Search results for: saccadic suppression
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 276

Search results for: saccadic suppression

66 Gene Expression Signature-Based Chemical Genomic to Identify Potential Therapeutic Compounds for Colorectal Cancer

Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

Abstract:

There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

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65 Tomato Endophytes Trichoderma asperellum AAUTLF and Stenotrophomonas maltophilia D1B Exhibits Plant Growth-Promotion and Fusarium Wilt Suppression

Authors: Bandana Saikia, Ashok Bhattacharyya

Abstract:

Endophytic microbes and their metabolites positively impact overall plant health, which may have a potential implication in agriculture. In the present study, 177 bacterial endophytes and 57 fungal endophytes were isolated, with the highest recovery rate from tomato roots. A maximum of 112 endophytes were isolated during monsoon, followed by 64 isolates and 58 isolates isolated during pre-monsoon and post-monsoon periods, respectively, indicating the rich diversity in bacterial and fungal endophytes of tomato crops from different locations of Assam, India. Further, the endophytes were evaluated for their antagonistic potential against Fusarium oxysporum f. sp. lycopersici. Fungal endophytic isolate AAUTLF (Endophytic Fungi of Tomato Leaf from Assam Agricultural University, Assam, India area) and bacterial endophyte D1B (Endophytic bacteria of tomato from Dhemiji, India district) showed the highest antifungal activity against the pathogen both in vitro and in vivo. Based on 5.8 rDNA sequence analysis of fungal and 16S rDNA sequence of bacteria endophytes, the most effective fungal and bacterial isolates against FOL were identified as Trichoderma asperellum AAUTLF and Stenotrophomonas maltophilia D1B, respectively. The isolates showed an antagonistic effect against Fusarium oxysporum f.sp. lycopersici in-vitro and reduced the disease index of Fusarium wilt in tomatoes by 64.4% under pot conditions. Trichoderma asperellum AAUTLF produced an antifungal compound viz., 6-pentyl-2H-pyran-2-one, which also possesses growth-promoting characteristics. The bacteria Stenotrophomonas maltophilia D1B produced antifungal compounds, including benzothiazole, oleic acid, phenylacetic acid, and 3-(Hydroxy-phenyl-methyl)-2,3-dimethyl-octan-4-one. This would be of high importance for the source of antagonistic strains and biocontrol of tomato Fusarium wilt, as well as other plant fungal diseases.

Keywords: root endophytes, Stemotrophomonas, Trichoderma, benzothiazole, 6-pentyl-2H-pyran-2-one

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64 Synthesis of TiO₂/Graphene Nanocomposites with Excellent Visible-Light Photocatalytic Activity Based on Chemical Exfoliation Method

Authors: Nhan N. T. Ton, Anh T. N. Dao, Kouichirou Katou, Toshiaki Taniike

Abstract:

Facile electron-hole recombination and the broad band gap are two major drawbacks of titanium dioxide (TiO₂) when applied in visible-light photocatalysis. Hybridization of TiO₂ with graphene is a promising strategy to lessen these pitfalls. Recently, there have been many reports on the synthesis of TiO₂/graphene nanocomposites, in most of which graphene oxide (GO) was used as a starting material. However, the reduction of GO introduced a large number of defects on the graphene framework. In addition, the sensitivity of titanium alkoxide to water (GO usually contains) significantly obstructs the uniform and controlled growth of TiO₂ on graphene. Here, we demonstrate a novel technique to synthesize TiO₂/graphene nanocomposites without the use of GO. Graphene dispersion was obtained through the chemical exfoliation of graphite in titanium tetra-n-butoxide with the aid of ultrasonication. The dispersion was directly used for the sol-gel reaction in the presence of different catalysts. A TiO₂/reduced graphene oxide (TiO₂/rGO) nanocomposite, which was prepared by a solvothermal method from GO, and the commercial TiO₂-P25 were used as references. It was found that titanium alkoxide afforded the graphene dispersion of a high quality in terms of a trace amount of defects and a few layers of dispersed graphene. Moreover, the sol-gel reaction from this dispersion led to TiO₂/graphene nanocomposites featured with promising characteristics for visible-light photocatalysts including: (I) the formation of a TiO₂ nano layer (thickness ranging from 1 nm to 5 nm) that uniformly and thinly covered graphene sheets, (II) a trace amount of defects on the graphene framework (low ID/IG ratio: 0.21), (III) a significant extension of the absorption edge into the visible light region (a remarkable extension of the absorption edge to 578 nm beside the usual edge at 360 nm), and (IV) a dramatic suppression of electron-hole recombination (the lowest photoluminescence intensity compared to reference samples). These advantages were successfully demonstrated in the photocatalytic decomposition of methylene blue under visible light irradiation. The TiO₂/graphene nanocomposites exhibited 15 and 5 times higher activity than TiO₂-P25 and the TiO₂/rGO nanocomposite, respectively.

Keywords: chemical exfoliation, photocatalyst, TiO₂/graphene, sol-gel reaction

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63 Exploring the Role of Immune-Modulators in Pathogen Recognition Receptor NOD2 Mediated Protection against Visceral Leishmaniasis

Authors: Junaid Jibran Jawed, Prasanta Saini, Subrata Majumdar

Abstract:

Background: Leishmania donovani infection causes severe host immune-suppression through the modulation of pathogen recognition receptors. Apart from TLRs (Toll Like Receptor), recent studies focus on the important contribution of NLR (NOD-Like Receptor) family member NOD1 and NOD2 as these receptors are capable of triggering host innate immunity. The aim of this study was to decipher the role of NOD1/NOD2 receptors during experimental visceral leishmaniasis (VL) and the important link between host failure and parasite evasion strategy. Method: The status of NOD1 and NOD2 receptors were analysed in uninfected and infected cells through western blotting and RT-PCR. The active contributions of these receptors in reducing parasite burden were confirmed by siRNA mediated silencing, and over-expression studies and the parasite numbers were calculated through microscopic examination of the Giemsa-stained slides. In-vivo studies were done by using non-toxic dose of Mw (Mycobacterium indicus pranii), Ara-LAM(Arabinoasylated lipoarabinomannan) along with MDP (Muramyl dipeptide) administration. Result: Leishmania donovani infection of the macrophages reduced the expression of NOD2 receptors whereas NOD1 remain unaffected. MDP, a NOD2-ligand, treatment during over-expression of NOD2, reduced the parasite burden effectively which was associated with increased pro-inflammatory cytokine generation and NO production. In experimental mouse model, Ara-LAM treatment increased the expression of NOD2 and in combination with MDP it showed active therapeutic potential against VL and found to be more effective than Mw which was already reported to be involved in NOD2 modulation. Conclusion: This work explores the essential contribution of NOD2 during experimental VL and mechanistic understanding of Ara-LAM + MDP combination therapy to work against this disease and highlighted NOD2 as an essential therapeutic target.

Keywords: Ara-LAM (Arabinoacylated Lipoarabinomannan), NOD2 (nucleotide binding oligomerization receptor 2), MDP (muramyl di peptide), visceral Leishmaniasis

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62 Chemotrophic Signal Exchange between the Host Plant Helianthemum sessiliflorum and Terfezia boudieri

Authors: S. Ben-Shabat, T. Turgeman, O. Leubinski, N. Roth-Bejerano, V. Kagan-Zur, Y. Sitrit

Abstract:

The ectomycorrhizal (ECM) desert truffle Terfezia boudieri produces edible fruit bodies and forms symbiosis with its host plant Helianthemum sessiliflorum (Cistaceae) in the Negev desert of Israel. The symbiosis is vital for both partners' survival under desert conditions. Under desert habitat conditions, ECMs must form symbiosis before entering the dry season. To secure a successful encounter, in the course of evolution, both partners have responded by evolving special signals exchange that facilitates recognition. Members of the Cistaceae family serve as host plants for many important truffles. Conceivably, during evolution a common molecule present in Cistaceae plants was recruited to facilitate successful encounter with ectomycorrhizas. Arbuscular vesicular fungi (AM) are promiscuous in host preferences, in contrast, ECM fungi show specificity to host plants. Accordingly, we hypothesize that H. sessiliflorum secretes a chemotrophic-signaling, which is common to plants hosting ECM fungi belonging to the Pezizales. However, thus far no signaling molecules have been identified in ECM fungi. We developed a bioassay for chemotrophic activity. Fractionation of root exudates revealed a substance with chemotrophic activity and molecular mass of 534. Following the above concept, screening the transcriptome of Terfezia, grown under chemoattraction, discovered genes showing high homology to G proteins-coupled receptors of plant pathogens involved in positive chemotaxis and chemotaxis suppression. This study aimed to identify the active molecule using analytical methods (LC-MS, NMR etc.). This should contribute to our understanding of how ECM fungi communicate with their hosts in the rhizosphere. In line with the ability of Terfezia to form also endomycorrhizal symbiosis like AM fungi, analysis of the mechanisms may likewise be applicable to AM fungi. Developing methods to manipulate fungal growth by the chemoattractant can open new ways to improve inoculation of plants.

