Suppression of ovarian hormones in adolescent rats has no effect on anxiety-like behaviour or c-fos activation in the amygdala

Support was provided the British Society for Neuroendocrinology, Carnegie Trust for the Universities of Scotland and School of Psychology & Neuroscience, University of St Andrews.In humans, sex differences in mood disorders emerge during adolescence, with prevalence rates being consistently higher in females than males. It has been hypothesised that exposure to endogenous ovarian hormones during adolescence enhances the susceptibility of females to mood disorders from this stage of life onwards. However, experimental evidence in favour of this hypothesis is lacking. In the present study, we examined the long‐term effects of suppressing adolescent gonadal hormone levels in a group of female Lister‐hooded rats via administration of a gonadotrophin‐releasing hormone antagonist (Antide; administered on postnatal day [PND] 28 and 42) compared to control females and males (n = 14 per group). We predicted that, in adulthood, Antide‐treated female rats would exhibit more male‐like behaviour than control females in novel environments (elevated‐plus maze, open field and light‐dark box), in response to novel objects and novel social partners, and in an acoustic startle task. Progesterone and luteinising hormone assays (which were conducted on blood samples collected on PND 55/56 and 69/70) confirmed that the hypothalamic‐pituitary‐gonadal axis was temporarily suppressed by Antide treatment. In addition, Antide‐treated females were found to exhibit a modest pubertal delay, as measured by vaginal opening, which was comparable in length to the pubertal delay that has been induced by adolescent exposure to alcohol or stress in previous studies of female rats. However, Antide‐treated females did not substantially differ from control females on any of the behavioural tests, despite the evidence for predicted sex differences in some measures. Following the acoustic startle response task, all subjects were culled and perfused, and c‐Fos staining was conducted in the medial and basolateral amygdala, with the results showing no significant differences in cell counts between the groups. These findings suggest that ovarian hormone exposure during adolescence does not have long‐term effects on anxiety‐related responses in female rats.Publisher PDFPeer reviewe

Direct Interaction of Endogenous Kv Channels with Syntaxin Enhances Exocytosis by Neuroendocrine Cells

K+ efflux through voltage-gated K+ (Kv) channels can attenuate the release of neurotransmitters, neuropeptides and hormones by hyperpolarizing the membrane potential and attenuating Ca2+ influx. Notably, direct interaction between Kv2.1 channels overexpressed in PC12 cells and syntaxin has recently been shown to facilitate dense core vesicle (DCV)-mediated release. Here, we focus on endogenous Kv2.1 channels and show that disruption of their interaction with native syntaxin after ATP-dependent priming of the vesicles by Kv2.1 syntaxin–binding peptides inhibits Ca2+ -triggered exocytosis of DCVs from cracked PC12 cells in a specific and dose-dependent manner. The inhibition cannot simply be explained by the impairment of the interaction of syntaxin with its SNARE cognates. Thus, direct association between endogenous Kv2.1 and syntaxin enhances exocytosis and in combination with the Kv2.1 inhibitory effect to hyperpolarize the membrane potential, could contribute to the known activity dependence of DCV release in neuroendocrine cells and in dendrites where Kv2.1 commonly expresses and influences release

Effectiveness of skills-based training using the Drink-less package to increase family practitioner confidence in intervening for alcohol use disorders

BACKGROUND: Misuse of alcohol is second only to tobacco as a leading cause of preventable death in Australia. There is an opportunity in family practice to detect problems and intervene with people at risk of alcohol-related harm before complications occur. However, family practitioners (FPs) report low levels of confidence in managing patients with drinking problems. The aim of this study was to determine whether the interactive training session using the 'Drink-less' package led to improvement in FPs' self-reported level of confidence in detecting and providing interventions for risky alcohol consumption. METHOD: FPs in urban and rural New South Wales were invited to training sessions in their local area. An introductory overview preceded a practical skills- based session, using the Drink-less package. Participants completed before and after evaluation forms. RESULTS: While 49% (CI 43 – 55) of the attending FPs indicated at baseline that they felt confident in identifying at-risk drinkers, this proportion rose to 90% (95% CI: 87 – 93) post-session, and they also reported increases in confidence from 36% (95% CI: 31 – 41) to 90% in their ability to advise patients. Urban FPs reported lower levels of confidence than rural FPs, both pre- and post-session. CONCLUSION: Training sessions in the Drink-less intervention resulted in increased self-reported confidence in detection and brief intervention for alcohol problems. Further research is needed to determine the duration of this effect and its influence on practice behaviour

