Evaluation of the effects of titanium dioxide nanoparticles on cultured Rana catesbeiana tailfin tissue

Nanoparticles (NPs), materials that have one dimension less than 100 nm, are used in manufacturing, health, and food products, and consumer products including cosmetics, clothing, and household appliances. Their utility to industry is derived from their high surface-area-to-volume ratios and physico-chemical properties distinct from their bulk counterparts, but the near-certainty that NPs will be released into the environment raises the possibility that they could present health risks to humans and wildlife. The thyroid hormones (THs), thyroxine, and 3,3′,5-triiodothyronine (T(3)), are involved in development and metabolism in vertebrates including humans and frogs. Many of the processes of anuran metamorphosis are analogous to human post-embryonic development and disruption of TH action can have drastic effects. These shared features make the metamorphosis of anurans an excellent model for screening for endocrine disrupting chemicals (EDCs). We used the cultured tailfin (C-fin) assay to examine the exposure effects of 0.1–10 nM (~8–800 ng/L) of three types of ~20 nm TiO(2) NPs (P25, M212, M262) and micron-sized TiO(2) (μ TiO(2)) ±10 nM T(3). The actual Ti levels were 40.9–64.7% of the nominal value. Real-time quantitative polymerase chain reaction (QPCR) was used to measure the relative amounts of mRNA transcripts encoding TH-responsive THs receptors (thra and thrb) and Rana larval keratin type I (rlk1), as well as the cellular stress-responsive heat shock protein 30 kDa (hsp30), superoxide dismutase (sod), and catalase (cat). The levels of the TH-responsive transcripts were largely unaffected by any form of TiO(2). Some significant effects on stress-related transcripts were observed upon exposure to micron-sized TiO(2), P25, and M212 while no effect was observed with M262 exposure. Therefore, the risk of adversely affecting amphibian tissue by disrupting TH-signaling or inducing cellular stress is low for these compounds relative to other previously-tested NPs

Predicting speech-sound disorder outcomes in school-age children with hearing loss : The VicCHILD experience

Background Congenital hearing loss is the most common birth anomaly, typically influencing speech and language development, with potential for later academic, social and employment impacts. Yet, surprisingly, the nuances of how speech is affected have not been well examined with regards to the subtypes of speech-sound disorder (SSD). Nor have the predictors of speech outcome been investigated within a sizeable population cohort. Aims (1) To describe the subtypes and prevalence of SSD in children with hearing loss. (2) To determine which characteristics of hearing loss predict the presence of SSD. Methods & Procedures A total of 90 children (5–12 years of age) with permanent hearing loss were recruited from an Australian population cohort. Children completed a standardized speech assessment to determine the presence and subtype of SSD. Logistic regression was used to determine the predictors of speech outcome. Demographic, developmental and hearing-related predictors were examined. Outcomes & Results The prevalence of speech disorder overall was 58%, with the most common subtype being phonological delay in 49% of the sample. Factors most predictive of speech disorder were being male, younger and a bimodal user (i.e., using both a hearing aid and a cochlear implant). Conclusions & Implications This is the first study, in a sizeable cohort, to describe the prevalence and predictive factors for SSD associated with hearing loss. Clinically, it could be beneficial to implement earlier targeted phonological interventions for children with hearing loss

Vaccinia virus GLV-1h153 is a novel agent for detection and effective local control of positive surgical margins for breast cancer

Introduction: Surgery is currently the definitive treatment for early-stage breast cancer. However, the rate of positive surgical margins remains unacceptably high. The human sodium iodide symporter (hNIS) is a naturally occurring protein in human thyroid tissue, which enables cells to concentrate radionuclides. The hNIS has been exploited to image and treat thyroid cancer. We therefore investigated the potential of a novel oncolytic vaccinia virus GLV1h-153 engineered to express the hNIS gene for identifying positive surgical margins after tumor resection via positron emission tomography (PET). Furthermore, we studied its role as an adjuvant therapeutic agent in achieving local control of remaining tumors in an orthotopic breast cancer model. Methods: GLV-1h153, a replication-competent vaccinia virus, was tested against breast cancer cell lines at various multiplicities of infection (MOIs). Cytotoxicity and viral replication were determined. Mammary fat pad tumors were generated in athymic nude mice. To determine the utility of GLV-1h153 in identifying positive surgical margins, 90% of the mammary fat pad tumors were surgically resected and subsequently injected with GLV-1h153 or phosphate buffered saline (PBS) in the surgical wound. Serial Focus 120 microPET images were obtained six hours post-tail vein injection of approximately 600 mu Ci of I-124-iodide. Results: Viral infectivity, measured by green fluorescent protein (GFP) expression, was time-and concentrationdependent. All cell lines showed less than 10% of cell survival five days after treatment at an MOI of 5. GLV-1h153 replicated efficiently in all cell lines with a peak titer of 27 million viral plaque forming units (PFU) ( < 10,000-fold increase from the initial viral dose) by Day 4. Administration of GLV-1h153 into the surgical wound allowed positive surgical margins to be identified via PET scanning. In vivo, mean volume of infected surgically resected residual tumors four weeks after treatment was 14 mm(3) versus 168 mm(3) in untreated controls (P < 0.05). Conclusions: This is the first study to our knowledge to demonstrate a novel vaccinia virus carrying hNIS as an imaging tool in identifying positive surgical margins of breast cancers in an orthotopic murine model. Moreover, our results suggest that GLV-1h153 is a promising therapeutic agent in achieving local control for positive surgical margins in resected breast tumors

The Financial Sector and Deregulation in Australia: Drivers of Reform or Reluctant Followers?

