Addiction research centres and the nurturing of creativity The Norwegian Centre for Addiction Research (SERAF).

The Norwegian Centre for Addiction Research (SERAF) at the University of Oslo is a newly established, clinical addiction research centre. It is located at the Oslo University Hospital and has a major focus on opioid dependency, investigating Norwegian opioid maintenance treatment (OMT), with special interest in OMT during pregnancy, mortality, morbidity and criminality before, during and after OMT and alternatives to OMT, such as the use of naltrexone implants. The well-developed health registries of Norway are core assets that also allow the opportunity for other types of substance abuse research.

A high-throughput O-glycopeptide discovery platform for seromic profiling.

Biomarker microarrays are becoming valuable tools for serological screening of disease-associated autoantibodies. Post-translational modifications (PTMs) such as glycosylation extend the range of protein function, and a variety of glycosylated proteins are known to be altered in disease progression. Here, we have developed a synthetic screening microarray platform for facile display of O-glycosylated peptides (O-PTMs).

Opioid maintenance patients with QTc prolongation: congenital long QT syndrome mutation may be a contributing risk factor.

Objectives: This study investigates opioid maintenance treatment (OMT) patients found to have corrected QT (QTc) interval above 500 ms, with particular focus on past medical history, genetic testing and cardiac investigations.

Methods: Detailed medical and cardiac history was obtained, with particular focus upon risk factors. Cardiac investigations, including genetic testing for the five most common long QT syndrome (LQTS) mutations, exercise electrocardiography (ECG) and 24-h ECG recordings, were performed.

Obstacles to 12-step group participation as seen by addiction professionals: comparing Norway to the United States.

Twelve-step groups (TSGs) are a valuable recovery resource for substance-dependent individuals. However, some aspects of these fellowships are controversial and may limit clinician referrals. This study describes attitude- and knowledge-based barriers to TSG participation as seen by addiction professionals in Norway, a treatment culture in which less than 5% of programs use the 12-step philosophy, and compares the findings with those of a similar study in the United States.

Hormonal and pharmacological modification of plasma potassium homeostasis.

Human skeletal muscles contain the largest single pool of K+ in the body (2600 mmol, 46 times the total K+ content of the extracellular space). Intense exercise may double arterial plasma K+ in one min. This is because of excitation-induced release of K+ from the working muscle cells via K+ channels.

Staff attitudes and the associations with treatment organisation, clinical practices and outcomes in opioid maintenance treatment.

Background: In opioid maintenance treatment (OMT) there are documented treatment differences both between countries and between OMT programmes. Some of these differences have been associated with staff attitudes. The aim of this study was to 1) assess if there were differences in staff attitudes within a national OMT programme, and 2) investigate the associations of staff attitudes with treatment organisation, clinical practices and outcomes.

HtrA proteases have a conserved activation mechanism that can be triggered by distinct molecular cues.

HtrA proteases are tightly regulated proteolytic assemblies that are essential for maintaining protein homeostasis in extracytosolic compartments. Though HtrA proteases have been characterized in detail, their precise molecular mechanism for switching between different functional states is still unknown. To address this, we carried out biochemical and structural studies of DegP from Escherichia coli.

Dynamics of the volatile defense of winter "dormant" balsam poplar (Populus balsamifera).

6-Hydroxycylohex-2-en-1-one (6-HCH) has been reported as a major chemical defense of the winter-dormant internodes of balsam poplar (Populus balsamifera) against feeding by herbivores such as the snowshoe hare (Lepus americanus). We report that the concentration of 6-HCH in the fall internodes is triggered by a single hard frost, and then undergoes an exponential decline through volatilization over the winter that results in barely detectable quantities by early spring. We conclude that the role of 6-HCH in the defense of mature balsam poplar is more complex than simply acting as a toxin.

Twenty-five years of expectation: where are the services for older people with mental illness in Africa?

Mental health disorders account for about 14% of the global burden of disease. Neuropsychiatric disorders may be responsible for more than 1.2 million deaths annually (Prince , 2007).

Induction of phenolic glycosides by quaking aspen (Populus tremuloides) leaves in relation to extrafloral nectaries and epidermal leaf mining.

We studied the effect of epidermal leaf mining on the leaf chemistry of quaking aspen, Populus tremuloides, during an outbreak of the aspen leaf miner, Phyllocnistis populiella, in the boreal forest of interior Alaska. Phyllocnistis populiella feeds on the epidermal cells of P. tremuloides leaves.

The prevalence and spatial clustering of Neospora caninum in dairy herds in Norway.

The aims of this study were to estimate the national herd prevalence and the general spatial distribution of Neospora caninum infection in Norwegian dairy cattle. Bulk milk samples from 1657 randomly selected dairy herds were analysed by iscom ELISA for the presence of N. caninum specific antibodies.

Molecular transformers in the cell: lessons learned from the DegP protease-chaperone.

Structure-function analysis of DegP revealed a novel mechanism for protease and chaperone regulation. Binding of unfolded proteins induces the oligomer reassembly from the resting hexamer (DegP6) into the functional protease-chaperone DegP12/24. The newly formed cage exhibits the characteristics of a proteolytic folding chamber, shredding those proteins that are severely misfolded while stabilizing and protecting proteins present in their native state.

Conversion of a regulatory into a degradative protease.

