Lifespan mental activity predicts diminished rate of hippocampal atrophy

Objective

Epidemiological studies suggest that complex mental activity may reduce the risk for dementia, however an underlying mechanism remains unclear. Our objective was to determine whether individual differences in lifespan complex mental activity are linked to altered rates of hippocampal atrophy independent of global measures of neurodegeneration.

Methods

Thirty seven healthy older individuals had their complex mental activity levels estimated using the Lifetime of Experiences Questionnaire (LEQ) and completed serial MRI investigations at baseline and three years follow-up. Hippocampal volume and semi-automatic quantitation of whole brain volume (WBV) and white matter hyperintensities (WMHs) were compared at both time points.

Results

Higher LEQ scores were correlated with hippocampal volume independent of covariates at the three year follow-up stage (r = 0.43, p = 0.012). Moreover, those with higher LEQ scores experienced less hippocampal atrophy over the follow-up period (r = 0.41, p = 0.02). High LEQ individuals had less than half the hippocampal volume decline of low LEQ individuals in a multivariate analysis (F = 4.47, p = 0.042). No parallel changes were found in measures of WBV and WMHs.

Conclusions

High level of complex mental activity across the lifespan was correlated with a reduced rate of hippocampal atrophy. This finding could not be explained by general differences in intracranial volume, larger hippocampi at baseline, presence of hypertensive disease, gender or low mood. Our results suggest that neuroprotection in medial temporal lobe may be one mechanism underlying the link between mental activity and lower rates of dementia observed in population-based studies. Additional studies are required to further explore this novel finding.     

A computational strategy to analyze label-free temporal bottom-up proteomics data

Biological systems are in a continual state of flux, which necessitates an understanding of the dynamic nature of protein abundances. The study of protein abundance dynamics has become feasible with recent improvements in mass spectrometry-based quantitative proteomics. However, a number of challenges still remain related to how best to extract biological information from dynamic proteomics data, for example, challenges related to extraneous variability, missing abundance values, and the identification of significant temporal patterns. This paper describes a strategy that addresses these issues and demonstrates its values for analyzing temporal bottom-up proteomics data using data from a Rhodobacter sphaeroides 2.4.1 time-course study.     

Production of 9-hydroxynonanoic Acid from methyl oleate and conversion into lactone monomers for the synthesis of biodegradable polylactones

The feasibility of a previously established method based on ozonolysis and hydrogenation reactions for the production of 9-hydroxynonanoic acid from oleic acid has been demonstrated. Metal catalyzed lactonization conditions have been used to convert 9-hydroxynonanoic acid into 1,11-dioxacycloicosane-2,12-dione, which is a potential monomer in the synthesis of polylactones. The structure of 9-hydroxynonanoic acid and 1,11-dioxacycloicosane-2,12-dione has been confirmed by 1H NMR, 13C NMR, and FTIR. In addition, 9-hydroxynonanoic acid was analyzed by high-resolution mass spectroscopy and 1,11-dioxacycloicosane-2,12-dione was analyzed by GC-MS. Aliphatic poly(nonanolactones) have been synthesized via ring-opening polymerization of the dilactone. The structure and number average molecular weight (M(n)) of the poly(nonanolactones) have been calculated by 1H NMR and GPC. The physical properties of these poly(nonanolactones) have been characterized by modulated differential scanning calorimetry (MDSC) and thermogravimetric analysis (TGA).     

