Delta opioid-receptor function in the dorsal striatum plays a role in high levels of ethanol consumption in rats

Binge-like patterns of excessive drinking during young adulthood increase the propensity for alcohol use disorders (AUDs) later in adult life; however, the mechanisms that drive this are not completely understood. Previous studies showed that the δ-opioid peptide receptor (DOP-R) is dynamically regulated by exposure to ethanol and that the DOP-R plays a role in ethanol-mediated behaviors. The aim of this study was to determine the role of the DOP-R in high ethanol consumption from young adulthood through to late adulthood by measuring DOP-R-mediated [(35)S]GTPγS binding in brain membranes and DOP-R-mediated analgesia using a rat model of high ethanol consumption in Long Evans rats. We show that DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia changes during development, being highest during early adulthood and reduced in late adulthood. Intermittent access to ethanol but not continuous ethanol or water from young adulthood leads to an increase in DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia into late adulthood. Multiple microinfusions of naltrindole into the dorsal striatum or multiple systemic administration of naltrindole reduces ethanol consumption, and following termination of treatment, DOP-R activity in the dorsal striatum is attenuated. These findings suggest that DOP-R activity in the dorsal striatum plays a role in high levels of ethanol consumption and suggest that targeting the DOP-R is an alternative strategy for the treatment of AUDs.

Agronomic and economic evaluation of irrigation strategies on cotton lint yield in Australia

Cotton is one of the most important irrigated crops in subtropical Australia. In recent years, cotton production has been severely affected by the worst drought in recorded history, with the 2007–08 growing season recording the lowest average cotton yield in 30 years. The use of a crop simulation model to simulate the long-term temporal distribution of cotton yields under different levels of irrigation and the marginal value for each unit of water applied is important in determining the economic feasibility of current irrigation practices. The objectives of this study were to: (i) evaluate the CROPGRO-Cotton simulation model for studying crop growth under deficit irrigation scenarios across ten locations in New South Wales (NSW) and Queensland (Qld); (ii) evaluate agronomic and economic responses to water inputs across the ten locations; and (iii) determine the economically optimal irrigation level. The CROPGRO-Cotton simulation model was evaluated using 2 years of experimental data collected at Kingsthorpe, Qld. The model was further evaluated using data from nine locations between northern NSW and southern Qld. Long-term simulations were based on the prevalent furrowirrigation practice of refilling the soil profile when the plant -available soil water content is<50%. The model closely estimated lint yield for all locations evaluated. Our results showed that the amounts of water needed to maximise profit and maximise yield are different, which has economic and environmental implications. Irrigation needed to maximise profits varied with both agronomic and economic factors, which can be quite variable with season and location. Therefore, better tools and information that consider the agronomic and economic implications of irrigation decisions need to be developed and made available to growers.

Exercise for health : a randomized, controlled trial evaluating impact of a pragmatic, translational exercise intervention on quality of life, function and treatment-related side effects following breast cancer

Purpose Exercise for Health was a randomized, controlled trial designed to evaluate two modes of delivering (face-to-face [FtF] and over-the-telephone [Tel]) an 8-month translational exercise intervention, commencing 6-weeks post-breast cancer surgery (PS). Methods Outcomes included quality of life (QoL), function (fitness and upper-body) and treatment-related side effects (fatigue, lymphoedema, body mass index, menopausal symptoms, anxiety, depression and pain). Generalised estimating equation modelling determined time (baseline [5-weeks PS], mid-intervention [6-months PS], post-intervention [12-months PS]), group (FtF, Tel, Usual Care [UC]) and time-by-group effects. 194 women representative of the breast cancer population were randomised to the FtF (n=67), Tel (n=67) and UC (n=60) groups. Results: There were significant (p<0.05) interaction effects on QoL, fitness and fatigue, with differences being observed between the treatment groups and the UC group. Trends observed for the treatment groups were similar. The treatment groups reported improved QoL, fitness and fatigue over time and changes observed between baseline and post-intervention were clinically relevant. In contrast, the UC group experienced no change, or worsening QoL, fitness and fatigue, mid-intervention. Although improvements in the UC group occurred by 12-months post-surgery, the change did not meet the clinically relevant threshold. There were no differences in other treatment-related side-effects between groups. Conclusion This translational intervention trial, delivered either face-to-face or over-the-telephone, supports exercise as a form of adjuvant breast cancer therapy that can prevent declines in fitness and function during treatment and optimise recovery post-treatment.