The PDZ protease DegS senses mislocalized outer membrane proteins and initiates the sigmaE pathway in the bacterial periplasm. This unfolded protein response pathway is activated by processing of the anti-sigma factor RseA by DegS and other proteases acting downstream of DegS. DegS mediates the rate-limiting step of sigma E induction and its activity must be highly specific and tightly regulated.

p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy.

Accumulation of ubiquitinated proteins in cytoplasmic and/or nuclear inclusions is a hallmark of several diseases associated with premature cell death. SQSTM1/p62 is known to bind ubiquitinated substrates and aid their aggregation and degradation by macroautophagy. We show here that p62 is required to recruit the large phosphoinositide-binding protein ALFY to cytoplasmic p62 bodies generated upon amino acid starvation or puromycin-treatment.

Cross-cultural adaptation of research instruments: language, setting, time and statistical considerations.

Background: Research questionnaires are not always translated appropriately before they are used in new temporal, cultural or linguistic settings. The results based on such instruments may therefore not accurately reflect what they are supposed to measure. This paper aims to illustrate the process and required steps involved in the cross-cultural adaptation of a research instrument using the adaptation process of an attitudinal instrument as an example.

Maternal folate and cobalamin status predicts vitamin status in newborns and 6-month-old infants.

Our aim in this longitudinal study was to determine predictors of folate and cobalamin status in infancy. Data were collected from 364 mother-infant pairs with blood measurements from pregnancy ( approximately 18 wk; n = 149), newborns (cord serum; n = 361), and 6-mo-old partially or exclusively breast-fed children (n = 221). Serum/plasma folate, cobalamin, holotranscobalamin (holoTC), holohaptocorrin (holoHC), methylmalonic acid (MMA) and total homocysteine (tHcy) at birth and 6 mo were related to maternal vitamin status, parity, lifestyle variables, and anthropometry.

[Overdose statistics--a complicated account].

Background: Norwegian media often claim that a disproportionately high number of deaths in Norway are caused by overdoses. The police statistics in 2007 showed an increase in the number of overdose deaths, and many media postings focused on this in autumn 2008. In this paper we investigate the basis for those police statistics and discuss problems associated with calculating deaths caused by use of illegal substances.

Effect of insulin catheter wear-time on subcutaneous adipose tissue blood flow and insulin absorption in humans.

Background: Insertion of an insulin catheter for continuous subcutaneous insulin infusion into the subcutaneous adipose tissue (SAT) causes a tissue trauma that may have consequences for insulin absorption. We evaluated the importance of insulin catheter wear-time on subcutaneous adipose tissue blood flow (ATBF) and absorption of the rapid-acting insulin analog insulin aspart over a period of 4 days.

Methods: Teflon insulin catheters (Medtronic, Minneapolis, MN) were inserted into the abdominal SAT of 10 healthy men without diabetes (mean +/- SEM age, 23.

Structure, function and regulation of the conserved serine proteases DegP and DegS of Escherichia coli.

Two members of the widely conserved HtrA family of serine proteases, DegP and DegS, are key players in extracytoplasmic protein quality control. The underlying mechanisms of their main functions in stress sensing, regulation and protection during the unfolded protein response are discussed.

Attitudes towards 12-step groups and referral practices in a 12-step naive treatment culture; a survey of addiction professionals in Norway.

Background: Addressing substance use disorders effectively requires a long-term approach. Substance abuse treatment is typically of short duration; referring patients to Twelve Step based self-help groups (TSGs) - e.g.

Peptidic small molecule activators of the stress sensor DegS.

Bacterial DegS is a regulatory protease that acts as a molecular stress sensor and initiates a periplasmic stress response pathway. Upon binding of misfolded proteins to its PDZ domain, the protease domain of DegS is allosterically activated, thereby initiating a signal cascade that results in the elevated expression of protein quality control factors. Although the structural basis of this activation mode has been elucidated previously, it is not yet fully understood if binding to the PDZ domain is sufficient for protease domain activation or if secondary interactions with the protease domain are required.

Structural basis of substrate specificity of plant 12-oxophytodienoate reductases.

12-Oxophytodienoate reductase 3 (OPR3) is a FMN-dependent oxidoreductase that catalyzes the reduction of the cyclopentenone (9S,13S)-12-oxophytodienoate [(9S,13S)-OPDA] to the corresponding cyclopentanone in the biosynthesis of the plant hormone jasmonic acid. In vitro, however, OPR3 reduces the jasmonic acid precursor (9S,13S)-OPDA as well as the enantiomeric (9R,13R)-OPDA, while its isozyme OPR1 is highly selective, accepting only (9R,13R)-OPDA as a substrate. To uncover the molecular determinants of this remarkable enantioselectivity, we determined the crystal structures of OPR1 and OPR3 in complex with the ligand p-hydroxybenzaldehyde.

McsB is a protein arginine kinase that phosphorylates and inhibits the heat-shock regulator CtsR.

All living organisms face a variety of environmental stresses that cause the misfolding and aggregation of proteins. To eliminate damaged proteins, cells developed highly efficient stress response and protein quality control systems. We performed a biochemical and structural analysis of the bacterial CtsR/McsB stress response.

Mortality among opiate users: opioid maintenance therapy, age and causes of death.

Aims: This study investigates how age of opioid users is related to causes of death prior to, during and after opioid maintenance treatment (OMT), and estimates risks of death from various causes in relation to age.

Design, Setting And Participants: Data on all opiate dependents in Norway (1997-2003) who applied for and were accepted for OMT (n = 3789) were cross-linked with the Norwegian death register. The total observation time was 10 934 person-years.