The alpha 7 nicotinic receptor agonist PHA-543613 hydrochloride inhibits <i>Porphyromonas gingivalis</i>-induced expression of interleukin-8 by oral keratinocytes

Objective: The alpha 7 nicotinic receptor (α7nAChR) is expressed by oral keratinocytes. α7nAChR activation mediates anti-inflammatory responses. The objective of this study was to determine if α7nAChR activation inhibited pathogen-induced interleukin-8 (IL-8) expression by oral keratinocytes.&lt;p&gt;&lt;/p&gt; Materials and methods: Periodontal tissue expression of α7nAChR was determined by real-time PCR. OKF6/TERT-2 oral keratinocytes were exposed to &lt;i&gt;Porphyromonas gingivalis&lt;/i&gt; in the presence and absence of a α7nAChR agonist (PHA-543613 hydrochloride) alone or after pre-exposure to a specific α7nAChR antagonist (α-bungarotoxin). Interleukin-8 (IL-8) expression was measured by ELISA and real-time PCR. Phosphorylation of the NF-κB p65 subunit was determined using an NF-κB p65 profiler assay and STAT-3 activation by STAT-3 in-cell ELISA. The release of ACh from oral keratinocytes in response to &lt;i&gt;P. gingivalis&lt;/i&gt; lipopolysaccharide was determined using a GeneBLAzer M3 CHO-K1-blacell reporter assay.&lt;p&gt;&lt;/p&gt; Results: Expression of α7nAChR mRNA was elevated in diseased periodontal tissue. PHA-543613 hydrochloride inhibited &lt;i&gt;P. Gingivalis&lt;/i&gt;-induced expression of IL-8 at the transcriptional level. This effect was abolished when cells were pre-exposed to a specific α7nAChR antagonist, α-bungarotoxin. PHA-543613 hydrochloride downregulated NF-κB signalling through reduced phosphorylation of the NF-κB p65-subunit. In addition, PHA-543613 hydrochloride promoted STAT-3 signalling by maintenance of phosphorylation. Furthermore, oral keratinocytes upregulated ACh release in response to &lt;i&gt;P. Gingivalis&lt;/i&gt; lipopolysaccharide.&lt;p&gt;&lt;/p&gt; Conclusion: These data suggest that α7nAChR plays a role in regulating the innate immune responses of oral keratinocytes.&lt;p&gt;&lt;/p&gt

Aquatic community response to volcanic eruptions on the Ecuadorian Andean flank: evidence from the palaeoecological record

Aquatic ecosystems in the tropical Andes are under increasing pressure from human modification of the landscape (deforestation and dams) and climatic change (increase of extreme events and 1.5 °C on average temperatures are projected for AD 2100). However, the resilience of these ecosystems to perturbations is poorly understood. Here we use a multi-proxy palaeoecological approach to assess the response of aquatic ecosystems to a major mechanism for natural disturbance, volcanic ash deposition. Specifically, we present data from two Neotropical lakes located on the eastern Andean flank of Ecuador. Laguna Pindo (1°27.132′S–78°04.847′W) is a tectonically formed closed basin surrounded by a dense mid-elevation forest, whereas Laguna Baños (0°19.328′S–78°09.175′W) is a glacially formed lake with an inflow and outflow in high Andean Páramo grasslands. In each lake we examined the dynamics of chironomids and other aquatic and semi-aquatic organisms to explore the effect of thick (> 5 cm) volcanic deposits on the aquatic communities in these two systems with different catchment features. In both lakes past volcanic ash deposition was evident from four large tephras dated to c.850 cal year BP (Pindo), and 4600, 3600 and 1500 cal year BP (Baños). Examination of the chironomid and aquatic assemblages before and after the ash depositions revealed no shift in composition at Pindo, but a major change at Baños occurred after the last event around 1500 cal year BP. Chironomids at Baños changed from an assemblage dominated by Pseudochironomus and Polypedilum nubifer-type to Cricotopus/Paratrichocladius type-II, and such a dominance lasted for approximately 380 years. We suggest that, despite potential changes in the water chemistry, the major effect on the chironomid community resulted from the thickness of the tephra being deposited, which acted to shallow the water body beyond a depth threshold. Changes in the aquatic flora and fauna at the base of the trophic chain can promote cascade effects that may deteriorate the ecosystem, especially when already influenced by human activities, such as deforestation and dams, which is frequent in the high Andes

