Physical stress on halibut larvae

Halibut larvae were exposed to physical stress in the form of different levels of airation. Survival rate, development, dry weight, RNA, DNA and protein were measured. At the end of the experiment the larvae exposed to gentle airation had the highest survival rate, total dry weight, dry weight of the yolk sac, content of RNA and RNA-DNA ratio. However, the group without airation had the highest dry weight of larval body, growth rate and yolk conversion efficiency. The functional jaw development had the same value and were highest in these two groups

Physical stress on halibut larvae

Halibut larvae were exposed to physical stress in the form of different levels of airation. Survival rate, development, dry weight, RNA, DNA and protein were measured. At the end of the experiment the larvae exposed to gentle airation had the highest survival rate, total dry weight, dry weight of the yolk sac, content of RNA and RNA-DNA ratio. However, the group without airation had the highest dry weight of larval body, growth rate and yolk conversion efficiency. The functional jaw development had the same value and were highest in these two groups

Discriminative stimulus properties of 1.25 mg/kg clozapine in rats: Mediation by serotonin 5-HT2 and dopamine D4 receptors

The atypical antipsychotic drug clozapine remains one of most effective treatments for schizophrenia, given a lack of extrapyramidal side effects, improvements in negative symptoms, cognitive impairment, and in symptoms in treatment-resistant schizophrenia. The adverse effects of clozapine, including agranulocytosis, make finding a safe clozapine-like a drug a goal for drug developers. The drug dis- crimination paradigm is a model of interoceptive stimulus that has been used in an effort to screen experimental drugs for clozapine-like atypical antipsychotic effects. The present study was conducted to elucidate the receptor-mediated stimulus properties that form this clozapine discriminative cue by testing selective receptor ligands in rats trained to discriminate a 1.25 mg/kg dose of clozapine from vehicle in a two choice drug discrimination task. Full substitution occurred with the 5-HT2A inverse agonist M100907 and the two preferential D4/5-HT2/α1 receptor antagonists Lu 37-114 ((S)-1-(3-(2-(4- (1H-indol-5-yl)piperazin-1-yl)ethyl)indolin-1-yl)ethan-1-one) and Lu 37-254 (1-(3-(4-(1H-indol-5-yl) piperazin-1-yl)propyl)-3,4-dihydroquinolin-2(1H)-one). Partial substitution occurred with the D4 re- ceptor antagonist Lu 38-012 and the α1 adrenoceptor antagonist prazosin. Drugs selective for 5-HT2C, 5-HT6 muscarinic, histamine H1, and benzodiazepine receptors did not substitute for clozapine. The present findings suggest that 5-HT2A inverse agonism and D4 receptor antagonism mediate the dis- criminative stimulus properties of 1.25 mg/kg clozapine in rats, and further confirm that clozapine produces a complex compound discriminative stimulus

Substance use and nicotine dependence in persistent, remittent, and late-onset ADHD:a 10-year longitudinal study from childhood to young adulthood

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with substance use disorders (SUD; alcohol and/or drug dependence) and nicotine dependence. This study aims to advance our knowledge about the association between SUD, nicotine dependence, and the course of ADHD (persistent versus remittent ADHD and late-onset ADHD).METHODS: ADHD, SUD, and nicotine dependence were longitudinally assessed (mean age at study entry 11.3 years, mean age at follow-up 21.1 years) using structured psychiatric interviews and multi-informant questionnaires in a subsample of the Dutch part of the International Multicenter ADHD Genetics study. Individuals with persistent ADHD (n = 62), remittent ADHD (n = 12), late-onset ADHD (n = 18; age of onset after 12 years), unaffected siblings (n = 50), and healthy controls (n = 47) were assessed. Hazard ratios (HR) with 95% confidence intervals (CIs) were estimated by Cox regression and adjusted for clustered family data, gender, follow-up length, and current age.RESULTS: Individuals with persistent ADHD were at significantly higher risk of development of SUD relative to healthy controls (HR = 4.56, CI 1.17-17.81). In contrast, levels of SUD in those with remittent ADHD were not different from healthy controls (HR = 1.00, CI .07-13.02). ADHD persisters had also higher prevalence rates of nicotine dependence (24.2%) than ADHD remitters (16.7%) and healthy controls (4.3%). A similar pattern was found in initially unaffected siblings who met ADHD criteria at follow-up ("late-onset" ADHD); they had also a higher prevalence of SUD (33%) compared to stable unaffected siblings (20%) and were at significantly increased risk of development of nicotine dependence compared to healthy controls (HR = 13.04, CI 2.08-81.83).CONCLUSIONS: SUD and nicotine dependence are associated with a negative ADHD outcome. Results further emphasize the need for clinicians to comprehensively assess substance use when diagnosing ADHD in adolescents and adults.</p

