Intermittent access to 20% ethanol induces high ethanol consumption in Long-Evans and Wistar rats

BACKGROUND: There has been some difficulty getting standard laboratory rats to voluntarily consume large amounts of ethanol without the use of initiation procedures. It has previously been shown that standard laboratory rats will voluntarily consume high levels of ethanol if given intermittent-access to 20% ethanol in a 2-bottle-choice setting [Wise, Psychopharmacologia 29 (1973), 203]. In this study, we have further characterized this drinking model. METHODS: Ethanol-naïve Long-Evans rats were given intermittent-access to 20% ethanol (three 24-hour sessions per week). No sucrose fading was needed and water was always available ad libitum. Ethanol consumption, preference, and long-term drinking behaviors were investigated. Furthermore, to pharmacologically validate the intermittent-access 20% ethanol drinking paradigm, the efficacy of acamprosate and naltrexone in decreasing ethanol consumption were compared with those of groups given continuous-access to 10 or 20% ethanol, respectively. Additionally, ethanol consumption was investigated in Wistar and out-bred alcohol preferring (P) rats following intermittent-access to 20% ethanol. RESULTS: The intermittent-access 20% ethanol 2-bottle-choice drinking paradigm led standard laboratory rats to escalate their ethanol intake over the first 5 to 6 drinking sessions, reaching stable baseline consumption of high amounts of ethanol (Long-Evans: 5.1 +/- 0.6; Wistar: 5.8 +/- 0.8 g/kg/24 h, respectively). Furthermore, the cycles of excessive drinking and abstinence led to an increase in ethanol preference and increased efficacy of both acamprosate and naltrexone in Long-Evans rats. P-rats initiate drinking at a higher level than both Long-Evans and Wistar rats using the intermittent-access 20% ethanol paradigm and showed a trend toward a further escalation in ethanol intake over time (mean ethanol intake: 6.3 +/- 0.8 g/kg/24 h). CONCLUSION: Standard laboratory rats will voluntarily consume ethanol using the intermittent-access 20% ethanol drinking paradigm without the use of any initiation procedures. This model promises to be a valuable tool in the alcohol research field.

Inhibition of orexin-1/hypocretin-1 receptors inhibits yohimbine-induced reinstatement of ethanol and sucrose seeking in Long-Evans rats

Abstract RATIONALE: Previous studies have shown that orexin-1/hypocretin-1 receptors play a role in self-administration and cue-induced reinstatement of food, drug, and ethanol seeking. In the current study, we examined the role of orexin-1/hypocretin-1 receptors in operant self-administration of ethanol and sucrose and in yohimbine-induced reinstatement of ethanol and sucrose seeking. MATERIALS AND METHODS: Rats were trained to self-administer either 10% ethanol or 5% sucrose (30 min/day). The orexin-1 receptor antagonist SB334867 (0, 5, 10, 15, 20 mg/kg, i.p.) was administered 30 min before the operant self-administration sessions. After these experiments, the operant self-administration behaviors were extinguished in both the ethanol and sucrose-trained rats. Upon reaching extinction criteria, SB334867 (0, 5, 10 mg/kg, i.p.) was administered 30 min before yohimbine (0 or 2 mg/kg, i.p.). In a separate experiment, the effect of SB334867 (0, 15, or 20 mg/kg, i.p.) on general locomotor activity was determined using the open-field test. RESULTS: The orexin-1 receptor antagonist, SB334867 (10, 15 and 20 mg/kg) decreased operant self-administration of 10% ethanol but not 5% sucrose self-administration. Furthermore, SB334867 (5 and 10 mg/kg) significantly decreased yohimbine-induced reinstatement of both ethanol and sucrose seeking. SB334867 did not significantly affect locomotor activity measured using the open-field test. CONCLUSIONS: The results suggest that inhibition of OX-1/Hcrt-1 receptors modulates operant ethanol self-administration and also plays a significant role in yohimbine-induced reinstatement of both ethanol and sucrose seeking in rats.

