Children' s Medical Center, Department of Radiology, Yokohama (Japan); University Medical Center Utrecht, Department of Radiology, Heidelberglaan 100, PO Box 85500, Utrecht (Netherlands); Aida, Noriko; Fujita, Kazutoshi; Shishikura, Ayako [Kanagawa Children' s Medical Center, Department of Radiology, Yokohama (Japan); Takahara, Taro; Kwee, Thomas C. [University Medical Center Utrecht, Department of Radiology, Heidelberglaan 100, PO Box 85500, Utrecht (Netherlands); Miyata, Daiki [Kanagawa Children' s Medical Center, Department of Circulation Medicine, Yokohama (Japan); Inoue, Tomio [Yokohama City University, Graduate School of Medicine, Department of Radiology, Yokohama (Japan)

    2010-10-15

    Microsusceptibility changes in the brain are well known to correspond with microbleeds or micrometal fragments in adults, but this phenomenon has not been explored well in children. To assess imaging and clinical characteristics of children with multiple foci of microsusceptibility changes using susceptibility-weighted imaging (SWI). Between 2006 and 2008, 12 children with multiple foci of microsusceptibility on SWI without corresponding abnormal signal on conventional MRI were identified and were retrospectively assessed. The locations of foci of microsusceptibility included the cerebral white matter, basal ganglia, brainstem and cerebellar white matter, without any clear systematic anatomic distribution. CT (n = 5) showed no calcification at the locations corresponding to the microsusceptibility on SWI. Conventional MR imaging showed white matter volume loss (n = 5), delayed myelination (n = 2), acute infarction (n = 1), chronic infarction (n = 1), meningitis (n = 1), slight signal abnormality in the white matter (n = 1) and no abnormal findings (n = 1). Follow-up SWI (n = 3) showed no change of the microsusceptibility foci. Interestingly, all children had a history of heart surgery under extracorporeal circulation for congenital heart disease. Multiple foci of microsusceptibility can be seen in the brain on SWI in children with congenital heart disease who underwent heart surgery with extracorporeal circulation. (orig.)

  12. On the role of deformed Coulomb potential in fusion using energy density formalism

    Indian Academy of Sciences (India)

    Lavneet Kaur; Raj Kumari

    2015-10-01

    Using the Skyrme energy density formalism, the effect of deformed Coulomb potential on fusion barriers and fusion cross-sections is studied. Our detailed study reveals that the fusion barriers as well as fusion probabilities depend on the shape deformation (due to deformed Coulomb potential) of the colliding nuclei. However, this dependence due to deformed Coulomb potential is found to be very weak.

  13. Complex Variables in Junior High School: The Role and Potential Impact of an Outreach Mathematician

    Science.gov (United States)

    Duke, Billy J.; Dwyer, Jerry F.; Wilhelm, Jennifer; Moskal, Barbara

    2008-01-01

    Outreach mathematicians are college faculty who are trained in mathematics but who undertake an active role in improving primary and secondary education. This role is examined through a study where an outreach mathematician introduced the concept of complex variables to junior high school students in the United States with the goal of stimulating…

  14. The potential role for use of mitochondrial DNA copy number as predictive biomarker in presbycusis

    Directory of Open Access Journals (Sweden)

    Falah M

    2016-10-01

    Full Text Available Masoumeh Falah,1,2 Massoud Houshmand,3 Mohammad Najafi,2 Maryam Balali,1 Saeid Mahmoudian,1 Alimohamad Asghari,4 Hessamaldin Emamdjomeh,1 Mohammad Farhadi1 1ENT and Head & Neck Research Center and Department, Iran University of Medical Sciences, Tehran, Iran; 2Cellular and Molecular Research Center, Biochemistry Department, Iran University of Medical Sciences, Tehran, Iran; 3Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran; 4Skull base research center, Iran University of Medical Sciences, Tehran, Iran Objectives: Age-related hearing impairment, or presbycusis, is the most common communication disorder and neurodegenerative disease in the elderly. Its prevalence is expected to increase, due to the trend of growth of the elderly population. The current diagnostic test for detection of presbycusis is implemented after there has been a change in hearing sensitivity. Identification of a pre-diagnostic biomarker would raise the possibility of preserving hearing sensitivity before damage occurs. Mitochondrial dysfunction, including the production of reactive oxygen species and induction of expression of apoptotic genes, participates in the progression of presbycusis. Mitochondrial DNA sequence variation has a critical role in presbycusis. However, the nature of the relationship between mitochondrial DNA copy number, an important biomarker in many other diseases, and presbycusis is undetermined.Methods: Fifty-four subjects with presbycusis and 29 healthy controls were selected after ear, nose, throat examination and pure-tone audiometry. DNA was extracted from peripheral blood samples. The copy number of mitochondrial DNA relative to the nuclear genome was measured by quantitative real-time polymerase chain reaction.Results: Subjects with presbycusis had a lower median mitochondrial DNA copy number than healthy subjects and the difference was statistically significant (P=0.007. Mitochondrial DNA

  15. Nitrate transporters in leaves and their potential roles in foliar uptake of nitrogen dioxide

    Directory of Open Access Journals (Sweden)

    Yanbo eHu

    2014-07-01

    Full Text Available While plant roots are specialized organs for the uptake and transport of water and nutrients, the absorption of gaseous or liquid mineral elements by aerial plant parts has been recognized since more than one century. Nitrogen (N is an essential macronutrient which generally absorbed either as nitrate (NO3- or ammonium (NH4+ by plant roots. Gaseous nitrogen pollutants like N dioxide (NO2 can also be absorbed by plant surfaces and assimilated via the NO3– assimilation pathway. The subsequent NO3– flux may induce or repress the expression of various NO3–-responsive genes encoding for instance, the transmembrane transporters, NO3–/NO2– (nitrite reductase, or assimilatory enzymes involved in N metabolism. Based on the existing information, the aim of this review was to theoretically analyze the potential link between foliar NO2 absorption and N transport and metabolism. For such purpose, an overview of the state of knowledge on the NO3– transporter genes identified in leaves or shoots of various species and their roles for NO3– transport across the tonoplast and plasma membrane, in addition to the process of phloem loading is briefly provided. It is assumed that a NO2-induced ac-cumulation of NO3–/NO2– may alter the expression of such genes, hence linking transmembrane NO3– transporters and foliar uptake of NO2. It is likely that NRT1/NRT2 gene expression and spe-cies-dependent apoplastic buffer capacity may be also related to the species-specific foliar NO2 uptake process. It is concluded that further work focusing on the expression of NRT1 (NRT1.1, NRT1.7, NRT1.11 and NRT1.12, NRT2 (NRT2.1, NRT2.4 and NRT2.5 and chloride channel family genes (CLCa and CLCd may help us elucidate the physiological and metabolic response of plants fumigated with NO2.

  16. Expression of renal cubilin and its potential role in tubulointerstitial inflammation induced by albumin overload

    Institute of Scientific and Technical Information of China (English)

    Jurong YANG; Yani HE; Haiying SHEN; Hanlu DING; Kailong LI; Huiming WANG

    2008-01-01

    Sustained proteinuria is an independent risk factor leading to kidney fibrosis and end-stage renal fail-ure. Over-reabsorption of filtered proteins, notably albu-min, has been proved to trigger interstitial inflammation and fibrosis in proteinuric renal disease. Cubilin, an endo-cytic receptor expressed on the renal tubular brush bor-der, is responsible for albumin reabsorption in physiologic condition. However, little is known about whether it is required for activation of tubular cells induced by albu-min overload. In this work, we investigated the change of cubilin expression and its potential role in albumin-induced up-regulation of chemokines synthesis in vivo and in vitro. Twenty-six patients with nephrotic syndrome were enrolled in this study. Proximal tubule uptake of albumin, expression of apical membrane cubilin and infiltrating cells in kidney interstitium were determined by immunocytochemistry. In vitro, the transcription of cubilin in HK2 cells after exposure to albumin was ana-lyzed by real-time PCR. Endocytosis of albumin in HK2 cells was examined by fluorescent microscope. The influ-ence of inhibition of cubilin on albumin-induced expres-sions of monocyte chemoattractant protein 1 (MCP-1) and regulated upon activation normal T-cell expressed and secreted (RANTES) was investigated by Western blot. The intensity of luminal cubilin and tubular accu-mulation of albumin were significantly increased in nephrotic kidneys. The expression of MCP-1 and RANTES was up-regulated, and there were spatial rela-tionships in localization between these chemokines and cubilin as well as intracellular albumin in kidney tissues. Infiltration of CD-3 and ED-1-positive cells was predom-inant in tubulointerstitial areas displaying signs of increases of cubilin expression and albumin accumula-tion. In vitro, the transcription of cubilin mRNA in HK2 cells was enhanced after 24 h exposure to albumin in a dose-dependent manner. Inhibition of endocytosis of albumin by antisense

