926 resultados para Serotonin uptake inhibitor


Relevância:

20.00% 20.00%

Publicador:

Resumo:

Prefabrication has been promoted as a means to improve the efficiency of the Australian house building industry. Issues affecting the uptake of prefabrication were identified through interviews with small and medium sized building companies. Prefabrication’s specific impact on housing construction and smaller organisations has not been frequently investigated. Similar past research has been conducted without the use of a clear theoretical grounding guiding the identification of relevant issues. The current study is guided by a combination of the Theory of Planned Behaviour (TPB) and the Technology Acceptance Model (TAM). This allowed the identification of a broad range of issues across attitudinal, normative, behavioural control and technology adaptation domains. Results revealed improved quality was often offset against practical cost implications. While a high quality of prefabricated products was reported, key technical challenges included coordinating the transporting of modules, and balancing standardisation and product flexibility. Resistance from traditional industry stakeholders regarding build methods, financing, and openness to encouraging prefabrication was commonly reported. The key role of government decision making in facilitating greater demand and competitiveness of prefabricated businesses in the consumer marketplace was also highlighted. Further research is currently being undertaken by the authors, which builds on the exploratory results of the current study through confirmatory, quantitative surveying.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Urban green infrastructure can help cities adapt to climate change. Spatial planning can play an important role in utilizing green infrastructure for adaptation. Yet climate change risks represent a different sort of challenge for planning institutions. This paper aims to address two issues arising from this challenge. First, it defines the concept of green infrastructure within the context of climate adaptation. Second, it identifies and puts into perspective institutional barriers to adopting green infrastructure for climate adaptation, including path dependence. We begin by arguing that there is growing confusion among planners and policy makers about what constitutes green infrastructure. Definitional ambiguity may contribute to inaction on climate change adaptation, because it muddies existing programs and initiatives that are to do with green-space more broadly, which in turn feeds path dependency. We then report empirical findings about how planners perceive the institutional challenge arising from climate change and the adoption of green infrastructure as an adaptive response. The paper concludes that spatial planners generally recognize multiple rationales associated with green infrastructure. However they are not particularly keen on institutional innovation and there is a tendency for path dependence. We propose a conceptual model that explicitly recognizes such institutional factors. This paper contributes to the literature by showing that agency and institutional dimensions are a limiting factor in advancing the concept of green infrastructure within the context of climate change adaptation.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

