Ambiguity in a trans-disciplinary stakeholder assessment of neglected and underutilized species in China, Cambodia, Thailand and Vietnam

Neglected and Underutilized Crop Species (NUS) are grown primarily by traditional farmers in developing countries. They were once more widely grown but are today falling into disuse for a variety of agronomic, genetic, economic and cultural factors. While these crops continue to be maintained by socio-cultural preferences and use practices, most of them remain inadequately characterized and neglected by research and conservation. The aim of our work was to improve the agricultural portfolio by identifying promising neglected and underutilised species in China, Cambodia, Northeastern Thailand and Northern Vietnam. We began with preparing a “Masterlist” containing 260 species, based on farmer interviews and literature review. After an initial pre-selection we identified 17 NUS for China, 13 for Cambodia, 12 for Thailand, and 22 for Vietnam as of highest priority. These NUS then underwent a multi-criteria and trans-disciplinary assessment involving 511 stakeholders such as scientists, farmers, NGOs and policy makers. Based on the assessment we identified the most promising NUS for each country. We also identified some limitations for the promotion of so-called priority NUS regarding to some substancial disagreement between the involved stakeholders. In China and Cambodia, for example, farmers judged the potential of NUS significantly lower than other stakeholders, and in Vietnam scientists and policy makers had substantially different opinions on NUS compared to farmers. Addressing these ambiguous views will be highly relevant to the develoment of an improved agricultural portfolio.

NMR investigation of chitosan derivatives formed by the reaction of chitosan with levulinic acid

Chitosan derivatives are obtained by reaction of chitosan with a low degree of acetylation and levulinic acid under different experimental conditions. The chemical structure of the different derivatives obtained is determined using ¹H and ¹³C NMR spectroscopies. The intrinsic viscosity is used to follow the molecular weight evolution. Finally, conditions are described in which water-soluble N-carboxybutylchitosan is obtained. In particular, the time of the reduction step and the ratio between reagents are investigated. Under mild conditions and short times of reduction there is a very low degree of substitution and only the monocarboxybutylchitosan is formed. The dicarboxylated form is never observed. The cyclic derivative (5-methylpyrrolidinone chitosan) is obtained when the reducing agent is added slowly to the reactants.     

Iridoid glucosides from roots of Vietnamese Paederia scandens

Four iridoid glucosides, three of which are dimeric were isolated from the methanol extract of roots of Vietnamese Paederia scandens (Lour) Merrill together with the five known glucosides, paederoside, asperuloside, paederosidic acid, asperulosidic acid and geniposide. Seven sulfur-containing iridoid glucosides were also isolated. The structures of the iridoid glucosides were determined by a combination of high-resolution NMR, MS, IR and UV spectra, and chemical reaction such as acetylation.     

Inhibition of endothelin-converting enzyme for protection against neointimal proliferation following balloon angioplasty of the rat carotid artery

Clinical success of percutaneous transluminal coronary angioplasty is limited by restenosis within months of the initial intervention. A number of vasoactive mediators and growth factors have been reported to participate in this process. The aim of the present experiments was to examine the effects of nonselective neutral endopeptidase (NEPi)/endothelin-converting enzyme (ECEi) inhibitors against neointimal proliferation (NIP) following balloon angioplasty of the left carotid artery of Sprague-Dawley rats with the right vessel serving as the uninjured control. The rats were divided in several groups: group 1, nontreated (vehicle); group 2, treated with a selective NEPi i.p.; groups 3-7, treated with nonselective NEPi/ECEi either i.p., s.c., i.v., or p.o. at various doses. After 2 weeks, cross-sectional histopathological and morphometrical examination of the left carotids revealed a severe NIP in vehicle-treated angioplastic rats compared with the control uninjured right carotid of the same rats. The selective NEPi CGS 24592 had no significant effect on restenosis, nor did the dual NEPi/ECEi CGS 26303 at 5 mg x kg(-1) x day(-1) i.p. Both s.c and i.v. NEPi/ECEi treatment (10 mg x kg(-1) x day(-1) b.i.d. s.c. or 10 mg x kg(-1) x day(-1) i.v.) reduced NIP by up to 35%. The prodrug CGS 26393 (p.o.) also attenuated NIP by 23%. Plasma concentrations of these compounds correlated with the degree of inhibition. These data support the participation of the endothelin system in the rat model of balloon angioplasty and suggest that selective ECEi may be effective.     

