Phosphorylation State-Dependent Regulation of SAPAP3 and mGluR5 Association

poster abstractThis study aims to characterize the interaction between SAP90/PSD-95-associated protein 3 (SAPAP3) and metabotropic Glutamate Receptor 5 (mGluR5); specifically focusing on how SAPAP3 phosphorylation state modulates association. SAPAP3 is a scaffolding protein localized to the postsynaptic density (PSD) of striatal neurons and SAPAP3 knockout mice have Obsessive-Compulsive Disorder-like symptoms. Here, we hypothesize that spinophilin modulates SAPAP3 phosphorylation and alterations in SAPAP3 phosphorylation regulate SAPAP3 binding to mGluR5. We will use in vitro and ex vivo studies to characterize the interaction between spinophilin and SAPAP3 and to determine the functional implications of SAPAP3 phosphorylation on mGluR5 binding. These data will enhance our understanding of molecular mechanisms that regulate SAPAP3 and mGluR5 function, two proteins with known roles in obsessive-compulsive disorder

Enhanced osteogenesis in co-cultures with human mesenchymal stem cells and endothelial cells on polymeric microfiber scaffolds

In this work, human mesenchymal stem cells (hMSCs) and their osteogenically precultured derivatives were directly co-cultured with human umbilical vein endothelial cells (HUVECs) on electrospun 3D poly(-caprolactone) microfiber scaffolds in order to evaluate the co-culture’s effect on the generation of osteogenic constructs. Specifically, cells were cultured on scaffolds for up to three weeks, and the cellularity, alkaline phosphatase activity (ALP), and bone-like matrix formation were assessed. Constructs with co-cultures and monocultures had almost identical cellularity after the first week, however lower cellularity was observed in co-cultures compared to monocultures during the subsequent two weeks of culture. Scaffolds with co-cultures showed significantly higher ALP activity, glycosaminoglycan and collagen production, as well as greater calcium deposition over the course of study compared to monocultures of hMSCs. Furthermore, the osteogenic outcome was equally robust in co-cultures containing osteogenically precultured and non-precultured hMSCs. The results demonstrate that the combination of MSC and HUVEC populations within a porous scaffold material under osteogenic culture conditions is an effective strategy to promote osteogenesis

Providing evidence to support obstetric practice change in Vietnam: episiotomy use among Vietnamese-born women living in Australia

OBJECTIVE: To describe the use of episiotomy among Vietnamese-born women in Australia, including risk factors for, and pregnancy outcomes associated with, episiotomy. METHODS: This population-based, retrospective cohort study included data on 598 305 singleton, term (i.e. ≥ 37 weeks’ gestation) and vertex-presenting vaginal births between 2001 and 2010. Data were obtained from linked, validated, population-level birth and hospitalization data sets. Contingency tables and multivariate analysis were used to compare risk factors and pregnancy outcomes in women who did or did not have an episiotomy. FINDINGS: The episiotomy rate in 12 208 Vietnamese-born women was 29.9%, compared with 15.1% in Australian-born women. Among Vietnamese-born women, those who had an episiotomy were significantly more likely than those who did not to be primiparous, give birth in a private hospital, have induced labour or undergo instrumental delivery. In these women, having an episiotomy was associated with postpartum haemorrhage (adjusted odds ratio, aOR: 1.26; 95% confidence interval, CI: 1.08–1.46) and postnatal hospitalization for more than 4 days (aOR: 1.14; 95% CI: 1.00–1.29). Among multiparous women only, episiotomy was positively associated with a third- or fourth-degree perineal tear (aOR: 2.00; 95% CI: 1.31–3.06); in contrast, among primiparous women the association was negative (aOR: 0.47; 95% CI: 0.37–0.60). CONCLUSION: Episiotomy was performed in far fewer Vietnamese-born women giving birth in Australia than in Viet Nam, where more than 85% undergo the procedure, and was not associated with adverse outcomes. A lower episiotomy rate should be achievable in Viet Nam

A Glasgow tipple-transjugular intrahepatic portosystemic shunt insertion prior to Whipple resection

Abdominal surgery performed in patients with significant liver disease and portal hypertension is associated with high mortality rates, with even poorer outcomes associated with complex pancreaticobiliary operations. We report on a patient requiring portal decompression via transjugular intrahepatic portosystemic shunt (TIPS) prior to a pancreaticoduodenectomy. The 49-year-old patient presented with pain, jaundice and weight loss. At ERCP an edematous ampulla was biopsied, revealing high-grade dysplasia within a distal bile duct adenoma. Liver biopsy was performed to investigate portal hypertension, confirming congenital hepatic fibrosis (CHF). A TIPS was performed to enable a pancreaticoduodenectomy. Prophylactic TIPS can be performed for preoperative portal decompression for patients requiring pancreatic resection. A potentially curative resection was performed when abdominal surgery was initially thought impossible. Notably, CHF has been associated with the development of cholangiocarcinoma in only four previous instances, with this case being only the second reported distal bile duct cholangiocarcinoma

