Fate of prions in soil: Degradation of recombinant prion in aqueous extracts from soil and casts of two earthworm species

Prions represent the active agent in transmissible spongiform encephalopathy (TSE) diseases and can remain infective to mammals even after prolonged periods in soil. The influence of mesofauna on prion dispersal and degradation in soil, however, remains unknown. In this study the effect of earthworms on the retention/dissemination of TSEs in soil was evaluated using a model recombinant prion protein (recPrP) and aqueous extracts from soil and fresh casts of two earthworm species, Lumbricus terrestris and Aporrectodea caliginosa. Our results showed that earthworm gut-derived enzymes did not enhance the degradation of recPrP in comparison to soil, even though non-prion related proteolytic activity was higher in fresh worm excrements than in soil samples. Complete degradation of recPrP occurred in the aqueous extracts from all samples within up to 6 days at +15 °C. The proteolytic enzymes responsible for degrading recPrP were inhibited by aprotinin and leupeptin and studies in pure cultures suggested these were most probably of soil microbial origin.     

Use of multiparental inbred populations to determine allelic relationships of molecular markers

The assessment of polymorphism exhibited by molecular markers is an arduous but essential task that facilitates the use of molecular tools by breeders and geneticists. For that purpose, the value of a wheat composite population was assessed for characterizing the diversity of restriction fragment length polymorphism (RFLP) markers developed by INRA-Génoblé. The polymorphism of 13 genomic probes was measured over a set of 80 inbred lines randomly extracted by single-seed descent from a composite-cross of 16 wheat lines. The 13 probéenzyme combinations revealed 27 loci with codominant polymorphism. As many bands were so far unmapped, the segregational analysis of the progenies appeared very suitable for complex patterns, both in determining allelic relationships and in revealing linkage between loci. Allelic diversity, band sizes and chromosomal location assessed from nullisomic-tetrasomic lines are given for the 27 loci.     

Detection of linkage between RFLP markers and genes affecting anthocyanin pigmentation in maize (Zea mays L.)

Summary Linkages between molecular markers and genes involved in the expression of agronomical traits have already been described in all of the major crops. In most cases, the genetic model underlying the Quantitative Traits Loci (QTL) is discussed. Here, Restriction Fragment Length Polymorphisms (RFLPs) and Mapmaker-QTL have been used to pinpoint seven regions of the genome significantly correlated with four pigmentation qualitative traits of maize (Zea mays L.). Two of these, located on chromosomes 2 and 10, explain most of the variation of these traits. The R and B gene loci known to be involved in the regulation of the anthocyanin pathway map to the same regions and we suggest that these loci could be the candidate genes involved in the correlations detected with RFLPs. This type of result is in accordance with the hypothesis of the candidate gene which supposes that, if we have a very high density map of randomly-selected cDNA clones, it should theoretically be possible to associate a cloned genic sequence with a phenotypic trait where correlations are found.     

Germline allele-specific expression of TGFBR1 confers an increased risk of colorectal cancer

Much of the genetic predisposition to colorectal cancer (CRC) in humans is unexplained. Studying a Caucasian-dominated population in the United States, we showed that germline allele-specific expression (ASE) of the gene encoding transforming growth factor-beta (TGF-beta) type I receptor, TGFBR1, is a quantitative trait that occurs in 10 to 20% of CRC patients and 1 to 3% of controls. ASE results in reduced expression of the gene, is dominantly inherited, segregates in families, and occurs in sporadic CRC cases. Although subtle, the reduction in constitutive TGFBR1 expression alters SMAD-mediated TGF-beta signaling. Two major TGFBR1 haplotypes are predominant among ASE cases, which suggests ancestral mutations, but causative germline changes have not been identified. Conservative estimates suggest that ASE confers a substantially increased risk of CRC (odds ratio, 8.7; 95% confidence interval, 2.6 to 29.1), but these estimates require confirmation and will probably show ethnic differences.     

Mutant enzymatic and cytological phenotypes in cultured human fibroblasts

Fibroblasts were cultured from the cells of two children who shared some characteristics of Hurler syndrome, but they did not show corneal clouding and excessive excretion of mucopolysaccharides. The fibroblasts differ from those of controls and of patients with typical Hurler syndrome or other mucopolysaccharidoses in that they have abundant cytoplasmic inclusions, striking diminutions in beta-glucuronidase, and elevations in acid phosphatase.     

A compound ovary with open carpels in winteraceae (magnoliales): evolutionary implications

"Bubbia" perrieri, a primitive angiosperm collected once in 1909 in northwestern Madagascar, differs from all other members of its genus and family (Winteraceae) in its bicarpellate, unilocular ovary. Moreover, its inflorescences are terminal, and its development is partially sympodial. It therefore represents the survivor of a previously undetected evolutionary line that should be accorded at least subfamilial status. If so, Winteraceae might, more likely than previously, be considered as allied to Canellaceae, a group of primitive angiosperms that has an ovary of "Bubbia" perrieri type and is specialized in some other respects.     

Multiple Ebola virus transmission events and rapid decline of central African wildlife

Several human and animal Ebola outbreaks have occurred over the past 4 years in Gabon and the Republic of Congo. The human outbreaks consisted of multiple simultaneous epidemics caused by different viral strains, and each epidemic resulted from the handling of a distinct gorilla, chimpanzee, or duiker carcass. These animal populations declined markedly during human Ebola outbreaks, apparently as a result of Ebola infection. Recovered carcasses were infected by a variety of Ebola strains, suggesting that Ebola outbreaks in great apes result from multiple virus introductions from the natural host. Surveillance of animal mortality may help to predict and prevent human Ebola outbreaks.     

Identification of a DNA nonhomologous end-joining complex in bacteria

In eukaryotic cells, double-strand breaks (DSBs) in DNA are generally repaired by the pathway of homologous recombination or by DNA nonhomologous end joining (NHEJ). Both pathways have been highly conserved throughout eukaryotic evolution, but no equivalent NHEJ system has been identified in prokaryotes. The NHEJ pathway requires a DNA end-binding component called Ku. We have identified bacterial Ku homologs and show that these proteins retain the biochemical characteristics of the eukaryotic Ku heterodimer. Furthermore, we show that bacterial Ku specifically recruits DNA ligase to DNA ends and stimulates DNA ligation. Loss of these proteins leads to hypersensitivity to ionizing radiation in Bacillus subtilis. These data provide evidence that many bacteria possess a DNA DSB repair apparatus that shares many features with the NHEJ system of eukarya and suggest that this DNA repair pathway arose before the prokaryotic and eukaryotic lineages diverged.     

TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterized pathologically by ubiquitinated TAR DNA binding protein (TDP-43) inclusions. The function of TDP-43 in the nervous system is uncertain, and a mechanistic role in neurodegeneration remains speculative. We identified neighboring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases. TARDBPM337V segregated with disease within one kindred and a genome-wide scan confirmed that linkage was restricted to chromosome 1p36, which contains the TARDBP locus. Mutant forms of TDP-43 fragmented in vitro more readily than wild type and, in vivo, caused neural apoptosis and developmental delay in the chick embryo. Our evidence suggests a pathophysiological link between TDP-43 and ALS.