  17. Triphenyl phosphate-induced developmental toxicity in zebrafish: Potential role of the retinoic acid receptor

    Energy Technology Data Exchange (ETDEWEB)

    Isales, Gregory M.; Hipszer, Rachel A.; Raftery, Tara D. [Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC (United States); Chen, Albert; Stapleton, Heather M. [Division of Environmental Sciences and Policy, Nicholas School of the Environment, Duke University, Durham, NC (United States); Volz, David C., E-mail: volz@mailbox.sc.edu [Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC (United States)

    2015-04-15

    Highlights: • Triphenyl phosphate-induced toxicity in zebrafish embryos is enhanced in the presence of a retinoic acid receptor antagonist. • Triphenyl phosphate uptake or metabolism within zebrafish embryos is not altered in the presence of a retinoic acid receptor antagonist. • Triphenyl phosphate decreases expression of cytochrome P450 26a1 in zebrafish embryos. • Triphenyl phosphate inhibits retinoic acid-induced activation of human retinoic acid receptors. - Abstract: Using zebrafish as a model, we previously reported that developmental exposure to triphenyl phosphate (TPP) – a high-production volume organophosphate-based flame retardant – results in dioxin-like cardiac looping impairments that are independent of the aryl hydrocarbon receptor. Using a pharmacologic approach, the objective of this study was to investigate the potential role of retinoic acid receptor (RAR) – a nuclear receptor that regulates vertebrate heart morphogenesis – in mediating TPP-induced developmental toxicity in zebrafish. We first revealed that static exposure of zebrafish from 5–72 h post-fertilization (hpf) to TPP in the presence of non-toxic concentrations of an RAR antagonist (BMS493) significantly enhanced TPP-induced toxicity (relative to TPP alone), even though identical non-toxic BMS493 concentrations mitigated retinoic acid (RA)-induced toxicity. BMS493-mediated enhancement of TPP toxicity was not a result of differential TPP uptake or metabolism, as internal embryonic doses of TPP and diphenyl phosphate (DPP) – a primary TPP metabolite – were not different in the presence or absence of BMS493. Using real-time PCR, we then quantified the relative change in expression of cytochrome P450 26a1 (cyp26a1) – a major target gene for RA-induced RAR activation in zebrafish – and found that RA and TPP exposure resulted in a ∼5-fold increase and decrease in cyp26a1 expression, respectively, relative to vehicle-exposed embryos. To address whether TPP may

  18. Raltegravir permeability across blood-tissue barriers and the potential role of drug efflux transporters.

    Science.gov (United States)

    Hoque, M Tozammel; Kis, Olena; De Rosa, María F; Bendayan, Reina

    2015-05-01

    cells, respectively. Our data suggest that raltegravir is a substrate but not an inhibitor of the drug efflux transporters P-gp and BCRP. These transporters might play a role in the restriction of raltegravir permeability across the blood-brain, blood-testicular, and blood-intestinal barriers, potentially contributing to its low tissue concentrations and/or low oral bioavailability observed in the clinic setting.

  19. ON STRUCTURED AND DIFFUSE SEISMICITY, STIFFNESS OF EARTHQUAKE FOCI, AND NONLINEARITY OF MAGNITUDE RECURRENCE GRAPHS

    Directory of Open Access Journals (Sweden)

    Evgeny G. Bugaev

    2015-09-01

    Full Text Available Geological, geophysical and seismogeological studies are now conducted in a more detail and thus provide for determining seismic sources with higher accuracy, from the first meters to first dozens of meters [Waldhauser, Schaff, 2008]. It is now possible to consider uncertainty ellipses of earthquake hypocenters, that are recorded in the updated Earthquake Catalogue, as surfaces of earthquake focus generators. In our article, it is accepted that a maximum horizontal size of an uncertainty ellipse corresponds to an area of a focus generator, and seismic events are thus classified into two groups, earthquakes with nonstiff and stiff foci. Criteria of such a classification are two limits of elastic strain and brittle strain in case of uniaxial (3⋅10–5 or omnidirectional (10–6 compression. The criteria are established from results of analyses of parameters of seismic dislocations and earthquake foci with regard to studies of surface parameters and deformation parameters of fault zones. It is recommendable that the uniaxial compression criterion shall be applied to zones of interaction between tectonic plates, and the unilateral compression criterion shall be applied to low active (interplate areas. Sample cases demonstrate the use of data sets on nonstiff and stiff foci for separate evaluation of magnitude reoccurrence curves, analyses of structured and dissipated seismicity, review of the physical nature of nonlinearity of recurrence curves and conditions of preparation of strong earthquakes. Changes of parameters of the recurrence curves with changes of data collection square areas are considered. Reviewed are changes of parameters of the recurrence curves during preparation for the Japan major earthquake of 11 March 2011 prior to and after the major shock. It is emphasized that it is important to conduct even more detailed geological and geophysical studies and to improve precision and sensitivity of local seismological monitoring networks

  20. Understanding Cortisol Reactivity across the Day at Child Care: The Potential Buffering Role of Secure Attachments to Caregivers

    Science.gov (United States)

    Badanes, Lisa S.; Dmitrieva, Julia; Watamura, Sarah Enos

    2012-01-01

    Full-day center-based child care has been repeatedly associated with rising cortisol across the child care day. This study addressed the potential buffering role of attachment to mothers and lead teachers in 110 preschoolers while at child care. Using multi-level modeling and controlling for a number of child, family, and child care factors,…

  1. Potential Pathogenetic Role of Bovine Herpesvirus 4 in Two Dairy Cows with Dermatitis-Pyrexia-Hemorrhagic Syndrome.

    Science.gov (United States)

    Bellino, Claudio; Iussich, Selina; Biasato, Ilaria; Peletto, Simone; Caruso, Claudio; Gianella, Paola; Cagnasso, Aurelio; D'Angelo, Antonio

    2015-08-01

    Dermatitis, pyrexia, and hemorrhagic syndrome (DPHS) is a rare bovine syndrome of unclear etiology. We describe two DPHS cases, the first to occur in Italy, with clinicopathological findings suggesting a potential pathogenetic role of bovine herpesvirus-4 (BoHV-4). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  2. Potential Pathogenetic Role of Bovine Herpesvirus 4 in Two Dairy Cows with Dermatitis-Pyrexia-Hemorrhagic Syndrome

    OpenAIRE

    Bellino, Claudio; Iussich, Selina; Biasato, Ilaria; Peletto, Simone; Caruso, Claudio; Gianella, Paola; Cagnasso, Aurelio; D?Angelo, Antonio

    2015-01-01

    Dermatitis, pyrexia, and hemorrhagic syndrome (DPHS) is a rare bovine syndrome of unclear etiology. We describe two DPHS cases, the first to occur in Italy, with clinicopathological findings suggesting a potential pathogenetic role of bovine herpesvirus-4 (BoHV-4).

  3. Understanding Cortisol Reactivity across the Day at Child Care: The Potential Buffering Role of Secure Attachments to Caregivers

    Science.gov (United States)

    Badanes, Lisa S.; Dmitrieva, Julia; Watamura, Sarah Enos

    2012-01-01

    Full-day center-based child care has been repeatedly associated with rising cortisol across the child care day. This study addressed the potential buffering role of attachment to mothers and lead teachers in 110 preschoolers while at child care. Using multi-level modeling and controlling for a number of child, family, and child care factors,…

  4. Activity-Dependent Calpain Activation Plays a Critical Role in Synaptic Facilitation and Post-Tetanic Potentiation

    Science.gov (United States)

    Khoutorsky, Arkady; Spira, Micha E.

