Genetic and gene expression analyses of the polycystic ovary syndrome candidate gene fibrillin-3 and other fibrillin family members in human ovaries

Several studies have demonstrated an association between polycystic ovary syndrome (PCOS) and the dinucleotide repeat microsatellite marker D19S884, which is located in intron 55 of the fibrillin-3 (FBN3) gene. Fibrillins, including FBN1 and 2, interact with latent transforming growth factor (TGF)-β-binding proteins (LTBP) and thereby control the bioactivity of TGFβs. TGFβs stimulate fibroblast replication and collagen production. The PCOS ovarian phenotype includes increased stromal collagen and expansion of the ovarian cortex, features feasibly influenced by abnormal fibrillin expression. To examine a possible role of fibrillins in PCOS, particularly FBN3, we undertook tagging and functional single nucleotide polymorphism (SNP) analysis (32 SNPs including 10 that generate non-synonymous amino acid changes) using DNA from 173 PCOS patients and 194 controls. No SNP showed a significant association with PCOS and alleles of most SNPs showed almost identical population frequencies between PCOS and control subjects. No significant differences were observed for microsatellite D19S884. In human PCO stroma/cortex (n = 4) and non-PCO ovarian stroma (n = 9), follicles (n = 3) and corpora lutea (n = 3) and in human ovarian cancer cell lines (KGN, SKOV-3, OVCAR-3, OVCAR-5), FBN1 mRNA levels were approximately 100 times greater than FBN2 and 200–1000-fold greater than FBN3. Expression of LTBP-1 mRNA was 3-fold greater than LTBP-2. We conclude that FBN3 appears to have little involvement in PCOS but cannot rule out that other markers in the region of chromosome 19p13.2 are associated with PCOS or that FBN3 expression occurs in other organs and that this may be influencing the PCOS phenotype.

Partial agonists of the [alpha]3[beta]4[ast] neuronal nicotinic acetylcholine receptor reduce ethanol consumption and seeking in rats

Alcohol use disorders (AUDs) impact millions of individuals and there remain few effective treatment strategies. Despite evidence that neuronal nicotinic acetylcholine receptors (nAChRs) have a role in AUDs, it has not been established which subtypes of the nAChR are involved. Recent human genetic association studies have implicated the gene cluster CHRNA3-CHRNA5-CHRNB4 encoding the α3, α5, and β4 subunits of the nAChR in susceptibility to develop nicotine and alcohol dependence; however, their role in ethanol-mediated behaviors is unknown due to the lack of suitable and selective research tools. To determine the role of the α3, and β4 subunits of the nAChR in ethanol self-administration, we developed and characterized high-affinity partial agonists at α3β4 nAChRs, CP-601932, and PF-4575180. Both CP-601932 and PF-4575180 selectively decrease ethanol but not sucrose consumption and operant self-administration following long-term exposure. We show that the functional potencies of CP-601932 and PF-4575180 at α3β4 nAChRs correlate with their unbound rat brain concentrations, suggesting that the effects on ethanol self-administration are mediated via interaction with α3β4 nAChRs. Also varenicline, an approved smoking cessation aid previously shown to decrease ethanol consumption and seeking in rats and mice, reduces ethanol intake at unbound brain concentrations that allow functional interactions with α3β4 nAChRs. Furthermore, the selective α4β2(*) nAChR antagonist, DHβE, did not reduce ethanol intake. Together, these data provide further support for the human genetic association studies, implicating CHRNA3 and CHRNB4 genes in ethanol-mediated behaviors. CP-601932 has been shown to be safe in humans and may represent a potential novel treatment for AUDs.

Early intervention music therapy : reporting on a 3-year project to address needs with at-risk families

Sing & Grow is an early intervention music therapy project presented to families with additional needs, or those at risk of experiencing disadvantage due to social and/or economic circumstances that may impact on their parenting experiences. The aim of the project is to provide short term music therapy programs to families in communities where access to such services may be limited. The program is strengths-based and focuses on building upon a parent’s capacity to relate to and respond to their child’s emotional and developmental needs.