Multilevel model to assess sources of variation in follicular growth close to the time of ovulation in women with normal fertility: a multicenter observational study

Mikolajczyk RT, Stanford JB, Ecochard R. Multilevel model to assess sources of variation in follicular growth close to the time of ovulation in women with normal fertility: a multicenter observational study. Reproductive Biology and Endocrinology. 2008;6(1): 61.Background: To assess the amount of variability in ovarian follicular growth rate and maximum follicular diameter related to different centers, women and cycles of the same women in a multicenter observational study of follicular growth. Methods: Secondary analysis of a prospective cohort study from eight centers in Europe. There were 533 ultrasound examinations in 282 cycles of 107 women with normal fertility. A random effects model with center, woman and cycle as hierarchical units of variation was used to analyze mean follicular diameter on days preceding ovulation. Results: Follicular growth did not differ by center. There was homogenous growth across women and cycles, and the maximum follicular diameter before ovulation varied substantially across cycles but not across women. Many (about 40%) women had small maximum follicular diameter on the day before ovulation (<19 mm). Pre-ovulatory cycle length was not related to maximum follicular diameter. Conclusion: In normal fecundity, there is a substantial variation in maximum follicular diameter from cycle to cycle based on variation in the duration of follicular development, but the variation could not be explained by different characteristics of different women. Explanation of variation in follicular growth has to be found on the cycle level

In vitro characterization and inhibition of the CXCR4/CXCL12 chemokine axis in human uveal melanoma cell lines

<p>Abstract</p> <p>Purpose</p> <p>The CXCR4/CXCL12 chemokine axis may play a critical role in guiding CXCR4+ circulating malignant cells to organ specific locations that actively secrete its ligand CXCL12 (SDF-1) such as bone, brain, liver, and lungs. We sought to characterize the presence of the CXCR4/CXCL12 axis in five uveal melanoma (UM) cell lines in vitro. The ability of TN14003, a synthetic peptide inhibitor that targets the CXCR4 receptor complex, to inhibit this axis was also assessed.</p> <p>Methods</p> <p>Immunocytochemistry was performed against CXCR4 to confirm expression of this chemokine receptor in all five UM cell lines. Flow cytometry was preformed to evaluate CXCR4 cell surface expression on all five UM cell lines. A proliferation assay was also used to test effects TN14003 would have on cellular proliferation. Inhibition of cellular migration by specifically inhibiting the CXCR4/CXCL12 axis with TN14003 was also investigated. The binding efficacy of TN14003 to the CXCR4 receptor was assessed through flow cytometric methods.</p> <p>Results</p> <p>The CXCR4 receptor was present on all five UM cell lines. All five cell lines expressed different relative levels of surface CXCR4. TN14003 did not affect the proliferation of the five cell lines (p > 0.05). All cell lines migrated towards the chemokine CXCL12 at a level greater than the negative control (p < 0.05). All 5 cell lines pre-incubated with TN14003 prevented cellular migration towards chemokine CXCL12 (p < 0.01). TN14003 preferentially binds CXCR4 to native ligand CXCL12.</p> <p>Conclusion</p> <p>Interfering with the CXCR4/CXCL12 axis, using TN14003 was shown to effectively down regulate UM cell migration in vitro. Knowing that UM expresses the CXCR4 receptor, these CXCR4+ cells may be less likely to colonize distant organs that secrete the CXCL12 ligand, if treated with an inhibitor that binds CXCR4. Further studies should be pursued in order to test TN14003 efficacy in vivo.</p