Evidence for a dual function of EphB4 as tumor promoter and suppressor regulated by the absence or presence of the ephrin-B2 ligand

Overexpression of the receptor tyrosine kinase EphB4 is common in epithelial cancers and linked to tumor progression by promoting angiogenesis, increasing survival and facilitating invasion and migration. However, other studies have reported loss of EphB4 suggesting a tumor suppressor function in some cancers. These opposing roles may be regulated by (i) the presence of the primary ligand ephrin-B2 that regulates pathways involved in tumor suppression or (ii) the absence of ephrin-B2 that allows EphB4 signaling via ligand-independent pathways that contribute to tumor promotion. To explore this theory, EphB4 was overexpressed in the prostate cancer cell line 22Rv1 and the mammary epithelial cell line MCF-10A. Overexpressed EphB4 localized to lipid-rich regions of the plasma membrane and confirmed to be ligand-responsive as demonstrated by increased phosphorylation of ERK1/2 and internalization. EphB4 overexpressing cells demonstrated enhanced anchorage-independent growth, migration and invasion, all characteristics associated with an aggressive phenotype, and therefore supporting the hypothesis that overexpressed EphB4 facilitates tumor promotion. Importantly, these effects were reversed in the presence of ephrin-B2 which led to a reduction in EphB4 protein levels, demonstrating that ligand-dependent signaling is tumor suppressive. Furthermore, extended ligand stimulation caused a significant decrease in proliferation that correlated with a rise in caspase-3/7 and -8 activities. Together, these results demonstrate that overexpression of EphB4 confers a transformed phenotype in the case of MCF-10A cells and an increased metastatic phenotype in the case of 22Rv1 cancer cells and that both phenotypes can be restrained by stimulation with ephrin-B2, in part by reducing EphB4 levels.

Relationship among CFH and ARMS2 genotypes, macular pigment optical density, and neuroretinal function in persons without age-related macular degeneration

Purpose: To determine whether there is a difference in neuroretinal function and in macular pigment optical density between persons with high- and low-risk gene variants for age-related macular degeneration (AMD) and no ophthalmoscopic signs of AMD, and to compare the results on neuroretinal function to patients with manifest early AMD. Methods and Participants: Neuroretinal function was assessed with the multifocal electroretinogram (mfERG) for 32 participants (22 healthy persons with no AMD and 10 early AMD patients). The 22 healthy participants with no AMD had high- or low-risk genotypes for either CFH (rs380390) and/or ARMS2 (rs10490924). Trough-to-peak response densities and peak-implicit times were analyzed in 5 concentric rings. Macular pigment optical densitometry was assessed by customized heterochromatic flicker photometry. Results: Trough-to-peak response densities for concentric rings 1 to 3 were, on average, significantly greater in participants with high-risk genotypes than in participants with low-risk genotypes and in persons with early AMD after correction for age and smoking (p<0.05). The group peak- implicit times for ring 1 were, on average, delayed in the patients with early AMD compared with the participants with high- or low-risk genotypes, although these differences were not significant. There was no significant correlation between genotypes and macular pigment optical density. Conclusion: Increased neuroretinal activity in persons who carry high-risk AMD genotypes may be due to genetically determined subclinical inflammatory and/or histological changes in the retina. Neuroretinal function in healthy persons genetically susceptible to AMD may be a useful additional early biomarker (in combination with genetics) before there is clinical manifestation.

Insights into the role and function of L2, the minor capsid protein of papillomaviruses

Human papillomaviruses (HPV) are responsible for the most common human sexually transmitted viral infections, and high-risk types are responsible for causing cervical and other cancers. The minor capsid protein L2 of HPV plays important roles in virus entry into cells, localisation of viral components to the nucleus, in DNA binding, capsid formation and stability. It also elicits antibodies that are more cross-reactive between HPV types than does the major capsid protein L1, making it an attractive potential target for new-generation, more broadly protective subunit vaccines against HPV infections. However, its low abundance in natural capsids-12-72 molecules per 360 copies of L1-limits its immunogenicity. This review will explore the biological roles of the protein, and prospects for its use in new vaccines. © 2009 Springer-Verlag.

