An absence of ex-companion stars in the type Ia supernova remnant SNR 0509-67.5

A type Ia supernova is thought to begin with the explosion of a white dwarf star. The explosion could be triggered by the merger of two white dwarfs (a 'double-degenerate' origin), or by mass transfer from a companion star (the 'single-degenerate' path). The identity of the progenitor is still controversial; for example, a recent argument against the single-degenerate origin has been widely rejected. One way to distinguish between the double- and single-degenerate progenitors is to look at the centre of a known type Ia supernova remnant to see whether any former companion star is present. A likely ex-companion star for the progenitor of the supernova observed by Tycho Brahe has been identified, but that claim is still controversial. Here we report that the central region of the supernova remnant SNR 0509-67.5 (the site of a type Ia supernova 400?±?50 years ago, based on its light echo) in the Large Magellanic Cloud contains no ex-companion star to a visual magnitude limit of 26.9 (an absolute magnitude of M(V) = +8.4) within a region of radius 1.43 arcseconds. (This corresponds to the 3σ maximum distance to which a companion could have been 'kicked' by the explosion.) This lack of any ex-companion star to deep limits rules out all published single-degenerate models for this supernova. The only remaining possibility is that the progenitor of this particular type Ia supernova was a double-degenerate system.     

Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17

Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. A large proportion of FTD patients (35-50%) have a family history of dementia, consistent with a strong genetic component to the disease. In 1998, mutations in the gene encoding the microtubule-associated protein tau (MAPT) were shown to cause familial FTD with parkinsonism linked to chromosome 17q21 (FTDP-17). The neuropathology of patients with defined MAPT mutations is characterized by cytoplasmic neurofibrillary inclusions composed of hyperphosphorylated tau. However, in multiple FTD families with significant evidence for linkage to the same region on chromosome 17q21 (D17S1787-D17S806), mutations in MAPT have not been found and the patients consistently lack tau-immunoreactive inclusion pathology. In contrast, these patients have ubiquitin (ub)-immunoreactive neuronal cytoplasmic inclusions and characteristic lentiform ub-immunoreactive neuronal intranuclear inclusions. Here we demonstrate that in these families, FTD is caused by mutations in progranulin (PGRN) that are likely to create null alleles. PGRN is located 1.7 Mb centromeric of MAPT on chromosome 17q21.31 and encodes a 68.5-kDa secreted growth factor involved in the regulation of multiple processes including development, wound repair and inflammation. PGRN has also been strongly linked to tumorigenesis. Moreover, PGRN expression is increased in activated microglia in many neurodegenerative diseases including Creutzfeldt-Jakob disease, motor neuron disease and Alzheimer's disease. Our results identify mutations in PGRN as a cause of neurodegenerative disease and indicate the importance of PGRN function for neuronal survival.     

Disruption of an imprinted gene cluster by a targeted chromosomal translocation in mice

Genomic imprinting is an epigenetic process in which the activity of a gene is determined by its parent of origin. Mechanisms governing genomic imprinting are just beginning to be understood. However, the tendency of imprinted genes to exist in chromosomal clusters suggests a sharing of regulatory elements. To better understand imprinted gene clustering, we disrupted a cluster of imprinted genes on mouse distal chromosome 7 using the Cre/loxP recombination system. In mice carrying a site-specific translocation separating Cdkn1c and Kcnq1, imprinting of the genes retained on chromosome 7, including Kcnq1, Kcnq1ot1, Ascl2, H19 and Igf2, is unaffected, demonstrating that these genes are not regulated by elements near or telomeric to Cdkn1c. In contrast, expression and imprinting of the translocated Cdkn1c, Slc22a1l and Tssc3 on chromosome 11 are affected, consistent with the hypothesis that elements regulating both expression and imprinting of these genes lie within or proximal to Kcnq1. These data support the proposal that chromosomal abnormalities, including translocations, within KCNQ1 that are associated with the human disease Beckwith-Wiedemann syndrome (BWS) may disrupt CDKN1C expression. These results underscore the importance of gene clustering for the proper regulation of imprinted genes.     

Genetic evidence for Near-Eastern origins of European cattle

The limited ranges of the wild progenitors of many of the primary European domestic species point to their origins further east in Anatolia or the fertile crescent. The wild ox (Bos primigenius), however, ranged widely and it is unknown whether it was domesticated within Europe as one feature of a local contribution to the farming economy. Here we examine mitochondrial DNA control-region sequence variation from 392 extant animals sampled from Europe, Africa and the Near East, and compare this with data from four extinct British wild oxen. The ancient sequences cluster tightly in a phylogenetic analysis and are clearly distinct from modern cattle. Network analysis of modern Bos taurus identifies four star-like clusters of haplotypes, with intra-cluster diversities that approximate to that expected from the time depth of domestic history. Notably, one of these clusters predominates in Europe and is one of three encountered at substantial frequency in the Near East. In contrast, African diversity is almost exclusively composed of a separate haplogroup, which is encountered only rarely elsewhere. These data provide strong support for a derived Near-Eastern origin for European cattle.