Identifying the neural circuitry of alcohol craving and relapse vulnerability

With no further intervention, relapse rates in detoxified alcoholics are high and usually exceed 80% of all detoxified patients. It has been suggested that stress and exposure to priming doses of alcohol and to alcohol-associated stimuli (cues) contribute to the relapse risk after detoxification. This article focuses on neuronal correlates of cue responses in detoxified alcoholics. Current brain imaging studies indicate that dysfunction of dopaminergic, glutamatergic and opioidergic neurotransmission in the brain reward system (ventral striatum including the nucleus accumbens) can be associated with alcohol craving and functional brain activation in neuronal systems that process attentional relevant stimuli, reward expectancy and experience. Increased functional brain activation elicited by such alcohol-associated cues predicted an increased relapse risk, whereas high brain activity elicited by affectively positive stimuli may represent a protective factor and was correlated with a decreased prospective relapse risk. These findings are discussed with respect to psychotherapeutic and pharmacological treatment options.     

Effect of slice thickness on brain magnetic resonance image texture analysis

Background  

The accuracy of texture analysis in clinical evaluation of magnetic resonance images depends considerably on imaging arrangements and various image quality parameters. In this paper, we study the effect of slice thickness on brain tissue texture analysis using a statistical approach and classification of T1-weighted images of clinically confirmed multiple sclerosis patients.     

Environmental enrichment in early life affects cortisol patterns in growing pigs

Effects of environmental enrichment at different stages of life on stress physiology of pigs were investigated in a trial with 63 groups, each of four siblings. In each of the three growing phases (suckling 0 to 4 weeks of age, nursery 5 to 9 weeks, fattening 10 to 24 weeks) pens either were (=E) or were not (=0) enriched. Accordingly, the treatments were (i) 000, (ii) E00, (iii) EE0, (iv) 00E, (v) 0EE and (vi) EEE. The enrichment material, renewed twice daily to leave a thin layer, consisted of wood shavings and chopped straw. Salivary cortisol was sampled hourly from 0700 to 1900 h at the age of 9 and 21 weeks. The presence of a circadian secretion rhythm was evaluated by an intra-assay coefficient of variation-based method. An adrenocorticotropic hormone test was performed at 21 weeks. Treatment effects on the odds of a physiological cortisol rhythm were assessed by logistic regression, and effects on cortisol concentrations with a repeated measures GLM. Substrate-enrichment from 0 to 9 weeks of age increased the odds of a rhythm as compared to barren housing (odds ratio (OR) = 30.0, P < 0.01). A flat cortisol secretion pattern may indicate chronic stress and/or delayed maturation of the rhythm. Barren as compared to enriched rearing (0 to 4 weeks of age) seemed to cause a blunted secretion rhythm at 21 weeks of age. Although behavioural and tail lesion observations provided support to the assumption that a blunted rhythm indicates chronic stress, the biological significance of these cortisol results needs confirmation in future studies.     

Women With Hypertensive Pregnancies Have Difficulties in Regaining Pre‐pregnancy Weight and Show Metabolic Disturbances

The aim was to determine maternal weight gain and body composition during pregnancy and 3 months postpartum in women with uncomplicated singleton and twin pregnancies and in women with gestational diabetes (GDM) and gestational hypertension (GH). This prospective study includes four groups of subjects: those with an uncomplicated pregnancy (n = 32), those with a diagnosis of GH (n = 28), those with a diagnosis of GDM (n = 52), and those with twin pregnancy (n = 11). Their body compositions were estimated by a bioimpedance analysis and fasting lipids and glucose levels were determined during the pregnancy and 3 months after pregnancy. Women with GDM were 11.7 kg heavier than the reference group before pregnancy, whereas weight before pregnancy was not different in other investigated groups. Weight loss after delivery was attenuated in GH group. Percentage body fat remained elevated in women with GDM (34.1 ± 7.0%) and hypertension (31.5 ± 6.4%) at 3 months after pregnancy. Also their total cholesterol and low‐density lipoprotein (LDL)‐cholesterol levels as well as fasting glucose remained elevated in comparison to values of the reference group. In conclusion, women with hypertensive pregnancies, though not overweight before pregnancy, gain and retain excess gestational weight and this leads to metabolic abnormalities similar to those seen in women GDM. Thus, postpartum period appears to be critical for weight management and interventional programs are called for.     