Keywords: chemotrophic signal, Helianthemum sessiliflorum, Terfezia boudieri, ECM

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61 ICAM1 Expression is Enhanced by TNFa through Histone Methylation in Human Brain Microvessel Cells

Authors: Ji-Young Choi, Jungjin Kim, Sang-Sun Yun, Sangmee Ahn Jo

Abstract:

Intracellular adhesion molecule1 (ICAM1) is a mediator of inflammation and involved in adhesion and transmigration of leukocytes to endothelial cells, resulting in enhancement of brain inflammation. We hypothesized that increase of ICAM1 expression in endothelial cells is an early step in the pathogenesis of brain diseases such as Alzheimer’s disease. Here, we report that ICAM1 expression is regulated by pro-inflammatory cytokine TNFa in human microvascular endothelial cell (HBMVEC). TNFa significantly increased ICAM1 mRNA and protein levels at the concentrations showing no cell toxicity. This increase was also shown in micro vessels of mouse brain 24 hours after treatment with TNFa (8 mg/kg, i.v). We then investigated the epigenetic mechanism involved in the induction of ICAM1 expression. Chromatin immunoprecipitation assay revealed that TNFa reduced methylation of histone3K9 (H3K9-2me) and histone3K27 (H3K27-3me), well-known modification as gene suppression, with in the ICAM1 promoter region. However, acetylation of H3K9 and H3K14, well-known modification as gene activation, was not changed by TNFa. Treatment of BIX01294, a specific inhibitor of histone methyltransferase G9a responsible for H3K9-2me, dramatically increased in ICAM1 mRNA and protein levels and overexpression of G9a gene suppressed TNFa-induced ICAM1 expression. In contrast, GSK126, an inhibitor of histone methyltransferase EZH2 responsible for H3K27-3me and valproic acid, an inhibitor of histone deacetylase (HDAC) did not affect ICAM1 expression. These results suggested that histone3 methylation is involved in ICAM1 repression. Moreover, TNFa or BIX01294-induced ICAM induction resulted in both enhancements in adhesion and transmigration of leukocyte on endothelial cell. This study demonstrates that TNFa upregulates ICAM1 expression through H3K9-2me and H3K27-3me within the ICAM1 promoter region, in which G9a is likely to play a pivotal role in ICAM1 transcription. Our study provides a novel mechanism for ICAM1 transcription regulation in HBMVEC.

Keywords: ICAM1, TNFa, HBMVEC, H3K9-2me

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60 Catamenial Pneumothorax: Report of Two Cases and Review of the Local Literature

Authors: Angeli Marie P. Lagman, Nephtali M. Gorgonio

Abstract:

Catamenial pneumothorax is defined as a recurrent accumulation of air in the pleural cavity, which occurs in the period of 72 hours before or after menses. In a menstruating woman presenting with the difficulty of breathing and chest pain with concomitant radiographic evidence of pneumothorax, a diagnosis of catamenial pneumothorax should be entertained. Two cases of catamenial pneumothorax were reported in our local literature. This report added two more cases. The first case is 45 years old G1P1, while the second case is 46 years old G2P2. These two patients had a history of pelvic endometriosis in the past. All other signs and symptoms were similar to the previously reported cases. All patients presented with difficulty of breathing associated with chest pain. Imaging studies showed right-sided pneumothorax in all patients. Intraoperatively, subpleural bleb, diaphragmatic fenestrations, and endometriotic implants were found. Three patients underwent video-assisted thoracosurgery (VATS), while one patient underwent open thoracotomy with pleurodesis. Histopathology revealed endometriosis in only two patients. All patients received postoperative hormonal therapy, and there were no recurrences noted in all patients. Endometriosis-related catamenial pneumothorax is a rare condition that needs early recognition of the symptoms. Several theories may be involved to explain the pathogenesis of catamenial pneumothorax. Two cases show a strong significant association between a history of pelvic endometriosis and the development of catamenial pneumothorax, while one case can be explained by the hormonal theory. The difficulty of breathing and chest pain in relation to menses may prompt early diagnosis. One case has shown that pneumothorax may occur even after menstruation. A biopsy of the endometrial implants may not always show endometrial glands and stroma, nor will immunostaining, which will not always show estrogen and progesterone receptors. Video-assisted thoracoscopic surgery is the gold standard in the diagnosis and treatment of catamenial pneumothorax. Postoperative hormonal suppression will further reduce the disease recurrence and facilitate the effectiveness of the surgical treatment.

Keywords: catamenial pneumothorax, endometriosis, menstruation, video assisted thoracosurgery

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59 Overcoming Barriers to Improve HIV Education and Public Health Outcomes in the Democratic Republic of Congo

Authors: Danielle A. Walker, Kyle L. Johnson, Tara B. Thomas, Sandor Dorgo, Jacen S. Moore

Abstract:

Approximately 37 million people worldwide are infected with the Human Immunodeficiency Virus (HIV), with the majority located in sub-Saharan Africa. The relationship existing between HIV incidence and socioeconomic inequity confirms the critical need for programs promoting HIV education, prevention and treatment access. This literature review analyzed 36 sources with a specific focus on the Democratic Republic of Congo, whose critically low socioeconomic status and education rate have resulted in a drastically high HIV rates. Relationships between HIV testing and treatment and barriers to care were explored. Cultural and religious considerations were found to be vital when creating and implementing HIV education and testing programs. Partnerships encouraging active support from community-based spiritual leaders to implement HIV educational programs were also key mechanisms to reach communities and individuals. Gender roles were highlighted as a key component for implementation of effective community trust-building and successful HIV education programs. The efficacy of added support by hospitals and clinics in rural areas to facilitate access to HIV testing and care for people living with HIV/AIDS (PLWHA) was discussed. This review highlighted the need for healthcare providers to provide a network of continued education for PLWHA in clinical settings during disclosure and throughout the course of treatment to increase retention in care and promote medication adherence for viral load suppression. Implementation of culturally sensitive models that rely on community familiarity with HIV educators such as ‘train-the-trainer’ were also proposed as efficacious tools for educating rural communities about HIV. Further research is needed to promote community partnerships for HIV education, understand the cultural context of gender roles as barriers to care, and empower local health care providers to be successful within the HIV Continuum of Care.

Keywords: cultural sensitivity, Democratic Republic of the Congo, education, HIV

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58 Characterization of Fungal Endophytes in Leaves, Stems and Roots of African Yam Bean (Sphenostylis sternocarpa Hochst ex. A. Rich Harms)

Authors: Iyabode A. Kehinde, Joshua O. Oyekanmi, Jumoke T. Abimbola, Olajumoke E. Ayanda

Abstract:

African yam bean (AYB), (Sphenostylis stenocarpa) is a leguminous crop that provides nutritionally rich seeds, tubers and leaves for human consumption. AYB potentials as an important food security crop is yet to be realized and thus classified as underutilized crop. Underutilization of the crop has been partly associated with scarce information on the incidence and characterization of fungal endophytes infecting vascular parts of AYB. Accurate and robust detection of these endophytic fungi is essential for diagnosis, modeling, surveillance and protection of germplasm (seed) health. This work aimed at isolating and identifying fungal endophytes associated with leaves, stems and roots of AYB in Ogun State, Nigeria. This study investigated both cultural and molecular properties of endophytic fungi in AYB for its characterization and diversity. Fungal endophytes were isolated and culturally identified. DNA extraction, PCR amplification using ITS primers and analyses of nucleotide sequences of ribosomal DNA fragments were conducted on selected isolates. BLAST analysis was conducted on consensus nucleotide sequences of 28 out of 30 isolates and results showed similar homology with genera of Rhizopus, Cunninghamella, Fusarium, Aspergillus, Penicillium, Alternaria, Diaporthe, Nigrospora, Purpureocillium, Corynespora, Magnaporthe, Macrophomina, Curvularia, Acrocalymma, Talaromyces and Simplicillium. Slight similarity was found with endophytes associated with soybean. Phylogenetic analysis by maximum likelihood method showed high diversity among the general. These organisms have high economic importance in crop improvement. For an instance, Purpureocillium lilacinum showed high potential in control of root rot caused by nematodes in tomatoes. Though some can be pathogens, but many of the fungal endophytes have beneficial attributes to plant in host health, uptake of nutrients, disease suppression, and host immunity.

