TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy

We carried out whole-genome homozygosity mapping, gene expression analysis and DNA sequencing in individuals with isolated mitochondrial ATP synthase deficiency and identified disease-causing mutations in TMEM70. Complementation of the cell lines of these individuals with wild-type TMEM70 restored biogenesis and metabolic function of the enzyme complex. Our results show that TMEM70 is involved in mitochondrial ATP synthase biogenesis in higher eukaryotes.     

A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia

We conducted a genome-wide association study of 299,983 tagging SNPs for chronic lymphocytic leukemia (CLL) and performed validation in two additional series totaling 1,529 cases and 3,115 controls. We identified six previously unreported CLL risk loci at 2q13 (rs17483466; P = 2.36 x 10(-10)), 2q37.1 (rs13397985, SP140; P = 5.40 x 10(-10)), 6p25.3 (rs872071, IRF4; P = 1.91 x 10(-20)), 11q24.1 (rs735665; P = 3.78 x 10(-12)), 15q23 (rs7176508; P = 4.54 x 10(-12)) and 19q13.32 (rs11083846, PRKD2; P = 3.96 x 10(-9)). These data provide the first evidence for the existence of common, low-penetrance susceptibility to a hematological malignancy and new insights into disease causation in CLL.     

LKB1 signaling in mesenchymal cells required for suppression of gastrointestinal polyposis

Germline mutations in STK11 (also known as LKB1) are found in individuals with Peutz-Jeghers syndrome (PJS) manifesting with gastrointestinal polyps that contain a prominent stromal component. Epithelia in polyps of Stk11(+/-) mice can retain a functional copy of Stk11 (refs. 2,3), and loss of heterozygosity is not an obligate feature of human polyps, raising the possibility of non-epithelial origins in tumorigenesis. Here we show that either monoallelic or biallelic loss of murine Stk11 limited to Tagln-expressing mesenchymal cells results in premature postnatal death as a result of gastrointestinal polyps indistinguishable from those in PJS. Stk11-deficient mesenchymal cells produced less TGFbeta, and defective TGFbeta signaling to epithelial cells coincided with epithelial proliferation. We also noted TGFbeta signaling defects in polyps of individuals with PJS, suggesting that the identified stromal-derived mechanism of tumor suppression is also relevant in PJS.     

Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci

Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) < P(overall) < 1.6 x 10(-23); odds ratio = 0.82-1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 x 10(-5)) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < 2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE.     

A nonsynonymous functional variant in integrin-alpha(M) (encoded by ITGAM) is associated with systemic lupus erythematosus

We identified and replicated an association between ITGAM (CD11b) at 16p11.2 and risk of systemic lupus erythematosus (SLE) in 3,818 individuals of European descent. The strongest association was at a nonsynonymous SNP, rs1143679 (P = 1.7 x 10(-17), odds ratio = 1.78). We further replicated this association in two independent samples of individuals of African descent (P = 0.0002 and 0.003; overall meta-analysis P = 6.9 x 10(-22)). The genetic association between ITGAM and SLE implicates the alpha(M)beta2-integrin adhesion pathway in disease development.     

Evaluation of the Heat,Entropy, and Rotational Changes Produced by Gravitational Segregation during Core Formation

Core formation by gravitational segregation allegedly released sufficient interior heat to melt the Earth. Analysis of the energetics, which compare gravitational potential energy (Ug) of a fictitious,...     

Use of Geochemical and Geophysical Techniques to Characterize and Prospect for Geothermal Resources and Hydrothermal Ore Deposits

Fluid-rock interactions alter the geochemical, isotopic, petrographic and physical character of host rocks, producing a permanent record of hydrothermal activity. Maps of altered rock properties show r...     

Diffusion effects on formation process of mesoporous molecular sieve MCM-41

The regular mesoporous molecular sieve MCM-41 has been investigated at different stages during its formation,using high resolution transmission electron microscopy and powder X-ray diffraction.The results not only support the liquid-crystal templating mechanism previously postulated,but allow the extension fo its scope to discribe ditails of MCM-41 formation.It has been observed that formation of the hexagonal liquid crystal phase on the one hand and of silica aggregates on the other,occurs simultaneously at the inception of gel formation and throughout the crystallisation.This process is most probably affected by diffusion of both the surfactant molecules and the oligomeric silicate ions.With this postulate it becomes possible to explain several experimental observation(both old and new)and to develop a multi-step synthesis method to grow large particles of MCM-41 using small calcined crystals of MCM-41 as seeds.     

Molecular phylogeny of European and African Barbus and their West Asian relatives in the Cyprininae (Teleostei: Cypriniformes) and orogenesis of the Qinghai-Tibetan Plateau

The phylogenetic relationships of European and African Barbus and their West Asian relatives in Cyprininae remain largely unresolved. Consequently, little is known about the drivers of their evolution, including the possible association of uplifting of the Qinghai-Tibetan Plateau (QTP) with the early divergence of the subfamily. We use complete sequence data of the mitochondrial DNA gene encoding the protein cytochrome b (Cytb) to hypothesize the phylogeny of 85 species belonging to 47 genera in the Cyprininae plus 6 species from the Leuciscinae. We employ 6 other species from Cypriniformes as outgroup taxa and estimate divergence times. Our results indicate that European Barbus sensu stricto lineage including Aulopyge shares a common ancestor with specialized and highly specialized schizothoracins and the genera Cyprinion and Scaphiodonichtys. The common ancestor appears to have originated in the Qinghai-Tibetan Plateau (QTP) region about 19.4–17.8 Ma. Barbus sensu stricto lineage appears to have originated about 16.6–15.5 Ma. Small to medium sized African Barbus sensu lato appear to have had an Oriental origin about 19.1–15.3 Ma and are closely related to Asian Puntius. West Asian Carasobarbus lineage including large African Barbus sensu lato might have originated about 9.94 Ma, also in Oriental Realm and has a close relationship to Asian Neolissochilus and Tor. The large-sized Barbus sensu lato appear to have diverged from Carasobarbus about 7.7 Ma. Finally, the Cyprininae appear to have radiated rapidly into nine lineages and many sublineages from about 27.8 to 17.8 Ma, close to the time of the second-stage tectonic movements of the QTP. Our analyses provide evidence that the uplifting of the QTP drove early diversification of the Cyprininae. Our extensive sampling of species involving all of the important areas results in clear evolutionary scenario for the Cyprininae.     

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Systemic Practice and Action Research -