High pro-inflammatory cytokine secretion and loss of high avidity cross-reactive cytotoxic T-cells during the course of secondary dengue virus infection

Background

Dengue is one of the most important human diseases transmitted by an arthropod vector and the incidence of dengue virus infection has been increasing – over half the world''s population now live in areas at risk of infection. Most infections are asymptomatic, but a subset of patients experience a potentially fatal shock syndrome characterised by plasma leakage. Severe forms of dengue are epidemiologically associated with repeated infection by more than one of the four dengue virus serotypes. Generally attributed to the phenomenon of antibody-dependent enhancement, recent observations indicate that T-cells may also influence disease phenotype.

Methods and Findings

Virus-specific cytotoxic T lymphocytes (CTL) showing high level cross reactivity between dengue serotypes could be expanded from blood samples taken during the acute phase of secondary dengue infection. These could not be detected in convalescence when only CTL populations demonstrating significant serotype specificity were identified. Dengue cross-reactive CTL clones derived from these patients were of higher avidity than serotype-specific clones and produced much higher levels of both type 1 and certain type 2 cytokines, many previously implicated in dengue pathogenesis.

Conclusion

Dengue serotype cross-reactive CTL clones showing high avidity for antigen produce higher levels of inflammatory cytokines than serotype-specific clones. That such cells cannot be expanded from convalescent samples suggests that they may be depleted, perhaps as a consequence of activation-induced cell death. Such high avidity cross-reactive memory CTL may produce inflammatory cytokines during the course of secondary infection, contributing to the pathogenesis of vascular leak. These cells appear to be subsequently deleted leaving a more serotype-specific memory CTL pool. Further studies are needed to relate these cellular observations to disease phenotype in a large group of patients. If confirmed they have significant implications for understanding the role of virus-specific CTL in pathogenesis of dengue disease.     

Role of Asn(2) and Glu(7) residues in the oxidative folding and on the conformation of the N-terminal loop of apamin

The X-ray structure of [N-acetyl]-apamin has been solved at 0.95 A resolution. It consists of an 1-7 N-terminal loop stabilized by an Asn-beta-turn motif (2-5 residues) and a helical structure spanning the 9-18 residues tightly linked together by two disulfide bonds. However, neither this accurate X-ray nor the available solution structures allowed us to rationally explain the unusual downfield shifts observed for the Asn(2) and Glu(7) amide signals upon Glu(7) carboxylic group ionization. Thus, apamin and its [N-acetyl], [Glu(7)Gln], [Glu(7)Asp], and [Asn(2)Abu] analogues and submitted to NMR structural studies as a function of pH. We first demonstrated that the Glu(7) carboxylate group is responsible for the large downfield shifts of the Asn(2) and Glu(7) amide signals. Then, molecular dynamics (MD) simulations suggested unexpected interactions between the carboxylate group and the Asn(2) and Glu(7) amide protons as well as the N-terminal alpha-amino group, through subtle conformational changes that do not alter the global fold of apamin. In addition, a structural study of the [Asn(2)Abu] analogue, revealed an essential role of Asn(2) in the beta-turn stability and the cis/trans isomerization of the Ala(5)-Pro(6) amide bond. Interestingly, this proline isomerization was shown to also depend on the ionization state of the Glu(7) carboxyl group. However, neither destabilization of the beta-turn nor proline isomerization drastically altered the helical structure that contains the residues essential for binding. Altogether, the Asn(2) and Glu(7) residues appeared essential for the N-terminal loop conformation and thus for the selective formation of the native disulfide bonds but not for the activity.     

Selenium nanoparticles as in vitro rooting agent,regulates stomata closure and antioxidant activity of gerbera to tolerate acclimatization stress

Plant Cell, Tissue and Organ Culture (PCTOC) - The acclimatization stress is responsible for high mortality in tissue cultured plants, which significantly reduces micropropagation efficiency. In...     