Keywords: molecular characterization, African Yam Bean, fungal endophyte, plant parts

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57 Canthin-6-One Alkaloid Inhibits NF-κB and AP-1 Activity: An Inhibitory Action At Transcriptional Level

Authors: Fadia Gafri, Kathryn Mckintosh, Louise Young, Alan Harvey, Simon Mackay, Andrew Paul, Robin Plevin

Abstract:

Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor found originally to play a key role in regulating inflammation. However considerable evidence links this pathway to the suppression of apoptosis, cellular transformation, proliferation and invasion (Aggarwal et al., 2006). Moreover, recent studies have also linked inflammation to cancer progression making NF-κB overall a promising therapeutic target for drug discovery (Dobrovolskaia & Kozlov, 2005). In this study we examined the effect of the natural product canthin-6-one (SU182) as part of a CRUK small molecule drug discovery programme for effects upon the NF-κB pathway. Initial studies demonstrated that SU182 was found to have good potency against the inhibitory kappa B kinases (IKKs) at 30M in vitro. However, at concentrations up to 30M, SU182 had no effect upon TNFα stimulated loss in cellular IκBα or p65 phosphorylation in the keratinocyte cell line NCTC2544. Nevertheless, 30M SU182 reduced TNF-α / PMA-induced NF-κB-linked luciferase reporter activity to (22.9 ± 5%) and (34.6± 3 %, P<0.001) respectively, suggesting an action downstream of IKK signalling. Indeed, SU182 neither decreased NF-κB-DNA binding as assayed by EMSA nor prevented the translocation of p65 (NF-κB) to the nucleus assessed by immunofluorescence and subcellular fractionation. In addition to the inhibition of transcriptional activity of TNFα-induced NF-κB reporter activity SU182 significantly reduced PMA-induced AP-1-linked luciferase reporter activity to about (48± 9% at 30M, P<0.001) . This mode of inhibition was not sufficient to prevent the activation of NF-κB dependent induction of other proteins such as COX-2 and iNOS, or activated MAP kinases (p38, JNK and ERK1/2) in LPS stimulated RAW 264.7 macrophages. Taken together these data indicate the potential for SU182 to interfere with the transcription factors NF-κB and AP-1 at transcriptional level. However, no potential anti-inflammatory effect was indicated, further investigation for other NF-κB dependent proteins linked to survival are also required to identify the exact mechanism of action.

Keywords: Canthin-6-one, NF-κB, AP-1, phosphorylation, Nuclear translocation, DNA-binding activity, inflammatory proteins.

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56 2106 kA/cm² Peak Tunneling Current Density in GaN-Based Resonant Tunneling Diode with an Intrinsic Oscillation Frequency of ~260GHz at Room Temperature

Authors: Fang Liu, JunShuai Xue, JiaJia Yao, GuanLin Wu, ZuMaoLi, XueYan Yang, HePeng Zhang, ZhiPeng Sun

Abstract:

Terahertz spectra is in great demand since last two decades for many photonic and electronic applications. III-Nitride resonant tunneling diode is one of the promising candidates for portable and compact THz sources. Room temperature microwave oscillator based on GaN/AlN resonant tunneling diode was reported in this work. The devices, grown by plasma-assisted molecular-beam epitaxy on free-standing c-plane GaN substrates, exhibit highly repeatable and robust negative differential resistance (NDR) characteristics at room temperature. To improve the interface quality at the active region in RTD, indium surfactant assisted growth is adopted to enhance the surface mobility of metal atoms on growing film front. Thanks to the lowered valley current associated with the suppression of threading dislocation scattering on low dislocation GaN substrate, a positive peak current density of record-high 2.1 MA/cm2 in conjunction with a peak-to-valley current ratio (PVCR) of 1.2 are obtained, which is the best results reported in nitride-based RTDs up to now considering the peak current density and PVCR values simultaneously. When biased within the NDR region, microwave oscillations are measured with a fundamental frequency of 0.31 GHz, yielding an output power of 5.37 µW. Impedance mismatch results in the limited output power and oscillation frequency described above. The actual measured intrinsic capacitance is only 30fF. Using a small-signal equivalent circuit model, the maximum intrinsic frequency of oscillation for these diodes is estimated to be ~260GHz. This work demonstrates a microwave oscillator based on resonant tunneling effect, which can meet the demands of terahertz spectral devices, more importantly providing guidance for the fabrication of the complex nitride terahertz and quantum effect devices.

Keywords: GaN resonant tunneling diode, peak current density, microwave oscillation, intrinsic capacitance

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55 Anti-Hypertensive Effect of Proteolysate Generated from Actinopyga lecanora in Rats

Authors: Mahdokht Sadeghvishkaei, Azizah Abdul-Hamid, Amin Ismail, Nazamid Saari

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Hypertension is a common and serious chronic health problem and known as the most important risk factor for development of many diseases such as stroke. Since angiotensin I-converting enzyme (ACE) is the key enzyme involved in blood pressure, one of the well accepted mechanisms to control hypertension is through ACE inhibition. The ACE inhibitory effect of Actinopyga lecanora (stone fish) proteolysate in vitro had been reported. Hence, this study aimed to evaluate the ACE inhibitory potential of Actinopyga lecanora proteolysate in vivo in normotensive rats. Therefore the ACE inhibitory capability of the proteolysate to prevent increasing systolic blood pressure, after inducing hypertension by angiotensin I was examined. The pre-fed rats with the proteolysates at various doses (200, 400, 800 mg/kg body weight) revealed the significant (p ≤ 0.05) suppression effect compared with control groups. Furthermore, different doses of the proteolysate (200, 400, 800 mg/kg body weight) were examined to find its optimum effective dose. Results depicted that 800 mg proteolysate/kg body weight significantly reduced systolic blood pressure without negative effect on normal blood pressure (p ≤ 0.05). Furthermore, Sub-acute toxicity study based on OECD guideline demonstrated the safety of the proteolysate in vivo. The present study indicated that the proteolysate at a dose of 1000 mg/kg daily for 14 days did not cause toxicity signs such as death, changes in activity, or piloerection. Since there are no significant differences between treated groups and control groups, hematological and biochemical analysis confirmed safety of the proteolysate (p > 0.05). In addition, there were no significant differences between organs weights of the treated groups and the control groups. Morphologically, neither histopathological changes, nor gross abnormalities were observed. However, the proteolysate caused significant decrease in body weight in relation to the control groups (p ≤ 0.05) probably due to appetite stimulation by the proteolysate, leading to decreased food consumption in sub-acute group. It is concluded that the proteolysate generated from Actinopyga lecanora possess a significant anti-hypertensive effect and would be potentially used as natural alternative of ACE inhibitors.

