INS VNTR is not associated with childhood obesity in 1,023 families: a family-based study

Previous studies have described genetic associations of the insulin gene variable number tandem repeat (INS VNTR) variant with childhood obesity and associated phenotypes. We aimed to assess the contribution of INS VNTR genotypes to childhood obesity and variance of insulin resistance, insulin secretion, and birth weight using family-based design. Participants were either French or German whites. We used transmission disequilibrium tests (TDTs) for assessing binary traits and quantitative pedigree disequilibrium tests for assessing continuous traits. In contrast to previous findings, we did not observe any familial association with childhood obesity (T = 50%, P = 0.77) in the 1,023 families tested. In French obese children, INS VNTR did not associate with fasting insulin levels (P = 0.23) and class I allele showed only borderline association with increased insulin secretion index at 30 min (P = 0.03). INS VNTR did not associate with birth weight in obese children (P = 0.98) and TDT analyses in 350 French families with history of low birth weight (LBW) showed no association with this condition (P = 0.92). In summary, our study, the largest performed so far, does not support the previously reported associations between INS VNTR and childhood obesity, insulin resistance, or birth weight, and does not suggest any major role for this variant in modulating these traits.     

Abundance and Impact on Soil Properties of Cathedral and Lenticular Termite Mounds in Southern Indian Woodlands

Despite the acknowledged roles of termites in tropical ecosystems, the majority of published studies of epigeal mounds still address the African fauna and are principally concerned with spatial patterns and putative inter-colony competition, rather than the links between parent soil properties and mound establishment. Further, information about the effects of habitat disturbance, and especially fragmentation, is lacking. This study assessed the abundance and distribution of the cathedral- and lenticular-type aboveground mounds of fungus-growing termites (Macrotermitinae), which are a common feature of South Indian woodlands, in relation to soil properties (vertisol vs. ferralsol) and habitat fragmentation (forest vs. highway margins). Mound abundance averaged 3.5 (standard error, SE 0.8) ha^?1 (cathedral) and 12.9 (SE 2.1) ha^?1 (lenticular), but was not influenced either by soil properties or disturbance. However, the volume of soil stored in the mounds varied between 27 (SE 8) m³ ha^?1 (ferralsol) and 47 (SE 6) m³ ha^?1 (vertisol). At the watershed scale, such volumes are equivalent to a 3.1-mm layer of soil if spread evenly across the landscape, roughly the same as the estimated erosion over the life of a typical mound. Significantly more nutrients were stored in lenticular mounds, especially on the vertisol, but the significance of these at the ecosystem level was considered small. In conclusion, this study suggests that termite mounds, and especially lenticular mounds, have a significant impact on soil dynamics at the watershed scale but a limited impact on the distribution of C and nutrients.     

Proteomics in clinical trials and practice: present uses and future promise

The study of clinical proteomics is a promising new field that has the potential to have many applications, including the identification of biomarkers and monitoring of disease, especially in the field of oncology. Expression proteomics evaluates the cellular production of proteins encoded by a particular gene and exploits the differential expression and post-translational modifications of proteins between healthy and diseased states. These biomarkers may be applied towards early diagnosis, prognosis, and prediction of response to therapy. Functional proteomics seeks to decipher protein-protein interactions and biochemical pathways involved in disease biology and targeted by newer molecular therapeutics. Advanced spectrometry technologies and new protein array formats have improved these analyses and are now being applied prospectively in clinical trials. Further advancement of proteomics technology could usher in an era of personalized molecular medicine, where diseases are diagnosed at earlier stages and where therapies are more effective because they are tailored to the protein expression of a patient's malignancy.     

Xanthanolides from Xanthium spinosum

The aerial parts of Xanthium spinosum afforded in addition to known xanthanolides three new ones. The structures were elucidated by spectroscopic methods and by partial synthesis. Furthermore one lactone was transformed to a known derivative.     

The function of the octamer-binding site in the DRA promoter

The octamer binding site, which is located immediately upstream of the poorly conserved DRA TATA sequence, is important fof high levels of expression of this human major histocompatibility class II gene in B cells. In this study, we demonstrate that the substitution of the DRA TATA sequence with the TATA box from the adenovirus E1b promoter revomes the requirements for the octamer binding site for high levels of expression from DRA promoter. Since only the TATA box from the E1b but bot the DRA promoters binds the TATA binding protein, we conclude that the octamer binding site helps to recruit TBP to the DRA promoter.     

