191 research outputs found
Decreased blood–brain barrier P-glycoprotein function in the progression of Parkinson’s disease, PSP and MSA
Decreased blood–brain barrier (BBB) efflux function of the P-glycoprotein (P-gp) transport system could facilitate the accumulation of toxic compounds in the brain, increasing the risk of neurodegenerative pathology such as Parkinson’s disease (PD). This study investigated in vivo BBB P-gp function in patients with parkinsonian neurodegenerative syndromes, using [11C]-verapamil PET in PD, PSP and MSA patients. Regional differences in distribution volume were studied using SPM with higher uptake interpreted as reduced P-gp function. Advanced PD patients and PSP patients had increased [11C]-verapamil uptake in frontal white matter regions compared to controls; while de novo PD patients showed lower uptake in midbrain and frontal regions. PSP and MSA patients had increased uptake in the basal ganglia. Decreased BBB P-gp function seems a late event in neurodegenerative disorders, and could enhance continuous neurodegeneration. Lower [11C]-verapamil uptake in midbrain and frontal regions of de novo PD patients could indicate a regional up-regulation of P-gp function
Spin-Glass Model for Inverse Freezing
We analyze the Blume-Emery-Griffiths model with disordered magnetic
interaction displaying the inverse freezing phenomenon. The behaviour of this
spin-1 model in crystal field is studied throughout the phase diagram and the
transition and spinodal lines for the model are computed using the Full Replica
Symmetry Breaking Ansatz that always yelds a thermodynamically stable phase. We
compare the results both with the quenched disordered model with Ising spins on
lattice gas - where no reentrance takes place - and with the model with
generalized spin variables recently introduced by Schupper and Shnerb [Phys.
Rev. Lett. 93, 037202 (2004)]. The simplest version of all these models, known
as Ghatak-Sherrington model, turns out to hold all the general features
characterizing an inverse transition to an amorphous phase, including the right
thermodynamic behavior.Comment: 6 pages, 4 figures, to appear in the Proceeding for the X
International Workshop on Disordered Systems (2006), Molveno, Ital
Organometallic iridium(III) anticancer complexes with new mechanisms of action: NCI-60 screening, mitochondrial targeting, and apoptosis
Platinum complexes related to cisplatin, cis-[PtCl2(NH3)2], are successful anticancer drugs; however, other transition metal complexes offer potential for combating cisplatin resistance, decreasing side effects, and widening the spectrum of activity. Organometallic half-sandwich iridium (IrIII) complexes [Ir(Cpx)(XY)Cl]+/0 (Cpx = biphenyltetramethylcyclopentadienyl and XY = phenanthroline (1), bipyridine (2), or phenylpyridine (3)) all hydrolyze rapidly, forming monofunctional G adducts on DNA with additional intercalation of the phenyl substituents on the Cpx ring. In comparison, highly potent complex 4 (Cpx = phenyltetramethylcyclopentadienyl and XY = N,N-dimethylphenylazopyridine) does not hydrolyze. All show higher potency toward A2780 human ovarian cancer cells compared to cisplatin, with 1, 3, and 4 also demonstrating higher potency in the National Cancer Institute (NCI) NCI-60 cell-line screen. Use of the NCI COMPARE algorithm (which predicts mechanisms of action (MoAs) for emerging anticancer compounds by correlating NCI-60 patterns of sensitivity) shows that the MoA of these IrIII complexes has no correlation to cisplatin (or oxaliplatin), with 3 and 4 emerging as particularly novel compounds. Those findings by COMPARE were experimentally probed by transmission electron microscopy (TEM) of A2780 cells exposed to 1, showing mitochondrial swelling and activation of apoptosis after 24 h. Significant changes in mitochondrial membrane polarization were detected by flow cytometry, and the potency of the complexes was enhanced ca. 5× by co-administration with a low concentration (5 μM) of the γ-glutamyl cysteine synthetase inhibitor L-buthionine sulfoximine (L-BSO). These studies reveal potential polypharmacology of organometallic IrIII complexes, with MoA and cell selectivity governed by structural changes in the chelating ligands