    2009-01-01

    Synaptic facilitation and post-tetanic potentiation (PTP) are believed to necessitate active regeneration of the release machinery and supply of synaptic vesicles to a ready-releasable site. The prevailing hypothesis assumes that synapsins play pivotal roles in these processes. Using a cholinergic synapse formed between cultured "Aplysia" neurons…

  5. The Potential Role of Nitric Oxide in Halting Cancer Progression Through Chemoprevention

    Science.gov (United States)

    Vahora, Huzefa; Khan, Munawwar Ali; Alalami, Usama; Hussain, Arif

    2016-01-01

    Nitric oxide (NO) in general plays a beneficial physiological role as a vasorelaxant and the role of NO is decided by its concentration present in physiological environments. NO either facilitates cancer-promoting characters or act as an anti-cancer agent. The dilemma in this regard still remains unanswered. This review summarizes the recent information on NO and its role in carcinogenesis and tumor progression, as well as dietary chemopreventive agents which have NO-modulating properties with safe cytotoxic profile. Understanding the molecular mechanisms and cross-talk modulating NO effect by these chemopreventive agents can allow us to develop better therapeutic strategies for cancer treatment. PMID:27051643

  6. Post-initiation chlorophyllin exposure does not modulate aflatoxin-induced foci in the liver and colon of rats

    Directory of Open Access Journals (Sweden)

    Orner Gayle A

    2006-02-01

    Full Text Available Abstract Chlorophyllin (CHL is a promising chemopreventive agent believed to block cancer primarily by inhibiting carcinogen uptake through the formation of molecular complexes with the carcinogens. However, recent studies suggest that CHL may have additional biological effects particularly when given after the period of carcinogen treatment. This study examines the post-initiation effects of CHL towards aflatoxin B1 (AFB1-induced preneoplastic foci of the liver and colon. The single concentration of CHL tested in this study (0.1% in the drinking water had no significant effects on AFB1-induced foci of the liver and colons of rats.

  7. Demonstration lessons in mathematics education: teachers' observation foci and intended changes in practice

    Science.gov (United States)

    Clarke, Doug; Roche, Anne; Wilkie, Karina; Wright, Vince; Brown, Jill; Downton, Ann; Horne, Marj; Knight, Rose; McDonough, Andrea; Sexton, Matthew; Worrall, Chris

    2013-06-01

    As part of a teacher professional learning project in mathematics education, university mathematics educators taught demonstration lessons in project primary schools. These lessons were part of a "pre-brief, teaching, and debrief" process, in which up to eight teachers observed each lesson. Using brief questionnaires completed in advance of the lesson, during the lesson, following the debrief, and several weeks later, data were collected on teachers' intended and actual observation foci and any anticipated changes in their beliefs and practices arising from the experience. There were several common themes in teachers' intended observations, including a focus on questioning, catering for individual differences, and building student engagement. As evident in other research, teachers' intended and actual observations gave greater attention to teacher actions and decision making than to student learning and thinking. In this paper, we situate demonstration lessons within teacher professional learning models, describe the features of our model, summarise teacher data, and discuss issues arising from our work.

  8. Canine Uterine Leiomyoma with Epithelial Tissue Foci, Adenomyosis, and Cystic Endometrial Hyperplasia

    Directory of Open Access Journals (Sweden)

    George S. Karagiannis

    2011-01-01

    Full Text Available An 11-year-old Labrador Retriever bitch with a history of intermittent, sanguineous vaginal discharge of a six-month duration was presented. During exploratory laparotomy, two well-delineated, intramural masses were identified bilaterally in the uterine horns. Histopathologic examination of the mass on the left horn showed that it was a typical leiomyoma. However, the second mass appeared with an unusual coexistence of histological lesions, involving epithelial tissue foci, mild focal adenomyosis, and cystic endometrial hyperplasia. Interestingly, such combination was never encountered before in dogs. Although uterine leiomyoma is quite usual in the reproductive system of female dogs, this case resembled relevant cases of human uterine adenomyomas in morphology, and thus it was offered a similar tentative diagnosis.

  9. Multistability in Chua's circuit with two stable node-foci

    Energy Technology Data Exchange (ETDEWEB)

    Bao, B. C.; Wang, N.; Xu, Q. [School of Information Science and Engineering, Changzhou University, Changzhou 213164 (China); Li, Q. D. [Research Center of Analysis and Control for Complex Systems, Chongqing University of Posts and Telecommunications, Chongqing 400065 (China)

    2016-04-15

    Only using one-stage op-amp based negative impedance converter realization, a simplified Chua's diode with positive outer segment slope is introduced, based on which an improved Chua's circuit realization with more simpler circuit structure is designed. The improved Chua's circuit has identical mathematical model but completely different nonlinearity to the classical Chua's circuit, from which multiple attractors including coexisting point attractors, limit cycle, double-scroll chaotic attractor, or coexisting chaotic spiral attractors are numerically simulated and experimentally captured. Furthermore, with dimensionless Chua's equations, the dynamical properties of the Chua's system are studied including equilibrium and stability, phase portrait, bifurcation diagram, Lyapunov exponent spectrum, and attraction basin. The results indicate that the system has two symmetric stable nonzero node-foci in global adjusting parameter regions and exhibits the unusual and striking dynamical behavior of multiple attractors with multistability.

  10. Aberrant crypt foci in the colo-rectal mucosa as reliable markers of tumor development

    DEFF Research Database (Denmark)

    Thorup, Inger

    The aim of the present thesis has been to evaluate a recently developed short term in vivo model, the aberrant crypt foci bioassay (ACF), for its ability to predict the development of colo-rectal tumors. Based on the knowledge obtained during the last decade, it can be stated that no simple...... connection exists between occurrence of ACF (neither qualitatively nor quantita- tively) and later development of tumors. However, the literature has shown that part of the ACF show morphologic and genetic features characteristic for the tumorigenic process and a recent investigation indicate that all ACF...... belong to the same unity with basically the same chances for gradual progressing into tumors. It may be speculated that the progression depends on promo- tional conditions in the environment....

  11. Potential role of DNA-dependent protein kinase in cellular resistance to ionizing radiation

    Institute of Scientific and Technical Information of China (English)

    LI Ning; ZHANG Hong; WANG Yanling; WANG Xiaohu; HAO Jifang

    2009-01-01

    In this paper, we study the ability of DNA-PK-deficient (M059J) and -proficient (M059K) cells to undergo the rate of cellular proliferation, cell cycle distribution and apoptosis after 10 Gy X-ray irradiation, and the role of DNA-PK in radiosensitivity. The results showed that M059J cells exhibited hyper-radiosensitivity compared with M059K cells. A strong G2 phase arrest was observed in M059J cells post irradiation. Significant accumulation in the G2 phase in M059J cells was accompanied by apoptosis at 12 h. Altogether, the data suggested that DNA-PK may have two roles in mammalian cells after DNA damage, a role in DNA DSB repair and a second role in DNA-damaged cells to traverse a G2 checkpoint, by which DNA-PK may affect cellular sensitivity to ionizing radiation.

  12. Omega-3 fatty acids: potential role in the management of early Alzheimer’s disease

    OpenAIRE

    Jicha, Gregory A.; Markesbery, William R.

    2010-01-01

    Omega-3 fatty acids are essential for brain growth and development. They play an important role throughout life, as critical modulators of neuronal function and regulation of oxidative stress mechanisms, in brain health and disease. Docosahexanoic acid (DHA), the major omega-3 fatty acid found in neurons, has taken on a central role as a target for therapeutic intervention in Alzheimer’s disease (AD). A plethora of in vitro, animal model, and human data, gathered over the past decade, highlig...

  13. Mismatch repair-deficient crypt foci in Lynch syndrome--molecular alterations and association with clinical parameters.