Geographical variation in temporal and spatial vocalization patterns of male harbour seals in the mating season

In the aquatically mating harbour seal, Phoca vitulina, oestrous females show marked differences in spatial and temporal distribution between geographical areas. This suggests that the males' display behaviour may also vary between areas. We recorded male vocalizations in two areas, the Moray Firth and Orkney, U.K. In the Moray Firth, females haul out on a few intertidal sandbars and travel along predictable routes to forage at sea. In Orkney, female haul out sites are much less influenced by tidal availability and females are much more dispersed. In the Moray Firth, males vocalized only during a short mating season, from 1 July to 12 August. Vocalizations varied significantly with the tide, the peak at high tide clearly coinciding with the period when most females were in the water. In contrast, vocalizations in Orkney were significantly related to both tidal and diel patterns. We suggest that the timing of male vocalizations reflects differences in female availability between sites. In the inner Moray Firth, vocalizations were heard throughout the females' range, whereas vocalizations in Orkney were heard only in two discrete areas. However, at both sites the density of vocalizing males was highest in narrow channels and/or along predictable female travel routes. Therefore, males clearly adapt their temporal and spatial behaviour patterns to variations in female distribution and density. These results suggest that male mating strategies in aquatically mating pinnipeds are more variable than was previously envisaged. Copyright 1999 The Association for the Study of Animal Behaviour.     

A novel human glycosyltransferase: primary structure and characterization of the gene and transcripts

We report the identification and primary structure of a novel human glycosyltransferase, B3GTL (beta3-glycosyltransferase-like). The 498 residue protein consists of a short cytoplasmic N-terminal "tail" (residues 1-4), a single transmembrane domain with type II topology (residues 5-28), a "stem" region (residues 29-260), and a catalytic domain (residues 261-498). The genomes of Anopheles gambiae, Drosophila melanogaster, and Caenorhabditis elegans encode potential orthologs which share 31-39% sequence identity with B3GTL, as well as the following features: a conserved catalytic domain containing a triple aspartate motif (DDD) at its core, a conserved pattern of cysteine residues, a C-terminal KDEL-like motif, and conserved residues and motifs that affiliate this novel group with a family of beta3-glycosyltransferases (GT31 in the CAZY classification). The B3GTL gene lacks canonical TATA and CAAT boxes and contains three functional polyadenylation sites. It is transcribed in a wide range of tissues and in TGF-beta-treated T84 epithelial cells.     

Silencing of Bruton's tyrosine kinase (Btk) using short interfering RNA duplexes (siRNA)

Tec family tyrosine kinases, Bruton's tyrosine kinase (Btk), Itk, Bmx, Tec, and Txk, are multi-domain proteins involved in hematopoietic signaling. Here, we demonstrate that human Btk protein can transiently be depleted using double-stranded short RNA interference (siRNA) oligonucleotides. Imaging and Western blotting analysis demonstrate that Btk expression is down regulated in heterologous systems as well as in hematopoietic lineages, following transfection or microinjection of Btk siRNA duplexes. The induction of histamine release, a pro-inflammatory mediator, in RBL-2H3 mast cells was reduced by 20-25% upon Btk down regulation. Similar, results were obtained when the Btk activity was inhibited using the kinase blocker LFM-A13. These results demonstrate a direct role of Btk for the efficient secretion of histamine in allergic responses.     

Adaptation of the cells ofEscherichia coli to the presence of hydroxyurea increases the level of inorganic pyrophosphatase activity

Hydroxyurea, an inhibitor of ribonucleoside diphosphate reductase, completely arrested the net synthesis of DNA for 3–4 h, when it was added in 30 mM concentration to growing cultures ofEscherichia coli K12. Thereafter the net synthesis of DNA started again, although slowly, and simultaneously with it the formation of inorganic pyrophosphatase activity was stimulated leading to a 2-fold increase in the specific activity of the enzyme in 2–3 h. Subsequently cell division began again. In this way a new steady state, stable in the presence of hydroxyurea, was reached. This new state was characterized by the high specific activity of inorganic pyrophosphatase, a small but constant amount of DNA/cell mass (1/4 of the normal value), and large elongated cells. All these changes were slowly reversed during 5–6 h, when the cells were transferred into a drug-free medium.The activity of isoleucyl-tRNA synthetase, assayed as a control, did not change significantly in the presence of hydroxyurea.Hydroxyurea had no effect on the activity of inorganic pyrophosphatase in vitro.