MYCN Silencing by RNA Interference Induces Neurogenesis and Suppresses Proliferation in Models of Neuroblastoma with Resistance to Retinoic Acid

Neuroblastoma (NB) is the most common solid tumor in childhood. Twenty percent of patients display MYCN amplification, which indicates a very poor prognosis. MYCN is a highly specific target for an NB tumor therapy as MYCN expression is absent or very low in most normal cells, while, as a transcription factor, it regulates many essential cell activities in tumor cells. We aim to develop a therapy for NB based on MYCN silencing by short interfering RNA (siRNA) molecules, which can silence target genes by RNA interference (RNAi), a naturally occurring method of gene silencing. It has been shown previously that MYCN silencing can induce apoptosis and differentiation in MYCN amplified NB. In this article, we have demonstrated that siRNA-mediated silencing of MYCN in MYCN-amplified NB cells induced neurogenesis in NB cells, whereas retinoic acid (RA) treatment did not. RA can differentiate NB cells and is used for treatment of residual disease after surgery or chemotherapy, but resistance can develop. In addition, MYCN siRNA treatment suppressed growth in a MYCN-amplified NB cell line more than that by RA. Our result suggests that gene therapy using RNAi targeting MYCN can be a novel therapy toward MYCN-amplified NB that have complete or partial resistance toward RA

Gametogenesis and Spawning of Solenastrea bournoni and Stephanocoenia intersepta in Southeast Florida, USA

This study constitutes the first report of the gametogenic cycle of the scleractinian corals Solenastrea bournoni and Stephanocoenia intersepta. Tissue samples were collected near Ft. Lauderdale, Florida, USA between July 2008 and November 2009 and processed for histological examination in an effort to determine reproductive mode and potential spawning times. Both S. bournoni and S. intersepta are gonochoric, broadcast spawning species. Gametogenesis of S. bournoni began in April or May while S. intersepta had a much longer oogenic cycle that began in December with spermatogenesis beginning in July. Though spawning was not observed in situ, spawning was inferred from the decrease of late stage gametes in histological samples. In addition, histological observations of oocyte resorption and released spermatozoa were used to corroborate spawning times. Data indicate that S. bournoni spawns in September while S. intersepta spawns after the full moon in late August or early Septemb

Gametogenesis and Spawning of Solenastrea bournoni and Stephanocoenia intersepta in Southeast Florida, USA

This study constitutes the first report of the gametogenic cycle of the scleractinian corals Solenastrea bournoni and Stephanocoenia intersepta. Tissue samples were collected near Ft. Lauderdale, Florida, USA between July 2008 and November 2009 and processed for histological examination in an effort to determine reproductive mode and potential spawning times. Both S. bournoni and S. intersepta are gonochoric, broadcast spawning species. Gametogenesis of S. bournoni began in April or May while S. intersepta had a much longer oogenic cycle that began in December with spermatogenesis beginning in July. Though spawning was not observed in situ, spawning was inferred from the decrease of late stage gametes in histological samples. In addition, histological observations of oocyte resorption and released spermatozoa were used to corroborate spawning times. Data indicate that S. bournoni spawns in September while S. intersepta spawns after the full moon in late August or early Septemb

An evaluation of the effect of an educational intervention for Australian social workers on competence in delivering brief cognitive behavioural strategies: A randomised controlled trial

Background: Broad community access to high quality evidence-based primary mental health care is an ongoing challenge around the world. In Australia one approach has been to broaden access to care by funding psychologists and other allied health care professionals to deliver brief psychological treatments to general practitioners' patients. To date, there has been a scarcity of studies assessing the efficacy of social worker delivered psychological strategies. This study aims to build the evidence base by evaluating the impact of a brief educational intervention on social workers' competence in delivering cognitive behavioural strategies (strategies derived from cognitive behavioural therapy). Methods. A randomised controlled trial design was undertaken with baseline and one-week follow-up measurement of both objective and self-perceived competence. Simulated consultations with standardised depressed patients were recorded on videotape and objective competence was assessed by blinded reviewers using the Cognitive Therapy Scale. Questionnaires completed by participants were used to measure self-perceived competence. The training intervention was a 15 hour face-to-face course involving presentations, video example consultations, written materials and rehearsal of skills in pairs. Results. 40 Melbourne-based (Australia) social workers enrolled and were randomised and 9 of these withdrew from the study before the pre training simulated consultation. 30 of the remaining 31 social workers (97%) completed all phases of the intervention and evaluation protocol (16 from intervention and 14 from control group). The intervention group showed significantly greater improvements than the control group in objective competence (mean improvement of 14.2 (7.38-21.02) on the 66 point Cognitive Therapy Scale) and in subjective confidence (mean improvement of 1.28 (0.84-1.72) on a 5 point Likert scale). On average, the intervention group improved from below to above the base competency threshold on the Cognitive Therapy Scale whilst the control group remained below. Conclusions. Social workers can attain significant improvements in competency in delivering cognitive behavioural strategies from undertaking brief face to face training. This is relevant in the context of health reforms that involve social worker delivery of evidence based psychological care. Further research is required to assess how these improvements in competence translate into performance in practice and clinical outcomes for patients

