Modification of chitosan-bead support materials with l-lysine and l-asparagine for α-amylase immobilization

Bioprocess and Biosystems Engineering - Maltose syrups have got wide-range utilizations in a variety of applications from bakery to drug-development. α-Amylases are among the most widely...     

Discovery and synthesis of tetrahydropyrimidinedione-4-carboxamides as endothelial lipase inhibitors

Endothelial lipase (EL) inhibitors have been shown to elevate HDL-C levels in pre-clinical murine models and have potential benefit in prevention and treatment of cardiovascular diseases. Modification of the 1-ethyl-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one (DHP) lead, 1, led to the discovery of a series of potent tetrahydropyrimidinedione (THP) EL inhibitors. Synthesis and SAR studies including modification of the amide group, together with changes on the pyrimidinone core led to a series of arylcycloalkyl, indanyl, and tetralinyl substituted 5-amino or 5-hydroxypyrimidinedione-4-carboxamides. Several compounds were advanced to PK evaluation. Among them, compound 4a was one of the most potent with measurable EL_HDL hSerum potency and compound 3g demonstrated the best overall pharmacokinetic parameters.     

Discovery of Mcl-1 inhibitors based on a thiazolidine-2,4-dione scaffold

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Care Wounds: Precarious Vulnerability and the Potential of Exposure

What does it mean to offer care when the act of caring is wounding to its giver? For peer specialists—individuals with lived experience as patients in the psychiatric system—this question shapes how they use their own histories to provide support for individuals experiencing psychiatric crisis. Peer support is unique in the way it draws on empathetic resonance and depends on carefully deployed vulnerability; where one connects with others through the recognition of shared experience and mutual hurt. For peers, care works when this guidance, reassurance, and "being with"—all of which draw upon their own stories of traumatic history and variegated suffering—mitigate the present crisis being experienced by another. Drawing on twenty-eight months of fieldwork with a peer-staffed crisis respite center in the eastern United States, I argue that the peer specialist becomes the embodiment of a novel intersection of intimacy and compensation; one that poses vulnerability not as a consequence, casualty, or risk factor in the commodification of care, but as its principle vector of resonance and the assumption on which it is based. For peers, care that works—in that it creates a mutual resonance for the recipient—becomes simultaneously care that wounds its giver.     

Echoes of the whispering land: interacting roles of vicariance and selection in shaping the evolutionary divergence of two <Emphasis Type="Italic">Calceolaria</Emphasis> (Calceolariaceae) species from Patagonia and Malvinas/Falkland Islands

A key to understanding the origin and identity of young species lays on the knowledge of the Quaternary climatic oscillations’ effect on gene flow and vicariance. Even though the effect of climatic fluctuations is relatively well understood for southern hemisphere plant species, little is known about their effect on the evolutionary histories of species from mainland and islands. Thus, we investigated whether Quaternary climate-driven fluctuations translated into lineage divergence and speciation, followed or not by climatic niche differentiation, in two allopatric plant species, Calceolaria uniflora and C. fothergillii from Patagonia and Malvinas/Falkland islands, respectively. We sampled the range of both species, and sequenced two chloroplastic (cpDNA; trnS–trnG and trnH–psbA), and one single copy “anonymous” non-coding nuclear region (nDNA). We performed phylogeographic and dating analyses, and adjusted spatio-temporal diffusion models. We complemented molecular evidence with climatic niche differentiation analyses and species paleo-distribution projections. A species coalescent reconstruction based on multi-locus data retrieved both species as monophyletic. Estimates from cpDNA indicated the species diverged during the Great Patagonian Glaciation. Chloroplast and nuclear DNA showed east–west distribution of the main genetic groups but with contrasting spatial genetic diversity. The spatio-temporal diffusion analyses showed that between 1–0.8 Mya and 570 Kya the lineage leading to C. fothergillii diverged from C. uniflora and arrived to the islands. Climatic niche projections hindcasted range expansions during glaciations, and contractions during the interglacial periods. Comparisons of climatic niches between the two study species indicated that temperature variables show evidence of niche conservatism while precipitation regimes supported niche divergence, even when considering the background environmental divergence. Our study indicates that glacial fluctuations affected the mainland/islands connections favouring speciation mediated not only by isolation, but also by climatic niche differentiation.     

Fusaria and Fusarium toxins in New Zealand maize plants

A time course study was made of the development of Fusarium infection and the appearance of the three Fusarium toxins, nivalenol (NV), deoxynivalenol (DON) and zearalenone (ZEN), in various fractions of maize plants from two sites in New Zealand, one in the Manawatu region and one in the Waikato. Fusarium infection was seen in leaf axil fractions in January, at the time of tassel emergence, and was detectable in stalks, leaf blades, rachis and peduncles during February and in kernels in April. NV, DON and ZEN were only detectable some time after infection was demonstrable. NV, in high concentrations relative to DON (up to 287 mg/kg for NV and up to 8 mg/kg for DON), was found in fractions from the Manawatu site where F. crookwellense and F. culmorum were the predominant toxigenic species. NV and DON at similar levels (up to 25 mg/kg) were found in fractions from the Waikato site at which F. graminearum and F. subglutinans predominated. Highest levels of NV and DON were in rachis and peduncle. ZEN was found most consistently in leaf axils and blades at both sites (up to 8 mg/kg at the Manawatu site and up to 75 mg/kg at the Waikato site) but at times there were high levels in rachis fractions (up to 417 mg/kg at the Manawatu site). This revised version was published online in June 2006 with corrections to the Cover Date.