Predicting residue-wise contact orders in proteins by support vector regression

Background The residue-wise contact order (RWCO) describes the sequence separations between the residues of interest and its contacting residues in a protein sequence. It is a new kind of one-dimensional protein structure that represents the extent of long-range contacts and is considered as a generalization of contact order. Together with secondary structure, accessible surface area, the B factor, and contact number, RWCO provides comprehensive and indispensable important information to reconstructing the protein three-dimensional structure from a set of one-dimensional structural properties. Accurately predicting RWCO values could have many important applications in protein three-dimensional structure prediction and protein folding rate prediction, and give deep insights into protein sequence-structure relationships. Results We developed a novel approach to predict residue-wise contact order values in proteins based on support vector regression (SVR), starting from primary amino acid sequences. We explored seven different sequence encoding schemes to examine their effects on the prediction performance, including local sequence in the form of PSI-BLAST profiles, local sequence plus amino acid composition, local sequence plus molecular weight, local sequence plus secondary structure predicted by PSIPRED, local sequence plus molecular weight and amino acid composition, local sequence plus molecular weight and predicted secondary structure, and local sequence plus molecular weight, amino acid composition and predicted secondary structure. When using local sequences with multiple sequence alignments in the form of PSI-BLAST profiles, we could predict the RWCO distribution with a Pearson correlation coefficient (CC) between the predicted and observed RWCO values of 0.55, and root mean square error (RMSE) of 0.82, based on a well-defined dataset with 680 protein sequences. Moreover, by incorporating global features such as molecular weight and amino acid composition we could further improve the prediction performance with the CC to 0.57 and an RMSE of 0.79. In addition, combining the predicted secondary structure by PSIPRED was found to significantly improve the prediction performance and could yield the best prediction accuracy with a CC of 0.60 and RMSE of 0.78, which provided at least comparable performance compared with the other existing methods. Conclusion The SVR method shows a prediction performance competitive with or at least comparable to the previously developed linear regression-based methods for predicting RWCO values. In contrast to support vector classification (SVC), SVR is very good at estimating the raw value profiles of the samples. The successful application of the SVR approach in this study reinforces the fact that support vector regression is a powerful tool in extracting the protein sequence-structure relationship and in estimating the protein structural profiles from amino acid sequences.

Cultural support workers and long day care services

In Australia, eligible long day care services may apply for support at the state level to assist with the transition of children from culturally or linguistically diverse backgrounds into childcare settings. For staff in childcare services, this support comes in the form of a cultural support worker (CSW). The primary role of a CSW is to build capacity in childcare staff to support children and families as they enter the childcare program. This paper draws on interview data and documentation from multiple sources to report the perspectives of key stakeholders affiliated with a cultural support program in an Australian childcare setting. It concludes that a more flexible approach to policy that directs the work of CSWs is needed, as well as further research into ways to build capacity for cultural competence for both CSWs and childcare staff who work collaboratively to support young children as they transition to childcare.

Quantification of the accuracy of MRI generated 3D models of long bones compared to CT generated 3D models

Orthopaedic fracture fixation implants are increasingly being designed using accurate 3D models of long bones based on computer tomography (CT). Unlike CT, magnetic resonance imaging (MRI) does not involve ionising radiation and is therefore a desirable alternative to CT. This study aims to quantify the accuracy of MRI-based 3D models compared to CT-based 3D models of long bones. The femora of five intact cadaver ovine limbs were scanned using a 1.5T MRI and a CT scanner. Image segmentation of CT and MRI data was performed using a multi-threshold segmentation method. Reference models were generated by digitising the bone surfaces free of soft tissue with a mechanical contact scanner. The MRI- and CT-derived models were validated against the reference models. The results demonstrated that the CT-based models contained an average error of 0.15mm while the MRI-based models contained an average error of 0.23mm. Statistical validation shows that there are no significant differences between 3D models based on CT and MRI data. These results indicate that the geometric accuracy of MRI based 3D models was comparable to that of CT-based models and therefore MRI is a potential alternative to CT for generation of 3D models with high geometric accuracy.

Population genetic structure and patterns of dispersal in the Giant Long-Armed Prawn, Macrobrachium lar (Fabricius, 1798) (Decapoda : Palaemonidae)

The Giant Long-Armed Prawn, Macrobrachium lar is a freshwater species native to the Indo-Pacific. M. lar has a long-lived, passive, pelagic marine larval stage where larvae need to colonise freshwater within three months to complete their development. Dispersal is likely to be influenced by the extensive distances larvae must transit between small oceanic islands to find suitable freshwater habitat, and by prevailing east to west wind and ocean currents in the southern Pacific Ocean. Thus, both intrinsic and extrinsic factors are likely to influence wild population structure in this species. The present study sought to define the contemporary broad and fine-scale population genetic structure of Macrobrachium lar in the south-western Pacific Ocean. Three polymorphic microsatellite loci were used to assess patterns of genetic variation within and among 19 wild adult sample sites. Statistical procedures that partition variation implied that at both spatial scales, essentially all variation was present within sample sites and differentiation among sites was low. Any differentiation observed also was not correlated with geographical distance. Statistical approaches that measure genetic distance, at the broad-scale, showed that all south-western Pacific Islands were essentially homogeneous, with the exception of a well supported divergent Cook Islands group. These findings are likely the result of some combination of factors that may include the potential for allelic homoplasy, through to the effects of sampling regime. Based on the findings, there is most likely a divergent M. lar Cook Islands clade in the south-western Pacific Ocean, resulting from prevailing ocean currents. Confirmation of this pattern will require a more detailed analysis of nDNA variation using a larger number of loci and, where possible, use of larger population sizes.