Keywords: ACE inhibition, Actinopyga lecanora, anti-hypertensive activity, bioactive peptides, normotensive rats

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54 Cost Effectiveness Analysis of a Community Intervention for Anti-Retroviral Therapy Delivery in Cambodia

Authors: Esabelle Lo Yan Yam, Pheak Chhoun, Sovannary Tuot, Emily Lancsar, Siyan Yi

Abstract:

Persons living with HIV (PLHIV) need lifelong antiretroviral treatment (ART) to keep their viral load suppressed to an undetectable level, maintain a healthy immune system, and reduce the risk of transmitting HIV to others. However, many factors affect PLHIV's adherence to ART, including access to antiretrovirals (ARV), stigma, lack of social support, and the burden of seeking lifelong care. Community-based care has been shown to be instrumental in the experience of PLHIV in many countries, including Cambodia. In this study based in Cambodia, a community-based ART delivery (CAD) intervention involving community action workers (CAWs) who are PLHIVs was introduced. These workers collect pre-packaged ARVs from the ART clinics and dispense them to PLHIVs in the communities. The quasi-experimental study involved approximately 2000 stable PLHIV in the intervention arm and another 2000 PLHIV in the control arm (receiving usual care). A cost-effectiveness analysis is currently conducted to complement the clinical effectiveness of the CAD intervention on the care continuum and treatment outcomes for stable PLHIV, as well as the operational effectiveness in increasing the efficiency of the ART clinics and the health system. The analysis will consider health system and societal perspectives based on primary outcomes, including retention in care, viral load suppression, and adherence to ART. Additionally, a consultation with the National Centre for HIV/AIDS, Dermatology, and STD under the Cambodia Ministry of Health will be done to discuss the conduct of a budget impact analysis that can quantify the financial impact on the government's budget when adopting the CAD intervention at the provincial and national levels. The budget impact analysis will take into consideration various scaling-up scenarios for the interventions in the country. The research will assess the cost-effectiveness of the CAD intervention to support national stakeholders in Cambodia to make an informed decision on the adoption and scaling up of the intervention in Cambodia. The results are currently being analyzed and will be available at the time of the conference.

Keywords: Cambodia, community intervention, economic evaluation, global health, HIV/AIDs, implementation research

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53 Inhibitory Effect of Coumaroyl Lupendioic Acid on Inflammation Mediator Generation in Complete Freund’s Adjuvant-Induced Arthritis

Authors: Rayhana Begum, Manju Sharma

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Careya arborea Roxb. belongs to the Lecythidaceae family, is traditionally used in tumors, anthelmintic, bronchitis, epileptic fits, astringents, inflammation, an antidote to snake-venom, skin disease, diarrhea, dysentery with bloody stools, dyspepsia, ulcer, toothache, and ear pain. The present study was focused on investigating the anti-arthritic effect of coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem bark in the chronic inflammatory model and further assessing its possible mechanism on the modulation of inflammatory biomarkers. Arthritis was induced by injecting 0.1 ml of Complete Freund’s Adjuvant (5 mg/ml of heat killed Mycobacterium tuberculosis) into the subplantar region of the left hind paw. Treatment with coumaroyl lupendioic acid (10 and 20 mg/kg, p.o.) and reference drugs (indomethacin and dexamethasone at the dose of 5 mg/kg, p.o.) were started on the day of induction and continued up to 28 days. The progression of arthritis was evaluated by measuring paw volume, tibio tarsal joint diameters, and arthritic index. The effect of coumaroyl lupendioic acid (CLA) on the production PGE₂, NO, MPO, NF-κB, TNF-α, IL-1β, and IL-6 on serum level as well as inflamed paw tissue were also assessed. In addition, ankle joints and spleen were collected and prepared for histological examination. CLA in inflamed rats resulted in significant amelioration of paw edema, tibio-tarsal joint swelling and arthritic score as compared to CFA control group. The results indicated that CLA treated groups markedly decreased the levels of inflammatory mediators (PGE₂, NO, MPO and NF-κB levels) and down-regulated the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in paw tissue homogenates as well as in serum. However, the more pronounced effect was observed in the inflamed paw tissue homogenates. CLA also revealed a protective effect to the tibio-tarsal joint cartilage and spleen. These results suggest that coumaroyl lupendioic acid inhibits inflammation may be through the suppression of the cascade of proinflammatory mediators via the down-regulation of NF-ҡB.

Keywords: complete Freund’s adjuvant , Coumaroyl lupendioic acid, pro-inflammatory cytokines, prostaglandin E2

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52 Human TP53 Three Dimentional (3D) Core Domain Hot Spot Mutations at Codon, 36, 72 and 240 are Associated with Oral Squamous Cell Carcinoma

Authors: Saima Saleem, Zubair Abbasi, Abdul Hameed, Mansoor Ahmed Khan, Navid Rashid Qureshi, Abid Azhar

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Oral Squamous Cell Carcinoma (OSCC) is the leading cause of death in the developing countries like Pakistan. This problem aggravates because of the excessive use of available chewing products. In spite of widespread information on their use and purported legislations against their use the Pakistani markets are classical examples of selling chewable carcinogenic mutagens. Reported studies indicated that these products are rich in reactive oxygen species (ROS) and polyphenols. TP53 gene is involved in the suppression of tumor. It has been reported that somatic mutations caused by TP53 gene are the foundation of the cancer. This study aims to find the loss of TP53 functions due to mutation/polymorphism caused by genomic alteration and interaction with tobacco and its related ingredients. Total 260 tissues and blood specimens were collected from OSCC patients and compared with age and sex matched controls. Mutations in exons 2-11 of TP53 were examined by PCR-SSCP. Samples showing mobility shift were directly sequenced. Two mutations were found in exon 4 at nucleotide position 108 and 215 and one in exon 7 at nucleotide position 719 of the coding sequences in patient’s tumor samples. These results show that substitution of proline with arginine at codon 72 and serine with threonine at codon 240 of p53 protein. These polymorphic changes, found in tumor samples of OSCC, could be involved in loss of heterozygocity and apoptotic activity in the binding domain of TP53. The model of the mutated TP53 gene elaborated a nonfunctional unfolded p53 protein, suggesting an important role of these mutations in p53 protein inactivation and malfunction. This nonfunctional 3D model also indicates that exogenous tobacco related carcinogens may act as DNA-damaging agents affecting the structure of DNA. The interpretations could be helpful in establishing the pathways responsible for tumor formation in OSCC patients.

Keywords: TP53 mutation/polymorphism, OSCC, PCR-SSCP, direct DNA sequencing, 3D structure

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51 Depolymerised Natural Polysaccharides Enhance the Production of Medicinal and Aromatic Plants and Their Active Constituents

Authors: M. Masroor Akhtar Khan, Moin Uddin, Lalit Varshney

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Recently, there has been a rapidly expanding interest in finding applications of natural polymers in view of value addition to agriculture. It is now being realized that radiation processing of natural polysaccharides can be beneficially utilized either to improve the existing methodologies used for processing the natural polymers or to impart value addition to agriculture by converting them into more useful form. Gamma-ray irradiation is employed to degrade and lower the molecular weight of some of the natural polysaccharides like alginates, chitosan and carrageenan into small sized oligomers. When these oligomers are applied to plants as foliar sprays, they elicit various kinds of biological and physiological activities, including promotion of plant growth, seed germination, shoot elongation, root growth, flower production, suppression of heavy metal stress, etc. Furthermore, application of these oligomers can shorten the harvesting period of various crops and help in reducing the use of insecticides and chemical fertilizers. In recent years, the oligomers of sodium alginate obtained by irradiating the latter with gamma-rays at 520 kGy dose are being employed. It was noticed that the oligomers derived from the natural polysaccharides could induce growth, photosynthetic efficiency, enzyme activities and most importantly the production of secondary metabolite in the plants like Artemisia annua, Beta vulgaris, Catharanthus roseus, Chrysopogon zizanioides, Cymbopogon flexuosus, Eucalyptus citriodora, Foeniculum vulgare, Geranium sp., Mentha arvensis, Mentha citrata, Mentha piperita, Mentha virdis, Papaver somniferum and Trigonella foenum-graecum. As a result of the application of these oligomers, the yield and/or contents of the active constituents of the aforesaid plants were significantly enhanced. The productivity, as well as quality of medicinal and aromatic plants, may be ameliorated by this novel technique in an economical way as a very little quantity of these irradiated (depolymerised) polysaccharides is needed. Further, this is a very safe technique, as we did not expose the plants directly to radiation. The radiation was used to depolymerize the polysaccharides into oligomers.

