Molecular and pedigree measures of relatedness provide similar estimates of inbreeding depression in a bottlenecked population.

Individual-based estimates of the degree of inbreeding or parental relatedness from pedigrees provide a critical starting point for studies of inbreeding depression, but in practice wild pedigrees are difficult to obtain. Because inbreeding increases the proportion of genomewide loci that are identical by descent, inbreeding variation within populations has the potential to generate observable correlations between heterozygosity measured using molecular markers and a variety of fitness related traits. Termed heterozygosity-fitness correlations (HFCs), these correlations have been observed in a wide variety of taxa. The difficulty of obtaining wild pedigree data, however, means that empirical investigations of how pedigree inbreeding influences HFCs are rare. Here, we assess evidence for inbreeding depression in three life-history traits (hatching and fledging success and juvenile survival) in an isolated population of Stewart Island robins using both pedigree- and molecular-derived measures of relatedness. We found results from the two measures were highly correlated and supported evidence for significant but weak inbreeding depression. However, standardized effect sizes for inbreeding depression based on the pedigree-based kin coefficients (k) were greater and had smaller standard errors than those based on molecular genetic measures of relatedness (RI), particularly for hatching and fledging success. Nevertheless, the results presented here support the use of molecular-based measures of relatedness in bottlenecked populations when information regarding inbreeding depression is desired but pedigree data on relatedness are unavailable.

Eliminating invalid self-report survey data.

A sample of 6,370 students in Grades 6 to 8 completed a questionnaire on their attitudes and use of alcohol, tobacco, and other drugs. A subsample showed questionable data based on three criteria: missing responses, invalid responses, and inconsistent responses. Analysis indicated that this subsample was significantly different from the main group on demographic variables and self-reported life-time tobacco use. Results support efforts to identify and eliminate invalid data.

Do participation rates change when active consent procedures replace passive consent.

Researchers face considerable ambiguity and controversy regarding the issue of informed consent. Decisions about consent procedures can affect study participation rates and prevalence estimates among specific populations. Changing from passive to active parental consent procedures was examined in a case study with an anonymous survey of sixth- through eighth-grade students' substance use. Four types of procedures for obtaining parental consent were examined. Results suggest that certain types of consent procedures can yield high levels of participation. This study also demonstrates that low participation rates with some active consent procedures can cause biases in sample characteristics and outcome data.

Salmonella enterica serovar Typhi possesses a unique repertoire of fimbrial gene sequences.

Salmonella enterica serotype Typhi differs from nontyphoidal Salmonella serotypes by its strict host adaptation to humans and higher primates. Since fimbriae have been implicated in host adaptation, we investigated whether the serotype Typhi genome contains fimbrial operons which are unique to this pathogen or restricted to typhoidal Salmonella serotypes. This study established for the first time the total number of fimbrial operons present in an individual Salmonella serotype. The serotype Typhi CT18 genome, which has been sequenced by the Typhi Sequencing Group at the Sanger Centre, contained a type IV fimbrial operon, an orthologue of the agf operon, and 12 putative fimbrial operons of the chaperone-usher assembly class. In addition to sef, fim, saf, and tcf, which had been described previously in serotype Typhi, we identified eight new putative chaperone-usher-dependent fimbrial operons, which were termed bcf, sta, stb, ste, std, stc, stg, and sth. Hybridization analysis performed with 16 strains of Salmonella reference collection C and 22 strains of Salmonella reference collection B showed that all eight putative fimbrial operons of serotype Typhi were also present in a number of nontyphoidal Salmonella serotypes. Thus, a simple correlation between host range and the presence of a single fimbrial operon seems at present unlikely. However, the serotype Typhi genome differed from that of all other Salmonella serotypes investigated in that it contained a unique combination of putative fimbrial operons.

Identification of a putative Salmonella enterica serotype typhimurium host range factor with homology to IpaH and YopM by signature-tagged mutagenesis.