    Directory of Open Access Journals (Sweden)

    Laura Staffa

    Full Text Available Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR genes, most frequently MLH1 and MSH2. Recently, MMR-deficient crypt foci (MMR-DCF have been identified as a novel lesion which occurs at high frequency in the intestinal mucosa from Lynch syndrome mutation carriers, but very rarely progress to cancer. To shed light on molecular alterations and clinical associations of MMR-DCF, we systematically searched the intestinal mucosa from Lynch syndrome patients for MMR-DCF by immunohistochemistry. The identified lesions were characterised for alterations in microsatellite-bearing genes with proven or suspected role in malignant transformation. We demonstrate that the prevalence of MMR-DCF (mean 0.84 MMR-DCF per 1 cm2 mucosa in the colorectum of Lynch syndrome patients was significantly associated with patients' age, but not with patients' gender. No MMR-DCF were detectable in the mucosa of patients with sporadic MSI-H colorectal cancer (n = 12. Microsatellite instability of at least one tested marker was detected in 89% of the MMR-DCF examined, indicating an immediate onset of microsatellite instability after MMR gene inactivation. Coding microsatellite mutations were most frequent in the genes HT001 (ASTE1 with 33%, followed by AIM2 (17% and BAX (10%. Though MMR deficiency alone appears to be insufficient for malignant transformation, it leads to measurable microsatellite instability even in single MMR-deficient crypts. Our data indicate for the first time that the frequency of MMR-DCF increases with patients' age. Similar patterns of coding microsatellite instability in MMR-DCF and MMR-deficient cancers suggest that certain combinations of coding microsatellite mutations, including mutations of the HT001, AIM2 and BAX gene, may contribute to the progression of MMR-deficient lesions into MMR-deficient cancers.

  14. The Adequacy of the Q Methodology for Clinical Validation of Nursing Diagnoses Related to Subjective Foci.

    Science.gov (United States)

    Miguel, Susana; Caldeira, Sílvia; Vieira, Margarida

    2016-11-17

    This article describes the adequacy of the Q methodology as a new option for the validation of nursing diagnoses related to subjective foci. Discussion paper about the characteristics of the Q methodology. This method has been used in nursing research particularly related to subjective concepts and includes both a quantitative and qualitative dimension. The Q methodology seems to be an adequate and innovative method for the clinical validation of nursing diagnoses. The validation of nursing diagnoses related to subjective foci using the Q methodology could improve the level of evidence and provide nurses with clinical indicators for clinical reasoning and for the planning of effective interventions. Descrever a adequação da metodologia Q como uma nova opção para a validação clínica de diagnósticos de enfermagem relacionados com focos subjetivos. MÉTODOS: Artigo de discussão sobre as características da metodologia Q. Este método tem sido utilizado na pesquisa em enfermagem relacionada com conceitos subjetivos e inclui em simultâneo uma vertente qualitativa e quantitativa. CONCLUSÕES: A metodologia Q parece ser uma opção metodológica adequada para a validação clínica de diagnósticos de enfermagem. IMPLICAÇÕES PARA A PRÁTICA: A utilização da metodologia Q na validação clínica de diagnósticos de enfermagem relacionados com focos subjetivos pode melhorar o nível e evidência e facilitar o raciocínio clínico dos enfermeiros, ao providenciar indicadores clínicos também necessários ao desenvolvimento de intervenções efetivas. © 2016 NANDA International, Inc.

  15. Angiogenesis inhibitor TNP-470 suppresses growth of peritoneal disseminating foci of human colon cancer line Lovo

    Institute of Scientific and Technical Information of China (English)

    Ying-Fang Fan; Zong-Hai Huang

    2002-01-01

    AIM: To study the effect of angiogenesis inhibitor TNP-470on peritoneal dissemination of colon cancer in nude mice,METHODS: The MTT assay was used to evaluate theinhibitory effect of TNP-470 on human colon cancer cell lineLovo. Lovo cells were injected into the peritoneal cavity ofBABL/C nu/nu mice and the models of peritonealdissemination were developed. Thirty nude mice wererandomly divided into control and TNP-470-treated group.In TNP-470-treated group, TNP-470 was injectedsubcutaneously every other day from day 1 until sacrifice ordeath (30 mg.kg-1). The control group received a shaminjection of the same volume saline solutionRESULTS: In vltro, TNP-470 inhibited the growth of Lovocells, with its IC50 at 2.14x102μg.L-1 In vivo, TNP-470demonstrated growth inhibition of tumors. Mice body weightand abdominal circumferences were significantly differentbetween TNP-470-treated group (24.5±3.2 g, 7.0±1.1 cm)and control group (29.5±2.1 g, 10.3±1.5 cm), P=0.005 andP=0.001. The number of disseminated foci was significantlydifferent between the control group (92.1±20.6) and theTNP-470-treated group (40.3±12.3), P<0.001. The maximalsize of foci was significantly smaller in TNP-470-treated group(3.3±0.7 mm) than that of control (7.3±2.3 mm), P=0.004.Mean survival time was significantly longer in TNP-470-treated group(98.00±12.06 d) than that in control group(41.86±9.51 d), P<0.001.CONCLUSION: Angiogenesis inhibitor TNP-470 might beeffective in treating peritoneal dissemination of colon cancerand improve the survival rate of nude mice.

  16. Potential impacts of ambient ozone on wheat rust diseases and the role of plant ozone sensitivity

    Science.gov (United States)

    The resurgence of rust diseases and the continued rise in tropospheric ozone (O3) levels have the potential to limit global wheat production. We conducted a series of experiments to understand the potential interactions between these two stress factors. Both stem rust and leaf rust were increased o...

  17. The role of orbital products in the optimized effective potential method

    NARCIS (Netherlands)

    Kollmar, Christian; Filatov, Michael

    2008-01-01

    The orbital products of occupied and virtual orbitals are employed as an expansion basis for the charge density generating the local potential in the optimized effective potential method thus avoiding the use of auxiliary basis sets. The high computational cost arising from the quadratic increase of

  18. Releasing Creativity in Teaching and Learning: The Potential Role of Organisational Legitimacy and Increased Dialogue

    Science.gov (United States)

    Deverell, Andrea; Moore, Sarah

    2014-01-01

    This paper reflects on the challenges of facilitating creativity in teaching and learning. The authors contend that if enabled, creativity has the potential to deliver substantive change to higher education but that its potential often remains unexploited. Our study suggests that creative practice is alive and well amongst teachers in higher…

  19. Exploring the actual and potential role of the primary care nurse in the prevention of cancer: a mixed methods study.

    Science.gov (United States)

    McIlfatrick, S; Keeney, S; McKenna, H; McCarley, N; McIlwee, G

    2014-05-01

    The aim of this study was to investigate the actual and the potential role of the primary care nurse (PCN) in the prevention of cancer. International studies have indicated that a range of strategies can have an impact on the incidence of cancer. Due to their frequent front-line contact with the public, PCNs can play an important role in the primary prevention of cancer. Nonetheless, there is a lack of information on their actual and potential role in cancer prevention. A sequential confirmatory mixed methods approach was used. Postal questionnaires were administered to PCNs [n = 500; 225 returns (response rate 45%)] followed by semi-structured interviews (n = 15). PCNs provided high levels of cancer prevention activities, specifically focusing on smoking cessation, obesity and cervical screening. They considered that their cancer prevention role could be improved through additional practice-based training and more collaborative inter-professional working. They also identified the need for a better understanding of how to change people's attitudes and behaviours regarding cancer prevention. Evidence from this study provide important insights into the potential of the PCN to empower individuals to take responsibility for their own health and make more informed lifestyle choices. © 2013 John Wiley & Sons Ltd.

