Genetic characterization of cassava (Manihot esculenta Crantz) genotypes using agro-morphological and single nucleotide polymorphism markers

Physiology and Molecular Biology of Plants - Dearth of information on extent of genetic variability in cassava limits the genetic improvement of cassava genotypes in Sierra Leone. The aim of this...     

Eradicating multiple invasive species on inhabited islands: the next big step in island restoration?

Invasive species are the greatest threat to island ecosystems, which harbour nearly half the world’s endangered biodiversity. However, eradication is more feasible on islands than on continents. We present a global analysis of 1,224 successful eradications of invasive plants and animals on 808 islands. Most involve single vertebrate species on uninhabited islands, but plant and invertebrate eradications occur more often on inhabited islands. Inhabited islands are often highly modified and support numerous introduced species. Consequently, targeting a single invasive species can be ineffective or counterproductive. The impacts of other pests will continue and, in some cases, be exacerbated. The presence of people also creates regulatory, logistical and socio-political constraints. Real or perceived health risks to inhabitants, pets and livestock may restrict the use of some eradication tools, and communities or individuals sometimes oppose eradication. Despite such challenges, managing invasive species is vital to conserve and restore the unique biodiversity of many inhabited islands, and to maintain or improve the welfare and livelihoods of island residents. We present a brief case study of the Juan Fernández Archipelago, Chile, and discuss the feasibility of eradicating large suites of invasive plants and animals from inhabited islands while managing other invaders for which eradication is not feasible or desirable. Eradications must be planned to account for species interactions. Monitoring and contingency plans must detect and address any ‘surprise effects’. Above all, it is important that the local community derives social, cultural and/or economic benefits, and that people support and are engaged in the restoration effort.     

Controlled Microwave Processing Applied to the Pharmaceutical Formulation of Ibuprofen

The first successful development of controlled microwave processing for pharmaceutical formulations is presented and illustrated with a model drug (ibuprofen) and two excipients (stearic acid and polyvinylpyrrolidone). The necessary fine temperature control for formulation with microwave energy has been achieved using a uniquely modified microwave oven with direct temperature measurement and pulse-width modulation power control. In addition to comparing microwave and conventional heating, the effect of the presence of liquid (water) in aiding the mixing of the drug and excipient during formulation was also investigated. Analysis of the prepared formulations using differential scanning calorimetry and dissolution studies suggest that microwave and conventional heating produce similar products when applied to mixtures of ibuprofen and stearic acid. However, the differences were observed for the ibuprofen and polyvinylpyrrolidone formulation in terms of the dissolution kinetics. In all cases, the presence of water did not appear to influence the formulation to any appreciable degree. The application of controllable microwave heating is noteworthy as fine temperature control opens up opportunities for thermally sensitive materials for which microwave methods have not been feasible prior to this work.     

Crohn disease: A current perspective on genetics,autophagy and immunity

Crohn disease (CD) is a chronic and debilitating inflammatory condition of the gastrointestinal tract.¹ Prevalence in western populations is 100–150/100,000 and somewhat higher in Ashkenazi Jews. Peak incidence is in early adult life, although any age can be affected and a majority of affected individuals progress to relapsing and chronic disease. Medical treatments rely significantly on empirical corticosteroid therapy and immunosuppression, and intestinal resectional surgery is frequently required. Thus, 80% of patients with CD come to surgery for refractory disease or complications. It is hoped that an improved understanding of pathogenic mechanisms, for example by studying the genetic basis of CD and other forms of inflammatory bowel diseases (IBD), will lead to improved therapies and possibly preventative strategies in individuals identified as being at risk.Key words: Atg16L1, dendritic cells, gastrointestinal, genome-wide association, gut microbiota, inflammatory bowel diseases, IRGM, Paneth cell, ulcerative colitis     

Thresholds in plant–herbivore interactions: predicting plant mortality due to herbivore browse damage