Beta diversity patterns reveal positive effects of farmland abandonment on moth communities

Farmland abandonment and the accompanying natural succession are largely perceived as unwanted amongst many European conservationists due to alleged negative effects on biodiversity levels. Here, we test this assumption by analysing alpha, beta and gamma diversity patterns of macro-moth communities in habitats on an ecological succession gradient, from extensively managed meadows to scrub-encroached and wooded sites. Macro-moths were light-trapped at 84 fixed circular sampling sites arranged in a semi-nested design within the National Park of Peneda-Gerês, NW-Portugal. In total, we sampled 22825 individuals belonging to 378 species. Alpha, beta and gamma diversity patterns suggest that farmland abandonment is likely to positively affect both overall macro-moth diversity and forest macro-moth diversity, and to negatively affect species diversity of non-forest macro-moth species. Our results also show that spatial habitat heterogeneity is important to maintain gamma diversity of macromoths, especially for rare non-forest species and habitat specialistsinfo:eu-repo/semantics/publishedVersio

Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes

Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable disorder, but specific genetic factors underlying risk remain elusive. To assess the role of structural variation in ADHD, we identified 222 inherited copy number variations (CNVs) within 335 ADHD patients and their parents that were not detected in 2026 unrelated healthy individuals. Although no excess CNVs, either deletions or duplications, were found in the ADHD cohort relative to controls, the inherited rare CNV-associated gene set was significantly enriched for genes reported as candidates in studies of autism, schizophrenia and Tourette syndrome, including A2BP1, AUTS2, CNTNAP2 and IMMP2L. The ADHD CNV gene set was also significantly enriched for genes known to be important for psychological and neurological functions, including learning, behavior, synaptic transmission and central nervous system development. Four independent deletions were located within the protein tyrosine phosphatase gene, PTPRD, recently implicated as a candidate gene for restless legs syndrome, which frequently presents with ADHD. A deletion within the glutamate receptor gene, GRM5, was found in an affected parent and all three affected offspring whose ADHD phenotypes closely resembled those of the GRM5 null mouse. Together, these results suggest that rare inherited structural variations play an important role in ADHD development and indicate a set of putative candidate genes for further study in the etiology of ADHD

Attentional control theory in childhood: enhanced attentional capture by non-emotional and emotional distractors in anxiety and depression

Attentional control theory (ACT) proposes that anxiety is associated with executive functioning deficits. The theory has been widely investigated in adults. The current study tested whether symptoms of childhood anxiety and depression were associated with experimentally measured attentional control in the context of non-emotional and emotional stimuli. Sixty-one children (mean age = 9.23 years, range = 8.39 - 10.41) reported their trait anxiety and depression symptoms and completed three visual search tasks. The tasks used a variant of an irrelevant singleton paradigm and measured attentional capture by task-irrelevant non-emotional (color) and emotional (facial expressions) distractors. Significant attentional capture by both non-emotional and emotional distractors was observed, and was significantly correlated with trait anxiety and symptoms of depression. The strength of relationship between attentional capture and the symptoms did not differ significantly for non-emotional and emotional distractors. The results suggest that symptoms of childhood anxiety and depression are associated with poorer attentional control both in the presence of emotional and non-emotional stimuli, supporting ACT in younger populations. This attentional deficit in the context of non-emotional information might be as central to childhood internalizing symptoms as attentional biases often observed on tasks investigating processing of emotional stimuli

Association study of promoter polymorphisms at the dopamine transporter gene in Attention Deficit Hyperactivity Disorder

