Synthesis of FF8181-A

Both enantiomers of FF8181-A were synthesized through optical resolution from the known Diels-Alder reaction product in 15 steps. The absolute configuration of the natural product was determined to be 1S,5S,5aS,9aS,9bS.     

An Ecological Risk Assessment of Hexachlorobutadiene

Hexachlorobutadiene (HCBD) has never been commercially produced in Canada and was imported in the past for use as a solvent. Anthropogenic activity is linked with the entry of this substance into the environment. While current Canadian sources of HCBD involve low-level releases, potentially they can be numerous. Until recently, the most significant point source of HCBD in Canada appeared to be the Cole Drain, which discharges into the St. Clair River at Sarnia, Ontario, and includes outfalls from an industrial landfill and a few industrial companies. HCBD has been detected in Canadian surface waters, sediments, aquatic organisms and, occasionally, air. Considering the properties of the substance, including its persistence and bioaccumulation characteristics, the environmental risk assessment of HCBD was focused on the aquatic environment. The results of a conservative assessment suggest that there is a risk of harmful effects for benthic organisms exposed to sediments contaminated by HCBD in the most contaminated part of the St. Clair River.     

Association between antibody response against cytomegalovirus strain-specific glycoprotein H epitopes and HLA-DR

The gH of CMV is a major target for strain-specific neutralizing antibodies. To verify whether there is a correlation between HLA-DR type and strain-specific antibodies, antibodies against CMV gH in potential donors and recipients for renal transplantation were investigated. Among 471 subjects, 404 (86%) showed reactivity to CMV gH, but no antibodies against gH were detected in 67 (14%) subjects. The positive rates were over 80% in most HLA subpopulations. Fewer subjects with HLA-DR10 and DR11 had antibodies to CMV gH than did those without HLA-DR10 and DR11. HLA-DR10 and DR11 may be associated with fewer/non-responders for strain-specific neutralizing antibodies.     

5-Aminopyrimidin-2-ylnitriles as Cathepsin K inhibitors

A series of pyrimidine nitrile inhibitors of Cathepsin K with reduced glutathione reactivity has been identified and Molecular Core Matching (MoCoM) has been used to quantify the effect of an amino substituent at C5.     

Genetic control of wheat quality: interactions between chromosomal regions determining protein content and composition, dough rheology, and sponge and dough baking properties

While the genetic control of wheat processing characteristics such as dough rheology is well understood, limited information is available concerning the genetic control of baking parameters, particularly sponge and dough (S&D) baking. In this study, a quantitative trait loci (QTL) analysis was performed using a population of doubled haploid lines derived from a cross between Australian cultivars Kukri × Janz grown at sites across different Australian wheat production zones (Queensland in 2001 and 2002 and Southern and Northern New South Wales in 2003) in order to examine the genetic control of protein content, protein expression, dough rheology and sponge and dough baking performance. The study highlighted the inconsistent genetic control of protein content across the test sites, with only two loci (3A and 7A) showing QTL at three of the five sites. Dough rheology QTL were highly consistent across the 5 sites, with major effects associated with the Glu-B1 and Glu-D1 loci. The Glu-D1 5 + 10 allele had consistent effects on S&D properties across sites; however, there was no evidence for a positive effect of the high dough strength Glu-B1-al allele at Glu-B1. A second locus on 5D had positive effects on S&D baking at three of five sites. This study demonstrated that dough rheology measurements were poor predictors of S&D quality. In the absence of robust predictive tests, high heritability values for S&D demonstrate that direct selection is the current best option for achieving genetic gain in this product category. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Is there evidence of adaptation to tidal flooding in saplings of baldcypress subjected to different salinity regimes?

Plant populations may adapt to environmental conditions over time by developing genetically based morphological or physiological characteristics. For tidal freshwater forested wetlands, we hypothesized that the conditions under which trees developed led to ecotypic difference in response of progeny to hydroperiod. Specifically, we looked for evidence of ecotypic adaptation for tidal flooding at different salinity regimes using growth and ecophysiological characteristics of two tidal and two non-tidal source collections of baldcypress (Taxodium distichum (L.) L.C. Rich) from the southeastern United States. Saplings were subjected to treatments of hydrology (permanent versus tidal flooding) and salinity (0 versus ～2 g l^?1) for two and a half growing seasons in a greenhouse environment. Saplings from tidal sources maintained 21–41% lower overall growth and biomass accumulation than saplings from non-tidal sources, while saplings from non-tidal sources maintained 14–19% lower overall rates of net photosynthetic assimilation, leaf transpiration, and stomatal conductance than saplings from tidal sources. However, we found no evidence for growth or physiological enhancement of saplings from tidal sources to tide, or of saplings from non-tidal sources to no tide. All saplings growing under permanent flooding exhibited reduced growth and leaf gas exchange regardless of source, with little evidence for consistent salinity effects across hydroperiods. While we reject our original hypothesis, we suggest that adaptations of coastal baldcypress to broad (rather than narrow) environmental conditions may promote ecophysiological and growth enhancements under a range of global-change-induced stressors, perhaps reflecting a natural resilience to environmental change while precluding adaptations for specific flood regimes.     

Insights into the catalytic roles of the polypeptide regions in the active site of thermolysin and generation of the thermolysin variants with high activity and stability

The active site of thermolysin is composed of one zinc ion and five polypeptide regions [N-terminal sheet (Asn112-Trp115), alpha-helix 1 (Val139-Thr149), C-terminal loop 1 (Asp150-Gly162), alpha-helix 2 (Ala163-Val176) and C-terminal loop 2 (Gln225-Ser234)]. To explore their catalytic roles, we introduced single amino-acid substitutions into these regions by site-directed mutagenesis and examined their effects on the activity and stability. Seventy variants, in which one of the twelve residues (Ala113, Phe114, Trp115, Asp150, Tyr157, Gly162, Ile168, Ser169, Asp170, Asn227, Val230 and Ser234) was replaced, were produced in Escherichia coli. The hydrolytic activities of thermolysin for N-[3-(2-furyl)acryloyl]-Gly-l-Leu amide (FAGLA) and casein revealed that the N-terminal sheet and alpha-helix 2 were critical in catalysis and the C-terminal loops 1 and 2 were in substrate recognition. Twelve variants were active for both substrates. In the hydrolysis of FAGLA and N-carbobenzoxy-L-Asp-L-Phe methyl ester, the k(cat)/K(m) values of the D150E (in which Asp150 is replaced with Glu) and I168A variants were 2-3 times higher than those of the wild-type (WT) enzyme. Thermal inactivation of thermolysin at 80 degrees C was greatly suppressed with the D150H, D150W, I168A, I168H, N227A, N227H and S234A. The evidence might provide the insights into the activation and stabilization of thermolysin.