Microscopic and spectroscopic investigation of poly(3-hexylthiophene) interaction with carbon nanotubes

The inclusion of carbon nanotubes in polymer matrix has been proposed to enhance the polymer’s physical and electrical properties. In this study, microscopic and spectroscopic techniques are used to investigate the interaction between poly(3-hexylthiophene) (P3HT) and nanotubes and the reciprocal modification of physical properties. The presence of P3HT-covered nanotubes dispersed in the polymer matrix has been observed by atomic force microscopy and transmission electron microscopy. Then, the modification of P3HT optical properties due to nanotube inclusion has been evidenced with spectroscopic techniques like absorption and Raman spectroscopy. The study is completed with detailed nanoscale analysis by scanning probe techniques. The ordered self assembly of polymer adhering on the nanotube is unveiled by showing an example of helical wrapping of P3HT. Scanning tunneling spectroscopy study provides information on the electronic structure of nanotube-polymer assembly, revealing the charge transfer from P3HT to the nanotube.

Mutations in exon 3 of the beta-catenin gene are rare in melanoma cell lines

Mutations in exon 3 of the CTNNB1 gene encoding beta-catenin have been reported in colorectal cancer cell lines and tumours. Although one study reported mutations or deletions affecting beta-catenin in 20% of melanoma cell lines, subsequent reports detected a much lower frequency of aberrations in uncultured melanomas. To determine whether this difference in mutation frequency reflected an in vitro culturing artefact, exon 3 of CTNNB1 was screened in a panel of 62 melanoma cell lines. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect intragenic deletions affecting exon 3. One out of 62 (1.6%) cell lines was found to carry a mutation, indicating that aberration of the Wnt-1/wingless pathway through activation of beta-catenin is a rare event, even in melanoma cell lines.

Poly[aqua([mu]3-2-hydroxy-5-nitrobenzoato-[kappa]3O1:O1':O2)rubidium]

In the structure of title compound [Rb2(C7H4NO2)2(H2O)2]n the centrosymmetric cyclic dimeric repeating unit comprises two irregular RbO4 complex centres bridged by the carboxylate groups of the 5-nitrosalicylate ligands. The coordination about each Rb is completed by a monodentate water molecule and a phenolic O donor which gives a bridging extension [Rb-O range 3.116(7)-3.135(5)A]. The two-dimensional polymeric structure is stabilized by intermolecular water O-H...O(carboxyl) hydrogen bonds and weak inter-ring pi--pi interactions [minimum ring centroid separation, 3.620(4)A].

Vibrational spectroscopic analysis of taranakite (K,NH4)Al3(PO4)3(OH) •9(H2O) from the Jenolan Caves, Australia

Many phosphate containing minerals are found in the Jenolan Caves. Such minerals are formed by the reaction of bat guano and clays from the caves. Among these cave minerals is the mineral taranakite (K,NH4)Al3(PO4)3(OH)•9(H2O) which has been identified by X-ray diffraction. Jenolan Caves taranakite has been characterised by Raman spectroscopy. Raman and infrared bands are assigned to H2PO4-, OH and NH stretching vibrations. By using a combination of XRD and Raman spectroscopy, the existence of taranakite in the caves has been proven.

Heritage refurbishment : National Trust House (Basement 3) [Architectural Practice Academy Office]

The refurbishment of The National Trust House (Basement3), undertaken in 2005, represents heritage consultation, architectural and interior design of a disused and deteriorating subbasement of a historically and culturally significant building situated in Brisbane. Research into rectification and restoration work of the existing structure and interior surfaces (inclusive of masonry work sourced from the Kangaroo Point quarry in the 1860's) formed a significant component of the project. The National Trust House sub basement 3 was refurbished to house the Architectural Practice Academy, a joint initiative of the Queensland Government and the Australian Institute of Architects.