  20. Sexing a sex-role-reversed species based on plumage: potential challenges in the red phalarope

    Directory of Open Access Journals (Sweden)

    Marie-Andrée Giroux

    2016-05-01

    Full Text Available Sex-role reversal, in which males care for offspring, can occur when mate competition is stronger between females than males. Secondary sex traits and mate attracting displays in sex-role-reversed species are usually more pronounced in females than in males. The red phalarope (Phalaropus fulicarius is a textbook example of a sex-role-reversed species. It is generally agreed that males are responsible for all incubation and parental care duties, whereas females typically desert males after having completed a clutch and may pair with new males to lay additional clutches. The breeding plumage of female red phalaropes is usually more brightly colored than male plumage, a reversed sexual dichromatism usually associated with sex-role reversal. Here, we confirm with PCR-based sexing that male red phalaropes can exhibit both the red body plumage typical of a female and the incubation behavior typical of a male. Our result, combined with previous observations of brightly colored red phalaropes incubating nests at the same arctic location (Igloolik Island, Nunavut, Canada, suggests that plumage dichromatism alone may not be sufficient to distinguish males from females in this breeding population of red phalaropes. This stresses the need for more systematic genetic sexing combined with standardized description of intersexual differences in red phalarope plumages. Determining whether such female-like plumage on males is a result of phenotypic plasticity or genetic variation could contribute to further understanding sex-role reversal strategies in the short Arctic summer.

  1. The Potential Role of Tree Diversity in Reducing Shallow Landslide Risk.

    Science.gov (United States)

    Kobayashi, Yuta; Mori, Akira S

    2017-05-01

    Recently, interest in utilizing ecosystems for disaster risk reduction has increased, even though there remains considerable uncertainty regarding the role of ecosystems in buffering against natural hazards. This ecosystem role can be considered an ecosystem service. Although a strong body of evidence shows that biodiversity enhances ecosystem services, there are only a few studies of the relationship between biodiversity and the role of the ecosystem in reducing the risk of natural disasters. To explore the desired state of an ecosystem for disaster risk reduction we applied the finding that biodiversity enhances ecosystem services to evaluate the role of woody vegetation in reducing the frequency and severity of shallow landslides. Using information related to shallow landslides and woody vegetation in Japan as a case study, we compared the severity of shallow landslides (i.e., landslide volume) with tree species richness. Although we provide no direct evidence that tree species richness reduces shallow landslide volume, we found that the predictability of the model, which evaluated relationships between landslide volume and environmental variables in watersheds throughout the Japanese Archipelago, increased with tree species richness. This finding suggests that biodiversity is likely associated with shallow landslide risk reduction, emphasizing a possible reduction of spatial and temporal uncertainty in the roles of woody vegetation. Our study identifies a need for socioecological systems to build new approaches found on the functionality of such ecosystems.

  2. Potential role of septins in oral carcinogenesis: An update and avenues for future research

    Directory of Open Access Journals (Sweden)

    Rooban Thavarajah

    2012-01-01

    Full Text Available Septins belong to the GTPase superclass of conserved proteins and have been identified to play a role in diverse aspects of cell biology, from cytokinesis to the maintenance of cellular morphology. At least 14 septins have been identified in humans. With their complex patterns in gene expressions and interaction, it has been reported that alterations in septin expression are observed in human diseases. Although much is not known about the role of human septins in oral carcinogenesis, circumstantial evidence does indicate that it may play a major role. This review intends to summarize the basis of septin biology, with the focus being on the evidence for septin involvement in human oral cancer.

  3. Potential for Drug Abuse: the Predictive Role of Parenting Styles, Stress and Type D Personality

    Directory of Open Access Journals (Sweden)

    mahin soheili

    2015-06-01

    Full Text Available Objective: This study was an attempt to predict potential for drug abuse on the basis of three predictors of parenting style, stress and type D personality. Method: In this descriptive-correlational study, 200 students (100 males and 100 females of Islamic Azad University of Karaj were selected by convenience sampling. For data collection, perceived parenting styles questionnaire, perceived stress scale, type D personality scale, and addiction potential scale were used. Results: The results showed that rejecting/neglecting parenting style and emotional warmth were positively and negatively correlated with addiction potential, respectively. Conclusion: The child-parent relationship and also the relationship between stress and type D personality can be considered as predictive factors in addiction potential.

  4. The potential role of open source software in overcoming digital poverty

    CSIR Research Space (South Africa)

    Kinyondo, J

    2012-09-01

    Full Text Available Developing countries, such as Tanzania, are characterized by digital poverty and a lack of information and communication technology (ICT) acceptance. The use of open source software (OSS) has been proposed as a potential strategy for addressing ICT...

  5. ROLE OF NMDA, NICOTINIC, AND GABA RECEPTORS IN THE STEADY STATE VISUAL EVOKED POTENTIAL IN RATS.

    Science.gov (United States)

    This manuscript characterizes the receptor pathways involved in pattern-evoked potential generation in rats" NMDA and nicotinic acetylcholine receptors appear to be involved in the generation of the steady-state pattern evoked response in vivo." The pattern evok...

  6. Understanding Infertility and the Potential Role of Stem Cells in Infertility Treatment: A Short Communication

    OpenAIRE

    Chirputkar R; Vaidya A

    2015-01-01

    Infertility is increasing at a great rate across the globe. Various male as well as female factors are known to contribute to infertility. Although hormonal replacement therapy and assisted reproduction treatments like in vitro fertilization and intracytoplasmic sperm injection are well established clinical modalities to treat infertility, stem cells are now being considered as potentially new therapeutic agents for the treatment of infertility due to their high differentiation potential. Sev...

  7. The Role of Meta-cognition in Students' Addiction Potential Tendency

    OpenAIRE

    Hajloo, Nader; Sadeghi, Hasan; Babayi Nadinloei, Karim; Habibi, Zahra

    2014-01-01

    Background: Addiction for narcotics is a dangerous reality, especially in teenagers and young persons, and is one of the most important socioeconomic and health problems, threatens the human society and leads to social stagnancy in various aspects. Objectives: The present study aimed at determining Meta-cognitive relationship with addiction potential tendency in students and determining the distribution of each Meta-cognitive dimension in predicting addiction potential tendency. Materials and...

  8. Effects of Caloric Restriction on Cardiac Oxidative Stress and Mitochondrial Bioenergetics: Potential Role of Cardiac Sirtuins

    Directory of Open Access Journals (Sweden)

    Ken Shinmura

    2013-01-01

    Full Text Available The biology of aging has not been fully clarified, but the free radical theory of aging is one of the strongest aging theories proposed to date. The free radical theory has been expanded to the oxidative stress theory, in which mitochondria play a central role in the development of the aging process because of their critical roles in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function associated with the accumulation of oxidative damage might be responsible, at least in part, for the decline in cardiac performance with age. In contrast, lifelong caloric restriction can attenuate functional decline with age, delay the onset of morbidity, and extend lifespan in various species. The effect of caloric restriction appears to be related to a reduction in cellular damage induced by reactive oxygen species. There is increasing evidence that sirtuins play an essential role in the reduction of mitochondrial oxidative stress during caloric restriction. We speculate that cardiac sirtuins attenuate the accumulation of oxidative damage associated with age by modifying specific mitochondrial proteins posttranscriptionally. Therefore, the distinct role of each sirtuin in the heart subjected to caloric restriction should be clarified to translate sirtuin biology into clinical practice.

  9. The potential role of lung microbiota in lung cancer attributed to household coal burning exposures

    NARCIS (Netherlands)

    Hosgood, H. Dean; Sapkota, Amy R.; Rothman, Nathaniel; Rohan, Thomas; Hu, Wei; Xu, Jun; Vermeulen, Roel; He, Xingzhou; White, James Robert; Wu, Guoping; Wei, Fusheng; Mongodin, Emmanuel F.; Lan, Qing

    2014-01-01

    Bacteria influence site-specific disease etiology and the host's ability to metabolize xenobiotics, such as polycyclic aromatic hydrocarbons (PAHs). Lung cancer in Xuanwei, China has been attributed to PAH-rich household air pollution from burning coal. This study seeks to explore the role of lung m

  10. Justification as a Teaching and Learning Practice: Its (Potential) Multifacted Role in Middle Grades Mathematics Classrooms

    Science.gov (United States)

    Staples, Megan E.; Bartlo, Joanna; Thanheiser, Eva

    2012-01-01

    Justification is a core mathematics practice. Although the purposes of justification in the mathematician community have been studied extensively, we know relatively little about its role in K-12 classrooms. This paper documents the range of purposes identified by 12 middle grades teachers who were working actively to incorporate justification…

