Genome-wide association study to identify genetic loci associated with gastrointestinal nematode resistance in Katahdin sheep.

Resistance to gastrointestinal nematodes has previously been shown to be a moderately heritable trait in some breeds of sheep, but the mechanisms of resistance are not well understood. Selection for resistance currently relies upon faecal egg counts (FEC), blood packed cell volumes and FAMACHA visual indicator scores of anaemia. Identifying genomic markers associated with disease resistance would potentially improve the selection process and provide a more reliable means of classifying and understanding the biology behind resistant and susceptible sheep. A GWAS was conducted to identify possible genetic loci associated with resistance to Haemonchus contortus in Katahdin sheep. Forty animals were selected from the top and bottom 10% of estimated breeding values for FEC from a total pool of 641 sires and ram lambs. Samples were genotyped using Applied Biosystems™ Axiom™ Ovine Genotyping Array (50K) consisting of 51 572 SNPs. Following quality control, 46 268 SNPs were included in subsequent analyses. Analyses were conducted using a linear regression model in plink v1.90 and a single-locus mixed model in snp and variation suite. Genome-wide significance was determined by a Bonferroni correction for multiple testing. Using linear regression, loci on chromosomes 2, 3, 16, 23 and 24 were significantly associated at the genome level with FEC estimated breeding values, and we identified a region on chromosome 2 that was significant using both statistical analyses. We suggest a potential role for the gene DIS3L2 for gastrointestinal nematode resistance in Katahdin sheep, although further research is needed to validate these findings.

Facilitation of parental behavior in ring doves by systemic or intracranial injections of prolactin.

Systemic administration of ovine prolactin (PRL) has been previously reported to stimulate parental feeding behavior toward 7-day-old foster squabs by nonbreeding ring doves with previous breeding experience. The first of the present experiments reexamined this claim in experienced, nonbreeding birds given test squabs of different ages. Each visually isolated male and female dove was given twice-daily subcutaneous injections of ovine PRL or vehicle for 7 days and then tested for parental responses toward a single 1-3, 6-8, or 11- to 13-day-old foster squab. Prolactin significantly increased the incidence or frequency of parental regurgitation-feeding episodes in tests with all three squab age groups and, in addition, increased the incidence of parental feeding invitations (squab-oriented bill openings) in tests with 6- to 8-day-old squabs. A second study explored the degree to which PRL can act directly on the central nervous system to facilitate parental activity in the absence of peripheral cues generated from PRL-induced changes in other target organs, such as those associated with crop sac growth and distension. In this experiment, 6- to 8-day-old test squabs were used to determine if parental behavior is enhanced by twice-daily intracerebroventricular (ICV) injections of PRL in doses below those required to stimulate peripheral target organs. Injection schedules and behavior testing procedures were the same as those used in Experiment 1. However, half of the ICV PRL-treated and ICV vehicle-treated birds were food deprived for 16 hr before and during the test in order to control for PRL-induced hyperphagia and resulting crop sac distension, which could confound the results by generating peripheral stimuli conductive to the display of regurgitation-feeding behavior. Intracranial injections of prolactin significantly increased the incidence of feeding behavior, parental feeding invitations, and crouching or sitting in the nest in food-deprived doves but not in freely fed animals. Empty crop sac weights of freely fed and food-deprived PRL-treated birds were not increased above control values, thus indicating that ICV PRL treatment did not result in significant stimulation of peripheral target organs. These results demonstrate a facilitative action of PRL on regurgitation-feeding responses and associated parental behaviors that is not restricted to squabs of one particular age range. They also indicate that PRL is capable of acting directly on the brain to promote these activities in the absence of PRL-induced changes in the crop sac and other peripheral target organs.

Imaging of cerebral arterio-venous malformations by transcranial colour-coded real-time sonography.

Transcranial color-coded real-time sonography (TCCS) is a new diagnostic method allowing the non-invasive imaging of parenchymal and vascular structures of the adult brain through the intact skull. A description of the sonographic findings in two patients presenting with a radiologically ascertained arterio-venous malformation is provided. The AVM's can be depicted in the two-dimensional B-mode image as echodense areas interspersed with zones of lower echodensity. Their extension correlated with corresponding MRI images. The color-coded illustration of intravascular flow phenomena allowed the distinct identification of the major afferent feeding vessels, the venous drainage and of the vascular convolution of both AVM's. Information on hemodynamics, as e.g. the blood supply of the angioma by the contralateral internal carotid artery, are obtained by color-coded identification of intravascular flow direction including analysis of the Doppler frequency spectrum. All findings obtained by TCCS complied with those established by angiography. We conclude, that TCCS is a suitable method for early diagnosis and long term follow up of cerebral AVM's.

Effects of cyclosporin A on a kidney epithelial cell line (LLC-PK1).

Cyclosporin A (CSA), a potent immunosuppressant with the adverse side effect of nephrotoxicity, inhibited cell growth of pig kidney tubule cells (LLC-PK1) in culture. CSA (10(-5) M) also induced intense cytoplasmic vacuolation and the formation of dense granules. At the same concentration an analogue of CSA, cyclosporin G, had much less effect. This cell line may prove useful for revealing the mechanism of CSA-nephrotoxicity and testing the nephrotoxic potential of new analogues of cyclosporine.

Alkylation of bronchiolar epithelial cells by 3-methylindole metabolites in the horse.