Keywords: essential oil, medicinal and aromatic plants, plant production, radiation processed polysaccharides, active constituents

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50 Modelling Forest Fire Risk in the Goaso Forest Area of Ghana: Remote Sensing and Geographic Information Systems Approach

Authors: Bernard Kumi-Boateng, Issaka Yakubu

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Forest fire, which is, an uncontrolled fire occurring in nature has become a major concern for the Forestry Commission of Ghana (FCG). The forest fires in Ghana usually result in massive destruction and take a long time for the firefighting crews to gain control over the situation. In order to assess the effect of forest fire at local scale, it is important to consider the role fire plays in vegetation composition, biodiversity, soil erosion, and the hydrological cycle. The occurrence, frequency and behaviour of forest fires vary over time and space, primarily as a result of the complicated influences of changes in land use, vegetation composition, fire suppression efforts, and other indigenous factors. One of the forest zones in Ghana with a high level of vegetation stress is the Goaso forest area. The area has experienced changes in its traditional land use such as hunting, charcoal production, inefficient logging practices and rural abandonment patterns. These factors which were identified as major causes of forest fire, have recently modified the incidence of fire in the Goaso area. In spite of the incidence of forest fires in the Goaso forest area, most of the forest services do not provide a cartographic representation of the burned areas. This has resulted in significant amount of information being required by the firefighting unit of the FCG to understand fire risk factors and its spatial effects. This study uses Remote Sensing and Geographic Information System techniques to develop a fire risk hazard model using the Goaso Forest Area (GFA) as a case study. From the results of the study, natural forest, agricultural lands and plantation cover types were identified as the major fuel contributing loads. However, water bodies, roads and settlements were identified as minor fuel contributing loads. Based on the major and minor fuel contributing loads, a forest fire risk hazard model with a reasonable accuracy has been developed for the GFA to assist decision making.

Keywords: forest, GIS, remote sensing, Goaso

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49 Serum Zinc Level in Patients with Multidrug Resistant Tuberculosis

Authors: Nilima Barman, M. Atiqul Haque, Debabrata Ghosh

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Background: Zinc, one of the vital micronutrients, has an incredible role in the immune system. Hypozincemia affects host defense by reducing the number of circulating T cells and phagocytosis activity of other cells which ultimately impair cell-mediated immunity 1, 2. The immune system is detrimentally suppressed in multidrug-resistant tuberculosis (MDR-TB) 3, 4, a major threat of TB control worldwide5. As zinc deficiency causes immune suppression, we assume that it might have a role in the development of MDR-TB. Objectives: To estimate the serum zinc level in newly diagnosed multidrug resistant tuberculosis (MDR-TB) in comparison with that of newly diagnosed pulmonary TB (NdPTB) and healthy individuals. Materials and Methods: This study was carried out in the department of Public Health and Informatics, Bangabandhu Sheikh Mujib Medical University, Dhaka in collaboration with National Institute of Diseases of the Chest Hospital (NIDCH), Bangladesh from March’ 2012 to February 2013. A total of 337 respondents, of them 107 were MDR TB patients enrolled from NIDCH, 69 were NdPTB and 161 were healthy adults. All NdPTB patients and healthy adults were randomly selected from Sirajdikhan subdistrict of Munshiganj District. It is a rural community 22 kilometer south from capital city Dhaka. Serum zinc level was estimated by atomic absorption spectrophotometry method from early morning fasting blood sample. The evaluation of serum zinc level was done according to normal range from 70 to120 µgm/dL6. Results: Males were predominant in study groups (p>0.05). Mean (sd) serum zinc levels in MDR-TB, NdPTB and healthy adult group were 65.14 (12.52), 75.22(15.89), and 87.98 (21.80) μgm/dL respectively and differences were statistically significant (F=52.08, P value<0.001). After multiple comparison test (Bonferroni test) significantly lower level of serum zinc was found in MDRTB group than NdPTB and healthy adults (p<.001). Point biserial correlation showed a negative association of having MDR TB and serum zinc level (r= -.578; p value <0.001). Conclusion: The significant low level of serum zinc in MDR-TB patients suggested impaired immune status. We recommended for further exploration of low level of serum zinc as risk factor of MDR TB.

Keywords: Bangladesh, immune status, multidrug-resistant tuberculosis, serum zinc

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48 Nuclear Resistance Movements: Case Study of India

Authors: Shivani Yadav

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The paper illustrates dynamics of nuclear resistance movements in India and how peoples’ power rises in response to subversion of justice and suppression of human rights. The need for democratizing nuclear policy runs implicit through the demands of the people protesting against nuclear programmes. The paper analyses the rationale behind developing nuclear energy according to the mainstream development model adopted by the state. Whether the prevalent nuclear discourse includes people’s ambitions and addresses local concerns or not is discussed. Primarily, the nuclear movements across India comprise of two types of actors i.e. the local population as well as the urban interlocutors. The first type of actor is the local population comprising of the people who are residing in the vicinity of the nuclear site and are affected by its construction, presence and operation. They have very immediate concerns against nuclear energy projects but also have an ideological stand against producing nuclear energy. The other types of actors are the urban interlocutors, who are the intellectuals and nuclear activists who have a principled stand against nuclear energy and help to aggregate the aims and goals of the movement on various platforms. The paper focuses on the nuclear resistance movements at five sites in India- Koodankulam (Tamil Nadu), Jaitapur (Maharashtra), Haripur (West Bengal), Mithivirdi (Gujrat) and Gorakhpur (Haryana). The origin, development, role of major actors and mass media coverage of all these movements are discussed in depth. Major observations from the Indian case include: first, nuclear policy discussions in India are confined to elite circles; secondly, concepts like national security and national interest are used to suppress dissent against mainstream policies; and thirdly, India’s energy policies focus on economic concerns while ignoring the human implications of such policies. In conclusion, the paper observes that the anti-nuclear movements question not just the feasibility of nuclear power but also its exclusionary nature when it comes to people’s participation in policy making, endangering the ecology, violation of human rights, etc. The character of these protests is non-violent with an aim to produce more inclusive policy debates and democratic dialogues.

Keywords: anti-nuclear movements, Koodankulam nuclear power plant, non-violent resistance, nuclear resistance movements, social movements

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47 Therapeutic Effect of Indane 1,3-Dione Derivatives in the Restoration of Insulin Resistance in Human Liver Cells and in Db/Db Mice Model: Biochemical, Physiological and Molecular Insights of Investigation

Authors: Gulnaz Khan, Meha F. Aftab, Munazza Murtaza, Rizwana S. Waraich

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Advanced glycation end products (AGEs) precursor and its abnormal accumulation cause damage to various tissues and organs. AGEs have pathogenic implication in several diseases including diabetes. Existing AGEs inhibitors are not in clinical use, and there is a need for development of novel inhibitors. The present investigation aimed at identifying the novel AGEs inhibitors and assessing their mechanism of action for treating insulin resistance in mice model of diabetes. Novel derivatives of benzylidene of indan-1,3-dione were synthesized. The compounds were selected to study their action mechanism in improving insulin resistance, in vitro, in human hepatocytes and murine adipocytes and then, in vivo, in mice genetic model of diabetes (db/db). Mice were treated with novel derivatives of benzylidene of indane 1,3-dione. AGEs mediated ROS production was measured by dihydroethidium fluorescence assay. AGEs level in the serum of treated mice was observed by ELISA. Gene expression of receptor for AGEs (RAGE), PPAR-gamma, TNF-alpha and GLUT-4 was evaluated by RT-PCR. Glucose uptake was measured by fluorescent method. Microscopy was used to analyze glycogen synthesis in muscle. Among several derivatives of benzylidene of indan-1,3-dione, IDD-24, demonstrated highest inhibition of AGESs. IDD-24 significantly reduced AGEs formation and expression of receptor for advanced glycation end products (RAGE) in fat, liver of db/db mice. Suppression of AGEs mediated ROS production was also observed in hepatocytes and fat cell, after treatment with IDD-24. Glycogen synthesis was increased in muscle tissue of mice treated with IDD-24. In adipocytes, IDD-24 prevented AGEs induced reduced glucose uptake. Mice treated with IDD-24 exhibited increased glucose tolerance, serum adiponectin levels and decreased insulin resistance. The result of present study suggested that IDD-24 can be a possible treatment target to address glycotoxins induced insulin resistance.

