Public health vaccination policies for containing an anthrax outbreak

Concern about biological weapons has raised questions about the most effective public health policies to contain an anthrax outbreak. We developed a probability model to predict the impact of different anthrax antibiotic and vaccination policies. An anthrax outbreak can be significantly contained by minimizing the delay until initiation of antibiotic prophylaxis. However, even if mass distribution of antibiotics is completed within six days of the initial exposure, then at most about 70% of cases can be prevented. Post-exposure vaccination will not significantly increase that prevention rate if adherence to antibiotic regimens is similar or higher than that attained in the 2001 US outbreak. However, post-exposure vaccination can be useful either in shortening the duration of a prolonged antibiotic regimen, in the event of an antibiotic-resistant strain, or if antibiotic adherence rates are very low. Here we show that a mass pre-exposure vaccination programme for the general population would require very high population coverage rates to significantly increase prevention rates from that achieved with targeted and rapid post-exposure prophylaxis programmes.     

A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac

With the availability of complete genome sequence for Drosophila melanogaster, one of the next strategic goals for fly researchers is a complete gene knockout collection. The P-element transposon, the workhorse of D. melanogaster molecular genetics, has a pronounced nonrandom insertion spectrum. It has been estimated that 87% saturation of the approximately 13,500-gene complement of D. melanogaster might require generating and analyzing up to 150,000 insertions. We describe specific improvements to the lepidopteran transposon piggyBac and the P element that enabled us to tag and disrupt genes in D. melanogaster more efficiently. We generated over 29,000 inserts resulting in 53% gene saturation and a more diverse collection of phenotypically stronger insertional alleles. We found that piggyBac has distinct global and local gene-tagging behavior from that of P elements. Notably, piggyBac excisions from the germ line are nearly always precise, piggyBac does not share chromosomal hotspots associated with P and piggyBac is more effective at gene disruption because it lacks the P bias for insertion in 5' regulatory sequences.     

Fluoride-resistant acid phosphatase system of nociceptive dorsal root afferents

Zusammenfassung Fluorid-resistente saure Phosphatase wird aus den kleinen (dunklen) Nervenzellen des Spinalganglions mittels axoplasmatischer Strömung durch die Hinterwurzeln in die Rolando-Substanz des Rückenmarkes transportiert, wo das Enzym in den Nervendendigungen eine freie axoplasmatische Lokalisation aufweist.     

Cdc6 synthesis regulates replication competence in Xenopus oocytes

The early division cycles of an embryo rely on the oocyte's ability to replicate DNA. During meiosis, oocytes temporarily lose this ability. After a single round of pre-meiotic S-phase, oocytes enter meiosis and rapidly arrest at prophase of meiosis I (G2). Upon hormonal stimulation, arrested oocytes resume meiosis, re-establish DNA replication competence in meiosis I shortly after germinal vesicle breakdown (GVBD), but repress replication until fertilization. How oocytes lose and regain replication competence during meiosis are important questions underlying the production of functional gametes. Here we show that the inability of immature Xenopus oocytes to replicate is linked to the absence of the Cdc6 protein and the cytoplasmic localization of other initiation proteins. Injection of Cdc6 protein into immature oocytes does not induce DNA replication. However, injection of Cdc6 into oocytes undergoing GVBD is sufficient to induce DNA replication in the absence of protein synthesis. Our results show that GVBD and Cdc6 synthesis are the only events that limit the establishment of the oocyte's replication competence during meiosis.     

Mutant deoxynucleotide carrier is associated with congenital microcephaly

The disorder Amish microcephaly (MCPHA) is characterized by severe congenital microcephaly, elevated levels of alpha-ketoglutarate in the urine and premature death. The disorder is inherited in an autosomal recessive pattern and has been observed only in Old Order Amish families whose ancestors lived in Lancaster County, Pennsylvania. Here we show, by using a genealogy database and automated pedigree software, that 23 nuclear families affected with MCPHA are connected to a single ancestral couple. Through a whole-genome scan, fine mapping and haplotype analysis, we localized the gene affected in MCPHA to a region of 3 cM, or 2 Mb, on chromosome 17q25. We constructed a map of contiguous genomic clones spanning this region. One of the genes in this region, SLC25A19, which encodes a nuclear mitochondrial deoxynucleotide carrier (DNC), contains a substitution that segregates with the disease in affected individuals and alters an amino acid that is highly conserved in similar proteins. Functional analysis shows that the mutant DNC protein lacks the normal transport activity, implying that failed deoxynucleotide transport across the inner mitochondrial membrane causes MCPHA. Our data indicate that mitochondrial deoxynucleotide transport may be essential for prenatal brain growth.     

Paxillin binds schwannomin and regulates its density-dependent localization and effect on cell morphology

Neurofibromatosis type 2 is an autosomal dominant disorder characterized by tumors, predominantly schwannomas, in the nervous system. It is caused by mutations in the gene NF2, encoding the growth regulator schwannomin (also known as merlin). Mutations occur throughout the 17-exon gene, with most resulting in protein truncation and undetectable amounts of schwannomin protein. Pathogenic mutations that result in production of defective schwannomin include in-frame deletions of exon 2 and three independent missense mutations within this same exon. Mice with conditional deletion of exon 2 in Schwann cells develop schwannomas, which confirms the crucial nature of exon 2 for growth control. Here we report that the molecular adaptor paxillin binds directly to schwannomin at residues 50-70, which are encoded by exon 2. This interaction mediates the membrane localization of schwannomin to the plasma membrane, where it associates with beta 1 integrin and erbB2. It defines a pathogenic mechanism for the development of NF2 in humans with mutations in exon 2 of NF2.     

A natural allele of Nxf1 suppresses retrovirus insertional mutations

Endogenous retroviruses have shaped the evolution of mammalian genomes. Host genes that control the effects of retrovirus insertions are therefore of great interest. The modifier-of-vibrator-1 locus (Mvb1) controls levels of correctly processed mRNA from genes mutated by endogenous retrovirus insertions into introns, including the Pitpn(vb) tremor mutation and the Eya1(BOR) model of human branchiootorenal syndrome. Positional complementation cloning identifies Mvb1 as the nuclear export factor Nxf1, providing an unexpected link between the mRNA export receptor and pre-mRNA processing. Population structure of the suppressive allele in wild Mus musculus castaneus suggests selective advantage. A congenic Mvb1(CAST) allele is a useful tool for modifying gene expression from existing mutations and could be used to manipulate engineered mutations containing retroviral elements.     

Estimates of site potential for Douglas-fir based on site index for several southwestern habitat types

Estimates of site potential for Douglas-fir based on measured site indexes in 450 stands are compared between 10 southwestern habitat types. Significant differences in site potential are found between the habitat types studied.     

Size, structure, and habitat characteristics of populations of Braya humilis var. humilis (Brassicaceae): an alpine disjunct from Colorado

Size, structure, and habitat characteristics were studied in three populations of Braya humilis var. humilis (C. A. Meyer) Robins, in Gray & Wats. (Brassicaceae), a small, herbaceous perennial of the alpine tundra in central Colorado. There was a significant association between numbers of reproductive, juvenile, and seedling individuals and population location. Plant size within reproductive, juvenile, and seedling size classes varied significantly among three populations. Plots containing Braya had significantly lower total plant cover, a different set of dominant plant species, more rock, bare ground, and less litter than plots without Braya . Braya appears to be restricted to calcareous substrates that experience a moderate level of disturbance, such as solifluction lobes and abandoned roads. Populations are small despite the existence of much potential habitat. Population studies are necessary for active conservation management of Braya .