CotB is essential for complete activation of green light-induced genes during complementary chromatic adaptation in Fremyella diplosiphon

The dramatic modifications of photosynthetic light harvesting antennae called phycobilisomes that occur during complementary chromatic adaptation in cyanobacteria are controlled by two separate photosensory systems. The first system involves the signal transduction components RcaE, RcaF and RcaC, which appear to make up a complex multistep phosphorelay. This system controls the light responsive expression of the cpcB2A2H2I2D2, cpeBA and cpeCDE operons, which encode phycobilisome proteins. The second system, which is not yet characterized, acts in concert with the first but only regulates the light responses of cpeBA and cpeCDE. We have generated and characterized a new mutant class, named the Tan mutants. In at least one member of this class, light-regulated RNA accumulation patterns are altered for cpeBA and cpeCDE, but not for cpcB2A2H2I2D2. Thus this mutant contains a lesion that may impair the operation of the second system. We demonstrate that several Tan mutants are the result of improper expression of the gene cotB. CotB has limited similarity to lyase class proteins, particularly those related to NblB, which is required for degradation of phycobilisomes in other cyanobacteria. Possible roles of CotB in the biogenesis of phycobilisomes are discussed.     

Variant mannose-binding lectin alleles are associated with celiac disease

In this study, we investigated the role of mannose-binding lectin (MBL) in celiac disease, by performing genotype analysis for the three point mutations in the first exon of the gene in 117 Italian celiac patients (characterized by flat biopsy and positive for anti-endomysium antibody and human transglutaminase antibodies) and 130 pan-ethnic healthy controls. The frequency of homozygous mutant 0/ 0 was significantly higher in the 117 Italian celiac patients (0.13) than in the 130 pan-ethnic healthy controls (0.05; P=0.0405). An increased frequency of homozygous 0/0 allele was found among patients with celiac disease compared with controls. These results suggest an involvement of MBL in the pathophysiology of celiac disease.     

Bacteria Associated with the Oesophageal Bulb of the Medfly Ceratitis capitata (Diptera:Tephritidae)

Extracellular Gram negative bacteria were found to be commonly associated to the oesophageal bulb of Ceratitis capitata with Klebsiella oxytoca and Enterobacter agglomerans as the most common species. All the isolates tested in vitro, except one, were sensitive to the antibacterial material present on the medfly laid egg surface. Received: 3 May 2001 / Accepted: 7 June 2001     

Myotonic dystrophy type 2: human founder haplotype and evolutionary conservation of the repeat tract

Myotonic dystrophy (DM), the most common form of muscular dystrophy in adults, can be caused by a mutation on either chromosome 19 (DM1) or 3 (DM2). In 2001, we demonstrated that DM2 is caused by a CCTG expansion in intron 1 of the zinc finger protein 9 (ZNF9) gene. To investigate the ancestral origins of the DM2 expansion, we compared haplotypes for 71 families with genetically confirmed DM2, using 19 short tandem repeat markers that we developed that flank the repeat tract. All of the families are white, with the majority of Northern European/German descent and a single family from Afghanistan. Several conserved haplotypes spanning >700 kb appear to converge into a single haplotype near the repeat tract. The common interval that is shared by all families with DM2 immediately flanks the repeat, extending up to 216 kb telomeric and 119 kb centromeric of the CCTG expansion. The DM2 repeat tract contains the complex repeat motif (TG)(n)(TCTG)(n)(CCTG)(n). The CCTG portion of the repeat tract is interrupted on normal alleles, but, as in other expansion disorders, these interruptions are lost on affected alleles. We examined haplotypes of 228 control chromosomes and identified a potential premutation allele with an uninterrupted (CCTG)(20) on a haplotype that was identical to the most common affected haplotype. Our data suggest that the predominant Northern European ancestry of families with DM2 resulted from a common founder and that the loss of interruptions within the CCTG portion of the repeat tract may predispose alleles to further expansion. To gain insight into possible function of the repeat tract, we looked for evolutionary conservation. The complex repeat motif and flanking sequences within intron 1 are conserved among human, chimpanzee, gorilla, mouse, and rat, suggesting a conserved biological function.     

Design and synthesis of potent RSK inhibitors

Utilizing the already described 3,4-bi-aryl pyridine series as a starting point, incorporation of a second ring system with a hydrogen bond donor and additional hydrophobic contacts yielded the azaindole series which exhibited potent, picomolar RSK2 inhibition and the most potent in vitro target modulation seen thus far for a RSK inhibitor. In the context of the more potent core, several changes at the phenol moiety were assessed to potentially find a tool molecule appropriate for in vivo evaluation.     

The dependency of fetal left ventricular biomechanics function on myocardium helix angle configuration

The helix angle configuration of the myocardium is understood to contribute to the heart function, as finite element (FE) modeling of postnatal hearts showed that altered configurations affected cardiac function and biomechanics. However, similar investigations have not been done on the fetal heart. To address this, we performed image-based FE simulations of fetal left ventricles (LV) over a range of helix angle configurations, assuming a linear variation of helix angles from epicardium to endocardium. Results showed that helix angles have substantial influence on peak myofiber stress, cardiac stroke work, myocardial deformational burden, and spatial variability of myocardial strain. A good match between LV myocardial strains from FE simulations to those measured from 4D fetal echo images could only be obtained if the transmural variation of helix angle was generally between 110 and 130°, suggesting that this was the physiological range. Experimentally discovered helix angle configurations from the literature were found to produce high peak myofiber stress, high cardiac stroke work, and a low myocardial deformational burden, but did not coincide with configurations that would optimize these characteristics. This may suggest that the fetal development of myocyte orientations depends concurrently on several factors rather than a single factor. We further found that the shape, rather than the size of the LV, determined the manner at which helix angles influenced these characteristics, as this influence changed significantly when the LV shape was varied, but not when a heart was scaled from fetal to adult size while retaining the same shape. This may suggest that biomechanical optimality would be affected during diseases that altered the geometric shape of the LV.