The Host-Pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains

<p>Abstract</p> <p>Background</p> <p>Cyclophilin A (CypA) represents a potential key molecule in future antiretroviral therapy since inhibition of CypA suppresses human immunodeficiency virus type 1 (HIV-1) replication. CypA interacts with the virus proteins Capsid (CA) and Vpr, however, the mechanism through which CypA influences HIV-1 infectivity still remains unclear.</p> <p>Results</p> <p>Here the interaction of full-length HIV-1 Vpr with the host cellular factor CypA has been characterized and quantified by surface plasmon resonance spectroscopy. A C-terminal region of Vpr, comprising the 16 residues ⁷⁵GCRHSRIGVTRQRRAR⁹⁰, with high binding affinity for CypA has been identified. This region of Vpr does not contain any proline residues but binds much more strongly to CypA than the previously characterized N-terminal binding domain of Vpr, and is thus the first protein binding domain to CypA described involving no proline residues. The fact that the mutant peptide Vpr^75-90R80A binds more weakly to CypA than the wild-type peptide confirms that Arg-80 is a key residue in the C-terminal binding domain. The N- and C-terminal binding regions of full-length Vpr bind cooperatively to CypA and have allowed a model of the complex to be created. The dissociation constant of full-length Vpr to CypA was determined to be approximately 320 nM, indicating that the binding may be stronger than that of the well characterized interaction of HIV-1 CA with CypA.</p> <p>Conclusions</p> <p>For the first time the interaction of full-length Vpr and CypA has been characterized and quantified. A non-proline-containing 16-residue region of C-terminal Vpr which binds specifically to CypA with similar high affinity as full-length Vpr has been identified. The fact that this is the first non-proline containing binding motif of any protein found to bind to CypA, changes the view on how CypA is able to interact with other proteins. It is interesting to note that several previously reported key functions of HIV-1 Vpr are associated with the identified N- and C-terminal binding domains of the protein to CypA.</p

Toezicht door private partijen: panacee voor alle kwalen?

Naast het traditionele verticale toezicht van de overheid op het bedrijfsleven hebben zich de afgelopen jaren steeds meer vormen van horizontaal toezicht ontwikkeld. Deze kenmerken zich door onderlinge samenwerking en vertrouwen tussen publieke en private partijen. Voorbeelden hiervan zijn onder meer compliance assistance, certificering en systeemtoezicht. De overheid (publieke toezichthouder) treedt in al die varianten terug en maakt plaats voor private toezichthouders die namens producenten, consumenten of andere belangengroepen optreden. Deze ontwikkelingen vormden de aanleiding voor het organiseren van een symposium over toezicht door private partijen op 26 maart 2009. Wetenschappers en practitioners stonden stil bij een tweetal vragen. In de eerste plaats de vraag op welke wijze deze nieuwe vormen van toezicht in de praktijk worden uitgeoefend en, ten tweede, in hoeverre kan het toezicht aan private partijen worden toevertrouwd? Zeker nu het maatschappelijk vertrouwen in het zelfregulerend vermogen van ondernemingen door de kredietcrisis ernstig is geschaad. Deze bundel bevat het verslag van het symposium in de vorm van de bijdragen van de sprekers en een algemene inleiding. Het toezicht in twee sectoren is onder de loep genomen: toezicht op financiële markten en op de naleving van milieuvoorschriften

The intriguing Cyclophilin A-HIV-1 Vpr interaction: prolyl cis/trans isomerisation catalysis and specific binding

