Chemical manipulation of pasture leys to regulate composition ll.

Introduction. Materials and methods. Experimental design. Sowing. Herbicides. Measurements. Results. Discussion. Conclusions

Tibetan sheep are better able to cope with low energy intake than Small-tailed Han sheep due to lower maintenance energy requirements and higher nutrient digestibilities

Tibetan sheep are indigenous to the Qinghai-Tibetan Plateau (QTP) and are well-adapted to and even thrive under the harsh alpine conditions. Small-tailed Han sheep were introduced to the plateau because of their high prolificacy and are maintained mainly in feedlots. Because of their different backgrounds, we hypothesised that Tibetan and Small-tailed Han sheep would differ in their utilization of energy intake and predicted that Tibetan sheep would cope better with low energy intake than Small-tailed Han sheep. To test this prediction, we determined nutrient digestibilities, energy requirements for maintenance and blood metabolite and hormone concentrations involved in energy metabolism in these breeds. Sheep of each breed (n = 24 of each, all wethers and 1.5 years of age) were distributed randomly into one of four groups and offered ad libitum diets of different digestible energy (DE) densities: 8.21, 9.33, 10.45 and 11.57 MJ DE/kg Dry matter (DM). Following 42 d of measuring feed intake, a 1-week digestion and metabolism experiment was done. DM intakes did not differ between breeds nor among treatments but, by design, DE intake increased linearly in both breeds as dietary energy level increased (P < 0.001). The average daily gain (ADG) was significantly greater in the Tibetan than Small-tailed Han sheep (P = 0.003) and increased linearly in both breeds (P < 0.001). In addition, from the regression analysis of ADG on DE intake, daily DE maintenance requirements were lower for Tibetan than for Small-tailed Han sheep (0.41 vs 0.50 MJ/BW0.75, P < 0.05). The DE and metabolizable energy (ME) digestibilities were higher in the Tibetan than Small-tailed Han sheep (P < 0.001) and increased linearly as the energy level increased in the diet (P < 0.001). At the lowest energy treatment, Tibetan sheep when compared with Small-tailed Han sheep, had: 1) higher serum glucose and glucagon, but lower insulin concentrations (P < 0.05), which indicated a higher capacity for gluconeogenesis and ability to regulate glucose metabolism; and 2) higher non-esterified fatty acids (NEFA) and lower very low density lipoprotein (VLDL) and triglyceride (TG) concentrations (P < 0.05), which indicated a higher capacity for NEFA oxidation but lower ability for triglyceride (TG) synthesis. We concluded that our prediction was supported as these differences between breeds conferred an advantage for Tibetan over Small-tailed Han sheep to cope better with low energy diets

CD32+CD4+memory T cells are enriched for total HIV-1 DNA in tissues from humanized mice

CD32 has raised conflicting results as a putative marker of the HIV-1 reservoir. We measured CD32 expression in tissues from viremic and virally suppressed humanized mice treated relatively early or late after HIV-1 infection with combined antiretroviral therapy. CD32 was expressed in a small fraction of the memory CD4(+) T-cell subsets from different tissues in viremic and aviremic mice, regardless of treatment initiation time. CD32(+) memory CD4(+) T cells were enriched in cell associated (CA) HIV-1 DNA but not in CA HIV-1 RNA as compared to the CD32(-) CD4(+) fraction. Using multidimensional reduction analysis, several memory CD4(+)CD32(+) T-cell clusters were identified expressing HLA-DR, TIGIT, or PD-1. Importantly, although tissue-resident CD32(+)CD4(+) memory cells were enriched with translation-competent reservoirs, most of it was detected in memory CD32-CD4(+) T cells. Our findings support that CD32 labels highly activated/exhausted memory CD4(+) T-cell subsets that contain only a small proportion of the translation-competent reservoir

