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Background: Mucopolysaccharidosis type IIID is caused by a deficiency of N-acetylglucosamine-6-sulfatase enzyme, which increases heparan sulfate accumulation in lysosomes and generate cytoplasmic vacuolation in central nervous system and somatic tissues. Goats kids with this disorder exhibit delayed motor development, growth retardation and sudden death. This is a transition mutation of cytosine to thymine at nucleotide 322 of the genetic sequence. The objective of this study was to determine the allelic frequency of the glucosamine N-acetyl-6-sulfatase gene (GNS) that causes mucopolysaccharidosis type IIID (MPS IIID) in a population of Nubian goats in Colima, Mexico. Methods: Genomic DNA was isolated from blood samples of 158 Mexican Nubian goats. The 96 bp fragment of GNS gene including the nonsense mutation was PCR amplified. The PCR amplicon was subjected to RFLP using AluI restriction enzyme to identify polymorphism at nucleotide position 322 (C>T). Genotypes were scored. Using Hardy-Weinberg equilibrium (HWE) testing we determined the population to be in genetic equilibrium. Result: Of the entire Nubian goat population genotyped, eight of which were MPS IIID carriers (1 male and 7 females). Observed allelic frequencies were 0.975 for the wild-type allele C and 0.025 for the mutant allele T. MPS IIID was first found in goats at the end of the last century, with considerable higher frequencies, but recent advances in diagnosis and marker-assisted selection against genetic diseases appear to have lowered MPS IIID mutation frequencies in North American Nubian goats. We identified for the first time the variant causing MPS IIID in Nubian goats in Mexico. [ABSTRACT FROM AUTHOR]

Background: The focus of this review is on methods that are currently being used to evaluate the behavioural effects of medication for individuals with intellectual disabilities. First we describe what has been identified as the ideal criteria for conducting clinical trials and how these criteria may be adapted to do less controlled evaluations. The central theme is a review of the biological measures (e.g. labs, drug levels), behavioural rating scales and direct observation measures that are often used to evaluate medication effects. Issues related to how the side effects of medication can affect behaviour will also be discussed. Conclusion: The importance of encouraging communication and collaboration across all systems of care and the use of socially valid measures are discussed.

Within the scope of a double-blind, placebo-controlled, crossover medication study, the Diagnostic Assessment of the Severely Handicapped-II (DASH-II) was evaluated as a measurement for determining the effectiveness of the medication risperidone in treating the problem behaviour of 21 people with intellectual disabilities (ID). Participants caregivers completed the DASH-II during the placebobaseline phase of the study and the maintenance phase of the study, and completed the Aberrant Behavior Checklist Community (ABC-C) weekly throughout the entire study. The results obtained using the DASH-II were compared to those obtained using the ABC-C, an instrument shown to be well correlated with the DASH-II. Results suggest that while the DASH-II and the ABC-C were well correlated during the placebo/baseline phase of the current study, they were not well correlated at completion of the 6-month maintenance phase of the medication trial. The DASH-II, while appropriate for assisting in the diagnosis of psychopathology in people with ID, does not appear to monitor changes in problem behaviour as a result of risperidone use as well as the ABC-C. Differences in the frequency of problem behaviour that each measure evaluated and the applicability of using the DASH-II to measure medication effects on problem behaviour are discussed.

The purpose of this study was to identify genotype variants in the beta-casein (CSN2) and kappa-case (CSN3) genes using the PCR-RFLP method in a population of 202 Holstein cattle from two highly technified farms in the state of Jalisco, Mexico. We further assessed the association of these variants with milk production during a second lactation period. In the first population (n = 102), the genotypic frequencies for CSN2 were A1 = 0.387 and A2 = 0.613, while for CSN3, they were A = 0.829 and B = 0.172. In the second population (n = 100), the genotypic frequencies for CSN2 were A1 = 0.430 and A2 = 0.570, while for CSN3, they were A = 0.795 and B = 0.205. No differences in frequency distribution were noted in either population, and both genes were in Hardy-Weinberg equilibrium. There was greater genetic diversity for the CSN2 gene (0.477 and 0.493) than for the CSN3 gene (0.286 and 0.328) in both populations, with no significant differences between them. The fixation index was low for both genes, suggesting that there was no significant decrease in heterozygosity. The same genetic changes occur in both genes, and give their high similarity index (0.99 and 0.99). The statistical association analysis between genotypes of both genes and milk production revealed there were no significant differences between populations. Furthermore, no significant additive or dominant effects of both casein genes on milk production were identified within our population samples. [ABSTRACT FROM AUTHOR]