  11. Masculine Gender Role Stress : a potential predictor of phobic and obsessive-compulsive behaviour

    NARCIS (Netherlands)

    Arrindell, WA; Kolk, AM; Martin, K; Kwee, MGT; Booms, EOH

    2003-01-01

    Eisler and Blalock (Clin. Psychol. Rev. 11 (1991) 45) developed a cognitively mediated notion of Masculine Gender Role Stress (MGRS) which assumes that rigid commitment to masculine schemata for appraisal and coping with life's problems may both produce stress and result in dysfunctional coping patt

  12. The potential role of lung microbiota in lung cancer attributed to household coal burning exposures

    NARCIS (Netherlands)

    Hosgood, H. Dean; Sapkota, Amy R.; Rothman, Nathaniel; Rohan, Thomas; Hu, Wei; Xu, Jun; Vermeulen, Roel; He, Xingzhou; White, James Robert; Wu, Guoping; Wei, Fusheng; Mongodin, Emmanuel F.; Lan, Qing

    2014-01-01

    Bacteria influence site-specific disease etiology and the host's ability to metabolize xenobiotics, such as polycyclic aromatic hydrocarbons (PAHs). Lung cancer in Xuanwei, China has been attributed to PAH-rich household air pollution from burning coal. This study seeks to explore the role of lung

  13. AFSC/RACE/EcoFOCI: 2011 Gulf of Alaska Late Larval Survey DY11-02/2DY11

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A total of 70 stations were occupied. The standard FOCI grid and line 8 were samped. At each station we sampled using paired 20 and 60 cm Bongo frames (150 and 500...

  14. Effect of dietary galacto-oligosaccharides on azoxymethane-induced aberrant crypt foci and colorectal cancer in Fischer 344 rats

    NARCIS (Netherlands)

    Wijnands, M.V.W.; Schoterman, H.C.; Bruijntjes, J.P.; Hollanders, V.M.H.; Woutersen, R.A.

    2001-01-01

    The aim of the present study was to investigate the effects of galacto-oligosaccharides (GOS, Elix'or) on the development of aberrant crypt foci (ACF) and colorectal tumours in rats treated with azoxymethane (AOM). Two groups of 102 male Fischer 344 rats were injected twice with AOM to induce colore

  15. Hexanucleotide repeats in ALS/FTD form length-dependent RNA foci, sequester RNA binding proteins, and are neurotoxic.

    Science.gov (United States)

    Lee, Youn-Bok; Chen, Han-Jou; Peres, João N; Gomez-Deza, Jorge; Attig, Jan; Stalekar, Maja; Troakes, Claire; Nishimura, Agnes L; Scotter, Emma L; Vance, Caroline; Adachi, Yoshitsugu; Sardone, Valentina; Miller, Jack W; Smith, Bradley N; Gallo, Jean-Marc; Ule, Jernej; Hirth, Frank; Rogelj, Boris; Houart, Corinne; Shaw, Christopher E

    2013-12-12

    The GGGGCC (G4C2) intronic repeat expansion within C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Intranuclear neuronal RNA foci have been observed in ALS and FTD tissues, suggesting that G4C2 RNA may be toxic. Here, we demonstrate that the expression of 38× and 72× G4C2 repeats form intranuclear RNA foci that initiate apoptotic cell death in neuronal cell lines and zebrafish embryos. The foci colocalize with a subset of RNA binding proteins, including SF2, SC35, and hnRNP-H in transfected cells. Only hnRNP-H binds directly to G4C2 repeats following RNA immunoprecipitation, and only hnRNP-H colocalizes with 70% of G4C2 RNA foci detected in C9ORF72 mutant ALS and FTD brain tissues. We show that expanded G4C2 repeats are potently neurotoxic and bind hnRNP-H and other RNA binding proteins. We propose that RNA toxicity and protein sequestration may disrupt RNA processing and contribute to neurodegeneration.

  16. The Role of Potential Agents in Making Spatial Perspective Taking Social

    Directory of Open Access Journals (Sweden)

    Amy M Clements-Stephens

    2013-09-01

    Full Text Available A striking relationship between visual spatial perspective taking (VSPT and social skills has been demonstrated for perspective-taking tasks in which the target of the imagined or inferred perspective is a potential agent, suggesting that the presence of a potential agent may create a social context for the seemingly spatial task of imagining a novel visual perspective. In a series of studies, we set out to investigate how and when a target might be viewed as sufficiently agent-like to incur a social influence on VSPT performance. By varying the perceptual and conceptual features that defined the targets as potential agents, we find that even something as simple as suggesting animacy for a simple wooden block may be sufficient. More critically, we found that experience with one potential agent influenced the performance with subsequent targets, either by inducing or eliminating the influence of social skills on VSPT performance. These carryover effects suggest that the relationship between social skills and VSPT performance is mediated by a complex relationship that includes the task, the target, and the context in which that target is perceived. These findings highlight potential problems that arise when identifying a task as belonging exclusively to a single cognitive domain and stress instead the highly interactive nature of cognitive domains and their susceptibility to cross-domain individual differences.

  17. The role of litter beetles as potential reservoir for Salmonella enterica and thermophilic Campylobacter spp. between broiler flocks

    DEFF Research Database (Denmark)

    Skov, M.N.; Spencer, A.G.; Hald, Birthe

    2004-01-01

    We evaluated the role of beetles infesting broiler chicken rearing facilities as potential reservoirs for Salmonella enterica infections between successive broiler flocks. In addition, their role as potential reservoirs for thermophilic Campylobacter spp. was also investigated. Fourteen broiler...... houses located at 11 different farms were included in the study. The houses were nonrandomly selected on the basis of their salmonella status; nine were persistently contaminated with salmonella whereas five were salmonella negative. For each broiler house, two consecutive broiler flocks (i.e., 28...... broiler flocks in all) as well as beetles collected during both rotations of production and in the empty period (after cleaning and disinfection) between these flocks were monitored for the presence of salmonella. Examinations for the presence of campylobacter in the same sample materials were also...

  18. Efficacy of praziquantel and reinfection patterns in single and mixed infection foci for intestinal and urogenital schistosomiasis in Cameroon.

    Science.gov (United States)

    Tchuem Tchuenté, Louis-Albert; Momo, Sabine C; Stothard, J Russell; Rollinson, David

    2013-11-01

    The regular administration of the anthelminthic drug praziquantel (PZQ) to school-aged children (and other high-risk groups) is the cornerstone of schistosomiasis control. Whilst the performance of PZQ against single schistosome species infections is well-known, performance against mixed species infections is less so, as are patterns of re-infection following treatment. To address this, a study using a double treatment with PZQ, administered at 40 mg/kg spaced by 3 weeks, took place in two mixed intestinal-urogenital schistosomiasis foci in northern Cameroon (Bessoum and Ouro-Doukoudje) and in one single intestinal schistosomiasis infection focus (Makenene). A total of just under 1000 children were examined and the Schistosoma-infected children were re-examined at several parasitological follow-ups over a 1-year period posttreatment. Overall cure rates against Schistosoma spp. in the three settings were good, 83.3% (95% confidence interval (CI)=77.9-87.7%) in Bessoum, 89.0% (95% CI=79.1-94.6%) in Ouro Doukoudje, and 95.3% (95% CI=89.5-98.0%) in Makenene. Interestingly, no case of mixed schistosome infection was found after treatment. Cure rates for S. mansoni varied from 99.5% to 100%, while that for S. haematobium were considerably lower, varying from 82.7% to 88.0%. Across transmission settings, patterns of re-infection for each schistosome species were different such that generalizations across foci were difficult. For example, at the 6-month follow-up, re-infection rates were higher for S. haematobium than for S. mansoni with re-infection rates for S. haematobium varying from 9.5% to 66.7%, while for S. mansoni, lower rates were observed, ranging between nil and 24.5%. At the 12-month follow-up, re-infection rates varied from 9.1% to 66.7% for S. haematobium and from nil to 27.6% for S. mansoni. Alongside these parasitological studies, concurrent malacological surveys took place to monitor the presence of intermediate host snails of schistosomiasis. In the two

  19. [Bacterial efflux pumps - their role in antibiotic resistance and potential inhibitors].