The Long-Term Irrelevance of Trust in Outsourcing Decisions for New Technologies: Insights from an Agent-Based Model

Significant empirical data from the fields of management and business strategy suggest that it is a good idea for a company to make in-house the components and processes underpinning a new technology. Other evidence suggests exactly the opposite, saying that firms would be better off buying components and processes from outside suppliers. One possible explanation for this lack of convergence is that earlier research in this area has overlooked two important aspects of the problem: reputation and trust. To gain insight into how these variables may impact make-buy decisions throughout the innovation process, the Sporas algorithm for measuring reputation was added to an existing agent-based model of how firms interact with each other throughout the development of new technologies. The model�s results suggest that reputation and trust do not play a significant role in the long-term fortunes of an individual firm as it contends with technological change in the marketplace. Accordingly, this model serves as a cue for management researchers to investigate more thoroughly the temporal limitations and contingencies that determine how the trust between firms may affect the R&D process.

Antecedents of Destination Brand Loyalty for a Long-Haul Market: Australia's Destination Loyalty Among Chilean Travelers

Limited extant research examines Latin American consumers' perceptions of holiday destinations. This article measures destination brand equity for Australia as a long-haul destination in the emerging Chilean market. Specifically, it develops a model of consumer-based brand equity (CBBE) to explain attitudinal destination loyalty. The proposed model is tested using data from a sample of Chilean travelers. The findings suggest that brand salience, brand image, and brand value are positively related to brand loyalty for Australia. Further, while brand salience for Australia is strong, as a long-haul destination the country faces significant challenges in converting awareness into intent to visit. Australia is a more compelling destination brand for previous visitors than non-visitors. This implies that a word-of-mouth recommendation from previous visitors, a key component of attitudinal loyalty, is a positive indicator of future growth opportunities for Australia's destination marketers to capitalize on.

Long-evans rats acquire operant self-administration of 20% ethanol without sucrose fading

A major obstacle in the development of new medications for the treatment of alcohol use disorders (AUDs) has been the lack of preclinical, oral ethanol consumption paradigms that elicit high consumption. We have previously shown that rats exposed to 20% ethanol intermittently in a two-bottle choice paradigm will consume two times more ethanol than those given continuous access without the use of water deprivation or sucrose fading (5-6 g/kg every 24 h vs 2-3 g/kg every 24 h, respectively). In this study, we have adapted the model to an operant self-administration paradigm. Long-Evans rats were given access to 20% ethanol in overnight sessions on one of two schedules: (1) intermittent (Monday, Wednesday, and Friday) or (2) daily (Monday through Friday). With the progression of the overnight sessions, both groups showed a steady escalation in drinking (3-6 g/kg every 14 h) without the use of a sucrose-fading procedure. Following the acquisition phase, the 20% ethanol groups consumed significantly more ethanol than did animals trained to consume 10% ethanol with a sucrose fade (1.5 vs 0.7 g/kg every 30 min) and reached significantly higher blood ethanol concentrations. In addition, training history (20% ethanol vs 10% ethanol with sucrose fade) had a significant effect on the subsequent self-administration of higher concentrations of ethanol. Administration of the pharmacological stressor yohimbine following extinction caused a significant reinstatement of ethanol-seeking behavior. Both 20% ethanol models show promise and are amenable to the study of maintenance, motivation, and reinstatement. Furthermore, training animals to lever press for ethanol without the use of sucrose fading removes a potential confound from self-administration studies. © 2010 Nature Publishing Group All rights reserved.

How long is a tweet? Mapping dynamic conversation networks on Twitter using Gawk and Gephi

Twitter is now well established as the world’s second most important social media platform, after Facebook. Its 140-character updates are designed for brief messaging, and its network structures are kept relatively flat and simple: messages from users are either public and visible to all (even to unregistered visitors using the Twitter website), or private and visible only to approved ‘followers’ of the sender; there are no more complex definitions of degrees of connection (family, friends, friends of friends) as they are available in other social networks. Over time, Twitter users have developed simple, but effective mechanisms for working around these limitations: ‘#hashtags’, which enable the manual or automatic collation of all tweets containing the same #hashtag, as well allowing users to subscribe to content feeds that contain only those tweets which feature specific #hashtags; and ‘@replies’, which allow senders to direct public messages even to users whom they do not already follow. This paper documents a methodology for extracting public Twitter activity data around specific #hashtags, and for processing these data in order to analyse and visualize the @reply networks existing between participating users – both overall, as a static network, and over time, to highlight the dynamic structure of @reply conversations. Such visualizations enable us to highlight the shifting roles played by individual participants, as well as the response of the overall #hashtag community to new stimuli – such as the entry of new participants or the availability of new information. Over longer timeframes, it is also possible to identify different phases in the overall discussion, or the formation of distinct clusters of preferentially interacting participants.