This paper presents simulation results for future electricity grids using an agent-based model developed with MODAM (MODular Agent-based Model). MODAM is introduced and its use demonstrated through four simulations based on a scenario that expects a rise of on-site renewable generators and electric vehicles (EV) usage. The simulations were run over many years, for two areas in Townsville, Australia, capturing variability in space of the technology uptake, and for two charging methods for EV, capturing people's behaviours and their impact on the time of the peak load. Impact analyses of these technologies were performed over the areas, down to the distribution transformer level, where greater variability of their contribution to the assets peak load was observed. The MODAM models can be used for different purposes such as impact of renewables on grid sizing, or on greenhouse gas emissions. The insights gained from using MODAM for technology assessment are discussed.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Background Influenza infection during pregnancy is associated with significant morbidity and mortality. Immunisation against influenza is recommended during pregnancy in several countries but uptake of vaccine is poor. There are limited data on vaccine uptake, and the determinants of vaccination, in Australian Aboriginal and/or Torres Islander women during pregnancy. This study aimed to establish an appropriate methodology and collect pilot data on vaccine uptake and attitudes towards, and perceptions of, maternal influenza vaccination in that population in order to inform the development of larger studies. Methods A mixed-methods study comprised of a cross-sectional survey and yarning circles (focus groups) amongst Aboriginal and Torres Strait Islander women attending two primary health care services. The women were between 28 weeks gestation and less than 16 weeks post-birth. These data were supplemented by data collected in an ongoing national Australian study of maternal influenza vaccination. Aboriginal research officers collected community data and data from the yarning circles which were based on a narrative enquiry framework. Descriptive statistics were used to analyse quantitative data and thematic analyses were applied to qualitative data. Results Quantitative data were available for 53 women and seven of these women participated in the yarning circles. The proportion of women who reported receipt of an influenza vaccine during their pregnancy was 9/53. Less than half of the participants (21/53) reported they had been offered the vaccine in pregnancy. Forty-three percent reported they would get a vaccine if they became pregnant again. Qualitative data suggested perceived benefits to themselves and their infants were important factors in the decision to be vaccinated but there was insufficient information available to women to make that choice. Conclusions The rates of influenza immunisation may continue to remain low for Aboriginal and/or Torres Strait Islander women during pregnancy. Access to services and recommendations by a health care worker may be factors in the lower rates. Our findings support the need for larger studies directed at monitoring and understanding the determinants of maternal influenza vaccine uptake during pregnancy in Australian Aboriginal and Torres Strait Islander women. This research will best be achieved using methods that account for the social and cultural contexts of Aboriginal and Torres Strait Islander communities in Australia.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Glutamine is conditionally essential in cancer cells, being utilized as a carbon and nitrogen source for macromolecule production, as well as for anaplerotic reactions fuelling the tricarboxylic acid (TCA) cycle. In this study, we demonstrated that the glutamine transporter ASCT2 (SLC1A5) is highly expressed in prostate cancer patient samples. Using LNCaP and PC-3 prostate cancer cell lines, we showed that chemical or shRNA-mediated inhibition of ASCT2 function in vitro decreases glutamine uptake, cell cycle progression through E2F transcription factors, mTORC1 pathway activation and cell growth. Chemical inhibition also reduces basal oxygen consumption and fatty acid synthesis, showing that downstream metabolic function is reliant on ASCT2-mediated glutamine uptake. Furthermore, shRNA knockdown of ASCT2 in PC-3 cell xenografts significantly inhibits tumour growth and metastasis in vivo, associated with the down-regulation of E2F cell cycle pathway proteins. In conclusion, ASCT2-mediated glutamine uptake is essential for multiple pathways regulating the cell cycle and cell growth, and is therefore a putative therapeutic target in prostate cancer.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Serine proteinase inhibitors play important and diverse roles in biological processes such as coagulation, defense mechanisms, and immune responses. Here, we identified and characterized a Kunitz-type proteinase inhibitor, designated FcKuSPI, of the BPTI/Kunitz family of serine proteinase inhibitors from the hemocyte cDNA library of the shrimp Fenneropenaeus chinensis. The deduced amino acid sequence of FcKuSPI comprises 80 residues with a putative signal peptide of 15 amino acids. The predicted molecular weight of the mature peptide is 7.66 kDa and its predicted isoelectric point is 8.84. FcKuSPI includes a Kunitz domain containing six conserved cysteine residues that are predicted to form three disulfide bonds. FcKuSPI shares 44e53% homology with BPTI/Kunitz family members from other species. FcKuSPI mRNAwas expressed highly in the hemocytes and moderately in muscle in healthy shrimp. Recombinant FcKuSPI protein demonstrated anti-protease activity against trypsin and anticoagulant activity against citrated human plasma in a dose-dependent manner in in vitro assays.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The role of Chlamydia trachomatis HtrA (CtHtrA) for the growth and pathogenesis of this organism is presented. Inhibition of CtHtrA led to loss of infectious progeny in Chlamydia, particularly during heat stress or recovery from penicillin persistence. Isolation of CtHtrA inhibitor resistant mutants identified positive selection for mutants in fatty acid related pathways. Importantly, HtrA inhibition was effective against clinical isolates of C. trachomatis. Thus the findings combined indicate that CtHtrA is an important chlamydial growth factor that has the potential to be targeted for the development of anti-chlamydial drugs in the future.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Developing novel drugs against the unicellular parasite Plasmodium is complicated by the paucity of simple screening systems. Heat-shock proteins are an essential class of proteins for the parasite's cyclical life style between different cellular milieus and temperatures. The molecular chaperone Hsp90 assists a large variety of proteins, but its supporting functions for many proteins that are important for cancer have made it into a well-studied drug target. With a better understanding of the differences between Hsp90 of the malarial parasite and Hsp90 of its human host, new therapeutic options might become available. We have generated a set of isogenic strains of the budding yeast Saccharomyces cerevisiae where the essential yeast Hsp90 proteins have been replaced with either of the two human cytosolic isoforms Hsp90 alpha or Hsp90 beta, or with Hsp90 from Plasmodium falciparum (Pf). All strains express large amounts of the Flag-tagged Hsp90 proteins and are viable. Even though the strain with Pf Hsp90 grows more poorly, it provides a tool to reconstitute additional aspects of the parasite Hsp90 complex and its interactions with substrates in yeast as a living test tube. Upon exposure of the set of Hsp90 test strains to the two Hsp90 inhibitors radicicol (Rd) and geldanamycin (GA), we found that the strain with Pf Hsp90 is relatively more sensitive to GA than to Rd compared to the strains with human Hsp90's. This indicates that this set of yeast strains could be used to screen for new Pf Hsp90 inhibitors with a wider therapeutic window.