Inheritance, mode of inheritance, and candidate genes for primary hyperparathyroidism in Keeshonden

BACKGROUND: Primary hyperparathyroidism (PHPT) is caused by inappropriate secretion of parathyroid hormone (PTH) by autonomously functioning neoplastic or hyperplastic parathyroid "chief" cells. Keeshonden are thought to be over-represented in studies on canine PHPT, but no proof of heritability or mode of inheritance has been published. The canine disease clinically resembles human familial isolated hyperparathyroidism (FIHP). HYPOTHESIS: Primary hyperparathyroidism in Keeshonden is genetically transmitted and is caused by a mutation in 1 of 4 genes implicated in human FIHP: MEN1, CASR, HRPT2, or RET. ANIMALS: Pedigrees consisting of 1647 Keeshonden were created including 219 Keeshonden with known PHPT phenotypes (69 positive). DNA samples were obtained from 176 of the 219 Keeshonden (34 positive). METHODS: Heritability and mode of inheritance were determined by segregation analysis. Canine homologs to the human genes were identified. Exons and surrounding intron regions were sequenced and scanned for sense-altering polymorphisms or polymorphisms that segregated with the disease. Messenger RNA from a parathyroid tumor of an affected Keeshond was analyzed for polymorphisms and splice alterations. RESULTS: PHPT follows an autosomal dominant mode of inheritance in Keeshonden with possible age-dependent penetrance. No polymorphisms identified in the genes analyzed were associated with a change in predicted protein or in hypothesized splice sites. CONCLUSIONS AND CLINICAL IMPORTANCE: PHPT is an autosomal dominant, genetically transmitted disease in Keeshonden. Once the mutation locus is identified, genetic testing should quickly decrease the incidence of PHPT in this breed. It is unlikely that mutations in MEN1, CASR, HRPT2, or RET cause PHPT in Keeshonden.     

Seroprevalence of Babesia bigemina in smallholder dairy cattle in Tanzania and associated risk factors

Variations in the seroprevalence of antibody to Babesia bigemina infection by farm and animal level risk factors were investigated for 2 contrasting regions of Tanga and Iringa in Tanzania. Tanga is situated in the eastern part of the country and has typical tropical coast climate while Iringa is situated in the Southern Highlands and has a tropical highland climate. Two hundred farms from each region were selected using simple random sampling procedure and visited once between January 1999 and April 1999. Blood samples were collected from 1329 smallholder dairy animals on selected farms for harvesting serum which was subsequently used for serodiagnosis of B. bigemina using an indirect enzyme linked immuno-sorbent assay (ELISA). Of the 1329 sera samples screened, 34.9 % were positive for B. bigemina. The prevalence was higher in Iringa Region [43%, 95% confidence intervals (CI) = 39.5-47.3] than in Tanga Region (27%, CI = 23.6-30.5). Using a logistic binomial regression model as an analytical method for predicting the likelihood of animal seropositivity, we found (in both regions) that the risk of positive reaction varied with the animal's age, history of grazing and geographical location. Seroprevalence increased with age (beta = 0.01 and 0.01 per year of age, P < 0.005 in Tanga and Iringa, respectively). Animals located in Lushoto and Iringa urban district were associated with increased risk of seropositivity [Odds ratio (OR) = 4.24, P = 0.001, for Lushoto, and OR = 1.81, P = 0.040, for Iringa Urban, respectively). Animals grazed 3 months prior to sampling had higher odds for seropositivity than zero/semi-grazed, despite farmer-reported high frequency of tick control (OR = 2.71, P = 0.0087, for Tanga, and OR = 4.53, P = 0.001, for Iringa). Our study suggests that even though herd sizes are small, B. bigemina infection is widespread in many smallholder dairy farms and endemic stability with respect to this disease has not yet been attained, but the observed levels are sufficiently high to ensure that clinical disease would be a risk.     

Grain boundary-mediated plasticity in nanocrystalline nickel

The plastic behavior of crystalline materials is mainly controlled by the nucleation and motion of lattice dislocations. We report in situ dynamic transmission electron microscope observations of nanocrystalline nickel films with an average grain size of about 10 nanometers, which show that grain boundary-mediated processes have become a prominent deformation mode. Additionally, trapped lattice dislocations are observed in individual grains following deformation. This change in the deformation mode arises from the grain size-dependent competition between the deformation controlled by nucleation and motion of dislocations and the deformation controlled by diffusion-assisted grain boundary processes.     