<p>Abstract</p> <p>Background</p> <p>Cyclophilin A (CypA) represents a potential target for antiretroviral therapy since inhibition of CypA suppresses human immunodeficiency virus type 1 (HIV-1) replication, although the mechanism through which CypA modulates HIV-1 infectivity still remains unclear. The interaction of HIV-1 viral protein R (Vpr) with the human peptidyl prolyl isomerase CypA is known to occur <it>in vitro </it>and <it>in vivo</it>. However, the nature of the interaction of CypA with Pro-35 of N-terminal Vpr has remained undefined.</p> <p>Results</p> <p>Characterization of the interactions of human CypA with N-terminal peptides of HIV-1 Vpr has been achieved using a combination of nuclear magnetic resonace (NMR) exchange spectroscopy and surface plasmon resonance spectroscopy (SPR). NMR data at atomic resolution indicate prolyl <it>cis</it>/<it>trans </it>isomerisation of the highly conserved proline residues Pro-5, -10, -14 and -35 of Vpr are catalyzed by human CypA and require only very low concentrations of the isomerase relative to that of the peptide substrates. Of the N-terminal peptides of Vpr only those containing Pro-35 bind to CypA in a biosensor assay. SPR studies of specific N-terminal peptides with decreasing numbers of residues revealed that a seven-residue motif centred at Pro-35 consisting of RHFPRIW, which under membrane-like solution conditions comprises the loop region connecting helix 1 and 2 of Vpr and the two terminal residues of helix 1, is sufficient to maintain strong specific binding.</p> <p>Conclusions</p> <p>Only N-terminal peptides of Vpr containing Pro-35, which appears to be vital for manifold functions of Vpr, bind to CypA in a biosensor assay. This indicates that Pro-35 is essential for a specific CypA-Vpr binding interaction, in contrast to the general prolyl <it>cis</it>/<it>trans </it>isomerisation observed for all proline residues of Vpr, which only involve transient enzyme-substrate interactions. Previously suggested models depicting CypA as a chaperone that plays a role in HIV-1 virulence are now supported by our data. In detail the SPR data of this interaction were compatible with a two-state binding interaction model that involves a conformational change during binding. This is in accord with the structural changes observed by NMR suggesting CypA catalyzes the prolyl <it>cis/trans </it>interconversion during binding to the RHFP³⁵RIW motif of N-terminal Vpr.</p

Regulating and Deregulating the Public Utilities 1830-2010

History can provide invaluable insights into important issues of the economic and social regulation of utilities, and offer lessons towards future debates. But the history of utility regulation – which speaks of changing, diverse and complex experiences around the world – was, unfortunately, sidelined or marginalised when economists and policymakers enthusiastically embraced the question of how to reform the utilities from the 1970s. This paper provides an overview of the three, overarching, `waves' of utility regulation from the nineteenth century to the present, documenting how, when and why the ways in which the roles of the state, the market and firms altered over time. It then contextualises and explains the main contributions of each of the papers included in this special issue of Business History, which cover energy, communications, water, transportation and other urban infrastructure regulation, across Western Europe, the United States and Australia

Exploring Brain Derived Neurotrophic Factor and Cell Adhesion Molecules as Biomarkers for the Transdiagnostic Symptom Anhedonia in Alcohol Use Disorder and Comorbid Depression

Background: Alcohol Use Disorder (AUD) and depressive disorder often co-exist and have a shared heritability. This study aimed to investigate Brain-Derived Neurotrophic Factor (BDNF) and three Cell Adhesion Molecules (CAMs) as transdiagnostic biomarkers in AUD and depression co-morbidity. Methods: In a cross-sectional study, patients with AUD (n=22), AUD and depression (n=19), and healthy controls (n=20) were examined. Depression and anxiety severity were assessed using the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale. Anhedonia, alcohol use and dependence, craving, and social adaptation were assessed through self-report questionnaires. BDNF and CAM concentrations in peripheral serum were measured after overnight fasting using a Luminex assay. After controlling for age and gender, biomarker levels were compared across groups. The association between biomarker concentrations and symptom severity scales were explored using correlation and multiple regression analyses. Results: BDNF and Neuronal CAM were lower in patients with AUD with and without depression compared to healthy controls. No differences were observed for Vascular CAM-1 and Interstitial CAM-1. BDNF correlated negatively with anhedonia levels. BDNF, age and gender together explained 21% of variability in anhedonia levels. Conclusion: This pilot study suggests that peripheral levels of BDNF and NCAM might be reduced in AUD with and without comorbid mood disorder. Since low BDNF levels were associated with self- reported anhedonia across these conditions, BDNF and anhedonia might reflect transdiagnostic aspects involved in AUD and depression