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Boron nitride nanomaterials have attracted significant interest due to their superior chemical and physical properties. Despite these novel properties, investigation on the interaction between boron nitride nanoparticle (BN NP) and living systems has been limited. In this study, BN NP (100–250 nm) is assessed as a promising biomaterial for medical applications. The toxicity of BN NP is evaluated by assessing the cells behaviours both biologically (MTT assay, ROS detection etc.) and physically (atomic force microscopy). The uptake mechanism of BN NP is studied by analysing the alternations in cellular morphology based on cell imaging techniques. The results demonstrate in vitro cytocompatibility of BN NP with immense potential for use as an effective nanoparticle for various bio-medical applications.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Pastoralists from 37 beef cattle and sheep properties in western Queensland developed and implemented an environmental management system (EMS) over 18 months. The EMS implemented by them was customised for the pastoral industry as part of a national EMS pilot project, and staff from this project encouraged and assisted pastoralists during this trial. The 31 pastoralists surveyed at the end of the pilot project identified few benefits of EMS implementation, and these were largely associated with environmental management and sustainability. In terms of the reasons for uptake of an EMS, these pastoralists identified drivers similar to those reported in other primary industry sectors. These included improving property and environmental management, financial incentives, a range of market benefits, assistance with red tape issues, access to other training opportunities and assistance and support with the development of their EMS. However, these drivers are weak, and are not motivating pastoralists to adopt an EMS. In contrast, barriers to adoption such as the time involved in developing and implementing EMS are tangible and immediate. Given a lack of effective drivers and that pastoralists are under considerable pressure from ongoing rural adjustment processes, it is not surprising that an EMS is a low priority. It is concluded that widespread uptake and on-going use of an EMS in the pastoral industry will not occur unless pastoralists are required or rewarded for this by markets, governments, financiers, and regional natural resource management bodies.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The effects of fertilisers on 8 tropical turfgrasses growing in 100-L bags of sand were studied over winter in Murrumba Downs, just north of Brisbane in southern Queensland (latitude 27.4°S, longitude 153.1°E). The species used were: Axonopus compressus (broad-leaf carpetgrass), Cynodon dactylon (bermudagrass 'Winter Green') and C. dactylon x C. transvaalensis hybrid ('Tifgreen'), Digitaria didactyla (Queensland blue couch), Paspalum notatum (bahiagrass '38824'), Stenotaphrum secundatum (buffalograss 'Palmetto'), Eremochloa ophiuroides (centipedegrass 'Centec') and Zoysia japonica (zoysiagrass 'ZT-11'). Control plots were fertilised with complete fertilisers every month from May to September (72 kg N/ha, 31 kg P/ha, 84 kg K/ha, 48 kg S/ha, 30 kg Ca/ha and 7.2 kg Mg/ha), and unfertilised plots received no fertiliser. Carpetgrass and standard bermudagrass were the most sensitive species to nutrient supply, with lower shoot dry weights in the unfertilised plots (shoots mowed to thatch level) compared with the fertilised plots in June. There were lower shoot dry weights in the unfertilised plots in July for all species, except for buffalograss, centipedegrass and zoysiagrass, and lower shoot dry weights in the unfertilised plots in August for all species, except for centipedegrass. At the end of the experiment in September, unfertilised plots were 11% of the shoot dry weights of fertilised plots, with all species affected. Mean shoot nitrogen concentrations fell from 3.2 to 1.7% in the unfertilised plots from May to August, below the sufficiency range for turfgrasses (2.8-3.5%). There were also declines in P (0.45-0.36%), K (2.4-1.5%), S (0.35-0.25%), Mg (0.24-0.18%) and B (9-6 mg/kg), which were all in the sufficiency range. The shoots in the control plots took up the following levels (kg/ha.month) of nutrients: N, 10.0-27.0; P, 1.6-4.0; K, 8.2-19.8; S, 1.0-4.2; Ca, 1.1-3.3; and Mg, 0.8-2.2, compared with applications (kg/ha.month) of: N, 72; P, 31; K, 84; S, 48; Ca, 30; and Mg, 7.2, indicating a recovery of 14-38% for N, 5-13% for P, 10-24% for K, 2-9% for S, 4-11% for Ca and 11-30% for Mg. These results suggest that buffalograss, centipedegrass and zoysiagrass are less sensitive to low nutrient supply than carpetgrass, bermudagrass, blue couch and bahiagrass. Data on nutrient uptake showed that the less sensitive species required only half or less of the nitrogen required to maintain the growth of the other grasses, indicating potential savings for turf managers in fertiliser costs and the environment in terms of nutrients entering waterways.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Parkinson’s disease (PD) is the second most common neurodegenerative disease among the elderly. Its etiology is unknown and no disease-modifying drugs are available. Thus, more information concerning its pathogenesis is needed. Among other genes, mutated PTEN-induced kinase 1 (PINK1) has been linked to early-onset and sporadic PD, but its mode of action is poorly understood. Most animal models of PD are based on the use of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP is metabolized to MPP+ by monoamine oxidase B (MAO B) and causes cell death of dopaminergic neurons in the substantia nigra in mammals. Zebrafish has been a widely used model organism in developmental biology, but is now emerging as a model for human diseases due to its ideal combination of properties. Zebrafish are inexpensive and easy to maintain, develop rapidly, breed in large quantities producing transparent embryos, and are readily manipulated by various methods, particularly genetic ones. In addition, zebrafish are vertebrate animals and results derived from zebrafish may be more applicable to mammals than results from invertebrate genetic models such as Drosophila melanogaster and Caenorhabditis elegans. However, the similarity cannot be taken for granted. The aim of this study was to establish and test a PD model using larval zebrafish. The developing monoaminergic neuronal systems of larval zebrafish were investigated. We identified and classified 17 catecholaminergic and 9 serotonergic neuron populations in the zebrafish brain. A 3-dimensional atlas was created to facilitate future research. Only one gene encoding MAO was found in the zebrafish genome. Zebrafish MAO showed MAO A-type substrate specificity, but non-A-non-B inhibitor specificity. Distribution of MAO in larval and adult zebrafish brains was both diffuse and distinctly cellular. Inhibition of MAO during larval development led to markedly elevated 5-hydroxytryptamine (serotonin, 5-HT) levels, which decreased the locomotion of the fish. MPTP exposure caused a transient loss of cells in specific aminergic cell populations and decreased locomotion. MPTP-induced changes could be rescued by the MAO B inhibitor deprenyl, suggesting a role for MAO in MPTP toxicity. MPP+ affected only one catecholaminergic cell population; thus, the action of MPP+ was more selective than that of MPTP. The zebrafish PINK1 gene was cloned in zebrafish, and morpholino oligonucleotides were used to suppress its expression in larval zebrafish. The functional domains and expression pattern of zebrafish PINK1 resembled those of other vertebrates, suggesting that zebrafish is a feasible model for studying PINK1. Translation inhibition resulted in cell loss of the same catecholaminergic cell populations as MPTP and MPP+. Inactivation of PINK1 sensitized larval zebrafish to subefficacious doses of MPTP, causing a decrease in locomotion and cell loss in one dopaminergic cell population. Zebrafish appears to be a feasible model for studying PD, since its aminergic systems, mode of action of MPTP, and functions of PINK1 resemble those of mammalians. However, the functions of zebrafish MAO differ from the two forms of MAO found in mammals. Future studies using zebrafish PD models should utilize the advantages specific to zebrafish, such as the ability to execute large-scale genetic or drug screens.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