Due to its low fertility, expressed as small litter size, a Mexican hairless boar was subjected to cytogenetic investigation. Analysis of G-banded mitotic chromosomes revealed a reciprocal chromosome translocation, rcp(3;6) (p14;q21). Synaptonemal complex analysis showed a regular pairing behavior of the translocation chromosome axes, always resulting in a quadrivalent configuration. However, due to extensive nonhomologous pairing between the axes of nonderivative chromosomes 3 and 6, the quadrivalent mostly had an asymmetrical cross-shaped morphology. The nonhomologous pairing occurred not only at mid and late pachytene, but also at the earliest stage of pachytene. It seems that early pachytene heterosynapsis is a common phenomenon in the pairing behavior of pig reciprocal translocations. Therefore, heterosynapsis may reduce apoptosis of germ cells due to partial absence of homologous synapsis during the pairing phase of meiosis. The frequency of spermatocytes showing quadrivalent configurations with unpaired axial segments apparently did not affect germ cell progression in the boar, since fairly normal testicular histology was noticed. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract Background Induction of osteoblast differentiation by paracrine Sonic hedgehog (Shh) signaling may be a mechanism through which Shh-expressing prostate cancer cells initiate changes in the bone microenvironment and promote metastases. A hallmark of osteoblast differentiation is the formation of matrix whose predominant protein is type 1 collagen. We investigated the formation of a collagen matrix by osteoblasts cultured with prostate cancer cells, and its effects on interactions between prostate cancer cells and osteoblasts. Results In the presence of exogenous ascorbic acid (AA), a co-factor in collagen synthesis, mouse MC3T3 pre-osteoblasts in mixed cultures with human LNCaP prostate cancer cells or LNCaP cells modified to overexpress Shh (LNShh cells) formed collagen matrix with distinct fibril ultrastructural characteristics. AA increased the activity of alkaline phosphatase and the expression of the alkaline phosphatase gene Akp2, markers of osteoblast differentiation, in MC3T3 pre-osteoblasts cultured with LNCaP or LNShh cells. However, the AA-stimulated increase in Akp2 expression in MC3T3 pre-osteoblasts cultured with LNShh cells far exceeded the levels observed in MC3T3 cells cultured with either LNCaP cells with AA or LNShh cells without AA. Therefore, AA and Shh exert a synergistic effect on osteoblast differentiation. We determined whether the effect of AA on LNShh cell-induced osteoblast differentiation was mediated by Shh signaling. AA increased the expression of Gli1 and Ptc1, target genes of the Shh pathway, in MC3T3 pre-osteoblasts cultured with LNShh cells to at least twice their levels without AA. The ability of AA to upregulate Shh signaling and enhance alkaline phosphatase activity was blocked in MC3T3 cells that expressed a dominant negative form of the transcription factor GLI1. The AA-stimulated increase in Shh signaling and Shh-induced osteoblast differentiation was also inhibited by the specific collagen synthesis inhibitor 3,4-dehydro-L-proline. Conclusions Matrix collagen, formed by osteoblasts in the presence of AA, potentiates Shh signaling between Shh-expressing prostate cancer cells and osteoblasts. Collagen and Shh signaling exert a synergistic effect on osteoblast differentiation, a defining event in prostate carcinoma bone metastasis. Investigations into paracrine interactions among prostate cancer cells, osteoblasts, and osteoblast-synthesized matrix proteins advance our understanding of mechanisms contributing to prostate cancer bone metastasis.