Keywords: advance glycation end product, hyperglycemia, indan-1, 3-dione, insulin resistance

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46 Novel Nickel Complex Compound Reactivates the Apoptotic Network, Cell Cycle Arrest and Cytoskeletal Rearrangement in Human Colon and Breast Cancer Cells

Authors: Nima Samie, Batoul Sadat Haerian, Sekaran Muniandy, M. S. Kanthimathi

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Colon and breast cancers are categorized as the most prevalent types of cancer worldwide. Recently, the broad clinical application of metal complex compounds has led to the discovery of potential therapeutic drugs. The aim of this study was to evaluate the cytotoxic action of a selected nickel complex compound (NCC) against human colon and breast cancer cells. In this context, we determined the potency of the compound in the induction of apoptosis, cell cycle arrest, and cytoskeleton rearrangement. HT-29, WiDr, CCD-18Co, MCF-7 and Hs 190.T cell lines were used to determine the IC50 of the compound using the MTT assay. Analysis of apoptosis was carried out using immunofluorescence, acridine orange/ propidium iodide double staining, Annexin-V-FITC assay, evaluation of the translocation of NF-kB, oxygen radical antioxidant capacity, quenching of reactive oxygen species content , measurement of LDH release, caspase-3/-7, -8 and -9 assays and western blotting. The cell cycle arrest was examined using flowcytometry and gene expression was assessed using qPCR array. Results showed that our nickel complex compound displayed a potent suppressive effect on HT-29, WiDr, MCF-7 and Hs 190.T after 24 h of treatment with IC50 value of 2.02±0.54, 2.13±0.65, 3.76±015 and 3.14±0.45 µM respectively. This cytotoxic effect on normal cells was insignificant. Dipping in the mitochondrial membrane potential and increased release of cytochrome c from the mitochondria indicated induction of the intrinsic apoptosis pathway by the nickel complex compound. Activation of this pathway was further evidenced by significant activation of caspase 9 and 3/7.The nickel complex compound (NCC) was also shown activate the extrinsic pathways of apoptosis by activation of caspase-8 which is linked to the suppression of NF-kB translocation to the nucleus. Cell cycle arrest in the G1 phase and up-regulation of glutathione reductase, based on excessive ROS production were also observed. The results of this study suggest that the nickel complex compound is a potent anti-cancer agent inducing both intrinsic and extrinsic pathways as well as cell cycle arrest in colon and breast cancer cells.

Keywords: nickel complex, apoptosis, cytoskeletal rearrangement, colon cancer, breast cancer

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45 Effect of Cooking Process on the Antioxidant Activity of Different Variants of Tomato-Based Sofrito

Authors: Ana Beltran Sanahuja, A. Valdés García, Saray Lopez De Pablo Gallego, Maria Soledad Prats Moya

Abstract:

Tomato consumption has greatly increased worldwide in the last few years, mostly due to a growing demand for products like sofrito. In this sense, regular consumption of tomato-based products has been consistently associated with a reduction in the incidence of chronic degenerative diseases. The sofrito is a homemade tomato sauce typical of the Mediterranean area, which contains as main ingredients: tomato, onion, garlic and olive oil. There are also sofrito’s variations by adding other spices which bring at the same time not only color, flavor, smell and or aroma; they also provide medicinal properties, due to their antioxidant power. This protective effect has mainly been attributed to the predominant bioactive compounds present in sofrito, such as lycopene and other carotenoids as well as more than 40 different polyphenols. Regarding the cooking process, it is known that it can modify the properties and the availability of nutrients in sofrito; however, there is not enough information regarding this issue. For this reason, the aim of the present work is to evaluate the cooking effect on the antioxidant capacity of different variants of tomato-based sofrito combined with other spices, through the analysis of total phenols content (TPC) and to evaluate the antioxidant capacity by using the method of free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). Based on the results obtained, it can be confirmed that the basic sofrito composed of tomato, onion, garlic and olive oil and the sofrito with 1 g of rosemary added, are the ones with the highest content of phenols presenting greater antioxidant power than other industrial sofrito, and that of other variables of sofrito with added thyme or higher amounts of garlic. Moreover, it has been observed that in the elaboration of the tomato-based sofrito, it is possible to cook until 60 minutes, since the cooking process increases the bioavailability of the carotenoids when breaking the cell walls, which weakens the binding forces between the carotenoids and increases the levels of antioxidants present, confirmed both with the TPC and DPPH methods. It can be concluded that the cooking process of different variants of tomato-based sofrito, including spices, can improve the antioxidant capacity. The synergistic effects of different antioxidants may have a greater protective effect; increasing, also, the digestibility of proteins. In addition, the antioxidants help to deactivate the free radicals of diseases such as atherosclerosis, aging, immune suppression, cancer, and diabetes.

Keywords: antioxidants, cooking process, phenols sofrito

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44 Neuroblastoma in Children and the Potential Involvement of Viruses in Its Pathogenesis

Authors: Ugo Rovigatti

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Neuroblastoma (NBL) has epitomized for at least 40 years our understanding of cancer cellular and molecular biology and its potential applications to novel therapeutic strategies. This includes the discovery of the very first oncogene aberrations and tumorigenesis suppression by differentiation in the 80s; the potential role of suppressor genes in the 90s; the relevance of immunotherapy in the millennium first, and the discovery of additional mutations by NGS technology in the millennium second decade. Similar discoveries were achieved in the majority of human cancers, and similar therapeutic interventions were obtained subsequently to NBL discoveries. Unfortunately, targeted therapies suggested by specific mutations (such as MYCN amplification –MNA- present in ¼ or 1/5 of cases) have not elicited therapeutic successes in aggressive NBL, where the prognosis is still dismal. The reasons appear to be linked to Tumor Heterogeneity, which is particularly evident in NBL but also a clear hallmark of aggressive human cancers generally. The new avenue of cancer immunotherapy (CIT) provided new hopes for cancer patients, but we still ignore the cellular or molecular targets. CIT is emblematic of high-risk disease (HR-NBL) since the mentioned GD2 passive immunotherapy is still providing better survival. We recently critically reviewed and evaluated the literature depicting the genomic landscapes of HR-NBL, coming to the qualified conclusion that among hundreds of affected genes, potential targets, or chromosomal sites, none correlated with anti-GD2 sensitivity. A better explanation is provided by the Micro-Foci inducing Virus (MFV) model, which predicts that neuroblasts infection with the MFV, an RNA virus isolated from a cancer-cluster (space-time association) of HR-NBL cases, elicits the appearance of MNA and additional genomic aberrations with mechanisms resembling chromothripsis. Neuroblasts infected with low titers of MFV amplified MYCN up to 100 folds and became highly transformed and malignant, thus causing neuroblastoma in young rat pups of strains SD and Fisher-344 and larger tumor masses in nu/nu mice. An association was discovered with GD2 since this glycosphingolipid is also the receptor for the family of MFV virus (dsRNA viruses). It is concluded that a dsRNA virus, MFV, appears to provide better explicatory mechanisms for the genesis of i) specific genomic aberrations such as MNA; ii) extensive tumor heterogeneity and chromothripsis; iii) the effects of passive immunotherapy with anti-GD2 monoclonals and that this and similar models should be further investigated in both pediatric and adult cancers.

Keywords: neuroblastoma, MYCN, amplification, viruses, GD2

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43 Grain Structure Evolution during Friction-Stir Welding of 6061-T6 Aluminum Alloy

Authors: Aleksandr Kalinenko, Igor Vysotskiy, Sergey Malopheyev, Sergey Mironov, Rustam Kaibyshev

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From a thermo-mechanical standpoint, friction-stir welding (FSW) represents a unique combination of very large strains, high temperature and relatively high strain rate. The material behavior under such extreme deformation conditions is not studied well and thus, the microstructural examinations of the friction-stir welded materials represent an essential academic interest. Moreover, a clear understanding of the microstructural mechanisms operating during FSW should improve our understanding of the microstructure-properties relationship in the FSWed materials and thus enables us to optimize their service characteristics. Despite extensive research in this field, the microstructural behavior of some important structural materials remains not completely clear. In order to contribute to this important work, the present study was undertaken to examine the grain structure evolution during the FSW of 6061-T6 aluminum alloy. To provide an in-depth insight into this process, the electron backscatter diffraction (EBSD) technique was employed for this purpose. Microstructural observations were conducted by using an FEI Quanta 450 Nova field-emission-gun scanning electron microscope equipped with TSL OIMTM software. A suitable surface finish for EBSD was obtained by electro-polishing in a solution of 25% nitric acid in methanol. A 15° criterion was employed to differentiate low-angle boundaries (LABs) from high-angle boundaries (HABs). In the entire range of the studied FSW regimes, the grain structure evolved in the stir zone was found to be dominated by nearly-equiaxed grains with a relatively high fraction of low-angle boundaries and the moderate-strength B/-B {112}<110> simple-shear texture. In all cases, the grain-structure development was found to be dictated by an extensive formation of deformation-induced boundaries, their gradual transformation to the high-angle grain boundaries. Accordingly, the grain subdivision was concluded to the key microstructural mechanism. Remarkably, a gradual suppression of this mechanism has been observed at relatively high welding temperatures. This surprising result has been attributed to the reduction of dislocation density due to the annihilation phenomena.