This paper argues that contrary to capture theory, a key feature of financial deregulation in Australia was the lack of support from financial sector interest groups. An examination of the Campbell Inquiry (1979-1981) reveals that deregulation was not initiated by either the regulated banks or unregulated non-bank financial institutions (NBFIs). In fact, both groups were resistant to change prior to the establishment of the Inquiry. During the Inquiry, neither group advocated wide-ranging deregulation, preferring the retention of many financial regulations.Financial deregulation, banks, non-bank financial institutions, Campbell Inquiry,

Ndfip1 is expressed in dopaminergic neurons containing α-synuclein deposits.

<p>(A) Bright field image of dopaminergic neurons in the substantia nigra of a PD brain. (B–D) Fluorescent labelling of α-synuclein and Ndfip1 from the bright field image shows deposits of α-synuclein which co-label with Ndfip1 in a dopaminergic neuron (arrow). Asterisk marks a dopaminergic neuron with neither α-synuclein nor Ndfip1 positive labelling. (E) Fluorescent labelling of Ndfip1 in a control brain. Scale bar: 25 µm.</p

Ndfip1 and DMT1 are expressed in dopaminergic neurons of the substantia nigra.

<p>(A) Quantification of neuromelanin levels from the substantia nigra of control and PD brains showed a significant decrease in PD, indicating a loss of dopaminergic neurons. (B) Ndfip1 is expressed (arrows) in some but not all dopaminergic neurons of the substantia nigra (brown pigment represents neuromelanin). (C) High power image of Ndfip1 staining of dopaminergic neurons showed a predominant cytoplasmic distribution. Asterisks in B and C show dopaminergic neurons with no Ndfip1 staining. (D) Quantification of Ndfip1 positive dopaminergic neurons of the substantia nigra showed no significant difference between control and PD brains. (E) DMT1 is expressed in the cytoplasm (arrows) of dopaminergic neurons of the substantia nigra. Scale bars: 100 µm (B, E), 25 µm (C). (A, D) Values are the mean ±SD, * p<0.05 Mann Whitney U tests.</p

Loss of Ndfip1 results in misregulation of DMT1 and increased susceptibility to iron induced death.

<p>(A) Staining of mouse dopaminergic neurons in culture showed that genetic deletion of Ndfip1 (Ndfip1^−/−) resulted in increased DMT1 staining compared to wild type (Ndfip1^+/+) dopaminergic neurons. (B) Increasing concentrations of iron resulted in a significant increase in dopaminergic neuronal cell death in Ndfip1 knockout neurons compared to wild type controls. Values are means ±SEM, ** p<0.005, *** p<0.001 un-paired Student t-test. Scale bar: 10 µm.</p

Ndfip1 is upregulated in the substantia nigra of PD brains.

<p>(A) Western blotting for Ndfip1 in the substantia nigra (SN) in both control and PD brains. (B) Quantification of Ndfip1 levels showed a significant increase of Ndfip1 in the substantia nigra of PD brains. (C) Iron content was analysed using ICP-MS on brain tissue from the substantia nigra of control and PD brains, a significant increase in iron levels in PD brains was observed. (D) Western blotting of Ndfip1 levels in the cortex of both control and PD brains. (E) Quantification of Ndfip1 levels showed no significant increase in Ndfip1 in the cortex in PD. (F) ICP-MS analysis for iron levels in the cortex showed no increase in iron concentrations between control and PD brains. (B, C, E, F) Values are means ±SEM, * p<0.05 un-paired Student t-test.</p

Ndfip1 is expressed in GFAP positive cells of the substantia nigra in PD.

<p>(A) Low power image of control brain showing no co-labelling of Ndfip1 (red) or GFAP (green) in the same cell (arrows). (B) Low power image of a PD brain showing co-labelling of Ndfip1 (red) with GFAP (green) in the same cell (arrows). (C-C″) High power image shows Ndfip1 (red) and GFAP (green) positive staining in the substantia nigra of the PD brain. (D) Quantification of GFAP-immunopositive cells co-labelled with Ndfip1 in substantia nigra of both control and PD brains. (D) Values are the mean ±SD, * p<0.05 Mann Whitney U tests. Scale bars: 50 µm (A, B), 10 µm (C).</p