Learning sets in an invertebrate.

Eight isopods, Porcellio scaber, were trained with water reinforcement to turn in a T-maze to criterion of correct responses. They were then tested through nine reversals of the turning response. An analysis of variance indicated that mean errors to criterion declined significantly over reversals (F = 4.78, d.f. = 9/63, P < .001).

Nonsyndromic deafness DFNA1 associated with mutation of a human homolog of the Drosophila gene diaphanous.

The gene responsible for autosomal dominant, fully penetrant, nonsyndromic sensorineural progressive hearing loss in a large Costa Rican kindred was previously localized to chromosome 5q31 and named DFNA1. Deafness in the family is associated with a protein-truncating mutation in a human homolog of the Drosophila gene diaphanous. The truncation is caused by a single nucleotide substitution in a splice donor, leading to a four-base pair insertion in messenger RNA and a frameshift. The diaphanous protein is a profilin ligand and target of Rho that regulates polymerization of actin, the major component of the cytoskeleton of hair cells of the inner ear.

Linkage of early-onset familial breast cancer to chromosome 17q21.

Human breast cancer is usually caused by genetic alterations of somatic cells of the breast, but occasionally, susceptibility to the disease is inherited. Mapping the genes responsible for inherited breast cancer may also allow the identification of early lesions that are critical for the development of breast cancer in the general population. Chromosome 17q21 appears to be the locale of a gene for inherited susceptibility to breast cancer in families with early-onset disease. Genetic analysis yields a lod score (logarithm of the likelihood ratio for linkage) of 5.98 for linkage of breast cancer susceptibility to D17S74 in early-onset families and negative lod scores in families with late-onset disease. Likelihood ratios in favor of linkage heterogeneity among families ranged between 2000:1 and greater than 10(6):1 on the basis of multipoint analysis of four loci in the region.

Mutation in transcription factor POU4F3 associated with inherited progressive hearing loss in humans.

The molecular basis for autosomal dominant progressive nonsyndromic hearing loss in an Israeli Jewish family, Family H, has been determined. Linkage analysis placed this deafness locus, DFNA15, on chromosome 5q31. The human homolog of mouse Pou4f3, a member of the POU-domain family of transcription factors whose targeted inactivation causes profound deafness in mice, was physically mapped to the 25-centimorgan DFNA15-linked region. An 8-base pair deletion in the POU homeodomain of human POU4F3 was identified in Family H. A truncated protein presumably impairs high-affinity binding of this transcription factor in a dominant negative fashion, leading to progressive hearing loss.

Long-term anti-nucleoprotein cellular and humoral immunity is induced by intramuscular injection of plasmid DNA containing NP gene.

Cytolytic T-lymphocyte-mediated killing is thought to be an important effector mechanism in controlling viral infections. Recently, we reported that intramuscular injection of plasmid DNA containing the nucleoprotein (NP) gene of the influenza virus resulted in generating nucleoprotein-specific cytolytic T cells and antibodies. Gene-injected mice were subsequently protected from a lethal challenge with live influenza virus. Here we show that a single intramuscular injection of a small dose of nucleoprotein plasmid DNA generates nucleoprotein-specific cellular and humoral immune responses that last 1 year. The cellular response is associated with the CD8+ subpopulation of T cells. Thus, plasmid DNA injections can be used to induce long-lasting immune responses against the viral gene product without an exposure to live virus itself.

Klebsielleae in drinking water emanating from redwood tanks.

A survey was made of the bacteriological quality and chlorine content of 33 public and private water systems that utilize redwood storage tanks. Coliforms of the genera Klebsiella and Enterobacter were isolated from 9 of 10 private drinking water systems and from 11 of 23 water systems in state and federal parks. Total coliform counts in the private systems exceeded federal membrane filter guidelines by as much as 10-to 40-fold. Coliform counts were highest in the newer reservoirs. Factors contributing to poor water quality are: lack of automated chlorination equipment or an insufficient supply to maintain a residual, common inlet/outlet plumbing design, and lengthy average retention periods. The latter two factors contribute to improper mixing and stagnation of the water, whereas the former allows microbes to multiply on the water-soluble nutrients that leach from the wood. Wooden reservoirs exert a high chlorine demand, and 0.4 ppm of chlorine residual in the incoming tank water proves inadequate. It is suggested that specific water-soluble nutrients in redwood (and in numerous other types of botanical material) induce a natural nutritional selection for coliforms of the tribe Klebsielleae.

Isolation of Klebsielleae from within living wood.

Previous studies from this laboratory have documented the presence of coliform bacteria emanating from wooden reservoirs containing finished drinking water. Coliforms were identified as Klebsiella pneumoniae and Enterobacter spp. In the present report, evidence is presented which suggests that the origin of these coliforms is from the wood used to construct the reservoirs. In liquid expressed from freshly cut redwood, total bacterial counts in the range of 10(5) to 10(6)/ml were commonly observed. When present, coliform counts were over 10(3)/ml of expressed liquid. E. agglomerans was the most prevalent coliform present, but Klebsiella was isolated from freshly cut logs. Citrobacter freundii was also occasionally isolated. No fecal coliform-positive Klebsiella were obtained from any of the samples. Highest total bacteria and coliform counts were observed in sapwood specimens. Coliforms were present throughout sapwood as evidenced by contact plating serial sections of freshly cut wood. Scanning electron micrographs illustrate the presence of bacterial colonies within sapwood tracheids. Other wood species also contained coliform bacteria but in numbers lower than found in redwood.

BRCA2 in American families with four or more cases of breast or ovarian cancer: recurrent and novel mutations, variable expression, penetrance, and the possibility of families whose cancer is not attributable to BRCA1 or BRCA2.

In order to evaluate the role of inherited BRCA2 mutations in American families--particularly the appearance in America of European founder mutations--the BRCA2 coding sequence, 5' UTR, and 3' UTR were screened in 22 Caucasian American kindreds with four or more cases of breast or ovarian cancer. Six mutations were found that cause a premature-termination codon; four of them have been reported elsewhere, and two are novel. In the four families with previously seen mutations, the distinct lineages at high risk of cancer were of Dutch, German, Irish, and Ashkenazi Jewish ancestry; mutations in Europe reflect these ancestries. The families with novel mutations were Puerto Rican Hispanic (exon 9 deletion 995delCAAAT) and Ashkenazi Jewish (exon 11 deletion 6425delTT). Among female BRCA2-mutation carriers, risks of breast cancer were 32% by age 50 years, 67% by age 70 years, and 80% by age 90 years, yielding a lifetime risk similar to that for BRCA1 but an older distribution of ages at onset. BRCA2 families also included multiple cases of cancers of the male breast (six cases), ovary (three cases), fallopian tube (two cases), pancreas (three cases), bladder (two cases), and prostate (two cases). Among 17 Ashkenazi Jewish families with four or more breast or ovarian cancers, 9 families (including 3 with ovarian cancer and 1 with male breast cancer) carried none of the three ancient mutations in BRCA1 or BRCA2. To date, both BRCA2 and BRCA1 have been screened by SSCA, supplemented by the protein-truncation test, in 48 families with four or more breast or ovarian cancers. Mutations have been detected in BRCA1 in 33 families, in BRCA2 in 6 families, and in neither gene in 9 families, suggesting both the probable cryptic nature of some mutations and the likelihood of at least one other BRCA gene.