<p>Abstract</p> <p>Background</p> <p>Attention deficit hyperactivity disorder (ADHD) is a complex neurobehavioral disorder. The dopamine transporter gene (DAT1/<it>SLC6A3</it>) has been considered a good candidate for ADHD. Most association studies with ADHD have investigated the 40-base-pair variable number of tandem repeat (VNTR) polymorphism in the 3'-untranslated region of DAT1. Only few studies have reported association between promoter polymorphisms of the gene and ADHD.</p> <p>Methods</p> <p>To investigate the association between the polymorphisms -67A/T (rs2975226) and -839C/T (rs2652511) in promoter region of DAT1 in ADHD, two samples of ADHD patients from the UK (n = 197) and Taiwan (n = 212) were genotyped, and analysed using within-family transmission disequilibrium test (TDT).</p> <p>Results</p> <p>A significant association was found between the T allele of promoter polymorphism -67A/T and ADHD in the Taiwanese population (<it>P </it>= 0.001). There was also evidence of preferential transmission of the T allele of -67A/T polymorphism in combined samples from the UK and Taiwan (<it>P </it>= 0.003). No association was detected between the -839C/T polymorphism and ADHD in either of the two populations.</p> <p>Conclusion</p> <p>The finding suggests that genetic variation in the promoter region of DAT1 may be a risk factor in the development of ADHD.</p

Parental alcohol use and adolescent school adjustment in the general population: Results from the HUNT study

<p>Abstract</p> <p>Background</p> <p>This study investigates the relationship between parental drinking and school adjustment in a total population sample of adolescents, with independent reports from mothers, fathers, and adolescents. As a group, children of alcohol abusers have previously been found to exhibit lowered academic achievement. However, few studies address which parts of school adjustment that may be impaired. Both a genetic approach and social strains predict elevated problem scores in these children. Previous research has had limitations such as only recruiting cases from clinics, relying on single responders for all measures, or incomplete control for comorbid psychopathology. The specific effects of maternal and paternal alcohol use are also understudied.</p> <p>Methods</p> <p>In a Norwegian county, 88% of the population aged 13-19 years participated in a health survey (N = 8984). Among other variables, adolescents reported on four dimensions of school adjustment, while mothers and fathers reported their own drinking behaviour. Mental distress and other control variables were adjusted for. Multivariate analysis including generalized estimation equations was applied to investigate associations.</p> <p>Results</p> <p>Compared to children of light drinkers, children of alcohol abusers had moderately elevated attention and conduct problem scores. Maternal alcohol abuse was particularly predictive of such problems. Children of abstainers did significantly better than children of light drinkers. Controlling for adolescent mental distress reduced the association between maternal abuse and attention problems. The associations between parental reported drinking and school adjustment were further reduced when controlling for the children's report of seeing their parents drunk, which itself predicted school adjustment. Controlling for parental mental distress did not reduce the associations.</p> <p>Conclusions</p> <p>Parental alcohol abuse is an independent risk factor for attention and conduct problems at school. Some of the risk associated with mothers' drinking is likely to be mediated by adolescent mental distress. Despite lowered adjustment on the externalizing dimensions, children of alcohol abusers report that they enjoy being at school as much as other children.</p

Effects of Alcohol on the Acquisition and Expression of Fear Potentiated Startle in Mouse Lines Selectively Bred for High and Low Alcohol Preference