    Science.gov (United States)

    Hricová, Kristýna; Kolář, Milan

    2014-12-01

    Efflux pumps capable of actively draining antibiotic agents from bacterial cells may be considered one of potential mechanisms of the development of antimicrobial resistance. The most important group of efflux pumps capable of removing several types of antibiotics include RND (resistance - nodulation - division) pumps. These are three proteins that cross the bacterial cell wall, allowing direct expulsion of the agent out from the bacterial cell. The most investigated efflux pumps are the AcrAB-TolC system in Escherichia coli and the MexAB-OprM system in Pseudomonas aeruginosa. Moreover, efflux pumps are able to export other than antibacterial agents such as disinfectants, thus decreasing their effectiveness. One potential approach to inactivation of an efflux pump is to use the so-called efflux pump inhibitors (EPIs). Potential inhibitors tested in vitro involve, for example, phenylalanyl-arginyl-b-naphthylamide (PAbN), carbonyl cyanide m-chlorophenylhydrazone (CCCP) or agents of the phenothiazine class.

  20. Refractory episodic vertigo: role of intratympanic gentamicin and vestibular evoked myogenic potentials.

    Science.gov (United States)

    Celis-Aguilar, Erika; Hinojosa-González, Ramon; Vales-Hidalgo, Olivia; Coutinho-Toledo, Heloisa

    Even today, the treatment of intractable vertigo remains a challenge. Vestibular ablation with intratympanic gentamicin stands as a good alternative in the management of refractory vertigo patients. To control intractable vertigo through complete saccular and horizontal canal vestibular ablation with intratympanic gentamicin treatment. Patients with refractory episodic vertigo were included. The inclusion criteria were: unilateral ear disease, moderate to profound sensorineural hearing loss, and failure to other treatments. Included patients underwent 0.5-0.8mL of gentamicin intratympanic application at a 30mg/mL concentration. Vestibular ablation was confirmed by the absence of response on cervical vestibular evoked myogenic potentials and no response on caloric tests. Audiometry, electronystagmography with iced water, and vestibular evoked myogenic potentials were performed in all patients. Ten patients were included; nine patients with Meniere's disease and one patient with (late onset) delayed hydrops. Nine patients showed an absent response on vestibular evoked myogenic potentials and no response on caloric tests. The only patient with low amplitude on cervical vestibular evoked myogenic potentials had vertigo recurrence. Vertigo control was achieved in 90% of the patients. One patient developed hearing loss >30dB. Cervical vestibular evoked myogenic potentials confirmed vestibular ablation in patients treated with intratympanic gentamicin. High-grade vertigo control was due to complete saccular and horizontal canal ablation (no response to iced water in electronystagmography and no response on cervical vestibular evoked myogenic potentials). Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  1. Potential role of marine algae on female health, beauty, and longevity.

    Science.gov (United States)

    Kim, Se-Kwon; Pangestuti, Ratih

    2011-01-01

    Marine environment has been known as a rich source of chemical structures with numerous health benefit effects. Among marine organisms, marine algae have been identified as an underexploited plant resource although they have long been recognized as valuable sources of structurally diverse bioactive compounds. Presently, several lines of studies have provided insight into biological activities of marine algae in promoting female health, beauty, and longevity. Hence, marine algae have a great potential to be used as a part of pharmaceuticals, nutraceuticals, and functional foods. This contribution presents an overview of marine algal potential effect in promoting female health, beauty, and longevity. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Potential role of kinetic Alfvén waves and whistler waves in solar wind plasmas

    Science.gov (United States)

    Nandal, P.; Yadav, N.; Sharma, R. P.; Goldstein, M. L.

    2016-07-01

    Spacecraft observations indicate the signatures of highly oblique kinetic Alfvén waves (KAWs) and whistler waves in the solar wind plasma. In the present work, we explore the possible role of KAWs and whistler waves in the observed solar wind magnetic turbulent spectrum. The nonlinear spatial evolution of KAW is studied including the effects of the ponderomotive force which results in intense localized structures due to the background density modification. Weak quasi-transverse whistler wave propagating through these localized structures also gets localized in the form of small-scale localized structures. We present numerically calculated magnetic power spectra for both KAW as well as for whistler wave. Our obtained results demonstrate the important role that KAWs and whistler waves play in the energy cascading from larger to smaller scales. The relevance of these results to recent spacecraft observations is also pointed out.

  3. The apelinergic system: the role played in human physiology and pathology and potential therapeutic applications.

    Science.gov (United States)

    Ladeiras-Lopes, Ricardo; Ferreira-Martins, João; Leite-Moreira, Adelino F

    2008-05-01

    Apelin is a recently discovered peptide, identified as an endogenous ligand of receptor APJ. Apelin and receptor APJ are expressed in a wide variety of tissues including heart, brain, kidneys and lungs. Their interaction may have relevant pathophysiologic effects in those tissues. In fact, the last decade has been rich in illustrating the possible roles played by apelin in human physiology, namely as a regulating peptide of cardiovascular, hypothalamus-hypophysis, gastrointestinal, and immune systems. The possible involvement of apelin in the pathogenesis of high prevalence conditions and comorbidities - such as hypertension, heart failure, and Diabetes Mellitus Type 2 (T2DM) - rank it as a likely therapeutic target to be investigated in the future. The present paper is an overview of apelin physiologic effects and presents the possible role played by this peptide in the pathogenesis of a number of conditions as well as the therapeutic implications that might, therefore, be investigated.

  4. Expression and Characterization of Purinergic Receptors in Rat Middle Meningeal Artery–Potential Role in Migraine

    DEFF Research Database (Denmark)

    Haanes, Kristian Agmund; Edvinsson, Lars

    2014-01-01

    The dura mater and its vasculature have for decades been central in the hypothesis of migraine and headache pathophysiology. Although recent studies have questioned the role of the vasculature as the primary cause, dural vessel physiology is still relevant in understanding the complex pathophysio......The dura mater and its vasculature have for decades been central in the hypothesis of migraine and headache pathophysiology. Although recent studies have questioned the role of the vasculature as the primary cause, dural vessel physiology is still relevant in understanding the complex...... be inhibited by SCH58261 (A2A receptor antagonist) and caffeine (adenosine receptor antagonist). This gives one putative molecular mechanism for the effect of caffeine, often used as an adjuvant remedy of cranial pain. Semi-quantitative RT-PCR expression data for the receptors correlate well...

  5. The prebiotic synthesis of modified purines and their potential role in the RNA world

    Science.gov (United States)

    Levy, M.; Miller, S. L.; Bada, J. L. (Principal Investigator)

    1999-01-01

    Modified purines are found in all organisms in the tRNA, rRNA, and even DNA, raising the possibility of an early role for these compounds in the evolution of life. These include N6-methyladenine, 1-methyladenine, N6,N6-dimethyladenine, 1-methylhypoxanthine, 1-methylguanine, and N2-methylguanine. We find that these bases as well as a number of nonbiological modified purines can be synthesized from adenine and guanine by the simple reaction of an amine or an amino group with adenine and guanine under the concentrated conditions of the drying-lagoon or drying-beach model of prebiotic synthesis with yields as high as 50%. These compounds are therefore as prebiotic as adenine and guanine and could have played an important role in the RNA world by providing additional functional groups in ribozymes, especially for the construction of hydrophobic binding pockets.

  6. Potential role of bacteria packaging by protozoa in the persistence and transmission of pathogenic bacteria

    Directory of Open Access Journals (Sweden)

    Alix M Denoncourt

    2014-05-01

    Full Text Available Many pathogenic bacteria live in close association with protozoa. These unicellular eukaryotic microorganisms are ubiquitous in various environments. A number of protozoa such as amoebae and ciliates ingest pathogenic bacteria, package them usually in membrane structures, and then release them into the environment. Packaged bacteria are more resistant to various stresses and are more apt to survive than free bacteria. New evidence indicates that protozoa and not bacteria control the packaging process. It is possible that packaging is more common than suspected and may play a major role in the persistence and transmission of pathogenic bacteria. To confirm the role of packaging in the propagation of infections, it is vital that the molecular mechanisms governing the packaging of bacteria by protozoa be identified as well as elements related to the ecology of this process in order to determine whether packaging acts as a Trojan Horse.

