Evidence for Orthologous Seed Weight Genes in Cowpea and Mung Bean Based on RFLP Mapping

A well saturated genomic map is a necessity for a breeding program based on marker assisted selection. To this end, we are developing genomic maps for cowpea (Vigna unguiculata 2N = 22) and mung bean (Vigna radiata 2N = 22) based on restriction fragment length polymorphism (RFLP) markers. Using these maps, we have located major quantitative trait loci (QTLs) for seed weight in both species. Two unlinked genomic regions in cowpea contained QTLs accounting for 52.7% of the variation for seed weight. In mung bean there were four unlinked genomic regions accounting for 49.7% of the variation for seed weight. In both cowpea and mung bean the genomic region with the greatest effect on seed weight spanned the same RFLP markers in the same linkage order. This suggests that the QTLs in this genomic region have remained conserved through evolution. This inference is supported by the observation that a significant interaction (i.e., epistasis) was detected between the QTL(s) in the conserved region and an unlinked RFLP marker locus in both species.     

Role of PAR2 in murine pulmonary pseudomonal infection

Proteinases can influence lung inflammation by various mechanisms, including via cleavage and activation of protease-activated receptors (PAR) such as PAR2. In addition, proteinases such as neutrophil and/or Pseudomonas-derived elastase can disarm PAR2 resulting in loss of PAR2 signaling. Currently, the role of PAR2 in host defense against bacterial infection is not known. Using a murine model of acute Pseudomonas aeruginosa pneumonia, we examined differences in the pulmonary inflammatory response between wild-type and PAR2(-/-) mice. Compared with wild-type mice, PAR2(-/-) mice displayed more severe lung inflammation and injury in response to P. aeruginosa infection as indicated by higher bronchoalveolar lavage fluid neutrophil numbers, protein concentration, and TNF-alpha levels. By contrast, IFN-gamma levels were markedly reduced in PAR2(-/-) compared with wild-type mice. Importantly, clearance of P. aeruginosa was diminished in PAR2(-/-) mice. In vitro testing revealed that PAR2(-/-) neutrophils killed significantly less bacteria than wild-type murine neutrophils. Further, both neutrophils and macrophages from PAR2(-/-) mice displayed significantly reduced phagocytic efficiency compared with wild-type phagocytes. Stimulation of PAR2 on macrophages using a PAR2-activating peptide resulted in enhanced phagocytosis directly implicating PAR2 signaling in the phagocytic process. We conclude that genetic deletion of PAR2 is associated with decreased clearance of P. aeruginosa. Our data suggest that a deficiency in IFN-gamma production and impaired bacterial phagocytosis are two potential mechanisms responsible for this defect.     

Centromere assembly and propagation

Centromere assembly provides a unique example of how elaborate protein structures can be assembled onto DNA, independent of sequence, and then stably propagated through numerous cell divisions. Here, we review the possible epigenetic strategies that organisms ranging from yeast to human use to assemble and propagate active centromeres.     

Assembly of the SIR complex and its regulation by O-acetyl-ADP-ribose, a product of NAD-dependent histone deacetylation

Assembly of silent chromatin domains in budding yeast involves the deacetylation of histone tails by Sir2 and the association of the Sir3 and Sir4 proteins with hypoacetylated histone tails. Sir2 couples deacetylation to NAD hydrolysis and the synthesis of a metabolite, O-acetyl-ADP-ribose (AAR), but the functional significance of NAD hydrolysis or AAR, if any, is unknown. Here we examine the association of the Sir2, Sir3, and Sir4 proteins with each other and histone tails. Our analysis reveals that deacetylation of histone H4-lysine 16 (K16), which is critical for silencing in vivo, is also critical for the binding of Sir3 and Sir4 to histone H4 peptides in vitro. Moreover, AAR itself promotes the association of multiple copies of Sir3 with Sir2/Sir4 and induces a dramatic structural rearrangement in the SIR complex. These results suggest that Sir2 activity modulates the assembly of the SIR complex through both histone deacetylation and AAR synthesis.     

Serum uric acid and coronary heart disease in 9,458 incident cases and 155,084 controls: prospective study and meta-analysis

BackgroundIt has been suggested throughout the past fifty years that serum uric acid concentrations can help predict the future risk of coronary heart disease (CHD), but the epidemiological evidence is uncertain.ConclusionsMeasurement of serum uric acid levels is unlikely to enhance usefully the prediction of CHD, and this factor is unlikely to be a major determinant of the disease in general populations.     

Lack of Innate Interferon Responses during SARS Coronavirus Infection in a Vaccination and Reinfection Ferret Model

In terms of its highly pathogenic nature, there remains a significant need to further define the immune pathology of SARS-coronavirus (SARS-CoV) infection, as well as identify correlates of immunity to help develop vaccines for severe coronaviral infections. Here we use a SARS-CoV infection-reinfection ferret model and a functional genomics approach to gain insight into SARS immunopathogenesis and to identify correlates of immune protection during SARS-CoV-challenge in ferrets previously infected with SARS-CoV or immunized with a SARS virus vaccine. We identified gene expression signatures in the lungs of ferrets associated with primary immune responses to SARS-CoV infection and in ferrets that received an identical second inoculum. Acute SARS-CoV infection prompted coordinated innate immune responses that were dominated by antiviral IFN response gene (IRG) expression. Reinfected ferrets, however, lacked the integrated expression of IRGs that was prevalent during acute infection. The expression of specific IRGs was also absent upon challenge in ferrets immunized with an inactivated, Al(OH)₃-adjuvanted whole virus SARS vaccine candidate that protected them against SARS-CoV infection in the lungs. Lack of IFN-mediated immune enhancement in infected ferrets that were previously inoculated with, or vaccinated against, SARS-CoV revealed 9 IRG correlates of protective immunity. This data provides insight into the molecular pathogenesis of SARS-CoV and SARS-like-CoV infections and is an important resource for the development of CoV antiviral therapeutics and vaccines.