Post-match changes in neuromuscular function and the relationship to match demands in amateur rugby league matches

Objectives: The current study investigated the change in neuromuscular contractile properties following competitive rugby league matches and the relationship with physical match demands. Design: Eleven trained, male rugby league players participated in 2–3 amateur, competitive matches (n = 30). Methods: Prior to, immediately (within 15-min) and 2 h post-match, players performed repeated counter-movement jumps (CMJ) followed by isometric tests on the right knee extensors for maximal voluntary contraction (MVC), voluntary activation (VA) and evoked twitch contractile properties of peak twitch force (Pt), rate of torque development (RTD), contraction duration (CD) and relaxation rate (RR). During each match, players wore 1 Hz Global Positioning Satellite devices to record distance and speeds of matches. Further, matches were filmed and underwent notational analysis for number of total body collisions. Results: Total, high-intensity, very-high intensity distances covered and mean speed were 5585 ± 1078 m, 661 ± 265, 216 ± 121 m and 75 ± 14 m min−1, respectively. MVC was significantly reduced immediately and 2 h post-match by 8 ± 11 and 12 ± 13% from pre-match (p < 0.05). Moreover, twitch contractile properties indicated a suppression of Pt, RTD and RR immediately post-match (p < 0.05). However, VA was not significantly altered from pre-match (90 ± 9%), immediately-post (89 ± 9%) or 2 h post (89 ± 8%), (p > 0.05). Correlation analyses indicated that total playing time (r = −0.50) and mean speed (r = −0.40) were moderately associated to the change in post-match MVC, while mean speed (r = 0.35) was moderately associated to VA. Conclusions: The present study highlights the physical demands of competitive amateur rugby league result in interruption of peripheral contractile function, and post-match voluntary torque suppression may be associated with match playing time and mean speeds.

Network interactions and performance of a multi-function IEC 61850 process bus

New substation technology, such as non-conventional instrument transformers,and a need to reduce design and construction costs, are driving the adoption of Ethernet based digital process bus networks for high voltage substations. Protection and control applications can share a process bus, making more efficient use of the network infrastructure. This paper classifies and defines performance requirements for the protocols used in a process bus on the basis of application. These include GOOSE, SNMP and IEC 61850-9-2 sampled values. A method, based on the Multiple Spanning Tree Protocol (MSTP) and virtual local area networks, is presented that separates management and monitoring traffic from the rest of the process bus. A quantitative investigation of the interaction between various protocols used in a process bus is described. These tests also validate the effectiveness of the MSTP based traffic segregation method. While this paper focusses on a substation automation network, the results are applicable to other real-time industrial networks that implement multiple protocols. High volume sampled value data and time-critical circuit breaker tripping commands do not interact on a full duplex switched Ethernet network, even under very high network load conditions. This enables an efficient digital network to replace a large number of conventional analog connections between control rooms and high voltage switchyards.

Executive function development and stress effects on driving performance : preliminary findings from a young adult sample.

This chapter presents a pilot study examining the interactive contributions of executive function development/impairment and psychosocial stress to young adults’ (17-30 years old) driving behaviour in a simulator city scenario.

Adapting wheat sowing dates to projected climate change in the Australian subtropics: analysis of crop water use and yield