Keywords: electron backscatter diffraction, friction-stir welding, heat-treatable aluminum alloys, microstructure

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42 Entomopathogenic Bacteria as Biological Control Agents: Review Paper

Authors: Tadesse Kebede Dabsu

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Insect pest is one the major limiting factor for sustainable food production. To overtake insect pest problem, since Second World War, producers have used excessive insecticide for insect pest management. However, in the era of 21st Century, the excessive use of insecticide caused insect resistant, insecticide bioaccumulation, insecticide hazard to environment, human health problem, and the like. Due to these problems, research efforts have been focused on the development of environmental free sustainable insect pest management method. To minimize all above mentioned risk utilizing of biological control such as entomopathogenicmicroorganism include bacteria, virus, fungus, and their productsare the best option for suppress insect population below certain density level. The objective of this review was to review the updated available studies and recent developments on the entomopathogenic bacteria (EPB) as biological control of insect pest and challenge of using them for control of insect pest. EPB’s mechanisms of insecticidal activities, type, taxonomy, and history are included in this paper body. EPB has been successfully used for the suppression of populations of insect pests. Controlling of harmful insect by entomopathogenic bacteria is an effective, low bioaccumulation in environment and food, very specific, reduce resistance risk in insect pest, economically and sustainable method of major insect pest management method. Identified and reported as potential major common type of entomopathogenic bacteria include Bacillus thuringiensis, Photorhabdus sp., Xenorhabdus spp.Walbachiaspp, Actinomycetesspp.etc. These bacteria being enter into insect body through natural opening or by vector release toxin protein inside of insect and disrupt the cell’s content cause natural mortality under natural condition. As per reported by different scientists, insect orders like Lepidoptera, Hemiptera, Hymenoptera, Coleoptera, and Dipterahave been successful controlled by entomopathogenic bacteria. As per coming across in different scientific research journals, much of the work was emphasised on Bacillus thuringiensisbsp. Therefore, for commercial production like Bacillus thuringiensi, detail research should be done on other bacteria species. The efficacy and practical application of EPB are restricted to some crops and greenhouse area, but their field application at farmers’ level very less. So still much work needs to be done to the practical application of the EPB at widely application. Their efficacy, pathogenicity, and host range test should be tested under environmental condition.

Keywords: insect pest, entomopathogenic bacteria, biological control, agent

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41 Anti-Acanthamoeba Activities of Fatty Acid Salts and Fatty Acids

Authors: Manami Masuda, Mariko Era, Takayoshi Kawahara, Takahide Kanyama, Hiroshi Morita

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Objectives: Fatty acid salts are a type of anionic surfactant and are produced from fatty acids and alkali. Moreover, fatty acid salts are known to have potent antibacterial activities. Acanthamoeba is ubiquitously distributed in the environment including sea water, fresh water, soil and even from the air. Although generally free-living, Acanthamoeba can be an opportunistic pathogen, which could cause a potentially blinding corneal infection known as Acanthamoeba keratitis. So, in this study, we evaluated the anti-amoeba activity of fatty acid salts and fatty acids to Acanthamoeba castellanii ATCC 30010. Materials and Methods: The antibacterial activity of 9 fatty acid salts (potassium butyrate (C4K), caproate (C6K), caprylate (C8K), caprate (C10K), laurate (C12K), myristate (C14K), oleate (C18:1K), linoleate (C18:2K), linolenate (C18:3K)) tested on cells of Acanthamoeba castellanii ATCC 30010. Fatty acid salts (concentration of 175 mM and pH 10.5) were prepared by mixing the fatty acid with the appropriate amount of KOH. The amoeba suspension mixed with KOH with a pH adjusted solution was used as the control. Fatty acids (concentration of 175 mM) were prepared by mixing the fatty acid with Tween 80 (20 %). The amoeba suspension mixed with Tween 80 (20 %) was used as the control. The anti-amoeba method, the amoeba suspension (3.0 × 104 cells/ml trophozoites) was mixed with the sample of fatty acid potassium (final concentration of 175 mM). Samples were incubated at 30°C, for 10 min, 60 min, and 180 min and then the viability of A. castellanii was evaluated using plankton counting chamber and trypan blue stainings. The minimum inhibitory concentration (MIC) against Acanthamoeba was determined using the two-fold dilution method. The MIC was defined as the minimal anti-amoeba concentration that inhibited visible amoeba growth following incubation (180 min). Results: C8K, C10K, and C12K were the anti-amoeba effect of 4 log-unit (99.99 % growth suppression of A. castellanii) incubated time for 180 min against A. castellanii at 175mM. After the amoeba, the suspension was mixed with C10K or C12K, destroying the cell membrane had been observed. Whereas, the pH adjusted control solution did not exhibit any effect even after 180 min of incubation with A. castellanii. Moreover, C6, C8, and C18:3 were the anti-amoeba effect of 4 log-unit incubated time for 60 min. C4 and C18:2 exhibited a 4-log reduction after 180 min incubation. Furthermore, the minimum inhibitory concentration (MIC) was determined. The MIC of C10K, C12K and C4 were 2.7 mM. These results indicate that C10K, C12K and C4 have high anti-amoeba activity against A. castellanii and suggest C10K, C12K and C4 have great potential for antimi-amoeba agents.

Keywords: Fatty acid salts, anti-amoeba activities, Acanthamoeba, fatty acids

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40 Coping Strategies among Caregivers of Children with Autism Spectrum Disorders: A Cluster Analysis

Authors: Noor Ismael, Lisa Mische Lawson, Lauren Little, Murad Moqbel

Abstract:

Background/Significance: Caregivers of children with Autism Spectrum Disorders (ASD) develop coping mechanisms to overcome daily challenges to successfully parent their child. There is variability in coping strategies used among caregivers of children with ASD. Capturing homogeneity among such variable groups may help elucidate targeted intervention approaches for caregivers of children with ASD. Study Purpose: This study aimed to identify groups of caregivers of children with ASD based on coping mechanisms, and to examine whether there are differences among these groups in terms of strain level. Methods: This study utilized a secondary data analysis, and included survey responses of 273 caregivers of children with ASD. Measures consisted of the COPE Inventory and the Caregiver Strain Questionnaire. Data analyses consisted of cluster analysis to group caregiver coping strategies, and analysis of variance to compare the caregiver coping groups on strain level. Results: Cluster analysis results showed four distinct groups with different combinations of coping strategies: Social-Supported/Planning (group one), Spontaneous/Reactive (group two), Self-Supporting/Reappraisal (group three), and Religious/Expressive (group four). Caregivers in group one (Social-Supported/Planning) demonstrated significantly higher levels than the remaining three groups in the use of the following coping strategies: planning, use of instrumental social support, and use of emotional social support, relative to the other three groups. Caregivers in group two (Spontaneous/Reactive) used less restraint relative to the other three groups, and less suppression of competing activities relative to the other three groups as coping strategies. Also, group two showed significantly lower levels of religious coping as compared to the other three groups. In contrast to group one, caregivers in group three (Self-Supporting/Reappraisal) demonstrated significantly lower levels of the use of instrumental social support and the use of emotional social support relative to the other three groups. Additionally, caregivers in group three showed more acceptance, positive reinterpretation and growth coping strategies. Caregivers in group four (Religious/Expressive) demonstrated significantly higher levels of religious coping relative to the other three groups and utilized more venting of emotions strategies. Analysis of Variance results showed no significant differences between the four groups on the strain scores. Conclusions: There are four distinct groups with different combinations of coping strategies: Social-Supported/Planning, Spontaneous/Reactive, Self-Supporting/Reappraisal, and Religious/Expressive. Each caregiver group engaged in a combination of coping strategies to overcome the strain of caregiving.