SAS6-like protein in Plasmodium indicates that conoid-associated apical complex proteins persist in invasive stages within the mosquito vector
The SAS6-like (SAS6L) protein, a truncated paralogue of the ubiquitous basal body/centriole protein SAS6, has been characterised recently as a flagellum protein in trypanosomatids, but associated with the conoid in apicomplexan Toxoplasma. The conoid has been suggested to derive from flagella parts, but is thought to have been lost from some apicomplexans including the malaria-causing genus Plasmodium. Presence of SAS6L in Plasmodium, therefore, suggested a possible role in flagella assembly in male gametes, the only flagellated stage. Here, we have studied the expression and role of SAS6L throughout the Plasmodium life cycle using the rodent malaria model P. berghei. Contrary to a hypothesised role in flagella, SAS6L was absent during gamete flagellum formation. Instead, SAS6L was restricted to the apical complex in ookinetes and sporozoites, the extracellular invasive stages that develop within the mosquito vector. In these stages SAS6L forms an apical ring, as we show is also the case in Toxoplasma tachyzoites. The SAS6L ring was not apparent in blood-stage invasive merozoites, indicating that the apical complex is differentiated between the different invasive forms. Overall this study indicates that a conoid-associated apical complex protein and ring structure is persistent in Plasmodium in a stage-specific manner
A Genome-Wide RNAi Screen for Factors Involved in Neuronal Specification in Caenorhabditis elegans
One of the central goals of developmental neurobiology is to describe and understand the multi-tiered molecular events that control the progression of a fertilized egg to a terminally differentiated neuron. In the nematode Caenorhabditis elegans, the progression from egg to terminally differentiated neuron has been visually traced by lineage analysis. For example, the two gustatory neurons ASEL and ASER, a bilaterally symmetric neuron pair that is functionally lateralized, are generated from a fertilized egg through an invariant sequence of 11 cellular cleavages that occur stereotypically along specific cleavage planes. Molecular events that occur along this developmental pathway are only superficially understood. We take here an unbiased, genome-wide approach to identify genes that may act at any stage to ensure the correct differentiation of ASEL. Screening a genome-wide RNAi library that knocks-down 18,179 genes (94% of the genome), we identified 245 genes that affect the development of the ASEL neuron, such that the neuron is either not generated, its fate is converted to that of another cell, or cells from other lineage branches now adopt ASEL fate. We analyze in detail two factors that we identify from this screen: (1) the proneural gene hlh-14, which we find to be bilaterally expressed in the ASEL/R lineages despite their asymmetric lineage origins and which we find is required to generate neurons from several lineage branches including the ASE neurons, and (2) the COMPASS histone methyltransferase complex, which we find to be a critical embryonic inducer of ASEL/R asymmetry, acting upstream of the previously identified miRNA lsy-6. Our study represents the first comprehensive, genome-wide analysis of a single neuronal cell fate decision. The results of this analysis provide a starting point for future studies that will eventually lead to a more complete understanding of how individual neuronal cell types are generated from a single-cell embryo
Improving cross-sectoral climate change adaptation for coastal settlements: insights from South East Queensland, Australia
A-002 (Varespladib), a phospholipase A2 inhibitor, reduces atherosclerosis in guinea pigs
