Testosterone administration in chicks affects responding in the presence of task irrelevant stimulus changes

Introduction: A series of studies have shown that circulating testosterone increases the persistence with which animals search for and select a particular visual cue to respond to (as a consequence of experience with it) - and hence incur a perseveration of response towards such cues (e.g. Rogers 1971; Andrew 1972, Archer 1976; Earley & Leonard 1978). We tested the effect of testosterone on such attention-related mechanisms by studying the effect of intradimensionsional colour changes to cues relevant and irrelevant to an operant discrimination on continuous reinforcement learning (non-reversal shifts). Methods: Treatment: Chicks (20 males) were given 12.5 mg testosterone enanthate im after training on a continuous reinforcement schedule of response (CRF); 19 controls received sesame oil vehicle and 8 males and 15 females had no treatment. Testing: Birds were given A) test sessions on day 10 and 11: whereby each session consisted of 2 minutes training, 5 minutes test then 2 minutes re-training: B) 4 types of test --(i) the negative key colour changed from red to deep blue, (ii) the positive key colour changed from pale blue to green, and (iii) both key colours changed as described, and (iv) the overhead lighting changed with the introduction of a pale red filter. Results: 1/ Treatment did not affect CRF patterns of discriminative responding. 2/ All birds decreased their response rate after a colour change. 3/ After changes on the non-reinforced key, testosterone treated birds showed significantly less attenuation of response rate. 4/ Testosterone treatment also maintained a higher rate of response (and hence fewer reinforcements) - seen especially after a change in the negative cue or overhead lighting vs. changes in the positive cue (irrelevant changes of stimulation). 5/ Testosterone treated birds also showed a shorter latency to respond after a colour change. 6/ The female birds did not differ from the males Conclusions: The results support a role for testosterone in the discrimination between relevant and irrelevant stimulus changes and the persistent expression of learned sets. The fact that responding after testosterone treatment was altered by irrelevant rather than relevant stimulus changes suggests that testosterone achieves its persistence effect by enhancing the activated set or what is at the focus of attention, rather than the inhibition of features irrelevant to the ongoing situation - these provide the reference for 'what is relevant' and changes in them disturb this mechanis

Novel Roles for Matrix Metalloproteinases in Cell-Matrix Interactions

The aim of this study was to elucidate the effect of type I collagen degradation by a physiological enzyme on cell-collagen interactions. Type I collagen is degraded in vivo by collagenases, which are members of the matrix metalloproteinase family of enzymes. The ability of HT1080 cells, which express the major cell-surface collagen receptor α2β1 integrin, to attach to and invade through collagenase-cleaved collagen was investigated in cell attachment and invasion assays in comparison with the intact molecule. Binding studies of purified, platelet α2β1 integrin, and of ligand-binding A domain of this integrin to native collagen and to purified 3/4 and 1/4 fragments of collagen, generated by collagenase-3 revealed the necessity for retention of the triple-helical conformation of the collagen fragments for α2β1 integrin binding. HT1080 cell attachment to type I collagen was α2β1 integrin-mediated, and collagenase-cleavage of type I collagen perturbed cell attachment via this integrin at physiological temperature. This is likely to be due to melting of the collagen fragments, destabilizing of the triple-helical conformation of type I collagen and the resultant loss of α2β1 integrin binding sites on the collagen molecules. However, cell attachment to the native collagen fragments was still possible at room temperature, indicating that collagenase does not destroy α2β1 integrin binding sites on type I collagen, and that attachment can occur below physiological temperature. HT1080 cell invasion assays through equivalent molar concentrations of native type I collagen and the 3/4 and 1/4 fragments of collagen revealed that HT 1080 cell invasion through both collagen fragments was significantly greater relative to cell invasion through native collagen. These results may reflect the decreased adhesion to heat-unwound collagen fragments seen in attachment assays. Collagenase degradation of type I collagen significantly alters α2β1 integrin-mediated cell interactions with collagen, and also results in increased cell invasion through the degraded substrate. Matrix metalloproteinases may thus have an important role in cell-collagen interactions during tumour invasion and metastasis, where upregulation of matrix metalloproteinase synthesis by tumour and stromal cells is often observed