Functional Conservation of the Drosophila gooseberry Gene and Its Evolutionary Alleles

The Drosophila Pax gene gooseberry (gsb) is required for development of the larval cuticle and CNS, survival to adulthood, and male fertility. These functions can be rescued in gsb mutants by two gsb evolutionary alleles, gsb-Prd and gsb-Pax3, which express the Drosophila Paired and mouse Pax3 proteins under the control of gooseberry cis-regulatory region. Therefore, both Paired and Pax3 proteins have conserved all the Gsb functions that are required for survival of embryos to fertile adults, despite the divergent primary sequences in their C-terminal halves. As gsb-Prd and gsb-Pax3 uncover a gsb function involved in male fertility, construction of evolutionary alleles may provide a powerful strategy to dissect hitherto unknown gene functions. Our results provide further evidence for the essential role of cis-regulatory regions in the functional diversification of duplicated genes during evolution

Scale-up and large-scale production of Tetraselmis sp CTP4 (Chlorophyta) for CO2 mitigation: from an agar plate to 100-m(3) industrial photobioreactors

Industrial production of novel microalgal isolates is key to improving the current portfolio of available strains that are able to grow in large-scale production systems for different biotechnological applications, including carbon mitigation. In this context, Tetraselmis sp. CTP4 was successfully scaled up from an agar plate to 35-and 100-m(3) industrial scale tubular photobioreactors (PBR). Growth was performed semi-continuously for 60 days in the autumn-winter season (17th October -14th December). Optimisation of tubular PBR operations showed that improved productivities were obtained at a culture velocity of 0.65-1.35 m s(-1) and a pH set-point for CO2 injection of 8.0. Highest volumetric (0.08 +/- 0.01 g L-1 d(-1)) and areal (20.3 +/- 3.2 g m(-2) d(-1)) biomass productivities were attained in the 100-m(3) PBR compared to those of the 35-m(3) PBR (0.05 +/- 0.02 g L-1 d(-1) and 13.5 +/- 4.3 g m(-2) d(-1), respectively). Lipid contents were similar in both PBRs (9-10% of ash free dry weight). CO2 sequestration was followed in the 100-m(3) PBR, revealing a mean CO2 mitigation efficiency of 65% and a biomass to carbon ratio of 1.80. Tetraselmis sp. CTP4 is thus a robust candidate for industrial-scale production with promising biomass productivities and photosynthetic efficiencies up to 3.5% of total solar irradiance.Portuguese national budget; Foundation for Science and Technology (FCT) [CCMAR/Multi/04326/2013]; INTERREG V-A Espana-Portugal project [0055 ALGARED + 5 E]; COST Action - European Network for Bio-products [1408]; FCT [SFRH/BD/105541/2014]; Nord Universityinfo:eu-repo/semantics/publishedVersio

Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes

This is the final version. Available from the publisher via the DOI in this record.UK Biobank Sleep Traits GWAS summary statistics are available at the Sleep Disorder Knowledge Portal (SDKP) website (http://www.sleepdisordergenetics.org). All other data are contained within the article and its supplementary information or available upon request.Excessive daytime sleepiness (EDS) affects 10–20% of the population and is associated with substantial functional deficits. Here, we identify 42 loci for self-reported daytime sleepiness in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirm the aggregate effect of a genetic risk score of 42 SNPs on daytime sleepiness in independent Scandinavian cohorts and on other sleep disorders (restless legs syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). However, individual daytime sleepiness signals vary in their associations with objective short vs long sleep, and with markers of sleep continuity. The 42 sleepiness variants primarily cluster into two predominant composite biological subtypes - sleep propensity and sleep fragmentation. Shared genetic links are also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing.Medical Research Council (MRC