The genetic basis for the host adaptation of Salmonella serotypes is currently unknown. We have explored a new strategy to identify Salmonella enterica serotype Typhimurium (S. typhimurium) genes involved in host adaptation, by comparing the virulence of 260 randomly generated signature-tagged mutants during the oral infection of mice and calves. This screen identified four mutants, which were defective for colonization of only one of the two host species tested. One mutant, which only displayed a colonization defect during the infection of mice, was further characterized. During competitive infection experiments performed with the S. typhimurium wild type, the mutant was defective for colonization of murine Peyer's patches but colonized bovine Peyer's patches at the wild-type level. No difference in virulence between wild type and mutant was observed when calves were infected orally with 10(10) CFU/animal. In contrast, the mutant possessed a sixfold increase in 50% lethal morbidity dose when mice were infected orally. The transposon in this mutant was inserted in a 2.9-kb pathogenicity islet, which is located between uvrB and yphK on the S. typhimurium chromosome. This pathogenicity islet contained a single gene, termed slrP, with homology to ipaH of Shigella flexneri and yopM of Yersinia pestis. These data show that comparative screening of signature-tagged mutants in two animal species can be used for scanning the S. typhimurium genome for genes involved in host adaptation.

Of mice, calves, and men. Comparison of the mouse typhoid model with other Salmonella infections.

Numerous Salmonella typhimurium virulence factors have been identified and characterized using experimental infection of mice. While the murine typhoid model has been used successfully for Salmonella typhi vaccine development and to infer virulence mechanisms important during typhoid fever, information derived from infection of mice has been of limited value in elucidating the mechanisms by which S. typhimurium causes enteritis in humans. Progress in our understanding of virulence mechanisms contributing to diarrheal disease comes from recent studies of bovine enteritis, a S. typhimurium infection, which manifests as acute gastroenteritis. This review compares virulence genes and mechanisms required during murine typhoid, typhoid fever, and bovine enteritis. Comparison of illnesses caused in different animal hosts identifies virulence mechanisms involved in species specific disease manifestations. The determination of the relative importance of virulence factors for disease manifestations in different host species provides an important link between the in vitro characterization of genes and their role during host pathogen interaction.

Protective effect of zinc against ethanol toxicity in mice.

Protection against the lethal effects of ethanol at 4.5 g/kg administered acutely was maximal when zinc was administered 60 min prior to ethanol. The timing of ethanol administration corresponded with elevated plasma levels of absorbed zinc. Protection was inversely related to the dose of zinc employed, as 0.5 mumol provided greater protection than 1.0 mumol, which provided greater protection than 2.0 mumol. Protection against ethanol lethality was greater if zinc was administered 60 min prior to each injection of ethanol. Acute zinc pretreatment did not alter the activity of liver alcohol dehydrogenase (ADH), nor did it alter the blood clearance of ethanol. Chronic zinc administration as ZnCl2, 100 micrograms/ml in the drinking water for 30 d, produced a 25% decrease in hepatic ADH activity, which was accompanied by a similar decrease in the intravascular clearance of ethanol.

Hemodynamic changes induced by prolonged NaCl and DOCA administration in spontaneously hypertensive rats.

The results of this study demonstrate that the spontaneously hypertensive rat is sensitive to salt excess. The hypertensinogenic effect of salt was mediated through elevation of peripheral vascular resistance. The addition of DOCA aggravated the hypertension, mainly be elevating the cardiac output without appreciably decreasing peripheral vascular resistance. SHR'S EXPOSED TO 1% NaCl consumed more fluids and excreted more sodium and urine than control rats. Those exposed to 1% NaCl and DOCA had higher fluid consumptions and excreted more sodium than the other two groups. These effects of sodium in a neurogenic strain of hypertensive rats suggest a possible interplay between the neurogenic and salt-dependent components in the development and maintenance of hypertension. They also suggest that SHRs, like other hypertensive rat models, are salt sensitive.

The effects of salt and meclofenamate administration on the hypertension of spontaneously hypertensive rats.

The effects of prolonged (3 mos) high sodium intake and meclofenamate were studied in 2 groups of male SHR. Group 1 (6 rats) received 1% NaCl in tap water and Group 2 (8 rats) received 1% NaCl in tap water plus 50 microgram of meclofenamate per ml of drinking fluid. Renal metabolic and hemodynamic studies in the unanesthetized unrestrained state, showed that the meclofenamate treated rats had higher arterial pressures (p less than .005), left ventricular weight (p less than .05) and renal vascular resistance (p less than .005); lower glomerular filtration rate (p less than .005) than the control rats. The hematocrit and right ventricular weight were similar in the two groups of rats. This study has demonstrated that the combination of high sodium intake and meclofenamate have a greater damaging effect on the arterial pressure and renal function of SHR than salt alone.