Walk well:a randomised controlled trial of a walking intervention for adults with intellectual disabilities: study protocol

Background - Walking interventions have been shown to have a positive impact on physical activity (PA) levels, health and wellbeing for adult and older adult populations. There has been very little work carried out to explore the effectiveness of walking interventions for adults with intellectual disabilities. This paper will provide details of the Walk Well intervention, designed for adults with intellectual disabilities, and a randomised controlled trial (RCT) to test its effectiveness. Methods/design - This study will adopt a RCT design, with participants allocated to the walking intervention group or a waiting list control group. The intervention consists of three PA consultations (baseline, six weeks and 12 weeks) and an individualised 12 week walking programme. A range of measures will be completed by participants at baseline, post intervention (three months from baseline) and at follow up (three months post intervention and six months from baseline). All outcome measures will be collected by a researcher who will be blinded to the study groups. The primary outcome will be steps walked per day, measured using accelerometers. Secondary outcome measures will include time spent in PA per day (across various intensity levels), time spent in sedentary behaviour per day, quality of life, self-efficacy and anthropometric measures to monitor weight change. Discussion - Since there are currently no published RCTs of walking interventions for adults with intellectual disabilities, this RCT will examine if a walking intervention can successfully increase PA, health and wellbeing of adults with intellectual disabilities

Quantitative analysis of tibial subchondral bone:Texture analysis outperforms conventional trabecular microarchitecture analysis

BACKGROUND: The aim of this study was to compare two different methods of quantitative assessment of tibial subchondral bone in osteoarthritis (OA): statistical texture analysis (sTA) and trabecular microarchitecture analysis (tMA).   METHODS: Asymptomatic controls aged 20-30 (n = 10), patients aged 40-50 with chronic knee pain but without established OA (n = 10) and patients aged 55-85 with advanced OA scheduled for knee replacement (n = 10) underwent knee MR imaging at 3 Tesla with a three-dimensional gradient echo sequence to allow sTA and tMA. tMA and sTA features were calculated using region of interest creation in the medial (MT) and lateral (LT) tibial subchondral bone. Features were compared between groups using one-way analysis of variance. The two most discriminating tMA and sTA features were used to construct exploratory discriminant functions to assess the ability of the two methods to classify participants.   RESULTS: No tMA features were significantly different between groups at either MT or LT. 17/20 and 11/20 sTA features were significantly different between groups at the MT/LT, respectively (P < 0.001). Discriminant functions created using tMA features classified 12/30 participants correctly (40% accuracy; 95% confidence interval [CI], 22-58%) based on MT data and 9/30 correctly (30%,; 95% CI, 14-46) based on LT data. Discriminant functions using sTA features classified 16/30 participants correctly (53%; 95% CI, 35-71) based on MT data and 14/30 correctly (47%; 95% CI, 29-65) based on LT data.   CONCLUSION: sTA features showed more significant differences between the three study groups and improved classification accuracy compared with tMA features. J. Magn. Reson. Imaging 2015

