Specific Oncogenic Activity of the Src-Family Tyrosine Kinase c-Yes in Colon Carcinoma Cells

c-Yes, a member of the Src tyrosine kinase family, is found highly activated in colon carcinoma but its importance relative to c-Src has remained unclear. Here we show that, in HT29 colon carcinoma cells, silencing of c-Yes, but not of c-Src, selectively leads to an increase of cell clustering associated with a localisation of β-catenin at cell membranes and a reduction of expression of β-catenin target genes. c-Yes silencing induced an increase in apoptosis, inhibition of growth in soft-agar and in mouse xenografts, inhibition of cell migration and loss of the capacity to generate liver metastases in mice. Re-introduction of c-Yes, but not c -Src, restores transforming properties of c-Yes depleted cells. Moreover, we found that c-Yes kinase activity is required for its role in β-catenin localisation and growth in soft agar, whereas kinase activity is dispensable for its role in cell migration. We conclude that c-Yes regulates specific oncogenic signalling pathways important for colon cancer progression that is not shared with c-Src

The STRANDS project: long-term autonomy in everyday environments

Thanks to the efforts of the robotics and autonomous systems community, the myriad applications and capacities of robots are ever increasing. There is increasing demand from end users for autonomous service robots that can operate in real environments for extended periods. In the Spatiotemporal Representations and Activities for Cognitive Control in Long-Term Scenarios (STRANDS) project (http://strandsproject.eu), we are tackling this demand head-on by integrating state-of-the-art artificial intelligence and robotics research into mobile service robots and deploying these systems for long-term installations in security and care environments. Our robots have been operational for a combined duration of 104 days over four deployments, autonomously performing end-user-defined tasks and traversing 116 km in the process. In this article, we describe the approach we used to enable long-term autonomous operation in everyday environments and how our robots are able to use their long run times to improve their own performance

Perceptual abstraction and attention

This is a report on the preliminary achievements of WP4 of the IM-CleVeR project on abstraction for cumulative learning, in particular directed to: (1) producing algorithms to develop abstraction features under top-down action influence; (2) algorithms for supporting detection of change in motion pictures; (3) developing attention and vergence control on the basis of locally computed rewards; (4) searching abstract representations suitable for the LCAS framework; (5) developing predictors based on information theory to support novelty detection. The report is organized around these 5 tasks that are part of WP4. We provide a synthetic description of the work done for each task by the partners

Multicenter evaluation of the clinical utility of laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass

Background and Aims The obesity epidemic has led to increased use of Roux-en-Y gastric bypass (RYGB). These patients have an increased incidence of pancreaticobiliary diseases yet standard ERCP is not possible due to surgically altered gastroduodenal anatomy. Laparoscopic-ERCP (LA-ERCP) has been proposed as an option but supporting data are derived from single center small case-series. Therefore, we conducted a large multicenter study to evaluate the feasibility, safety, and outcomes of LA-ERCP. Methods This is retrospective cohort study of adult patients with RYGB who underwent LA-ERCP in 34 centers. Data on demographics, indications, procedure success, and adverse events were collected. Procedure success was defined when all of the following were achieved: reaching the papilla, cannulating the desired duct and providing endoscopic therapy as clinically indicated. Results A total of 579 patients (median age 51, 84% women) were included. Indication for LA-ERCP was biliary in 89%, pancreatic in 8%, and both in 3%. Procedure success was achieved in 98%. Median total procedure time was 152 minutes (IQR 109-210) with median ERCP time 40 minutes (IQR 28-56). Median hospital stay was 2 days (IQR 1-3). Adverse events were 18% (laparoscopy-related 10%, ERCP-related 7%, both 1%) with the clear majority (92%) classified as mild/moderate whereas 8% were severe and 1 death occurred. Conclusion Our large multicenter study indicates that LA-ERCP in patients with RYGB is feasible with a high procedure success rate comparable with that of standard ERCP in patients with normal anatomy. ERCP-related adverse events rate is comparable with conventional ERCP, but the overall adverse event rate was higher due to the added laparoscopy-related events

Using the Millon Behavioral Medicine Diagnostic (MBMD) to Evaluate the Need for Mental Health Services in Association with Biomarkers of Disease Status Among HIV Positive Men and Women