Quinazolin‐4(3H)‐one‐Based Hydroxamic Acids: Design,Synthesis and Evaluation of Histone Deacetylase Inhibitory Effects and Cytotoxicity

The present article describes the synthesis and biological activity of various series of novel hydroxamic acids incorporating quinazolin‐4(3H)‐ones as novel small molecules targeting histone deacetylases. Biological evaluation showed that these hydroxamic acids were potently cytotoxic against three human cancer cell lines (SW620, colon; PC‐3, prostate; NCI?H23, lung). Most compounds displayed superior cytotoxicity than SAHA (suberoylanilide hydroxamic acid, Vorinostat) in term of cytotoxicity. Especially, N‐hydroxy‐7‐(7‐methyl‐4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5b ) and N‐hydroxy‐7‐(6‐methyl‐4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5c ) (IC₅₀ values, 0.10–0.16 μm ) were found to be approximately 30‐fold more cytotoxic than SAHA (IC₅₀ values of 3.29–3.67 μm ). N‐Hydroxy‐7‐(4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5a ; IC₅₀ values of 0.21–0.38 μm ) was approximately 10‐ to 15‐fold more potent than SAHA in cytotoxicity assay. These compounds also showed comparable HDAC inhibition potency with IC₅₀ values in sub‐micromolar ranges. Molecular docking experiments indicated that most compounds, as represented by 5b and 5c , strictly bound to HDAC2 at the active binding site with binding affinities much higher than that of SAHA.     

High Treatment Retention Rate in HIV-Infected Patients Receiving Antiretroviral Therapy at Two Large HIV Clinics in Hanoi,Vietnam

Background

Loss to follow-up (LTFU) is viewed as a major challenge in improving retention in HIV treatment. In Vietnam, the reasons for disengagement from clinics and the effect of injection drug use (IDU) on LTFU with unknown outcome (true LTFU) are not well known.

Methods

Patients receiving antiretroviral therapy (ART) from two HIV clinics in Hanoi were included in this observational study between 2007 and 2012, and followed up every 6 months until the end of 2013. The reasons for disengagement from the clinic, and ART status during imprisonment were investigated in patients with a history of IDU to identify true LTFU. The retention rate at 6–54 months and true LTFU rate were calculated. Cox proportional hazards regression models were performed to identify factors associated with true LTFU.

Results

There were 1,431 patients, with a follow-up time of 4,371 person-years (median 2.49 years). At the end of the follow-up period, 71 (5.0%) patients died, 79 (5.5%) transferred to other clinics, 16 (1.1%) disengaged from the clinics, and the calculated true LTFU was 45 (3.1%), with 12-month ART retention rate of 95.3% for the entire study population. Imprisonment was the most frequent reason for disengagement from the clinics. True LTFU correlated significantly with low CD4 count and high plasma viral load, but not history of IDU.

Conclusion

Imprisonment is a major cause of disengagement from HIV care among patients with a history of IDU.     

Inhibition of melanogenesis by dioctyl phthalate isolated from Nigella glandulifera Freyn

Although a number of melanogenesis inhibitors have recently been reported and used as cosmetic additives, none is completely satisfactory, leaving a need for novel skin-depigmenting agents. Thus, to develop a novel skin-depigmenting agent from natural sources, the inhibition of melanogenesis by Chinese plants was evaluated. A methanolic extract of Nigella glandulifera Freyn was found to inhibit the melanin synthesis of murine B16F10 melanoma cells by 43.7% and exhibited a low cytotoxicity (8.1 %) at a concentration of 100 microg/ml. Thus, to identify the melanogenesis-inhibiting mechanism, the inhibitory activity towards tyrosinase, the key enzyme of melanogenesis, was further evaluated, and the results showed inhibitory effects on the activity of intracellular tyrosinase yet not on mushroom tyrosinase. Finally, to isolate the compounds with a hypopigmenting capability, activity-guided isolation was performed, and Dioctyl phthalate identified as inhibiting melanogenesis.