Multiplex PCR and Next Generation Sequencing for the Non-Invasive Detection of Bladder Cancer

Highly sensitive and specific urine-based tests to detect either primary or recurrent bladder cancer have proved elusive to date. Our ever increasing knowledge of the genomic aberrations in bladder cancer should enable the development of such tests based on urinary DNA

Study on Gas Permeation and CO2 Separation through Ionic Liquid Based Membranes with Siloxane-Functionalized Cations

This work explores ionic liquid-based membranes with siloxane functionalized cations using two different approaches: supported ionic liquid membranes (SILMs) and poly(ionic liquid)–ionic liquid (PIL–IL) composite membranes. Their CO2, CH4, and N2 permeation properties were measured at T = 293 K with a trans-membrane pressure differential of 100 kPa. The thermophysical properties of the synthesized siloxane-functionalized ILs, namely viscosity and density (data in the Supporting Information), were also determined. Contrary to what was expected, the gas permeation results show that the SILMs containing siloxane-functionalized cations have CO2 permeabilities that are lower than those of their analogues without the siloxane functionality. The addition of siloxane-based ILs into PILs increases both CO2 permeability and CO2/N2 permselectivity, although it does not significantly change the CO2/CH4 permselectivity. The prepared membranes present very diverse CO2 permeabilities, between 57 and 568 Barrer, while they show permselectivities varying from 16.8 to 36.8 for CO2/N2 and from 9.8 to 11.5 for CO2/CH4. As observed for other ILs, superior CO2 separation performances were obtained when the IL containing [C(CN)3]− is used compared to that having the [NTf2]− anion

The Distress Thermometer and Its Validity: A First Psychometric Study in Indonesian Women with Breast Cancer.

Purpose: This study aims to translate the Distress Thermometer (DT) into Indonesian, test its validity in Indonesian women with breast cancer and determine norm scores of the Indonesian DT for clinically relevant distress. Methods: First, the original version of the DT was translated using a forward and backward translation procedure according to the guidelines. Next, a group of 120 breast cancer patients who were treated at the Outpatient Surgical Oncology Clinic in Hasan Sadikin Hospital in Indonesia completed a standard socio-demographic form, the DT and the Problem List, the Hospital Anxiety and Depression Scale (HADS) and the WHO Quality of Life (WHOQOL-BREF). Results: Receiver operating characteristic (ROC) curve analyses identified an area under the curve = 0.81 when compared to the HADS cutoff score of 15. A cutoff score of 5 on the DT had the best sensitivity (0.81) and specificity (0.64). Patients who scored above this cutoff reported more problems in the practical, family, emotional, spiritual/religious and physical domains (30 out of 36 problems, p-value<0.05) than patients below the cutoff score. Patients at advanced stages of cancer experienced more emotional and physical problems. Patient's distress level was negatively correlated with overall quality of life, general health and all quality of life domains. Conclusions: The DT was found to be a valid tool for screening distress in Indonesian breas

Examining the relationship between early axon growth and transcription factor expression in the developing cerebral cortex

The transcription factors Satb2 (special AT-rich sequence binding protein 2) and Ctip2 (COUP-TF interacting protein 2) have been shown to be required for callosal and corticospinal axon growth respectively from subtypes of cerebral cortex projection neurons. In this study we investigated early stages of directed axon growth in the embryonic mouse cerebral cortex, and studied the possible correlation with the expression of Satb2 and Ctip2. Electroporation of an EYFP-expressing plasmid at embryonic day13.5 to label developing projection neurons revealed that directed axon growth is first seen in radially migrating neurons in the intermediate zone (IZ), prior to migration into the cortical plate, as has been suggested previously. Onset of expression of SATB2 and CTIP2 was also observed in the IZ, correlating well with this stage of migration and initiation of axon growth. Immunohistochemical staining through embryonic and early postnatal development revealed a significant population of Satb2/Ctip2 co-expressing cells, while retrograde axon tracing from the corpus callosum at embryonic day18.5 back-labelled many neurons with bi-directional axon processes. However, through retrograde tracing and simultaneous immunohistochemical staining we show that these bi-directional processes do not correlate with Satb2/Ctip2 co-expression. Our work shows that although expression of these transcription factors correlates well with the appearance of directed axon growth during cortical development, the transcriptional code underlying the bi-directional axonal projections of early neocortical neurons is not likely to be the result of Satb2/Ctip2 co-expression. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society

Laf4/Aff3, a gene involved in intellectual disability, is required for cellular migration in the mouse cerebral cortex.