Abstract Background Sonic hedgehog (Shh) and components of its signalling pathway have been identified in human prostate carcinoma and increased levels of their expression appear to correlate with disease progression and metastasis. The mechanism through which Shh signalling could promote metastasis in bone, the most common site for prostate carcinoma metastasis, has not yet been investigated. The present study determined the effect of Shh signalling between prostate cancer cells and pre-osteoblasts on osteoblast differentiation, a requisite process for new bone formation that characterizes prostate carcinoma metastasis. Results LNCaP human prostate cancer cells modified to overexpress Shh (designated LNShh cells) and MC3T3 mouse pre-osteoblasts were maintained as mixed populations within the same culture chamber. In this non-conventional mixed culture system, LNShh cells upregulated the expression of Shh target genes Gli1 and Patched 1 (Ptc1) in MC3T3 cells and this was inhibited by cyclopamine, a specific chemical inhibitor of hedgehog signalling. Concomitantly, MC3T3 cells exhibited time-dependent decreased cell proliferation, upregulated alkaline phosphatase Akp2 gene expression, and increased alkaline phosphatase activity indicative of early phase osteoblast differentiation. LNShh cell-induced differentiation was inhibited in MC3T3 cells stably transfected with a dominant negative form of Gli1, a transcription factor that mediates Shh signalling. Interestingly, LNShh cells did not significantly increase the endogenous expression of the osteoblast differentiation transcription factor Runx2 and its target genes osteocalcin and osteopontin. Consistent with these results, exogenous Shh peptide did not upregulate Runx2 expression in MC3T3 cells. However, Runx2 levels were increased in MC3T3 cells by ascorbic acid, a known stimulator of osteoblast differentiation. Conclusion Altogether, these data demonstrate that Shh-expressing prostate cancer cells can directly and specifically induce differentiation in pre-osteoblasts via a Gli1-dependent mechanism that does not require transcriptional upregulation of Runx2. Paracrine activation of the Shh pathway in osteoblast progenitors and subsequent induction of osteoblast differentiation could be a mechanism through which high levels of Shh expression in prostate carcinoma contribute to bone metastasis. Targeting of paracrine Shh signalling may provide an effective therapeutic strategy against prostate carcinoma metastasis in bone.

A total of 84 Yorkshire x Landrace x Duroc pigs, female and castrated male in the same proportion, were used. These animals were housed in groups of two, to be randomly assigned to three treatments that consisted in the addition of 0, 2.5 and 5.0 g of agave oligofructans (Agave tequilana) per kilogram of diet. Animals were fed ad libitum with a diet of cereals and grains from 28 d of age, with an initial weight of around 7 kg. There was no significant effect (P>0.05) in any measure for sex x oligofructan level interaction. Oligofructans determined a lower food intake (P<0.001), but there was no effect of treatment on weight gain, thus food conversion also decreased (P = 0.09). Oligofructans determined the lowest numeric values, without significant effect (P > 0.05) for thickness of dorsal fat, and the highest for lean yield, regarding control treatment and significantly (P < 0.001) lower for losses by leaking and for pH at 24 h. It is suggested that agave oligofructans may have a positive influence on carcass and meat characteristics of growing finishing pigs, with more marked effect than in performance traits. [ABSTRACT FROM AUTHOR]

In the present study, we compared the genetic variability of fragments from the internal transcribed spacer region (ITS) and the small subunit ribosomal DNA (SSUrDNA) as nuclear markers, in contrast with the ribosomal protein large two ( rpl2 ) loci , placed in the mitochondrion-related organelles (MROs) within and among human fecal samples with Blastocystis . Samples were analyzed using polymerase chain reaction (PCR)-sequencing, phylogenies, and genetics of population structure analyses were performed. In total, 96 sequences were analyzed, i.e., 33 of SSUrDNA, 35 of rpl2 , and 28 of ITS. Only three subtypes (STs) were identified, i.e., ST1 (11.4%), ST2 (28.6%), and ST3 (60%); in all cases, kappa indexes were 1, meaning a perfect agreement among ST assignations. The topologies of phylogenetic inferences were similar among them, clustering to each ST in its specific cluster; discrepancies between phylogeny and assignment of STs were not observed. The STRUCTURE v2.3.4 software assigned three subpopulations corresponding to the STs 1-3, respectively. The population indices were consistent with those previously reported by other groups. Our results suggest the potential use of the ITS and rpl2 genes as molecular markers for Blastocystis subtyping as an alternative approach for the study of the genetic diversity observed within and between human isolates of this microorganism.