<p>Abstract</p> <p>Background</p> <p>The association of elevated serum levels of secretory phospholipase A<sub>2 </sub>(sPLA<sub>2</sub>) in patients with cardiovascular disease and their presence in atherosclerotic lesions suggest the participation of sPLA<sub>2 </sub>enzymes in this disease. The presence of more advanced atherosclerotic lesions in mice that overexpress sPLA<sub>2 </sub>enzymes suggest their involvement in the atherosclerotic process. Therefore, the sPLA<sub>2 </sub>family of enzymes could provide reasonable targets for the prevention and treatment of atherosclerosis. Thus, A-002 (varespladib), an inhibitor of sPLA<sub>2</sub>enzymes, is proposed to modulate the development of atherosclerosis.</p> <p>Methods</p> <p>Twenty-four guinea pigs were fed a high saturated fat, high cholesterol diet (0.25%) for twelve weeks. Animals were treated daily with A-002 (n = 12) or vehicle (10% aqueous acacia; n = 12) by oral gavage. After twelve weeks, animals were sacrificed and plasma, heart and aorta were collected. Plasma lipids were measured by enzymatic methods, lipoprotein particles size by nuclear magnetic resonance, aortic cytokines by a colorimetric method, and aortic sinus by histological analyses.</p> <p>Results</p> <p>Plasma total cholesterol, HDL cholesterol and triglycerides were not different among groups. However, the levels of inflammatory cytokines interleukin (IL)-10, IL-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly reduced in the treatment group. This group also had a significant 27% reduction in cholesterol accumulation in aorta compared with placebo group. Morphological analysis of aortic sinus revealed that the group treated with A-002 reduced atherosclerotic lesions by 24%.</p> <p>Conclusion</p> <p>The use of A-002 may have a beneficial effect in preventing diet-induced atherosclerosis in guinea pigs.</p
Global Prediction of Tissue-Specific Gene Expression and Context-Dependent Gene Networks in Caenorhabditis elegans
Tissue-specific gene expression plays a fundamental role in metazoan biology and is an important aspect of many complex diseases. Nevertheless, an organism-wide map of tissue-specific expression remains elusive due to difficulty in obtaining these data experimentally. Here, we leveraged existing whole-animal Caenorhabditis elegans microarray data representing diverse conditions and developmental stages to generate accurate predictions of tissue-specific gene expression and experimentally validated these predictions. These patterns of tissue-specific expression are more accurate than existing high-throughput experimental studies for nearly all tissues; they also complement existing experiments by addressing tissue-specific expression present at particular developmental stages and in small tissues. We used these predictions to address several experimentally challenging questions, including the identification of tissue-specific transcriptional motifs and the discovery of potential miRNA regulation specific to particular tissues. We also investigate the role of tissue context in gene function through tissue-specific functional interaction networks. To our knowledge, this is the first study producing high-accuracy predictions of tissue-specific expression and interactions for a metazoan organism based on whole-animal data
Crop Updates 2002 - Farming Systems
This session covers forty one papers from different authors:
INTRODUCTION
1. Future Farming Systems session for Crop Updates 2002 Peter Metcalf, FARMING SYSTEMS SUBPROGRAM MANAGER GRAINS PROGRAM Department of Agriculture
2. Perennial pastures in annual cropping systems: Lucerne and beyond, the ‘Big Picture’, Mike Ewing, Deputy CEO CRC for Plant-based Management of Dryland Salinity, Department of Agriculture
3. Perennial pastures in annual cropping systems: lucerne and beyond, Roy Latta and Keith Devenish, Department of Agriculture
4. Establishing Lucerne with a cover crop, Diana Fedorenko1, Clayton Butterly1, Chantelle Butterly1, Kim and Neil Diamond2, Stuart McAlpine2, Bill Bowden1, Jessica Johns3, 1Centre for Cropping Systems, Northam, 2Farmer, Buntine, 3Department of Agriculture