The silica balance in the world ocean: a reestimate

The net inputs of silicic acid (dissolved silica) to the world ocean have been revised to 6.1 +/- 2.0 teramoles of silicon per year (1 teramole = 10(12) moles). The major contribution (about 80 percent) comes from rivers, whose world average silicic acid concentration is 150 micromolar. These inputs are reasonably balanced by the net ouputs of biogenic silica of 7.1 +/- 1.8 teramoles of silicon per year in modern marine sediments. The gross production of biogenic silica (the transformation of dissolved silicate to particulate skeletal material) in surface waters was estimated to be 240 +/- 40 teramoles of silicon per year, and the preservation ratio (opal accumulation in sediment/gross production in surface waters) averages 3 percent. In the world ocean the residence time of silicon, relative to total biological uptake in surface waters, is about 400 years.     

The role of discharge variation in scaling of drainage area and food chain length in rivers

Food chain length (FCL) is a fundamental component of food web structure. Studies in a variety of ecosystems suggest that FCL is determined by energy supply, environmental stability, and/or ecosystem size, but the nature of the relationship between environmental stability and FCL, and the mechanism linking ecosystem size to FCL, remain unclear. Here we show that FCL increases with drainage area and decreases with hydrologic variability and intermittency across 36 North American rivers. Our analysis further suggests that hydrologic variability is the mechanism underlying the correlation between ecosystem size and FCL in rivers. Ecosystem size lengthens river food chains by integrating and attenuating discharge variation through stream networks, thereby enhancing environmental stability in larger river systems.     

The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling

The mammalian target of rapamycin (mTOR) protein kinase is a master growth promoter that nucleates two complexes, mTORC1 and mTORC2. Despite the diverse processes controlled by mTOR, few substrates are known. We defined the mTOR-regulated phosphoproteome by quantitative mass spectrometry and characterized the primary sequence motif specificity of mTOR using positional scanning peptide libraries. We found that the phosphorylation response to insulin is largely mTOR dependent and that mTOR exhibits a unique preference for proline, hydrophobic, and aromatic residues at the +1 position. The adaptor protein Grb10 was identified as an mTORC1 substrate that mediates the inhibition of phosphoinositide 3-kinase typical of cells lacking tuberous sclerosis complex 2 (TSC2), a tumor suppressor and negative regulator of mTORC1. Our work clarifies how mTORC1 inhibits growth factor signaling and opens new areas of investigation in mTOR biology.     

Evaluation of formalin-fixed paraffin-embedded tissues from vaccine site-associated sarcomas of cats for polyomavirus DNA and antigen

OBJECTIVE: To determine whether vaccine site-associated sarcomas (VSS) from cats contain polyomavirus antigen or DNA. SAMPLE POPULATION: 50 formalin-fixed paraffin-embedded tissue blocks of VSS from cats. PROCEDURE: Sections from each tissue block were evaluated for polyomavirus antigen by use of an avidin-biotin-complex immunohistochemical staining method, using rabbit anti-murine polyomavirus polyclonal antiserum as the primary antibody. The DNA was extracted from sections of each tissue block, and a polymerase chain reaction assay was performed, using primers designed to amplify regions of the bovine polyomavirus genome and consensus polyomavirus primers designed to detect unknown polyomaviruses. RESULTS: Polyomavirus antigen and DNA were not detected in any of the VSS. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that polyomaviruses likely do not have any direct involvement in the pathogenesis of VSS in cats.     

The(13)C-octanoic acid breath test for detection of effects of meal composition on the rate of solid-phase gastric emptying in ponies

The aim of this study was to apply the(13)C-octanoic acid breath test for detection of alterations in the rate of solid-phase gastric emptying, induced by changes in test meal composition, in ponies. After a 14 hour fast the ponies (n = 4) ingested a test meal with 0, 35 or 70 ml soya oil, and labelled with 250 mg(13)C-octanoic acid. Each pony was given each of the three test meals on three separate occasions, in a randomised order. Exhaled breath samples were collected for 12 hours after ingestion of the test meal. Breath samples were analysed by continuous flow isotope ratio mass spectrometry. Three indices of breath(13)C-enrichment were computed, half-dose recovery time (t 1/2), gastric emptying coefficient (GEC) and time to peak breath(13)C-excretion t(max). The(13)C-octanoic acid breath test was a reliable means of assessing the significantly decreased rate of gastric emptying in the pony, associated with addition of soya oil to the test meal.