Exercise training attenuates increases in lumbar sympathetic nerve activity produced by stimulation of the rostral ventrolateral medulla.

Exercise training (ExTr) has been associated with blunted activation of the sympathetic nervous system in several animal models and in some human studies. Although these data are consistent with the hypothesis that ExTr reduces the incidence of cardiovascular diseases via reduced sympathoexcitation, the mechanisms are unknown. The rostral ventrolateral medulla (RVLM) is important in control of sympathetic nervous system activity in both physiological and pathophysiological states. The purpose of the present study was to test the hypothesis that ExTr results in reduced sympathoexcitation mediated at the level of the RVLM. Male Sprague-Dawley rats were treadmill trained or remained sedentary for 8-10 wk. RVLM microinjections were performed under Inactin anesthesia while mean arterial pressure, heart rate, and lumbar sympathetic nerve activity (LSNA) were recorded. Bilateral microinjections of the GABA(A) antagonist bicuculline (5 mM, 90 nl) into the RVLM increased LSNA in sedentary animals (169 +/- 33%), which was blunted in ExTr animals (100 +/- 22%, P < 0.05). Activation of the RVLM with unilateral microinjections of glutamate (10 mM, 30 nl) increased LSNA in sedentary animals (76 +/- 13%), which was also attenuated by training (26 +/- 2%, P < 0.05). Bilateral microinjections of the ionotropic glutamate receptor antagonist kynurenate (40 mM, 90 nl) produced small increases in mean arterial pressure and LSNA that were similar between groups. Results suggest that ExTr may reduce increases in LSNA due to reduced activation of the RVLM. Conversely, we speculate that the relatively enhanced activation of LSNA in sedentary animals may be related to the increased incidence of cardiovascular disease associated with a sedentary lifestyle.     

Use of Wishart Prior and Simple Extensions for Sparse Precision Matrix Estimation

A conjugate Wishart prior is used to present a simple and rapid procedure for computing the analytic posterior (mode and uncertainty) of the precision matrix elements of a Gaussian distribution. An interpretation of covariance estimates in terms of eigenvalues is presented, along with a simple decision-rule step to improve the performance of the estimation of sparse precision matrices and associated graphs. In this, elements of the estimated precision matrix that are zero or near zero can be detected and shrunk to zero. Simulated data sets are used to compare posterior estimation with decision-rule with two other Wishart-based approaches and with graphical lasso. Furthermore, an empirical Bayes procedure is used to select prior hyperparameters in high dimensional cases with extension to sparsity.     

Alterations of Dermal Connective Tissue Collagen in Diabetes: Molecular Basis of Aged-Appearing Skin

Alterations of the collagen, the major structural protein in skin, contribute significantly to human skin connective tissue aging. As aged-appearing skin is more common in diabetes, here we investigated the molecular basis of aged-appearing skin in diabetes. Among all known human matrix metalloproteinases (MMPs), diabetic skin shows elevated levels of MMP-1 and MMP-2. Laser capture microdissection (LCM) coupled real-time PCR indicated that elevated MMPs in diabetic skin were primarily expressed in the dermis. Furthermore, diabetic skin shows increased lysyl oxidase (LOX) expression and higher cross-linked collagens. Atomic force microscopy (AFM) further indicated that collagen fibrils were fragmented/disorganized, and key mechanical properties of traction force and tensile strength were increased in diabetic skin, compared to intact/well-organized collagen fibrils in non-diabetic skin. In in vitro tissue culture system, multiple MMPs including MMP-1 and MM-2 were induced by high glucose (25 mM) exposure to isolated primary human skin dermal fibroblasts, the major cells responsible for collagen homeostasis in skin. The elevation of MMPs and LOX over the years is thought to result in the accumulation of fragmented and cross-linked collagen, and thus impairs dermal collagen structural integrity and mechanical properties in diabetes. Our data partially explain why old-looking skin is more common in diabetic patients.     

An initial top-down proteomic analysis of the standard cuprizone mouse model of multiple sclerosis

An initial proteomic analysis of the cuprizone mouse model to characterise the breadth of toxicity by assessing cortex, skeletal muscle, spleen and peripheral blood mononuclear cells. Cuprizone treated vs. control mice for an initial characterisation. Select tissues from each group were pooled, analysed in triplicate using two-dimensional gel electrophoresis (2DE) and deep imaging and altered protein species identified using liquid chromatography tandem mass spectrometry (LC/MS/MS). Forty-three proteins were found to be uniquely detectable or undetectable in the cuprizone treatment group across the tissues analysed. Protein species identified in the cortex may potentially be linked to axonal damage in this model, and those in the spleen and peripheral blood mononuclear cells to the minimal peripheral immune cell infiltration into the central nervous system during cuprizone mediated demyelination. Primary oligodendrocytosis has been observed in type III lesions in multiple sclerosis. However, the underlying mechanisms are poorly understood. Cuprizone treatment results in oligodendrocyte apoptosis and secondary demyelination. This initial analysis identified proteins likely related to axonal damage; these may link primary oligodendrocytosis and secondary axonal damage. Furthermore, this appears to be the first study of the cuprizone model to also identify alterations in the proteomes of skeletal muscle, spleen and peripheral blood mononuclear cells. Notably, protein disulphide isomerase was not detected in the cuprizone cohort; its absence has been linked to reduced major histocompatibility class I assembly and reduced antigen presentation. Overall, the results suggest that, like experimental autoimmune encephalomyelitis, results from the standard cuprizone model should be carefully considered relative to clinical multiple sclerosis.     

Costs and benefits of joint colony founding in Australian Acacia thrips

Facultative joint colony founding by social insects (pleometrosis) provides an outstanding opportunity to analyze the costs and benefits of sociality. Pleometrosis has been documented for a range of social insects, but most studies on the adaptive benefits of this behavior are restricted to the Hymenoptera. In this study, we provide the first analysis of costs and benefits associated with pleometrosis for Australian Dunatothrips, which form domiciles by glueing together phyllodes (leaves) of their Acacia host plant. In Dunatothrips aneurae, the distribution of foundress numbers per nest indicated that females formed associations non-randomly. Furthermore, average group size was independent of both the number of foundresses on the host plant and the number of mature colonies, suggesting that this behavior was not simply a response to limited availability of nesting sites. Although per capita reproduction declined with increasing group size, we also identified two benefits of pleometrosis: (1) individual foundresses in groups had higher survival than solitary foundresses during the brood development period, and (2) larger colony sizes resulting from pleometrosis provided a benefit later in colony development, because a higher proportion of D. aneurae adults survived invasions by the kleptoparasite Xaniothrips mulga when colony size was larger. These results demonstrate that the reproductive costs of pleometrosis are at least partially counterbalanced by survival benefits. Received 4 April 2006; revised 9 September 2006; accepted 20 September 2006.     

Fish population structuring in the North Sea: understanding processes and mechanisms from studies of the movements of adults

Few fish species form single, panmictic populations throughout their geographic range, most form subpopulations or 'stocks' with differing levels of interconnectivity. Different patterns of interconnectivity between subpopulations will give rise to different responses to exploitation and management, but they will also have different capacities to generate the genetic and phenotypic differences often used to discriminate between stocks. Consequently, knowledge of ontogenetic and seasonal patterns in the distribution, movement and behaviour of individuals is crucial to identifying population substructure. This paper considers the evidence gathered about movements and behaviour of adult fishes from mark-recapture and electronic tagging studies for a number of fish species in the North Sea and elsewhere in U.K. waters in an attempt to understand population structure and the processes that may give rise to it.