A model of root water extraction is proposed, in which a linear variation of extraction rate with depth is assumed. Five crops are chosen for simulation studies of the model, and soil moisture depletion under optimal conditions from different layers for each crop is calculated. Similar calculations are also made using the constant extraction rate model. Rooting depth is assumed to vary linearly with potential evapotranspiration for each crop during the vegetative phase. The calculated depletion patterns are compared with measured mean depletion patterns for each crop. It is shown that the constant extraction rate model results in large errors in the prediction of soil moisture depletion, while the proposed linear extraction rate model gives satisfactory results. Hypothetical depletion patterns predicted by the model in combination with a moisture tension-dependent sink term developed elsewhere are indicated.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

N-[2-Naphthyl]-glycine hydrazide has been shown for the first time as a potent inhibitor of the DNA-dependent RNA polymerase (EC 2.7.7.6) of Mycobacterium tuberculosis H37Rv. At a concentration of 10 to the power -9 M, the compound shows maximum inhibition of the enzyme, the inhibition being less at higher concentrations. It is suggested that the novel type of inhibition pattern may be due to hydrophobic interactions occurring between the molecules of the compound at higher concentrations. The finding that there is a shift in the max of the compound could also account for this phenomenon. The effect of this compound was also tested on DNA-dependent RNA polymerases from an eukaryotic fungus, Microsporum canis. At a concentration of 10 to the power-9 M it inhibits RNA polymerase II (32 percent) but not RNA polymerases I and III.