  7. Potential role of bacteria packaging by protozoa in the persistence and transmission of pathogenic bacteria.

    Science.gov (United States)

    Denoncourt, Alix M; Paquet, Valérie E; Charette, Steve J

    2014-01-01

    Many pathogenic bacteria live in close association with protozoa. These unicellular eukaryotic microorganisms are ubiquitous in various environments. A number of protozoa such as amoebae and ciliates ingest pathogenic bacteria, package them usually in membrane structures, and then release them into the environment. Packaged bacteria are more resistant to various stresses and are more apt to survive than free bacteria. New evidence indicates that protozoa and not bacteria control the packaging process. It is possible that packaging is more common than suspected and may play a major role in the persistence and transmission of pathogenic bacteria. To confirm the role of packaging in the propagation of infections, it is vital that the molecular mechanisms governing the packaging of bacteria by protozoa be identified as well as elements related to the ecology of this process in order to determine whether packaging acts as a Trojan Horse.

  8. The potential role of sea spray droplets in facilitating air-sea gas transfer

    Science.gov (United States)

    Andreas, E. L.; Vlahos, P.; Monahan, E. C.

    2016-05-01

    For over 30 years, air-sea interaction specialists have been evaluating and parameterizing the role of whitecap bubbles in air-sea gas exchange. To our knowledge, no one, however, has studied the mirror image process of whether sea spray droplets can facilitate air-sea gas exchange. We are therefore using theory, data analysis, and numerical modeling to quantify the role of spray on air-sea gas transfer. In this, our first formal work on this subject, we seek the rate-limiting step in spray-mediated gas transfer by evaluating the three time scales that govern the exchange: τ air , which quantifies the rate of transfer between the atmospheric gas reservoir and the surface of the droplet; τ int , which quantifies the exchange rate across the air-droplet interface; and τ aq , which quantifies gas mixing within the aqueous solution droplet.

  9. Silicon: A Review of Its Potential Role in the Prevention and Treatment of Postmenopausal Osteoporosis

    Directory of Open Access Journals (Sweden)

    Charles T. Price

    2013-01-01

    Full Text Available Physicians are aware of the benefits of calcium and vitamin D supplementation. However, additional nutritional components may also be important for bone health. There is a growing body of the scientific literature which recognizes that silicon plays an essential role in bone formation and maintenance. Silicon improves bone matrix quality and facilitates bone mineralization. Increased intake of bioavailable silicon has been associated with increased bone mineral density. Silicon supplementation in animals and humans has been shown to increase bone mineral density and improve bone strength. Dietary sources of bioavailable silicon include whole grains, cereals, beer, and some vegetables such as green beans. Silicon in the form of silica, or silicon dioxide (SiO2, is a common food additive but has limited intestinal absorption. More attention to this important mineral by the academic community may lead to improved nutrition, dietary supplements, and better understanding of the role of silicon in the management of postmenopausal osteoporosis.

  10. Cytokines: Their Role in Stroke and Potential Use as Biomarkers and Therapeutic Targets

    OpenAIRE

    Doll, Danielle N.; Barr, Taura L.; Simpkins, James W.

    2014-01-01

    Inflammatory mechanisms both in the periphery and in the CNS are important in the pathophysiologic processes occurring after the onset of ischemic stroke (IS). Cytokines are key players in the inflammatory mechanism and contribute to the progression of ischemic damage. This literature review focuses on the effects of inflammation on ischemic stroke, and the role pro-inflammatory and anti-inflammatory cytokines play on deleterious or beneficial stroke outcome. The discovery of biomarkers and n...

  11. Wnt/Fz signaling and the cytoskeleton: potential roles in tumorigenesis

    Institute of Scientific and Technical Information of China (English)

    Shih-Lei Lai; Andy J Chien; Randall T Moon

    2009-01-01

    Wnt/β-catenin regulates cellular functions related to tumor initiation and progression, cell proliferation, differ-entiation, survival, and adhesion. β-Catenin-independent Wnt pathways have been proposed to regulate cell polarity and migration, including metastasis, In this review, we discuss the possible roles of both β-catenin-dependent and -independent signaling pathways in tumor progression, with an emphasis on their regulation of Rho-family GTPases, cytoskeletal remodeling, and relationships with cell-cell adhesion and cilia/ciliogenesis.

  12. The potential role of migratory birds in the transmission of zoonoses

    OpenAIRE

    2008-01-01

    The instinct for survival leads migratory birds to exploit seasonal opportunities for breeding habitats and food supplies. Consequently, they travel across national and international borders. These birds are distinguished in local migrants, short-distance, long-distance and vagrant and nomadic migrants. They can transfer micro-organisms across the globe and play a significant role in the ecology and circulation of pathogenic organisms. They are implicated in the transmission of zoonoses as bi...

  13. Obesity Epidemics: The Potential Role of Retailing Sector in Promoting Fruit and Vegetable Consumption

    OpenAIRE

    2012-01-01

    After a deep review of the main economic studies and applications about the emerging problem of obesity, this paper focuses on a particular aspect of the issue: the improvement of FRUIT AND VEGETABLE purchasing in retailing sector. First of all it has been analyzed the actual presence of strategies aimed at improving FRUIT AND VEGETABLE consumption in the main retailing companies operating in Italy. Then the study investigates the role of price in consumers’ purchasing choices. High price ela...

  14. Potential etiologic role of brushite in the formation of calcium (renal) stones

    Science.gov (United States)

    Pak, Charles Y. C.

    1981-05-01

    Brushite may play an important regulatory role in the formation of calcium -containing renal stones. The urinary environment from patients with hypercalciuric nephrolithiasis is typically supersaturated and shows an increased propensity for the spontaneous nucleation of brushite. Brushite has been identified in "stone-forming" urine and in stones. This crystalline phase may undergo phase transformation to hydroxyapatite or cause heterogeneous nucleation or epitaxial growth of calcium oxalate. Thus, brushite may also participate in the formation of stones of hydroxypatite or calcium oxalate.

  15. The Potential Protective Role of Caveolin-1 in Intestinal Inflammation in TNBS-Induced Murine Colitis

    Science.gov (United States)

    Ma, Yanbing; Qing, Gefei; Bernstein, Charles N.; Warrington, Richard J.; Peng, Zhikang

    2015-01-01

    Background Caveolin-1 (Cav-1) is a multifunctional scaffolding protein serving as a platform for the cell’s signal-transduction and playing an important role in inflammation. However, its role in inflammatory bowel disease is not clear. A recent study showed that Cav-1 is increased and mediates angiogenesis in dextran sodium sulphate-induced colitis, which are contradictory to our pilot findings in 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. In the present study, we further clarified the role of Cav-1 in TNBS-induced colitis. Methods In BALB/c mice, acute colitis was induced by intra-rectal administration of one dose TNBS, while chronic colitis was induced by administration of TNBS once a week for 7 weeks. To assess the effects of complete loss of Cav-1, Cav-1 knockout (Cav-1−/−) and control wild-type C57 mice received one TNBS administration. Body weight and clinical scores were monitored. Colon Cav-1 and pro-inflammatory cytokine levels were quantified through ELISAs. Inflammation was evaluated through histological analysis. Results Colon Cav-1 levels were significantly decreased in TNBS-induced colitis mice when compared to normal mice and also inversely correlated with colon inflammation scores and proinflammatory cytokine levels (IL-17, IFN-γ and TNF) significantly. Furthermore, after administration of TNBS, Cav-1−/− mice showed significantly increased clinical and colon inflammatory scores and body weight loss when compared with control mice. Conclusions and Significance Cav-1 may play a protective role in the development of TNBS-induced colitis. Our findings raise an important issue in the evaluation of specific molecules in animal models that different models may exhibit opposite results because of the different mechanisms involved. PMID:25756273

  16. The Potential Role of Solvation in Antibody Recognition of the Lewis Y Antigen

    OpenAIRE<