5. Overcropping: Chemical suppression of Lucerne, Terry Piper1, Diana Fedorenko1, Clayton Butterly1, Chantelle Butterly1, Stuart McAlpine2, Jessica Johns3, 1Centre for Cropping Systems, Northam, 2Farmer, Buntine, 3Department of Agriculture
6. Overcropping: Effect of Lucerne density on crop yield, Diana Fedorenko1, Bill Bowden1, Clayton Butterly1, Chantelle Butterly1, Stuart McAlpine2, Terry Piper1,1Centre for Cropping Systems, Department of Agriculture, Northam, 2Farmer, Buntine
7. Residual effect of weed management in the third year of Lucerne on the following wheat crop, Diana Fedorenko1, Clayton Butterly1, Chantelle Butterly1, Stuart McAlpine2,Terry Piper1, David Bowran1, Jessica Johns3,1Centre for Cropping Systems, Northam, 2Farmer, Buntine, 3Department of Agriculture
8. Production of Lucerne and serradella in four soil types, Diana Fedorenko1 Clayton Butterly1, Chantelle Butterly1, Robert Beard2 1Centre for Cropping Systems, Department of Agriculture, 2Farmer, Cunderdin
9. The effect of spray topping on newly established Lucerne, Keith Devenish, Agriculture Western Australia
10. Leakage from phase rotations involving Lucerne, Phil Ward, CSIRO Plant Industry
11. Fungal diseases present in Western Australian Lucerne crops, Dominie Wright and Nichole Burges, Department of Agriculture
12. Survey of Western Australian Lucerne stands reveals widespread virus infection, Roger Jones and Danae Harman, Crop Improvement Institute, Department of Agriculture, and Centre for Legumes in Mediterranean Agriculture, University of WA
ANNUAL PASTURE SYSTEMS
13. The use of Twist Fungus as a biosecurity measure against Annual Ryegrass Toxicity (ARGT), Greg Shea, GrainGuard Coordinator and George Yan, Biological and Resource Technology
14.Limitations and opportunities for increasing water use by annual crops and pastures, David Tennant1, Phil Ward2and David Hall1 1Department of Agriculture, 2CSIRO, Plant Industries, Floreat Park
15. Developing pasture species mixtures for more productive and sustainable cropping systems – 2001 crop performance, Anyou Liu, Clinton Revell and Candy Hudson, Centre for Cropping Systems, Department of Agriculture
16. Developing pasture species mixtures for more productive and sustainable cropping systems – weed management in regenerating mixtures, Anyou Liu and Clinton Revell, Centre for Cropping Systems, Department of Agriculture
17. Aphid tolerance of annual pasture legumes, Andrew Blake, Natalie Lauritsen, Department of Agriculture
18. Selecting the right variety for phase pasture systems, Keith Devenish, Department of Agriculture
19. Responses of alternative annual pasture and forage legumes to challenge with infectious subterranean clover mottle virus, John Fosu-Nyarko, Roger Jones, Lisa Smith, Mike Jones and Geoff Dwyer, State Agricultural Biotechnology Centre and Centre for Bioinformatics and Biological Computing, Murdoch University, Department of Agriculture, and Centre for Legumes in Mediterranean Agriculture
SOIL AND LAND MANAGEMENT
20. Nutrition in 2002: Decisions to be made as a result of last season, Bill Bowden,Western Australia Department of Agriculture
21. Profitability of deep banding lime, Michael O\u27Connell, Chris Gazey and David Gartner, Department of Agriculture
22. Lime efficiency percentage…the new measure of lime effectiveness for Western Australia, Amanda Miller, Department of Agriculture
23. Boron – should we be worried about it, Richard W. BellA, K. FrostA, Mike WongBand Ross BrennanC ASchool of Environmental Science, Murdoch University,
BCSIRO Land and Water, CDepartment of Agriculture
24. Impact of claying and other amelioration on paddock profit, N.J. Blake1, G. McConnell2, D. Patabendige1and N. Venn11Department of Agriculture, 2PlanFarm P/L
25. Raised bed farming in the 2001 growing season, Derk Bakker, Greg Hamilton, Dave Houlbrooke and Cliff Spann, Department of Agriculture
26. Economics of tramline farming systems, Paul Blackwell and Bindi Webb, Department of Agriculture, Stuart McAlpine, Liebe Group.
