Cortical thickness abnormalities in cocaine addiction--a reflection of both drug use and a pre-existing disposition to drug abuse?

The structural effects of cocaine on neural systems mediating cognition and motivation are not well known. By comparing the thickness of neocortical and paralimbic brain regions between cocaine-dependent and matched control subjects, we found that four of 18 a priori regions involved with executive regulation of reward and attention were significantly thinner in addicts. Correlations were significant between thinner prefrontal cortex and reduced keypresses during judgment and decision making of relative preference in addicts, suggesting one basis for restricted behavioral repertoires in drug dependence. Reduced effortful attention performance in addicts also correlated with thinner paralimbic cortices. Some thickness differences in addicts were correlated with cocaine use independent of nicotine and alcohol, but addicts also showed diminished thickness heterogeneity and altered hemispheric thickness asymmetry. These observations suggest that brain structure abnormalities in addicts are related in part to drug use and in part to predisposition toward addiction.     

Decreased absolute amygdala volume in cocaine addicts

The amygdala is instrumental to a set of brain processes that lead to cocaine consumption, including those that mediate reward and drug craving. This study examined the volumes of the amygdala and hippocampus in cocaine-addicted subjects and matched healthy controls and determined that the amygdala but not the hippocampus was significantly reduced in volume. The right-left amygdala asymmetry in control subjects was absent in the cocaine addicts. Topological analysis of amygdala isosurfaces (population averages) revealed that the isosurface of the cocaine-dependent group undercut the anterior and superior surfaces of the control group, implicating a difference in the corticomedial and basolateral nuclei. In cocaine addicts, amygdala volume did not correlate with any measure of cocaine use. The amygdala symmetry coefficient did correlate with baseline but not cocaine-primed craving. These findings argue for a condition that predisposes the individual to cocaine dependence by affecting the amygdala, or a primary event early in the course of cocaine use.     

Evidence for altered basal ganglia-brainstem connections in cervical dystonia

Background

There has been increasing interest in the interaction of the basal ganglia with the cerebellum and the brainstem in motor control and movement disorders. In addition, it has been suggested that these subcortical connections with the basal ganglia may help to coordinate a network of regions involved in mediating posture and stabilization. While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, thus far, there is only indirect evidence for this in humans with dystonia.

Methodology/Principal Findings

In the current study we investigated probabilistic diffusion tractography in DYT1-negative patients with cervical dystonia and matched healthy control subjects, with the goal of showing that patients exhibit altered microstructure in the connectivity between the pallidum and brainstem. The brainstem regions investigated included nuclei that are known to exhibit strong connections with the cerebellum. We observed large clusters of tractography differences in patients relative to healthy controls, between the pallidum and the brainstem. Tractography was decreased in the left hemisphere and increased in the right hemisphere in patients, suggesting a potential basis for the left/right white matter asymmetry we previously observed in focal dystonia patients.

Conclusions/Significance

These findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia.     

Living with myotonic dystrophy; what can be learned from couples? a qualitative study

Background  

Myotonic dystrophy type 1 (MD1) is one of the most prevalent neuromuscular diseases, yet very little is known about how MD1 affects the lives of couples and how they themselves manage individually and together. To better match health care to their problems, concerns and needs, it is important to understand their perspective of living with this hereditary, systemic disease.     

Sex and age differences in AMPK phosphorylation,mitochondrial homeostasis,and inflammation in hearts from inflammatory cardiomyopathy patients

Linked to exacerbated inflammation, myocarditis is a cardiovascular disease, which may lead to dilated cardiomyopathy. Although sex and age differences in the development of chronic myocarditis have been postulated, underlying cellular mechanisms remain poorly understood. In the current study, we aimed to investigate sex and age differences in mitochondrial homeostasis, inflammation, and cellular senescence. Cardiac tissue samples from younger and older patients with inflammatory dilated cardiomyopathy (DCMI) were used. The expression of Sirt1, phosphorylated AMPK, PGC-1α, Sirt3, acetylated SOD2, catalase, and several mitochondrial genes was analyzed to assess mitochondrial homeostasis. The expression of NF-κB, TLR4, and interleukins was used to examine the inflammatory state in the heart. Finally, several senescence markers and telomere length were investigated. Cardiac AMPK expression and phosphorylation were significantly elevated in male DCMI patients, whereas Sirt1 expression remained unchanged in all groups investigated. AMPK upregulation was accompanied by a preserved expression of all mitochondrial proteins/genes investigated in older male DCMI patients, whereas the expression of TOM40, TIM23, and the mitochondrial oxidative phosphorylation genes was significantly reduced in older female patients. Mitochondrial homeostasis in older male patients was further supported by the reduced acetylation of mitochondrial proteins as indicated by acetylated SOD2. The inflammatory markers NF-κB and TLR4 were downregulated in older male DCMI patients, whereas the expression of IL-18 was increased in older female patients. This was accompanied by progressed senescence in older DCMI hearts. In conclusion, older women experience more dramatic immunometabolic disorders on the cellular level than older men.     