Dynamic regulation of ryanodine receptor type 1 (RyR1) channel activity by Homer 1

Homer, a family of scaffolding proteins originally identified in neurons, is also expressed in skeletal muscle. Previous studies showed that splice variants of Homer 1 (H1) amplify the gain of the ryanodine receptor type 1 (RyR1) channel complex. Using [3H]ryanodine ([3H]Ry) to probe the conformational state of RyR1, the actions of long- and short-forms of H1 are examined singly and in combination. At < or =200 nM, H1 long-forms (H1b or H1c possessing coiled-coil (CC) domains) and short-forms (H1a or H1EVH1 lacking CC domains) enhance specific [3H]Ry binding to RyR1. However, at a concentration > 200 nM, either H1 form completely inhibited [3H]Ry binding. Importantly, the combinations of H1c+H1EVH1, or H1b+H1a acted in an additive manner to enhance or inhibit [3H]Ry-binding activity. H1a and H1c individually or in combination produced the same dynamic pattern in regulating purified RyR1 channels reconstituted in planar lipid bilayers. In combination, their net action on RyR1 channels depends on total concentrations of H1. These data provide a mechanism by which constitutively and transiently expressed H1 forms can tightly regulate RyR1 channel activity in response to changing levels of expression and degradation of H1 proteins.     

Pigmentation in Black-boned sheep (<Emphasis Type="Italic">Ovis aries</Emphasis>): association with polymorphism of the <Emphasis Type="Italic">Tyrosinase</Emphasis> gene

Measurements were made in Black-boned (n = 40) and normal (n = 23) sheep (Ovis aries) from a flock in Nanping County of Yunnan Province, China, as well as a group (n = 21) of Romney Marsh sheep (O. aries) with the view to explaining the basis of the dark pigmentation occurring in the Black-boned animals. Plasma colour was significantly darker (P < 0.01) in Black-boned sheep than in their normal flock mates, which in turn had significantly darker plasma (P < 0.01) than the Romney Marsh sheep. Similar significant (P < 0.01) differences were measured for plasma tyrosinase activity and both groups of sheep from Nanping County had similar plasma concentrations of glutathione which were significantly smaller (P < 0.01) than for the Romney Marsh sheep.A partial fragment of 750 bp of exon 1 of the gene encoding tyrosinase was constructed and found to contain two silent mutation sites (G192C and C462T) but there was no effect on amino acid sequences of tyrosinase. Using restriction fragment length polymorphism analyses two allelic variants of site G192C were identified giving rise to the genotypes GG, GC and CC; the frequencies of allele G being 0.914, 0.824 and 0.286 in the Black-boned sheep, their flock mates and the Romney Marsh sheep respectively. Plasma tyrosinase activity was similar for genotypes GG and GC and for both genotypes significantly higher (P < 0.05) than for genotype CC. The sheep from Nanping County displayed only the GG and GC genotypes and had predominantly black or black and white coat colour whereas the Romney Marsh sheep were of either genotype GC or CC and exhibited only white coat colouration. It is not appears that the dark pigmentation of the Black-boned sheep arises because of polymorphisms in the exon 1 of tyrosinase gene. However, this result could explain the differences between Black-boned and Romney Marsh sheep but not for differences between Black-boned and Nanping Normal sheep. Moreover, this result has provided evidence of genetic markers in the form of polymorphisms of the tyrosinase gene which may help to find the black traits causing mutations. There would be merit in further studies using histochemical and molecular techniques to elucidate the causes of the dark pigmentation in these Black-boned sheep.     

Primary function analysis of human mental retardation related gene <Emphasis Type="Italic">CRBN</Emphasis>

The mutation of human cereblon gene (CRBN) is revealed to be related with mild mental retardation. Since the molecular characteristics of CRBN have not been well presented, we investigated the general properties of CRBN. We analyzed its gene structure and protein homologues. The CRBN protein might belong to a family of adenosine triphosphate (ATP)-dependent Lon protease. We also found that CRBN was widely expressed in different tissues, and the expression level in testis is significantly higher than other tissues. This may suggested it could play some important roles in several other tissues besides brain. Transient transfection experiment in AD 293 cell lines suggested that both CRBN and CRBN mutant (nucleotide position 1,274(C > T)) are located in the whole cells. This may suggest new functions of CRBN in cell nucleolus besides its mitochondria protease activity in cytoplasm.