Association of periodontal disease and histologic lesions in multiple organs from 45 dogs

Male and female subjects (n = 125) were measured on a battery of anthropometric tests every six months for a period of five years. Using maturity status as the temporal component (pubescent assessment stages one through five), proportionality characteristics of subjects were monitored as they matured toward the adult form. Subjects were assigned to one of the Hi, Mid and Lo sub-groups based on their score at PA stage one for each of 15 proportionality characteristics. Subsequently, those in the Mid group were removed from the analysis, while male and female subjects were pooled for the final ANOVA model. The results showed that a number of variables remained stable from PA stages one through five. That is, differences between the Hi and Lo groups were maintained throughout maturation. Predominantly, these included the proportional body segment breadth measures. Proportionality characteristics of the upper limbs appeared to stabilise from mid-adolescence. However, those related to the lower limb were not stable. In other words, a significant difference for the lower limb variables at PA stage one was not maintained through stages four and five. The results raised some doubts as to the suitability of using lower limb proportions as selection criteria in talent identification programs.     

Limbic circuits and neuropsychiatric disorders. Functional anatomy and neuroimaging findings

The limbic system seems to be involved in the pathophysiology of neuropsychiatric disorders, including dementia, schizophrenia, affective disorders, and amnestic disorders. These findings are subtle and largely went undetected until the advent of modern neuroimaging. This article discusses some of the neuroimaging findings in these disorders.     

The T cell surface protein, CD28

The cluster of differentiation (CD) antigen CD28 is a 44-kDa, disulphide-bonded, homodimeric glycoprotein, which is constitutively expressed on the surface of all murine T cells and the majority of human T cells. Ligation of CD28 by its counter receptor, B7, expressed on the surface of antigen presenting cells, has been shown to induce signals that, in synergy with those derived from engagement of the T cell receptor by an antigen bound to a major histocompatibility complex, enhance proliferation and cytokine production. Manipulation of this interaction can have dramatic effects on the outcome of T cell activation. Blocking CD28/B7 interactions may be useful in preventing unwanted activation in allergy and autoimmune diseases, whereas enhancing this interaction can promote tumour rejection. Thus, CD28 and its signalling pathways may prove to be useful targets in the development of new therapeutic treatments.     

Adequacy of amino acids in diets fed to lactating dairy cows

The Cornell Net Carbohydrate and Protein System was used to evaluate absorbable limiting amino acids (AA) for milk yield. The system was utilized to characterize whether diets in five previous experiments met AA requirements for milk protein synthesis. Twenty-nine treatment means for milk yield from 367 cows constituted the database for the evaluation. Using the mechanistic relationships of nutrient metabolism described in the Cornell system, absorbed amounts were predicted of each essential AA from a diet and milk yields allowed by the most limiting AA. Regression of observed milk yield (Y) on predicted milk yield (X) using all treatment means (n = 29) was Y = 2.3 + 0.799X (r2 = 0.72). The linear relationship was stronger using 6 treatment means (n = 18) when protein supplements were fed rather than when ruminally protected AA were fed or when AA were postruminally infused (Y = -1.8 + 0.983X; r2 = 0.93). The Cornell system predicted that, for diets based on corn, Met or Lys was limiting when soybean meal was the protein source, but Lys was limiting when corn gluten meal or brewers grains were the source of protein. By AA limitation, the Cornell system explained differences in milk yield for diets that differed in supplemental protein sources in some of the experiments. As determined from milk protein yields in these studies, requirements for individual essential AA were expressed as a percentage of dietary dry matter or total essential AA, and values were relatively constant among dietary treatments and experiments.     

Characterization of a multicomponent receptor for GDNF

Glial-cell-line-derived neurotrophic factor (GDNF) is a potent survival factor for central and peripheral neurons, and is essential for the development of kidneys and the enteric nervous system. Despite the potential clinical and physiological importance of GDNF, its mechanism of action is unknown. Here we show that physiological responses to GDNF require the presence of a novel glycosyl-phosphatidylinositol (GPI)-linked protein (designated GDNFR-alpha) that is expressed on GDNF-responsive cells and binds GDNF with a high affinity. We further demonstrate that GDNF promotes the formation of a physical complex between GDNFR-alpha and the orphan tyrosin kinase receptor Ret, thereby inducing its tyrosine phosphorylation. These findings support the hypothesis that GDNF uses a multi-subunit receptor system in which GDNFR-alpha and Ret function as the ligand-binding and signalling components, respectively.     

Human MSH2 binds to trinucleotide repeat DNA structures associated with neurodegenerative diseases

The expansion of trinucleotide repeat sequences is associated with several neurodegenerative diseases. The mechanism of this expansion is unknown but may involve slipped-strand structures where adjacent rather than perfect complementary sequences of a trinucleotide repeat become paired. Here, we have studied the interaction of the human mismatch repair protein MSH2 with slipped-strand structures formed from a triplet repeat sequence in order to address the possible role of MSH2 in trinucleotide expansion. Genomic clones of the myotonic dystrophy locus containing disease-relevant lengths of (CTG)n x (CAG)n triplet repeats were examined. We have constructed two types of slipped-strand structures by annealing complementary strands of DNA containing: (i) equal numbers of trinucleotide repeats (homoduplex slipped structures or S-DNA) or (ii) different numbers of repeats (heteroduplex slipped intermediates or SI-DNA). SI-DNAs having an excess of either CTG or CAG repeats were structurally distinct and could be separated electrophoretically and studied individually. Using a band-shift assay, the MSH2 was shown to bind to both S-DNA and SI-DNA in a structure-specific manner. The affinity of MSH2 increased with the length of the repeat sequence. Furthermore, MSH2 bound preferentially to looped-out CAG repeat sequences, implicating a strand asymmetry in MSH2 recognition. Our results are consistent with the idea that MSH2 may participate in trinucleotide repeat expansion via its role in repair and/or recombination.     

The hippocampal formation participates in novel picture encoding: evidence from functional magnetic resonance imaging

Considerable evidence exists to support the hypothesis that the hippocampus and related medial temporal lobe structures are crucial for the encoding and storage of information in long-term memory. Few human imaging studies, however, have successfully shown signal intensity changes in these areas during encoding or retrieval. Using functional magnetic resonance imaging (fMRI), we studied normal human subjects while they performed a novel picture encoding task. High-speed echo-planar imaging techniques evaluated fMRI signal changes throughout the brain. During the encoding of novel pictures, statistically significant increases in fMRI signal were observed bilaterally in the posterior hippocampal formation and parahippocampal gyrus and in the lingual and fusiform gyri. To our knowledge, this experiment is the first fMRI study to show robust signal changes in the human hippocampal region. It also provides evidence that the encoding of novel, complex pictures depends upon an interaction between ventral cortical regions, specialized for object vision, and the hippocampal formation and parahippocampal gyrus, specialized for long-term memory.