Initial steps towards a production platform for DNA sequence analysis on the grid

Background  

Bioinformatics is confronted with a new data explosion due to the availability of high throughput DNA sequencers. Data storage and analysis becomes a problem on local servers, and therefore it is needed to switch to other IT infrastructures. Grid and workflow technology can help to handle the data more efficiently, as well as facilitate collaborations. However, interfaces to grids are often unfriendly to novice users.     

The r.b.e. of fast fission neutrons (2 MeV) for chronic radiation damage of the large bowel of rats after single dose and fractionated irradiation

Late damage in the rectum of rats was studied after local irradiation with 2 MeV fast fission neutrons and the results were compared with those for 300 kV X-rays. A similarity between latency times, and between clinical, gross pathological and histological appearances of the rectal obstruction after the two types of radiation was observed. The r.b.e. evaluated from ED 50/200 days values was 1.8 for single doses, 2.1 for two fractions and 3 for five fractions and these are similar to r.b.e.s from other investigations of chronic intestinal radiation damage. Using linear quadratic analysis, a limiting r.b.e. of 5 was obtained. The beta-values are similar for both radiation qualities. Because of the high gamma-contamination (25 per cent) in the RENT I beam a possible correction of the r.b.e. for neutrons only, assuming interaction, is discussed.     

Inactivation of <Emphasis Type="Italic">Dicer1</Emphasis> in Steroidogenic factor 1-positive cells reveals tissue-specific requirement for <Emphasis Type="Italic">Dicer1</Emphasis>in adrenal,testis, and ovary

Background  

The synthesis of microRNA (miRNA) is a multi-step process that requires the action of the ribonuclease Dicer1. Dicer1 is responsible for the final processing of miRNA and has been implicated in cellular processes such as proliferation, apoptosis, and differentiation. Mouse embryos lacking Dicer1 die in early embryogenesis. In this study, we investigated whether Dicer1 is required for development of adrenal, testis, and ovary in mouse embryos.     

Beautiful faces have variable reward value: fMRI and behavioral evidence.

The brain circuitry processing rewarding and aversive stimuli is hypothesized to be at the core of motivated behavior. In this study, discrete categories of beautiful faces are shown to have differing reward values and to differentially activate reward circuitry in human subjects. In particular, young heterosexual males rate pictures of beautiful males and females as attractive, but exert effort via a keypress procedure only to view pictures of attractive females. Functional magnetic resonance imaging at 3 T shows that passive viewing of beautiful female faces activates reward circuitry, in particular the nucleus accumbens. An extended set of subcortical and paralimbic reward regions also appear to follow aspects of the keypress rather than the rating procedures, suggesting that reward circuitry function does not include aesthetic assessment.     

Biosurfactants from thermophilic dairy streptococci and their potential role in the fouling control of heat exchanger plates

Recent work on biosurfactant release by thermophilic dairy streptococci is reviewed. There is a suggestion thatStreptococcus thermophilus isolates may release biosurfactants that stimulate detachment of already-adhering cells and leave an anti-adhesive coating on a substratum. A previously published rapid screening method is described for the identification of biosurfactant-releasing microorganisms, and growth medium supplements to enhance biosurfactant release by thermophilic dairy streptococci are reported. New experimental work described includes the isolation and purification of biosurfactants from dairy isolates by thin layer chromatography. Many compounds isolated were extremely surface-active and reduced the water surface tension to values around 30 mJ m^–2 at a concentration of 10 mg ml^–1. Most importantly, the thin layer chromatograms of various isolates resembled each other, and an adsorbed purified compound from one isolate retarded the deposition to glass of another isolate by a factor of two. Provided our findings implicate that these biosurfactants could also be adsorbed to heat exchanger plates in pasteurizers and thereby retard colonization by thermophilic streptococci, these compounds may have major economic implications. Further work is required, however.