Seemingly Unrelated Generalized Linear Models

By using deviance standardized residuals, the seemingly unrelated regression estimation procedure is extended to generalized linear models, and fitted by an iterative procedure. The matrix of cross products of standardized residuals is asymptotically multivariate normal, and can be used for further multivariate analyses and for hypothesis testing.     

Combination of cyclohexane and piperazine based κ-opioid receptor agonists: Synthesis and pharmacological evaluation of trans,trans-configured perhydroquinoxalines

Desymmetrization of the pseudochiral (2r)-configured cyclohexane-1,2,3-triamines 8 with dimethyl oxalate led to racemic aminoquinoxaline-2,3-diones 9. Selective introduction of the κ pharmacophoric structural elements pyrrolidine and 3,4-dichlorophenylacetamide with a two-carbon distance afforded conformationally restricted κ agonists 13–15 based on the quinoxaline ring system. In competitive radioligand receptor binding studies the benzylamine 13b, the secondary amine 14b, and the carbamate 15 displayed high κ receptor affinity. The K_i value of the lead compound derived methoxycarbonyl derivative 15 is 9.7 nM. However, the κ affinity of 15 is exceeded by 13b and 14b with a basic functional group instead of the methoxycarbonyl group in 1-position of the quinoxaline system. The chlorine atoms of the dichlorophenylacetyl residue are essential, since the corresponding phenylacetyl analogs show considerably reduced κ affinity. The potent κ ligands 13b, 14b and 15 are selective over the related μ- and δ-opioid receptors, σ₁, σ₂ and NMDA receptors. In the [³⁵S]GTPγS-binding assay 13b behaved as partial agonist with lower activity than U-69,593.     

Ascorbic acid prolongs the viability and stability of isolated perfused lungs: A mechanistic study using 31P and hyperpolarized 13C nuclear magnetic resonance

Ex vivo lung perfusion (EVLP) has recently shown promise as a means of more accurately gauging the health of lung grafts and improving graft performance post-transplant. However, reperfusion of ischemic lung promotes the depletion of high-energy compounds and a progressive loss of normal mitochondrial function, and it remains unclear how and to what extent the EVLP approach contributes to this metabolic decline. Although ascorbate has been used to mitigate the effects of ischemia–reperfusion injury, the nature of its effects during EVLP are also not clear. To address these uncertainties, this study monitored the energy status of lungs during EVLP and after the administration of ascorbate using ³¹P and hyperpolarized ¹³C NMR (nuclear magnetic resonance). Our experiments demonstrated that the oxidative phosphorylation capacity and pyruvate dehydrogenase flux of lungs decline during ex vivo perfusion. The addition of ascorbate to the perfusate prolonged lung viability by 80% and increased the hyperpolarized ¹³C bicarbonate signal by a factor of 2.7. The effect of ascorbate is apparently due not to its antioxidant quality but rather to its ability to energize cellular respiration given that it increased the lung’s energy charge significantly, whereas other antioxidants (glutathione and α-lipoic acid) did not alter energy metabolism. During ascorbate administration, inhibition of mitochondrial complex I with rotenone depressed energy charge and shifted the metabolic state of the lung toward glycolysis; reenergizing the electron transport chain with TMPD (N,N,N',N'-tetramethyl-p-phenylenediamine) recovered metabolic activity. This indicates that ascorbate slows the decline of the ex vivo perfused lung’s mitochondrial activity through an independent interaction with the electron transport chain complexes.     

CLIX: a search algorithm for finding novel ligands capable of binding proteins of known three-dimensional structure.

A computer algorithm, CLIX, capable of searching a crystallographic data-base of small molecules for candidates which have both steric and chemical likelihood of binding a protein of known three-dimensional structure is presented. The algorithm is a significant advance over previous strategies which consider solely steric or chemical requirements for binding. The algorithm is shown to be capable of predicting the correct binding geometry of sialic acid to a mutant influenza-virus hemagglutinin and of proposing a number of potential new ligands to this protein.     

Effects of habitat complexity and predator exclusion on the abundance of juvenile red snapper

Predator exclusion and habitat complexity factors that may affect juvenile red snapper Lutjanus campechanus habitat selection were examined in field and laboratory experiments. A significant predator exclusion effect was detected. Uncaged shell habitats showed significantly lower numbers of age 0 year red snapper, and both uncaged shell and block-shell habitats showed significantly lower numbers of age 1 year red snapper compared with caged habitats ( P < 0·001). Habitat complexity also affected age 0 year red snapper, as mean abundance significantly decreased with decreased habitat complexity ( P < 0·001). In the laboratory, age 0 year red snapper association with complex habitats significantly increased with exposure to a predator Gulf flounder Paralichthys albigutta ( P < 0·001). This study showed that predator exclusion and habitat complexity were significant factors that affected the abundance of juvenile red snapper in nursery areas of the northern Gulf of Mexico. Predation may affect juvenile red snapper abundance directly through mortality and indirectly by influencing habitat selection.     

Reproductive performance of four aphidophagous ladybirds on cowpea aphid, Aphis craccivora Koch

Abstract:  This study investigated prey consumption, egg production, percent progeny loss, reproductive, pre- and post-reproductive periods, reproductive time ratio, reproductive rate and bioconversion efficiency of four aphidophagous ladybirds, viz. Cheilomenes sexmaculata (Fabricius), Coccinella septempunctata Linnaeus, Coccinella transversalis Fabricius and Propylea dissecta (Mulsant) on Dolichos lablab Linnaeus infested with cowpea aphid, Aphis craccivora Koch. C. sexmaculata had the highest bioconversion efficiency, reproductive rate and reproductive time ratio followed in rank order by P. dissecta , C. transversalis and C. septempunctata . This study indicates that C. sexmaculata has a narrow ecological relationship with A. craccivora . The increased allocation of resources to reproduction as indicated through a high reproductive time ratio and high bioconversion efficiency of C. sexmaculata and P. dissecta suggest that they may be better adapted to compete for this prey with larger species like C. transversalis and C. septempunctata .