Genetic and Environmental Factors in Complex Neurodevelopmental Disorders

Complex neurodevelopmental disorders, such as schizophrenia, autism, attention deficit (hyperactivity) disorder, (manic) depressive illness and addiction, are thought to result from an interaction between genetic and environmental factors. Association studies on candidate genes and genome-wide linkage analyses have identified many susceptibility chromosomal regions and genes, but considerable efforts to replicate association have been surprisingly often disappointing. Here, we summarize the current knowledge of the genetic contribution to complex neurodevelopmental disorders, focusing on the findings from association and linkage studies. Furthermore, the contribution of the interaction of the genetic with environmental and epigenetic factors to the aetiology of complex neurodevelopmental disorders as well as suggestions for future research are discussed

Process for injection moulding multilayered articles

The invention relates to a process for injection moulding of objects consisting of a number of layers of different materials, in which process the different materials ar successively and/or coaxially injected, in plasticated form, into a mould. Before being injected, the different materials are brought into a cavity (7) in the desired order and amounts, with the help of separate injection units (4-6) or by means of a distributor (3), which distributor consists of elementary modules (8-13), each of which is capable of creating a certain combination and configuration of materials in the cavity (7), upon which the contents of the cavity are injected into the mould. The invention relates also to a device for injection moulding objects consisting of a number of layers of different materials

Report of the Sydney Women and Sexual Health (SWASH) Survey 2006, 2008, 2010, 2012, 2014

The Sydney Women and Sexual Health (SWASH) survey is a comprehensive survey of important health issues relevant to lesbian, bisexual and queer (LBQ) women including sexual health and wellbeing, violence, mental health, tobacco use, illicit drug use, alcohol consumption, and cancer screening behaviours. This report presents results from surveys conducted at the Sydney Gay and Lesbian Mardi Gras Fair Day and other community events and venues during the Sydney Gay and Lesbian Mardi Gras seasons in 2006, 2008, 2010, 2012, and 2014. It highlights several health issues of particular concern – many of which have persisted over time – where mainstream preventive health interventions that are inclusive of this group or targeted to LBQ, are needed.ACON (formerly the AIDS Council of NSW) is NSW’s leading health promotion organisation specialising in HIV prevention, care and support, and lesbian, gay, bisexual, transgender and intersex (LGBTI) health

Kinetics of neuroendocrine differentiation in an androgen-dependent human prostate xenograft model

It was previously shown in the PC-295 xenograft that the number of chromogranin A (CgA)-positive neuroendocrine (NE) cells increased after androgen withdrawal. NE cells did not proliferate and differentiated from G0-phase-arrested cells. Here we further characterized NE differentiation, androgen receptor status, and apoptosis-associated Bcl-2 expression in the PC-295 model after androgen withdrawal to assess the origin of NE cells. PC-295 tumor volumes decreased by 50% in 4 days. Intraperitoneal bromodeoxyuridine (BrdU) incorporation and MIB-1 labeling decreased to 0%, and the apoptosis was maximal at day 4. Androgen receptor expression and prostate-specific antigen (PSA) serum levels decreased rapidly within 2 days. The number of NE cells increased 6-fold at day 4 and 30-fold at day 7. Five and ten percent of the CgA-positive cells were BrdU positive after continuous BrdU labeling for 2 and 4 days, respectively. However, no MIB-1 expression was observed in CgA-positive cells. NE cells expressed the regulated secretory pathway marker secretogranin III but were negative for androgen receptor and Bcl-2. Bcl-2 expression did increase in the non-NE tumor cells. In conclusion, androgen withdrawal leads to a rapid PC-295 tumor regression and a proliferation-independent induction of NE differentiation. The strictly androgen-independent NE cells that were still present after 21 days differentiated mainly from G0-phase-arrested cells

PhP.B enhanced adeno-associated virus mediated-expression following systemic delivery or direct brain administration