Psychological distress states have been related to rate of disease progression among HIV-positive individuals. However, the measures that have been used in this research as well as the treatment context of the populations studied are highly variable, making it challenging for clinicians to incorporate such measures into screening batteries. The present study examined the association of two summary scales of the Millon Behavioral Medicine Diagnostic (MBMD; Millon et al., Millon Behavioral Medicine Diagnostic. NCS Assessments, Minneapolis, 2001), with markers of HIV disease status (CD4 and CD8 cell counts, viral load) among an ethnically diverse sample of 147 HIV-positive individuals (52 men who have sex with men, 34 men who have sex with women, and 51 women) who had recently initiated Highly Active Antiretroviral Therapy (HAART). After controlling for age and months since HIV diagnosis, we found that higher scores on the overall MBMD Psych Referral Summary Scale, reflecting a need for mental health treatment, were related to greater HIV viral load but did not relate to CD4 or CD8 cell counts. Subgroup analyses revealed that Psych Referral scores were related to greater HIV viral load only for the men who have sex with men (MSM) subgroup. These results suggest that the MBMD may help in identifying psychosocial characteristics associated with some markers of disease status in persons with HIV and perhaps may also be useful in identifying individual differences in response to treatment and eventual disease outcome

The evaluation of processed cancellous bovine bone as a bone graft substitute

Objective: To determine the ability of a novel bovine cancellous bone xenoimplant to act as an osteoconductive graft in an ovine femoral defect model. An autograft harvested from the xenoimplant site was placed in a contralateral limb defect for comparison. Material and methods: The xenoimplant used had been rendered immunologically inert by a novel defatting and deproteinating process. Following surgical implantation of cores into condylar cancellous bone defects, fluorochrome labels were administered to 12 sheep at 2 1/2, 4 1/2 and 8 weeks. Incorporation of the xenoimplants and autografts into the host bone was compared radiographically and histomorphometrically at 10 weeks. Results: Radiographically, the degree of osteointegration was comparable. Histomorphometric data, consisting of labelled surface (LS) estimates, confirmed osteoconductive properties of both the xenoimplants and autografts. Remodelling activity was greatest in the xenoimplants at 2 1/2, weeks. At 4 1/2 weeks, there was more activity in the autograft, but by 8 weeks they were performing similarly. Xenoimplant-LS estimates were comparable or greater than those of the autograft at all times. Conclusions: Processed bovine cancellous bone xenoimplants were osteoconductive in this model and show promise for development as a biomaterial in human and veterinary orthopaedic surgery

Antiepileptic drugs for older people

Epilepsy in older people is a common problem. It is estimated that in Europe there are 85 000 new cases of epilepsy annually in those over 65 years old, equivalent to an incidence of 100 per 100 000. Incidence increases with age and the rate in older people is higher than in all but the first year of life. The older population has a median prevalence of 4.7 per 1000 (range 3.0 to 7.3) from nine studies and may be underestimated by case-ascertainment bias common to many studies of older people. © 2008 Copyright Cambridge University Press.link_to_subscribed_fulltex

Reciprocal Connections Between Cortex and Thalamus Contribute to Retinal Axon Targeting to Dorsal Lateral Geniculate Nucleus

The dorsal Lateral Geniculate Nucleus (dLGN) is the primary image-forming target of the retina and shares a reciprocal connection with primary visual cortex (V1). Previous studies showed that corticothalamic input is essential for the development of thalamocortical projections, but less is known about the potential role of this reciprocal connection in the development of retinal projections. Here, we show a deficit of retinal innervation in the dLGN around E18.5 in Tra2 beta conditional knockout (cKO) cortexless mice, an age when apoptosis occurs along the thalamocortical tract and in some dLGN neurons. In vivo electrophysiology experiments in the dLGN further confirmed the loss of functional retinal input. Experiments with N-methyl-d-aspartic acid-induced V1 lesion as well as Fezf2 cKO mice confirmed that the disruption of connections between the dLGN and V1 lead to abnormal retinal projections to the dLGN. Interestingly, retinal projections to the ventral Lateral Geniculate Nucleus (vLGN) and Superior Colliculus (SC) were normal in all 3 mice models. Finally, we show that the cortexless mice had worse performance than control mice in a go-no go task with visual cues. Our results provide evidence that the wiring of visual circuit from the retina to the dLGN and V1 thereafter is coordinated at a surprisingly early stage of circuit development