Members of the AFF (AF4/FMR2) family of putative transcription factors are involved in infant acute leukaemia and intellectual disability (ID), although very little is known about their transcriptional targets. For example, deletion of human lymphoid nuclear protein related to AF4/AFF member 3 (LAF4/AFF3) is known to cause severe neurodevelopmental defects, and silencing of the gene is also associated with ID at the folate-sensitive fragile site (FSFS) FRA2A; yet the normal function of this gene in the nervous system is unclear. The aim of this study was to further investigate the function of Laf4 in the brain by focusing on its role in the cortex. By manipulating expression levels in organotypic slices, we demonstrate here that Laf4 is required for normal cellular migration in the developing cortex and have subsequently identified Mdga2, an important structural protein in neurodevelopment, as a target of Laf4 transcriptional activity. Furthermore, we show that the migration deficit caused by loss of Laf4 can be partially rescued by Mdga2 over-expression, revealing an important functional relationship between these genes. Our study demonstrates the key transcriptional role of Laf4 during early brain development and reveals a novel function for the gene in the process of cortical cell migration relevant to the haploinsufficiency and silencing observed in human neurodevelopmental disorders

GABAergic interneurons form transient layer-specific circuits in early postnatal neocortex

GABAergic interneurons play key roles in cortical circuits, yet little is known about their early connectivity. Here we use glutamate uncaging and a novel optogenetic strategy to track changes in the afferent and efferent synaptic connections of developing neocortical interneuron subtypes. We find that Nkx2-1-derived interneurons possess functional synaptic connections prior to emerging pyramidal cell networks. Subsequent interneuron circuit maturation is both subtype and layer dependent. Glutamatergic input onto fast spiking (FS), but not somatostatin-positive, non-FS interneurons increases over development. Interneurons of both subtype located in layers (L)4 and L5b engage in transient circuits that disappear after the somatosensory critical period. These include a pathway mediated by L5b somatostatin-positive interneurons that specifically targets L4 during the first postnatal week. The innervation patterns of immature cortical interneuron circuits are thus neither static nor progressively strengthened but follow a layer-specific choreography of transient connections that differ from those of the adult brain

Disruption of Visc-2, a Brain-Expressed Conserved Long Noncoding RNA, Does Not Elicit an Overt Anatomical or Behavioral Phenotype.

Although long noncoding RNAs (lncRNAs) are proposed to play essential roles in mammalian neurodevelopment, we know little of their functions from their disruption in vivo. Combining evidence for evolutionary constraint and conserved expression data, we previously identified candidate lncRNAs that might play important and conserved roles in brain function. Here, we demonstrate that the sequence and neuronal transcription of lncRNAs transcribed from the previously uncharacterized Visc locus are conserved across diverse mammals. Consequently, one of these lncRNAs, Visc-2, was selected for targeted deletion in the mouse, and knockout animals were subjected to an extremely detailed anatomical and behavioral characterization. Despite a neurodevelopmental expression pattern of Visc-2 that is highly localized to the cortex and sites of neurogenesis, anomalies in neither cytoarchitecture nor neuroproliferation were identified in knockout mice. In addition, no abnormal motor, sensory, anxiety, or cognitive behavioral phenotypes were observed. These results are important because they contribute to a growing body of evidence that lncRNA loci contribute on average far less to brain and biological functions than protein-coding loci. A high-throughput knockout program focussing on lncRNAs, similar to that currently underway for protein-coding genes, will be required to establish the distribution of their organismal functions