Mg isotope evidence for contemporaneous formation of chondrules and refractory inclusions

Primitive or undifferentiated meteorites (chondrites) date back to the origin of the Solar System, and thus preserve a record of the physical and chemical processes that occurred during the earliest evolution of the accretion disk surrounding the young Sun. The oldest Solar System materials present within these meteorites are millimetre- to centimetre-sized calcium-aluminium-rich inclusions (CAIs) and ferromagnesian silicate spherules (chondrules), which probably originated by thermal processing of pre-existing nebula solids. Chondrules are currently believed to have formed approximately 2-3 million years (Myr) after CAIs (refs 5-10)--a timescale inconsistent with the dynamical lifespan of small particles in the early Solar System. Here, we report the presence of excess (26)Mg resulting from in situ decay of the short-lived (26)Al nuclide in CAIs and chondrules from the Allende meteorite. Six CAIs define an isochron corresponding to an initial (26)Al/(27)Al ratio of (5.25 +/- 0.10) x 10(-5), and individual model ages with uncertainties as low as +/- 30,000 years, suggesting that these objects possibly formed over a period as short as 50,000 years. In contrast, the chondrules record a range of initial (26)Al/(27)Al ratios from (5.66 +/- 0.80) to (1.36 +/- 0.52) x 10(-5), indicating that Allende chondrule formation began contemporaneously with the formation of CAIs, and continued for at least 1.4 Myr. Chondrule formation processes recorded by Allende and other chondrites may have persisted for at least 2-3 Myr in the young Solar System.     

Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by features reminiscent of marked premature ageing. Here, we present evidence of mutations in lamin A (LMNA) as the cause of this disorder. The HGPS gene was initially localized to chromosome 1q by observing two cases of uniparental isodisomy of 1q-the inheritance of both copies of this material from one parent-and one case with a 6-megabase paternal interstitial deletion. Sequencing of LMNA, located in this interval and previously implicated in several other heritable disorders, revealed that 18 out of 20 classical cases of HGPS harboured an identical de novo (that is, newly arisen and not inherited) single-base substitution, G608G(GGC > GGT), within exon 11. One additional case was identified with a different substitution within the same codon. Both of these mutations result in activation of a cryptic splice site within exon 11, resulting in production of a protein product that deletes 50 amino acids near the carboxy terminus. Immunofluorescence of HGPS fibroblasts with antibodies directed against lamin A revealed that many cells show visible abnormalities of the nuclear membrane. The discovery of the molecular basis of this disease may shed light on the general phenomenon of human ageing.     

Suppression of CED-3-independent apoptosis by mitochondrial betaNAC in Caenorhabditis elegans

To ensure cell survival, it is essential that the ubiquitous pro-apoptotic machinery is kept quiescent. As death is irreversible, cells must continually integrate developmental information with regulatory inputs to control the switch between repressing and activating apoptosis. Inappropriate activation or suppression of apoptosis can lead to degenerative pathologies or tumorigenesis, respectively. Here we report that Caenorhabditis elegans inhibitor of cell death-1 (ICD-1) is necessary and sufficient to prevent apoptosis. Loss of ICD-1 leads to inappropriate apoptosis in developing and differentiated cells in various tissues. Although this apoptosis requires CED-4, it occurs independently of CED-3--the caspase essential for developmental apoptosis--showing that these core pro-apoptotic proteins have separable roles. Overexpressing ICD-1 inhibits the apoptosis of cells that are normally programmed to die. ICD-1 is the beta-subunit of the nascent polypeptide-associated complex (betaNAC) and contains a putative caspase-cleavage site and caspase recruitment domain. It localizes primarily to mitochondria, underscoring the role of mitochondria in coordinating apoptosis. Human betaNAC is a caspase substrate that is rapidly eliminated in dying cells, suggesting that ICD-1 apoptosis-suppressing activity may be inactivated by caspases.     

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.     

Recent Northern Hemisphere tropical expansion primarily driven by black carbon and tropospheric ozone

Observational analyses have shown the width of the tropical belt increasing in recent decades as the world has warmed. This expansion is important because it is associated with shifts in large-scale atmospheric circulation and major climate zones. Although recent studies have attributed tropical expansion in the Southern Hemisphere to ozone depletion, the drivers of Northern Hemisphere expansion are not well known and the expansion has not so far been reproduced by climate models. Here we use a climate model with detailed aerosol physics to show that increases in heterogeneous warming agents--including black carbon aerosols and tropospheric ozone--are noticeably better than greenhouse gases at driving expansion, and can account for the observed summertime maximum in tropical expansion. Mechanistically, atmospheric heating from black carbon and tropospheric ozone has occurred at the mid-latitudes, generating a poleward shift of the tropospheric jet, thereby relocating the main division between tropical and temperate air masses. Although we still underestimate tropical expansion, the true aerosol forcing is poorly known and could also be underestimated. Thus, although the insensitivity of models needs further investigation, black carbon and tropospheric ozone, both of which are strongly influenced by human activities, are the most likely causes of observed Northern Hemisphere tropical expansion.