Rationale: Anxiety disorders and alcohol-use disorders frequently co-occur in humans perhaps because alcohol relieves anxiety. Studies in humans and rats indicate that alcohol may have greater anxiolytic effects in organisms with increased genetic propensity for high alcohol consumption. Objectives and Methods: The purpose of this study was to investigate the effects of moderate doses of alcohol (0.5, 1.0, 1.5 g/kg) on the acquisition and expression of anxiety-related behavior using a fear-potentiated startle (FPS) procedure. Experiments were conducted in two replicate pairs of mouse lines selectively bred for high- (HAP1 and HAP2) and low- (LAP1 and LAP2) alcohol preference; these lines have previously shown a genetic correlation between alcohol preference and FPS (HAP\u3eLAP; Barrenha and Chester 2007). In a control experiment, the effect of diazepam (4.0 mg/kg) on the expression of FPS was tested in HAP2 and LAP2 mice. Results: The 1.5 g/kg alcohol dose moderately decreased the expression of FPS in both HAP lines but not LAP lines. Alcohol had no effect on the acquisition of FPS in any line. Diazepam reduced FPS to a similar extent in both HAP2 and LAP2 mice. Conclusions: HAP mice may be more sensitive to the anxiolytic effects of alcohol than LAP mice when alcohol is given prior to the expression of FPS. These data collected in two pairs of HAP/LAP mouse lines suggest that the anxiolytic response to alcohol in HAP mice may be genetically correlated with their propensity toward high alcohol preference and robust FPS

Working with pain : sustainable work participation of workers with chronic nonspecific musculoskeletal pain

Dit proefschrift is een van de eerste studies specifiek gericht op mensen die blijven werken met chronische pijn aan het bewegingsapparaat. Unieke kennis over duurzame arbeidsparticipatie van werknemers met chronische pijn werd vergaard. Doel van dit promotieonderzoek was meer inzicht te krijgen in de groep mensen die werkt met pijn en te achterhalen hoe zij in staat zijn ondanks hun klachten te blijven werken. In het proefschrift staan kenmerken en determinanten beschreven van werknemers die doorwerken met chronische pijn, waardoor een completer beeld is ontstaan van arbeidsparticipatie bij mensen met chronische pijn aan het bewegingsapparaat. Uit de vergelijking van mensen die doorwerken ondanks chronische pijn en mensen met arbeidsverzuim die in revalidatiebehandeling komen met chronische pijn blijkt dat deze groepen op diverse factoren significant verschillen. In het onderzoek werd onder andere aangetoond dat de motivatie voor werk, zelfmanagementvaardigheden en het belang dat wordt toegekend aan pijn, belangrijke factoren zijn die werken met chronische pijn faciliteren. Chronische pijn op zichzelf is vaak niet de reden voor arbeidsverzuim, maar meestal spelen persoonlijke- en omgevingsfactoren daarin een beslissende rol. Deze factoren kunnen dienen als aangrijpingspunt voor het verhogen van duurzame inzetbaarheid en preventie van arbeidsverzuim van mensen met chronische pijn aan het bewegingsapparaat. De effectieve manier waarop deelnemende werknemers in het onderzoek met hun pijn omgingen en productief bleven, kan anderen inspireren aan het werk te blijven. Daarnaast biedt het onderzoek een nieuw referentiekader voor de bedrijfs-, verzekerings-, en revalidatiegeneeskunde. This thesis was one of the first studies that focused specifically on people who continued work with chronic nonspecific musculoskeletal pain (CMP), and collected (identified) unique data concerning sustainable work participation of workers with CMP. It provides a large range of characteristics of workers with CMP who continued work despite pain, which has added to our understanding of sustainable work participation in people suffering from CMP. Comparison of workers who continued work with CMP with sick listed workers with CMP admitted for rehabilitation revealed that these groups differ significantly on several factors. In this thesis, evidence was found that the workers’ motivation to work, self-management skills, and the attributed importance of pain on their (working) lives are important factors to manage staying at work with CMP. It is recommended to be aware of the fact that CMP standing on itself is often not the reason for sick leave and disability, but regularly personal and environmental factors play an additional decisive role. Because these factors can be influenced, they offer opportunity to promote staying at work. In the process of guiding workers back to work, the results of the project ‘Working with pain’ may be used. The findings of this thesis potentially contribute to promotion of sustained work participation and prevention of sick-leave in workers with CMP. The effective way workers in this project coped with CMP and remained productive, may inspire others in their efforts to stay work. Finally, this thesis offers a new reference for rehabilitation-, occupational-,and insurance medicine.