Projected increases in atmospheric carbon dioxide concentration ([CO2]) and air temperature associated with future climate change are expected to affect crop development, crop yield, and, consequently, global food supplies. They are also likely to change agricultural production practices, especially those related to agricultural water management and sowing date. The magnitude of these changes and their implications to local production systems are mostly unknown. The objectives of this study were to: (i) simulate the effect of projected climate change on spring wheat (Triticum aestivum L. cv. Lang) yield and water use for the subtropical environment of the Darling Downs, Queensland, Australia; and (ii) investigate the impact of changing sowing date, as an adaptation strategy to future climate change scenarios, on wheat yield and water use. The multimodel climate projections from the IPCC Coupled Model Intercomparison Project (CMIP3) for the period 2030–2070 were used in this study. Climate scenarios included combinations of four changes in air temperature (08C, 18C, 28C, and 38C), three [CO2] levels (380 ppm, 500 ppm, and 600 ppm), and three changes in rainfall (–30%, 0%, and +20%), which were superimposed on observed station data. Crop management scenarios included a combination of six sowing dates (1 May, 10 May, 20 May, 1 June, 10 June, and 20 June) and three irrigation regimes (no irrigation (NI), deficit irrigation (DI), and full irrigation (FI)). Simulations were performed with the model DSSAT4.5, using 50 years of daily weather data.Wefound that: (1) grain yield and water-use efficiency (yield/evapotranspiration) increased linearly with [CO2]; (2) increases in [CO2] had minimal impact on evapotranspiration; (3) yield increased with increasing temperature for the irrigated scenarios (DI and FI), but decreased for the NI scenario; (4) yield increased with earlier sowing dates; and (5) changes in rainfall had a small impact on yield for DI and FI, but a high impact for the NI scenario.

Cloning of a novel insulin-regulated ghrelin transcript in prostate cancer

Ghrelin is a multifunctional hormone, with roles in stimulating appetite and regulating energy balance, insulin secretion and glucose homeostasis. The ghrelin gene locus (GHRL) is highly complex and gives rise to a range of novel transcripts derived from alternative first exons and internally spliced exons. The wild-type transcript encodes a 117 amino acid preprohormone that is processed to yield the 28 amino acid peptide ghrelin. Here, we identified insulin-responsive transcription corresponding to cryptic exons in intron 2 of the human ghrelin gene. A transcript, termed in2c-ghrelin (intron 2-cryptic), was cloned from the testis and the LNCaP prostate cancer cell line. This transcript may encode an 83 AA preproghrelin isoform that codes for the ghrelin, but not obestatin. It is expressed in a limited number of normal tissues and in tumours of the prostate, testis, breast and ovary. Finally, we confirmed that in2c-ghrelin transcript expression, as well as the recently described in1-ghrelin transcript, is significantly upregulated by insulin in cultured prostate cancer cells. Metabolic syndrome and hyperinsulinaemia has been associated with prostate cancer risk and progression. This may be particularly significant after androgen deprivation therapy for prostate cancer, which induces hyperinsulinaemia, and this could contribute to castrate resistant prostate cancer growth. We have previously demonstrated that ghrelin stimulates prostate cancer cell line proliferation in vitro. This study is the first description of insulin regulation of a ghrelin transcript in cancer, and should provide further impetus for studies into the expression, regulation and function of ghrelin gene products.

On the probability density function of the product of Rayleigh distributed random variables

In this paper we investigate the distribution of the product of Rayleigh distributed random variables. Considering the Mellin-Barnes inversion formula and using the saddle point approach we obtain an upper bound for the product distribution. The accuracy of this tail-approximation increases as the number of random variables in the product increase.

Analysis of productive performance of crop production systems: an integrated analytical framework

Recent literature has argued that environmental efficiency (EE), which is built on the materials balance (MB) principle, is more suitable than other EE measures in situations where the law of mass conversation regulates production processes. In addition, the MB-based EE method is particularly useful in analysing possible trade-offs between cost and environmental performance. Identifying determinants of MB-based EE can provide useful information to decision makers but there are very few empirical investigations into this issue. This article proposes the use of data envelopment analysis and stochastic frontier analysis techniques to analyse variation in MB-based EE. Specifically, the article develops a stochastic nutrient frontier and nutrient inefficiency model to analyse determinants of MB-based EE. The empirical study applies both techniques to investigate MB-based EE of 96 rice farms in South Korea. The size of land, fertiliser consumption intensity, cost allocative efficiency, and the share of owned land out of total land are found to be correlated with MB-based EE. The results confirm the presence of a trade-off between MB-based EE and cost allocative efficiency and this finding, favouring policy interventions to help farms simultaneously achieve cost efficiency and MP-based EE.