Study protocol for a randomised controlled trial of internet-based cognitive-behavioural therapy for obsessive-compulsive disorder.

Obsessive-Compulsive Disorder (OCD) is a common chronic psychiatric disorder that constitutes a leading cause of disability. Although Cognitive-Behaviour Therapy (CBT) has been shown to be an effective treatment for OCD, this specialised treatment is unavailable to many due to access issues and the social stigma associated with seeing a mental health specialist. Internet-based psychological treatments have shown to provide effective, accessible and affordable treatment for a range of anxiety disorders, and two Randomised Controlled Trials (RCTs) have demonstrated the efficacy and acceptability of internet-based CBT (iCBT) for OCD, as compared to waitlist or supportive therapy. Although these initial findings are promising, they do not isolate the specific effect of iCBT. This paper details the study protocol for the first randomised control trial evaluating the efficacy of therapist-assisted iCBT for OCD, as compared to a matched control intervention; internet-based therapist-assisted progressive relaxation training (iPRT). It will aim to examine whether therapist-assisted iCBT is an acceptable and efficacious treatment, and to examine how effectiveness is influenced by patient characteristics

Optimising allied health psychological treatments in primary health care: Piloting a randomised controlled trial of social worker training in focused psychological strategies (The SW-fps Study)

The SW-fps Study was part of a broader body of research which aims to improve access to evidence-based psychological treatments in primary health care. Over the last decade, major mental health reforms in Australia, such as the Better Outcomes and Better Access programs, have greatly increased community access to psychological treatments through a range of funding models designed to support provision of psychological treatments by allied health providers. More recently social workers, amongst other allied health professionals, are beginning to utilise the Medicare incentives to provide psychological treatments in primary mentalThe research reported in this paper is a project of the Australian Primary Health Care Research Institute, which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research, Evaluation and Development Strategy

Cellular Hydraulics Suggests a Poroelastic Cytoplasm Rheology

The cytoplasm represents the largest part of the cell by volume and hence its rheology sets the rate at which cellular shape change can occur. Recent experimental evidence suggests that cytoplasmic rheology can be described using a poroelastic formulation in which the cytoplasm is considered a biphasic material constituted of a porous elastic solid meshwork (cytoskeleton, organelles, macromolecules) bathed in an interstitial fluid (cytosol). In this picture, the rate of cellular deformation is limited by the rate at which intracellular water can redistribute within the cytoplasm. Though this is a conceptually attractive model, direct supporting evidence has been lacking. Here we present such evidence and directly validate this concept to explain cellular rheology at physiologically relevant time-scales using microindentation tests in conjunction with mechanical, chemical and genetic treatments. Our results show that water redistribution through the solid phase of cytoplasm (cytoskeleton and crowders) plays a fundamental role in setting cellular rheology.Engineering and Applied Science

The cytoplasm of living cells behaves as a poroelastic material

The cytoplasm is the largest part of the cell by volume and hence its rheology sets the rate at which cellular shape changes can occur. Recent experimental evidence suggests that cytoplasmic rheology can be described by a poroelastic model, in which the cytoplasm is treated as a biphasic material consisting of a porous elastic solid meshwork (cytoskeleton, organelles, macromolecules) bathed in an interstitial fluid (cytosol). In this picture, the rate of cellular deformation is limited by the rate at which intracellular water can redistribute within the cytoplasm. However, direct supporting evidence for the model is lacking. Here we directly validate the poroelastic model to explain cellular rheology at physiologically relevant timescales using microindentation tests in conjunction with mechanical, chemical and genetic treatments. Our results show that water redistribution through the solid phase of the cytoplasm (cytoskeleton and macromolecular crowders) plays a fundamental role in setting cellular rheology