Re-engineering Nascom's network management architecture

The development of Nascom systems for ground communications began in 1958 with Project Vanguard. The low-speed systems (rates less than 9.6 Kbs) were developed following existing standards; but, there were no comparable standards for high-speed systems. As a result, these systems were developed using custom protocols and custom hardware. Technology has made enormous strides since the ground support systems were implemented. Standards for computer equipment, software, and high-speed communications exist and the performance of current workstations exceeds that of the mainframes used in the development of the ground systems. Nascom is in the process of upgrading its ground support systems and providing additional services. The Message Switching System (MSS), Communications Address Processor (CAP), and Multiplexer/Demultiplexer (MDM) Automated Control System (MACS) are all examples of Nascom systems developed using standards such as, X-windows, Motif, and Simple Network Management Protocol (SNMP). Also, the Earth Observing System (EOS) Communications (Ecom) project is stressing standards as an integral part of its network. The move towards standards has produced a reduction in development, maintenance, and interoperability costs, while providing operational quality improvement. The Facility and Resource Manager (FARM) project has been established to integrate the Nascom networks and systems into a common network management architecture. The maximization of standards and implementation of computer automation in the architecture will lead to continued cost reductions and increased operational efficiency. The first step has been to derive overall Nascom requirements and identify the functionality common to all the current management systems. The identification of these common functions will enable the reuse of processes in the management architecture and promote increased use of automation throughout the Nascom network. The MSS, CAP, MACS, and Ecom projects have indicated the potential value of commercial-off-the-shelf (COTS) and standards through reduced cost and high quality. The FARM will allow the application of the lessons learned from these projects to all future Nascom systems

MRI texture analysis of subchondral bone at the tibial plateau

OBJECTIVES: To determine the feasibility of MRI texture analysis as a method of quantifying subchondral bone architecture in knee osteoarthritis (OA).   METHODS: Asymptomatic subjects aged 20-30 (group 1, n = 10), symptomatic patients aged 40-50 (group 2, n = 10) and patients scheduled for knee replacement aged 55-85 (group 3, n = 10) underwent high spatial resolution T1-weighted coronal 3T knee MRI. Regions of interest were created in the medial (MT) and lateral (LT) tibial subchondral bone from which 20 texture parameters were calculated. T2 mapping of the tibial cartilage was performed in groups 1 and 2. Mean parameter values were compared between groups using ANOVA. Linear discriminant analysis (LDA) was used to evaluate the ability of texture analysis to classify subjects correctly.   RESULTS: Significant differences in 18/20 and 12/20 subchondral bone texture parameters were demonstrated between groups at the MT and LT respectively. There was no significant difference in mean MT or LT cartilage T2 values between group 1 and group 2. LDA demonstrated subject classification accuracy of 97 % (95 % CI 91-100 %).   CONCLUSION: MRI texture analysis of tibial subchondral bone may allow detection of alteration in subchondral bone architecture in OA. This has potential applications in understanding OA pathogenesis and assessing response to treatment.   KEY POINTS: • Improved techniques to monitor OA disease progression and treatment response are desirable • Subchondral bone (SB) may play significant role in the development of OA • MRI texture analysis is a method of quantifying changes in SB architecture • Pilot study showed that this technique is feasible and reliable • Significant differences in SB texture were demonstrated between individuals with/without OA

Direct Evidence for the Co-Expression of URP and GnRH in a Sub-Population of Rat Hypothalamic Neurones: Anatomical and Functional Correlation

Urotensin-II-related peptide (URP) is an eight amino-acid neuropeptide recently isolated from rat brain and considered as the endogenous ligand for the GPR14 receptor. Using single and double immunohistochemical labelling, in situ hybridization and ultrastructural immunocytochemistry, we explored the cellular and subcellular localization of URP in the male rat brain. URP peptide was detected in numerous varicose fibres of the median eminence (ME) and organum vasculosum laminae terminalis (OVLT) as well as in neuronal cell bodies of the medial septal nucleus and diagonal band of Broca where corresponding mRNA were also detected. Combining in situ hybridization with immunohistochemistry, we showed that cell bodies of the rat anterior hypothalamus contained both URP mRNA and GnRH peptide. In addition, double ultrastructural immunodetection of URP and GnRH peptides clearly revealed, in the median eminence, the co-localization of both peptides in the same neuronal processes in the vicinity of fenestrated portal vessels. This remarkable cellular and subcellular distribution led us to test the effect of URP on the GnRH-induced gonadotrophins release in the anterior pituitary, and to discuss its putative role at the level of the median eminence