Map-based isolation of disease resistance genes from bread wheat: cloning in a supersize genome

The genome of bread wheat is hexaploid and contains 1.6 x 10 10 bp of DNA, of which more than 80% is repetitive sequences. Its size and complexity represent a challenge for the isolation of agronomically important genes, for which we frequently know only their position on the genetic map. Recently, new genomic resources and databases from genome projects have simplified the molecular analysis of the wheat genome. The first genes to be isolated from wheat by map-based cloning include three resistance genes against the fungal diseases powdery mildew and leaf rust. In this review, we will describe the approaches and resources that have contributed to this progress, and discuss genomic strategies that will simplify positional cloning in wheat in the near future.     

Differential role of three major New Zealand Black-derived loci linked with Yaa-induced murine lupus nephritis

By assessing the development of Y-linked autoimmune acceleration (Yaa) gene-induced systemic lupus erythematosus in C57BL/6 (B6) x (New Zealand Black (NZB) x B6.Yaa)F(1) backcross male mice, we mapped three major susceptibility loci derived from the NZB strain. These three quantitative trait loci (QTL) on NZB chromosomes 1, 7, and 13 differentially regulated three different autoimmune traits: anti-nuclear autoantibody production, gp70-anti-gp70 immune complex (gp70 IC) formation, and glomerulonephritis. Contributions to the disease traits were further confirmed by generating and analyzing three different B6.Yaa congenic mice, each carrying one individual NZB QTL. The chromosome 1 locus that overlapped with the previously identified Nba2 (NZB autoimmunity 2) locus regulated all three traits. A newly identified chromosome 7 locus, designated Nba5, selectively promoted anti-gp70 autoantibody production, hence the formation of gp70 IC and glomerulonephritis. B6.Yaa mice bearing the NZB chromosome 13 locus displayed increased serum gp70 production, but not gp70 IC formation and glomerulonephritis. This locus, called Sgp3 (serum gp70 production 3), selectively regulated the production of serum gp70, thereby contributing to the formation of nephritogenic gp70 IC and glomerulonephritis, in combination with Nba2 and Nba5 in NZB mice. Among these three loci, a major role of Nba2 was demonstrated, because B6.Yaa Nba2 congenic male mice developed the most severe disease. Finally, our analysis revealed the presence in B6 mice of an H2-linked QTL, which regulated autoantibody production. This locus had no apparent individual effect, but most likely modulated disease severity through interaction with NZB-derived susceptibility loci.     

Allelic series of four powdery mildew resistance genes at the Pm3 locus in hexaploid bread wheat

At the Pm3 locus in hexaploid wheat (Triticum aestivum), 10 alleles conferring race-specific resistance to powdery mildew (Blumeria graminis f. sp. tritici) are known. A cluster of genes encoding coiled-coil-nucleotide-binding site-leucine-rich repeat proteins spans the Pm3 locus on wheat chromosome 1A, and one member of this gene family has recently been identified as the Pm3b resistance gene. Using molecular markers closely linked to Pm3b, we performed haplotype analysis of 10 lines carrying different Pm3 alleles. All these lines have a conserved genomic region delimited by markers cosegregating with Pm3b and including a structurally conserved Pm3b-like gene. A polymerase chain reaction-based strategy allowed the amplification of one Pm3b-like sequence from lines carrying Pm3a, Pm3d, and Pm3f alleles. These candidate genes for Pm3a, Pm3d, and Pm3f conferred AvrPm3a-, AvrPm3d-, and AvrPm3f-dependent resistance, respectively, to wheat powdery mildew in a single cell transient transformation assay. A high level of amino acid similarity (97.8%) was found between the PM3A, PM3B, PM3D, and PM3F proteins. The coiled-coil domain was 100% conserved, whereas, in the nucleotide binding site region, sequence exchange was detected, indicating intragenic recombination or gene conversion between alleles. All these results indicate that Pm3a, Pm3b, Pm3d, and Pm3f form a true allelic series. The low level of sequence divergence between the four characterized alleles as well as the finding of a conserved Pm3 haplotype are in agreement with the hypothesis of a recent evolution of Pm3-based resistance, suggesting that some or most of the diversity found at the Pm3 locus in modern wheat has evolved after wheat domestication.