Of the adeno-associated viruses (AAVs), AAV9 is known for its capability to cross the blood-brain barrier (BBB) and can, therefore, be used as a noninvasive method to target the central nervous system. Furthermore, the addition of the peptide PhP.B to AAV9 increases its transduction across the BBB by 40-fold. Another neurotropic serotype, AAV5, has been shown as a gene therapeutic delivery vehicle to ameliorate several neurodegenerative diseases in preclinical models, but its administration requires invasive surgery. In this study, AAV9-PhP.B and AAV5-PhP.B were designed and produced in an insect cell-based system. To AAV9, the PhP.B peptide TLAVPFK was added, whereas in AAV5-PhP.B (AQTLAVPFKAQAQ), with AQ-AQAQ sequences used to swap with the corresponding sequence of AAV5. The addition of PhP.B to AAV5 did not affect its capacity to cross the mouse BBB, while increased transduction of liver tissue was observed. Then, intravenous (IV) and intrastriatal (IStr) delivery of AAV9-PhP.B and AAV5 were compared. For AAV9-PhP.B, similar transduction and expression levels were achieved in the striatum and cortex, irrespective of the delivery method used. IStr administration of AAV5 resulted in significantly higher amounts of vector DNA and therapeutic miRNA in the target regions such as striatum and cortex when compared with an IV administration of AAV9-PhP.B. These results illustrate the challenge in developing a vector that can be delivered noninvasively while achieving a transduction level similar to that of direct administration of AAV5. Thus, for therapeutic miRNA delivery with high local expression requirements, intraparenchymal delivery of AAV5 is preferred, whereas a humanized AAV9-PhP.B may be useful when widespread brain (and peripheral) transduction is needed.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Portfolio of compositions

My Masters research has been to the aim of my development as a composer of original music with an individual voice that is nonetheless informed by the musical and aesthetic currents alive in our contemporary society. This paper is an exegesis on my portfolio of compositions, written during my Masters candidature from 2006-08, in which I pursue a generally-consistent language towards a music that situates itself across a number of dualities with the aim to resolve their opposing strands, while exploring a wide range of thematic and philosophical concerns. The musical analyses contained within demonstrate my compositional technical apparatus which bridges between microstructural cellular detail and an organically unified whole, and promotes a consideration of metaphorical issues that arise through further aesthetic contemplation

Circulating tumor cell enumeration and characterization in metastatic castration-resistant prostate cancer patients treated with cabazitaxel

(1) Background: Markers identifying which patients with metastatic, castration-resistant prostate cancer (mCRPC) will benefit from cabazitaxel therapy are currently lacking. Therefore, the aim of this study was to identify markers associated with outcome to cabazitaxel therapy based on counts and gene expression profiles of circulating tumor cells (CTCs). (2) Methods: From 120 mCRPC patients, CellSearch enriched CTCs were obtained at baseline and after 6 weeks of cabazitaxel therapy. Furthermore, 91 genes associated with prostate cancer were measured in mRNA of these CTCs. (3) Results: In 114 mCRPC patients with an evaluable CTC count, the CTC count was independently associated with poor progression-free survival (PFS) and overall survival (OS) in multivariable analysis with other commonly used variables associated with outcome in mCRPC (age, prostate specific antigen (PSA), alkaline phosphatase, lactate dehydrogenase (LDH), albumin, hemoglobin), together with alkaline phosphatase and hemoglobin. A five-gene expression profile was generated to predict for outcome to cabazitaxel therapy. However, even though this signature was associated with OS in univariate analysis, this was not the case in the multivariate analysis for OS nor for PFS. (4) Conclusion: The established five-gene expression profile in CTCs was not independently associated with PFS nor OS. However, along with alkaline phosphatase and hemoglobin, CTC-count is independently associated with PFS and OS in mCRPC patients who are treated with cabazitaxel

Neuronenweek 29 November - 3 November

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