Trypanosome co-infections increase in a declining marsupial population

Understanding the impacts of parasites on wildlife is growing in importance as diseases pose a threat to wildlife populations. Woylie (syn. brush-tailed bettong, Bettongia penicillata) populations have undergone enigmatic declines in south-western Western Australia over the past decade. Trypanosomes have been suggested as a possible factor contributing towards these declines because of their high prevalence in the declining population. We asked whether temporal patterns of infection with Trypanosoma spp. were associated with the decline patterns of the host, or if other factors (host sex, body condition, co-infection or rainfall) were more influential in predicting infection patterns. Species-specific nested PCRs were used to detect the two most common trypanosomes (T. copemani and T. vegrandis) from 444 woylie blood samples collected between 2006 and 2012. Time relative to the decline (year) and an interaction with co-infection by the other trypanosome best explained patterns of infection for both trypanosomes. The prevalence of single species infections for both T. copemani and T. vegrandis was lower after the population crash, however, the occurrence of co-infections increased after the crash compared to before the crash. Our results suggest an interaction between the two parasites with the decline of their host, leading to a higher level of co-infection after the decline. We discuss the possible mechanisms that may have led to a higher level of co-infection after the population crash, and highlight the importance of considering co-infection when investigating the role of parasites in species declines

Fine root production in a chronosequence of mature reforested mangroves

Mangroves are among the world’s most carbon-dense ecosystems, but have suffered extensive deforestation, prompting reforestation projects. The effects of mangrove reforestation on belowground carbon dynamics are poorly understood. In particular, we do not know how fine root production develops following mangrove reforestation, despite fine root production being a major carbon sink and an important control of mangrove soil accretion. Using minirhizotrons, we investigated fine root production and its depth variation along a chronosequence of mature Vietnamese mangroves. Our results showed that fine root production decreases strongly with stand age in the uppermost 32 cm of our soil profiles. In younger mangrove stands, fine root production declines with depth, possibly due to a vertical gradient in soil nutrient availability; while root production in the oldest stand is low at all depths and exhibits no clear vertical pattern. A major fraction of fine root production occurs deeper than 30 cm, depths that are commonly omitted from calculations of mangrove carbon budgets. Younger mangroves may accrue shallow soil organic matter faster than older mangroves. Therefore, root productivity and forest stand age should be accounted for when forecasting mangrove carbon budgets and resistance to sea-level rise

Human airway smooth muscle maintain in situ cell orientation and phenotype when cultured on aligned electrospun scaffolds

Human airway smooth muscle (HASM) contraction plays a central role in regulating airway resistance in both healthy and asthmatic bronchioles. In vitro studies that investigate the intricate mechanisms that regulate this contractile process are predominantly conducted on tissue culture plastic, a rigid, 2D geometry, unlike the 3D microenvironment smooth muscle cells are exposed to in situ. It is increasingly apparent that cellular characteristics and responses are altered between cells cultured on 2D substrates compared with 3D topographies. Electrospinning is an attractive method to produce 3D topographies for cell culturing as the fibers produced have dimensions within the nanometer range, similar to cells' natural environment. We have developed an electrospun scaffold using the nondegradable, nontoxic, polymer polyethylene terephthalate (PET) composed of uniaxially orientated nanofibers and have evaluated this topography's effect on HASM cell adhesion, alignment, and morphology. The fibers orientation provided contact guidance enabling the formation of fully aligned sheets of smooth muscle. Moreover, smooth muscle cells cultured on the scaffold present an elongated cell phenotype with altered contractile protein levels and distribution. HASM cells cultured on this scaffold responded to the bronchoconstrictor bradykinin. The platform presented provides a novel in vitro model that promotes airway smooth muscle cell development toward a more in vivo-like phenotype while providing topological cues to ensure full cell alignment

Millisecond optical phase modulation using multipass configurations with liquid-crystal devices

We present two configurations for analog 0 to 2π optical phase modulation using liquid crystals (LCs), each of which achieve switching times that are 1 ms or less. One configuration is based on the switching behavior of a so-called nematic pi cell, and the other is based on the flexoelectro-optic effect in chiral nematic LCs when operated in the uniform lying helix geometry. Both configurations exploit a multipass optical arrangement to enhance the available optical phase range, while maintaining a fast switching speed. Moreover, these devices can be operated at or close to room temperature. Experimental data are found to be in good agreement with results predicted from theory for these multipass phase-modulation configurations