Patterns of herbivore browse at small scales, such as the rate of leaf consumption or plant preferences, drive the impact of herbivores on whole-plant processes, such as growth or survival, and subsequent changes in plant population structure. However, herbivore impacts are often non-linear, highly variable and context-dependent. Understanding the effect of herbivores on plant populations therefore requires a detailed understanding of the relationships that drive small-scale processes, and how these interact to generate dynamics at larger scales. We derive a mathematical model to predict annual rates of browse-induced tree mortality. We model individual plant mortality as a result of rates of foliage production, turnover and herbivore intake, and extend the model to the population scale by allowing for between-tree variation in levels of herbivore browse. The model is configurable for any broadleaved tree species subject to vertebrate or invertebrate browse, and is designed to be parameterized from field data typically collected as part of browse damage assessments. We parameterized and tested the model using data on foliage cover and browse damage recorded on kamahi trees (Weinmannia racemosa) browsed by possums (Trichosurus vulpecula) in New Zealand forests. The model replicated observed patterns of tree mortality at 12 independent validation sites with a wide range of herbivore densities and browse damage. The model reveals two key thresholds; in plant foliar cover, indicating when individual trees may be at high risk from browse-induced mortality, and in herbivore intake, leading to high rates of mortality across the whole population.     

Design and synthesis of HIV-1 protease inhibitors for a long-acting injectable drug application

The design and synthesis of novel HIV-1 protease inhibitors (PIs) (1–22), which display high potency against HIV-1 wild-type and multi-PI-resistant HIV-mutant clinical isolates, is described. Lead optimization was initiated from compound 1, a Phe–Phe hydroxyethylene peptidomimetic PI, and was directed towards the discovery of new PIs suitable for a long-acting (LA) injectable drug application. Introducing a heterocyclic 6-methoxy-3-pyridinyl or a 6-(dimethylamino)-3-pyridinyl moiety (R³) at the para-position of the P1′ benzyl fragment generated compounds with antiviral potency in the low single digit nanomolar range. Halogenation or alkylation of the metabolic hot spots on the various aromatic rings resulted in PIs with high stability against degradation in human liver microsomes and low plasma clearance in rats. Replacing the chromanolamine moiety (R¹) in the P2 protease binding site by a cyclopentanolamine or a cyclohexanolamine derivative provided a series of high clearance PIs (16–22) with EC₅₀s on wild-type HIV-1 in the range of 0.8–1.8 nM. PIs 18 and 22, formulated as nanosuspensions, showed gradual but sustained and complete release from the injection site over two months in rats, and were therefore identified as interesting candidates for a LA injectable drug application for treating HIV/AIDS.     

Biological activity of AC3174, a peptide analog of exendin-4

Exenatide, the active ingredient of BYETTA (exenatide injection), is an incretin mimetic that has been developed for the treatment of patients with type 2 diabetes. Exenatide binds to and activates the known GLP-1 receptor with a potency comparable to that of the mammalian incretin GLP-1(7-36), thereby acting as a glucoregulatory agent. AC3174 is an analog of exenatide with leucine substituted for methionine at position 14, [Leu(14)]exendin-4. The purpose of these studies was to evaluate the glucoregulatory activity and pharmacokinetics of AC3174. In RINm5f cell membranes, the potency of AC3174 for the displacement of [(125)I]GLP-1 and activation of adenylate cyclase was similar to that of exenatide and GLP-1. In vivo, AC3174, administered as a single IP injection, significantly decreased plasma glucose concentration and glucose excursion following the administration of an oral glucose challenge in both non-diabetic (C57BL/6) and diabetic db/db mice (P<0.05 vs. vehicle-treated). The magnitude of glucose lowering of AC3174 was comparable to exenatide. The ED(50) values of AC3174 for glucose lowering (60 minute post-dose) were 1.2 microg/kg in db/db mice and 1.3 microg/kg in C57BL/6 mice. AC3174 has insulinotropic activity in vivo. Administration of AC3174 resulted in a 4-fold increase in insulin concentrations in normal mice following an IP glucose challenge. AC3174 was also shown to inhibit food intake and decrease gastric emptying in rodent models. AC3174 was stable in human plasma (>90% of parent peptide was present after 5 h of incubation). In rats, the in vivo half-life of AC3174 was 42-43 min following SC administration. In summary, AC3174 is an analog of exenatide that binds to the GLP-1 receptor in vitro and shares many of the biological and glucoregulatory activities of exenatide and GLP-1 in vivo.