Keywords: autism, caregivers, cluster analysis, coping strategies

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39 Effect of Whey Proteins and Caffeic Acid Interactions on Antioxidant Activity and Protein Structure

Authors: Tassia Batista Pessato, Francielli Pires Ribeiro Morais, Fernanda Guimaraes Drummond Silva, Flavia Maria Netto

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Proteins and phenolic compounds can interact mainly by hydrophobic interactions. Those interactions may lead to structural changes in both molecules, which in turn could affect positively or negatively their functional and nutritional properties. Here, the structural changes of whey proteins (WPI) due to interaction with caffeic acid (CA) were investigated by intrinsic and extrinsic fluorescence. The effects of protein-phenolic compounds interactions on the total phenolic content and antioxidant activity were also assessed. The WPI-CA complexes were obtained by mixture of WPI and CA stock solutions in deionized water. The complexation was carried out at room temperature during 60 min, using 0.1 M NaOH to adjust pH at 7.0. The WPI concentration was fixed at 5 mg/mL, whereas the CA concentration varied in order to obtain four different WPI:CA molar relations (1:1; 2:1; 5:1; 10:1). WPI and phenolic solutions were used as controls. Intrinsic fluorescence spectra of the complexes (mainly due to Trp fluorescence emission) were obtained at λex = 280 nm and the emission intensities were measured from 290 to 500 nm. Extrinsic fluorescence was obtained as the measure of protein surface hydrophobicity (S0) using ANS as a fluorescence probe. Total phenolic content was determined by Folin-Ciocalteau and the antioxidant activity by FRAP and ORAC methods. Increasing concentrations of CA resulted in decreasing of WPI intrinsic fluorescence. The emission band of WPI red shifted from 332 to 354 nm as the phenolic concentration increased, which is related to the exposure of Trp residue to the more hydrophilic environment and unfolding of protein structure. In general, the complexes presented lower S0 values than WPI, suggesting that CA hindered ANS binding to hydrophobic sites of WPI. The total phenolic content in the complexes was lower than the sum of two compounds isolated. WPI showed negligible AA measured by FRAP. However, as the relative concentration of CA increased in the complexes, the FRAP values enhanced, indicating that AA measure by this technique comes mainly from CA. In contrast, the WPI ORAC value (82.3 ± 1.5 µM TE/g) suggest that its AA is related to the capacity of H+ transfer. The complexes exhibited no important improvement of AA measured by ORAC in relation to the isolated components, suggesting complexation partially suppressed AA of the compounds. The results hereby presented indicate that interaction of WPI and CA occurred, and this interaction caused a structural change in the proteins. The complexation can either hide or expose antioxidant sites of both components. In conclusion, although the CA can undergo an AA suppression due to the interaction with proteins, the AA of WPI could be enhanced due to protein unfolding and exposure of antioxidant sites.

Keywords: bioactive properties, milk proteins, phenolic acids, protein-phenolic compounds complexation

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38 Studies on Pre-ignition Chamber Dynamics of Solid Rockets with Different Port Geometries

Authors: S. Vivek, Sharad Sharan, R. Arvind, D. V. Praveen, J. Vigneshwar, S. Ajith, V. R. Sanal Kumar

Abstract:

In this paper numerical studies have been carried out to examine the starting transient flow features of high-performance solid propellant rocket motors with different port geometries but with same propellant loading density. Numerical computations have been carried out using a 3D SST k-ω turbulence model. This code solves standard k-omega turbulence equations with shear flow corrections using a coupled second order implicit unsteady formulation. In the numerical study, a fully implicit finite volume scheme of the compressible, Reynolds-Averaged, Navier-Stokes equations are employed. We have observed from the numerical results that in solid rocket motors with highly loaded propellants having divergent port geometry the hot igniter gases can create pre-ignition thrust oscillations due to flow unsteadiness and recirculation. Under these conditions the convective flux to the surface of the propellant will be enhanced, which will create reattachment point far downstream of the transition region and it will create a situation for secondary ignition and formation of multiple-flame fronts. As a result the effective time required for the complete burning surface area to be ignited comes down drastically giving rise to a high pressurization rate (dp/dt) in the second phase of starting transient. This in effect could lead to starting thrust oscillations and eventually a hard start of the solid rocket motor. We have also observed that the igniter temperature fluctuations will be diminished rapidly and will reach the steady state value faster in the case of solid propellant rocket motors with convergent port than the divergent port irrespective of the igniter total pressure. We have concluded that the thrust oscillations and unexpected thrust spike often observed in solid rockets with non-uniform ports are presumably contributed due to the joint effects of the geometry dependent driving forces, transient burning and the chamber gas dynamics forces. We also concluded that the prudent selection of the port geometry, without altering the propellant loading density, for damping the total temperature fluctuations within the motor is a meaningful objective for the suppression and control of instability and/or pressure/thrust oscillations often observed in solid propellant rocket motors with non-uniform port geometry.

Keywords: ignition transient, solid rockets, starting transient, thrust transient

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37 NK Cells Expansion Model from PBMC Led to a Decrease of CD4+ and an Increase of CD8+ and CD25+CD127- T-Reg Lymphocytes in Patients with Ovarian Neoplasia

Authors: Rodrigo Fernandes da Silva, Daniela Maira Cardozo, Paulo Cesar Martins Alves, Sophie Françoise Derchain, Fernando Guimarães

Abstract:

T-reg lymphocytes are important for the control of peripheral tolerance. They control the adaptive immune system and prevent autoimmunity through its suppressive action on CD4+ and CD8+ lymphocytes. The suppressive action also includes B lymphocytes, dendritic cells, monocytes/macrophages and recently, studies have shown that T-reg are also able to inhibit NK cells, therefore they exert their control of the immune response from innate to adaptive response. Most tumors express self-ligands, therefore it is believed that T-reg cells induce tolerance of the immune system, hindering the development of successful immunotherapies. T-reg cells have been linked to the suppression mechanisms of the immune response against tumors, including ovarian cancer. The goal of this study was to disclose the sub-population of the expanded CD3+ lymphocytes reported by previous studies, using the long-term culture model designed by Carlens et al 2001, to generate effector cell suspensions enriched with cytotoxic CD3-CD56+ NK cells, from PBMC of ovarian neoplasia patients. Methods and Results: Blood was collected from 12 patients with ovarian neoplasia after signed consent: 7 benign (Bng) and 5 malignant (Mlg). Mononuclear cells were separated by Ficoll-Paque gradient. Long-term culture was conducted by a 21 day culturing process with SCGM CellGro medium supplemented with anti-CD3 (10ng/ml, first 5 days), IL-2 (1000UI/ml) and FBS (10%). After 21 days of expansion, there was an increase in the population of CD3+ lymphocytes in the benign and malignant group. Within CD3+ population, there was a significant decrease in the population of CD4+ lymphocytes in the benign (median Bgn D-0=73.68%, D-21=21.05%) (p<0.05) and malignant (median Mlg D-0=64.00%, D-21=11.97%) (p < 0.01) group. Inversely, after 21 days of expansion, there was an increase in the population of CD8+ lymphocytes within the CD3+ population in the benign (median Bgn D-0=16.80%, D-21=38.56%) and malignant (median Mlg D-0=27.12%, D-21=72.58%) group. However, this increase was only significant on the malignant group (p<0.01). Within the CD3+CD4+ population, there was a significant increase (p < 0.05) in the population of T-reg lymphocytes in the benign (median Bgn D-0=9.84%, D-21=39.47%) and malignant (median Mlg D-0=3.56%, D-21=16.18%) group. Statistical analysis inter groups was performed by Kruskal-Wallis test and intra groups by Mann Whitney test. Conclusion: The CD4+ and CD8+ sub-population of CD3+ lymphocytes shifts with the culturing process. This might be due to the process of the immune system to produce a cytotoxic response. At the same time, T-reg lymphocytes increased within the CD4+ population, suggesting a modulation of the immune response towards cells of the immune system. The expansion of the T-reg population can hinder an immune response against cancer. Therefore, an immunotherapy using this expansion procedure should aim to halt the expansion of T-reg or its immunosuppresion capability.

Keywords: regulatory T cells, CD8+ T cells, CD4+ T cells, NK cell expansion

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