Autoradiographs of horse-lung explants incubated with [3H]3-methylindole (3MI) showed 8 times greater labeling per area to bronchiolar epithelial cells than to the interalveolar septa. Incubations of horse-lung microsomes with [14C]3MI resulted in alkylation of microsomal proteins, which could be reduced by exogenous glutathione. An apparent covalent adduct of glutathione and 3MI was isolated from these incubations. These results suggest that the target cells of 3MI-induced injury in the horse, the bronchiolar epithelial cells, are alkylated by an electrophilic 3MI intermediate.

Chlordecone (Kepone) induced ultrastructural and morphometric alterations in the cells of the immature quail oviduct.

Groups of sexually immature Japanese quail females, kept in a reduced photoperiod, received either daily intraperitoneal injections of 40 micrograms estradiol-17 beta for 26 days or were fed diets containing 0, 10, 40, 80 or 160 ppm chlordecone for the same duration. Estradiol-17 beta induced rapid cellular hypertrophy, cytodifferentiation, tubular gland formation, organelle proliferation and secretory granule formation in different cells of the quail oviduct. Higher chlordecone doses mimicked these estradiol-17 beta actions, but in addition induced atypical cell and organelle morphology, such as protruding or swollen cell apices, increased mitochondrial volume densities and diameters and disorganized Golgi apparati. The possible effects of these chlordecone-induced atypical cell alterations on avian reproduction are discussed.

Gastric epithelial cell proliferation in monkeys fed 3,4,3',4'-tetrachlorobiphenyl.

Rhesus monkeys (Macaca mulatta) fed diets containing 1 or 3 mg/kg of 3,4,3',4'-tetrachlorobiphenyl (3,4-TCB), became moribund after 7-14 weeks. In the body of the stomach the mucosa was thick and cystic gastric glands penetrated the muscularis mucosae. The zymogenic and parietal cells were replaced by or converted into mucus-secreting cells. Autoradiographs of animals labelled with [3H]thymidine showed that in control monkeys gastric epithelial cell proliferation was limited to the isthmus and neck regions of the glands throughout the stomach. In the 3,4-TCB-fed animals most DNA synthesis also occurred in these regions, but [3H]thymidine labelled cells were also seen in the bases of the glands. The labelling indices were not elevated, and therefore the submucosal glands and cysts in this lesion may develop by a failure of the newly formed, downward migrating cells to differentiate and lose their proliferative capacity.

Autoradiographic evidence of 3-methylindole covalent binding to pulmonary epithelial cells in the goat.

3-Methylindole (3MI), the main ruminal fermentation product of L-tryptophan, causes acute pulmonary edema and interstitial emphysema in ruminants. Intravenous infusion of 3MI in goats causes necrosis and sloughing of pneumocytes and bronchial epithelial cells. Previous studies indicate that a reactive metabolite or metabolites of 3MI bind covalently to tissue macromolecules in the lung and this binding is associated with the pneumotoxicity of 3MI. We undertook this autoradiographic study of 3MI covalent binding to test the hypothesis that reactive 3MI metabolite(s) bind to the lung cells susceptible to 3MI-induced injury. We infused goats with [3H]3MI and killed them either 0.5, 2 or 6 h after start of the infusion. Sections of fixed lung were extensively washed, alcohol dehydrated and embedded in plastic. Only covalently bound radioactivity remained. Silver grains were quantitated per area in the developed autoradiographs. There was a 2:1 ratio of binding to the small airway epithelium compared to the interalveolar septa in all the goats. Both ciliated and non-ciliated bronchiolar cells were labeled, as were both types I and II pneumocytes. Normal goat lung slices incubated in vitro with [3H]3MI were labeled in the same pattern. Inclusion of either of the inhibitors of cytochrome P-450, SKF-525-A or piperonyl butoxide significantly reduced this binding to both the pneumocytes and the bronchiolar cells. We consider these results supportive of our hypothesis that 3MI is metabolized to reactive intermediates by the epithelial cells of the lung, where they bind to macromolecules, which may cause cellular damage.

Self-actualizations and experience with Zen meditation: is a learning period necessary for meditation?

Tested the hypothesis that inconsistencies found in research on the relationship between Zen meditation and self-actualization were due in part to the existence of a learning period for Zen meditation. It was hypothesized that increases in self-actualization would be observed only after the completion of the learning period. The Personal Orientation Inventory (POI) was given to 36 students of Soto Zen and 34 undergraduate students who never had mediated. Analysis of covariance adjusted the group means for differences in age, education, and sex. t-tests revealed that all hypotheses were supported for the Inner Directed scale of the POI and supported in part for the Time Competent scale. Results were discussed as supporting the hypothesized learning period for Zen meditation. Implications for future research on Zen meditation were discussed.

Polychlorinated biphenyl-induced morphologic changes in the gastric mucosa of the rhesus monkey.

The early morphologic events in polychlorinated biphenyl-induced lesions of the gastric mucosa of immature male rhesus monkeys (Macaca mulatta) were studied in serial biopsies taken during consumption of diets containing 3, 10, 30, and 100 mg. per kg. (p.p.m.) of Aroclor 1242. The severity of the lesions correlated directly with both the duration and the level of exposure. The first changes were seen after ingestion of 30 and 100 mg. per kg. for 2 weeks; changes were not seen until 10 weeks at 3 and 10 mg. per kg. The principal effect was an apparent arrest of the differentiation of generative cells of the isthmus and neck regions into parietal and zymogenic (chief) cells. Mature parietal and zymogenic cells were found only in the bases of the glands, where the oldest cells are normally found, and these showed signs of injury including dilation of the rough endoplasmic reticulum in zymogenic cells, irregularity of the mitochondria in parietal cells and irregular luminal membranes, and an increase in the number of large autophagic vesicles in both cell types.