27. Relay planting from Tramlines to increase water use and productivity os summer crops, Dr Paul Blackwell, Department of Agriculture, Neil and Kim Diamond, Buntine. Liebe Group
28.Evidence-based zone management of paddock variability to improve profits and environmental outcomes, M.T.F. WongA, D. PatabendigeB, G. LyleA and K. WittwerA ACSIRO Land and Water, BDepartment of Agriculture
29. How much soil water is lost over summer in sandy soils? Perry Dolling1, Senthold Asseng2, Ian Fillery2, Phil Ward2and Michael Robertson3 1University of Western Australia/Department of Agriculture Western Australia/CSIRO, 2CSIRO Plant Industry 3CSIRO Sustainable Ecosystems, Indooroopilly, Queensland
FARMER DECISION SUPPORT AND ADOPTION
30. Economic comparisons of farming systems for the medium rainfall northern sandplain, No 1, Caroline Peek and David Rogers, Department of Agriculture
31. Sensitivity analysis of farming systems for the medium rainfall northern sandplain No 2, Caroline Peek and David Rogers, Department of Agriculture
32. Transition analysis of farming systems in the medium rainfall northern sandplain. No 3, Caroline Peek and David Rogers, Department of Agriculture
33. Implementing on-farm quality assurance, Peter Portmann, Manager Research and Development, The Grain Pool of Western Australia
34. On-farm research – principles of the ‘Test As You Grow’ kit, Jeff Russell, Department of Agriculture
35. Broadscale wheat variety comparisons featuring Wyalkatchem, Jeff Russell, Department of Agriculture
36. GrainGuardÔ - A biosecurity plan for the Canola Industry,Greg Shea Department of Agriculture
37. Are Western Australian broadacre farms efficient? Ben Henderson, University of Western Australia, Ross Kingwell, Department of Agriculture and University of Western Australia
DISEASE MODELLING WORKSHOP
38. WORKSHOP: Pest and disease forecasts for you! An interactive forum, Tresslyn Walmsley, Jean Galloway, Debbie Thackray, Moin Salam and Art Diggle, Centre for Legumes in Mediterranean Agriculture and Department of Agriculture
39. Blackspot spread: Disease models are based in reality (Workshop paper 1), JeanGalloway,Department of Agriculture
40. Blackspot spread: Scaling-up field data to simulate ‘Baker’s farm’ (Workshop paper 2), Moin U. Salam, Jean Galloway, Art J. Diggle and William J. MacLeod, Department of Agriculture, Western Australia
41. A decision support system for control of aphids and CMV in lupin crops (Workshop paper 3), Debbie Thackray, Jenny Hawkes and Roger Jones, Centre for Legumes in Mediterranean Agriculture and Department of Agricultur
A gene expression fingerprint of C. elegans embryonic motor neurons
BACKGROUND: Differential gene expression specifies the highly diverse cell types that constitute the nervous system. With its sequenced genome and simple, well-defined neuroanatomy, the nematode C. elegans is a useful model system in which to correlate gene expression with neuron identity. The UNC-4 transcription factor is expressed in thirteen embryonic motor neurons where it specifies axonal morphology and synaptic function. These cells can be marked with an unc-4::GFP reporter transgene. Here we describe a powerful strategy, Micro-Array Profiling of C. elegans cells (MAPCeL), and confirm that this approach provides a comprehensive gene expression profile of unc-4::GFP motor neurons in vivo. RESULTS: Fluorescence Activated Cell Sorting (FACS) was used to isolate unc-4::GFP neurons from primary cultures of C. elegans embryonic cells. Microarray experiments detected 6,217 unique transcripts of which ~1,000 are enriched in unc-4::GFP neurons relative to the average nematode embryonic cell. The reliability of these data was validated by the detection of known cell-specific transcripts and by expression in UNC-4 motor neurons of GFP reporters derived from the enriched data set. In addition to genes involved in neurotransmitter packaging and release, the microarray data include transcripts for receptors to a remarkably wide variety of signaling molecules. The added presence of a robust array of G-protein pathway components is indicative of complex and highly integrated mechanisms for modulating motor neuron activity. Over half of the enriched genes (537) have human homologs, a finding that could reflect substantial overlap with the gene expression repertoire of mammalian motor neurons. CONCLUSION: We have described a microarray-based method, MAPCeL, for profiling gene expression in specific C. elegans motor neurons and provide evidence that this approach can reveal candidate genes for key roles in the differentiation and function of these cells. These methods can now be applied to generate a gene expression map of the C. elegans nervous system
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