Crop Updates - 2003 Lupins

This session covers twenty one papers from different authors LUPIN ISSUES AND R & D DIRECTIONS Mark Sweetingham, Department of Agriculture ACKNOWLEDGEMENTS VARIETIES AND BREEDING New lupin line for release – WALAN2141, Bevan J, Buirchell, Mark Sweetingham, Geoff Thomas, Amelia McLarty, Harmohinder Dhammu and CVT and Lupin Breeding teams, Department of Agriculture Lupin variety trial, Martin Harries and Wayne Parker, Department of Agriculture Herbicide tolerance of new lupins, Harmohinder S. Dhammu, Terry Piper and David Nicholson, Department of Agriculture YELLOW AND ALBUS LUPINS Selection for high lupin yield under terminal drought, Jairo A. Palta1&2, Neil C. Turner1&2 Bob French2&3 and Bevan Buirchell2&3 , 1CSIRO Plant Industry, Floreat, WA, 2CLIMA, University of Western Australia, Crawley, WA, 3Department of Agriculture Outcrossing and isolation distance in yellow lupins, Kedar Adhikari, Bevan Buirchell and Katia Stefanova, Department of Agriculture Development of aphid tolerant yellow lupins in Western Australia, Kedar Adhikari, Bevan Buirchell, Mark Sweetingham and Françoise Berlandier, Department of Agriculture ESTABLISHMENT Development of anthracnose resistant albus lupins for Western Australia, Kedar Adhikari, Bevan Buirchell, Mark Sweetingham and Geoff Thomas, Department of Agriculture Lupin sowing methods for improved yields, Glen Riethmuller, Department of Agriculture Moisture delving = more reliable lupin establishment, Paul Blackwell and Wayne Parker, Department of Agriculture Effect of time of sewing, plant density and row orientation on lupins at various row spacings, Geoff Fosbery, Farm Focus Consultants, Bill Crabtree, Crabtree Consulting and Tracy Gilham, WANTFA Influence of row spacing on water stress and water use of lupins, Bob French and Laurie Wahlsten, Department of Agriculture AGRONOMY Effect on lupin protein and yield from variety, planting time and seed rate, Pierre Fievez, Pierre Fievez and Associates Lupin row cropping: herbicides to band, shield design and economics, Mike Collins, WANTFA and John Holmes, 4 Farmers Harvest options for narrow leaf lupins, Martin Harries and Dirranie Kirby, Department of Agriculture NUTRITION Additional nutrients on lupin yield and protein, Pierre Fievez, Pierre Fievez and Associates Demonstrating the effect of phosphorous placement on yields of narrow leaf lupin and yellow lupin on high phosphorus retention soils, Martin Harries and Wayne Parker, Department of Agriculture PESTS AND DISEASES How far are anthracnose spores spread by rain splash? Geoff Thomas, Mark Sweetingham and Ken Adcock, Department of Agriculture Height of cereal stubble affects spread of lupin anthracnose, Geoff Thomas, Bill MacLeod and Ken Adcock, Department of Agriculture Controlling non-necrotic strains of bean yellow mosaic virus in lupins by cultural methods, Roger Jones and Rohan Prince, Department of Agriculture, and Centre for Legumes in Mediterranean Agriculture MARKET DEVELOPMENT Australian sweet lupin – is it the next human health food? Stuart Johnson, Deakin University; Ramon Hall, ARC SPIRT PhD Scholar; Madeleine Ball, University of Tasmania; Sofia Sipsas and David Petterson; Department of Agriculture CONTACT DETAILS FOR PRINCIPAL AUTHOR

Comparative Lipidomics in Clinical Isolates of Candida albicans Reveal Crosstalk between Mitochondria, Cell Wall Integrity and Azole Resistance

Prolonged usage of antifungal azoles which target enzymes involved in lipid biosynthesis invariably leads to the development of multi-drug resistance (MDR) in Candida albicans. We had earlier shown that membrane lipids and their fluidity are closely linked to the MDR phenomenon. In one of our recent studies involving comparative lipidomics between azole susceptible (AS) and azole resistant (AR) matched pair clinical isolates of C. albicans, we could not see consistent differences in the lipid profiles of AS and AR strains because they came from different patients and so in this study, we have used genetically related variant recovered from the same patient collected over a period of 2-years. During this time, the levels of fluconazole (FLC) resistance of the strain increased by over 200-fold. By comparing the lipid profiles of select isolates, we were able to observe gradual and statistically significant changes in several lipid classes, particularly in plasma membrane microdomain specific lipids such as mannosylinositolphosphorylceramides and ergosterol, and in a mitochondrial specific phosphoglyceride, phosphatidyl glycerol. Superimposed with these quantitative and qualitative changes in the lipid profiles, were simultaneous changes at the molecular lipid species levels which again coincided with the development of resistance to FLC. Reverse transcriptase-PCR of the key genes of the lipid metabolism validated lipidomic picture. Taken together, this study illustrates how the gradual corrective changes in Candida lipidome correspond to the development of FLC tolerance. Our study also shows a first instance of the mitochondrial membrane dysfunction and defective cell wall (CW) in clinical AR isolates of C. albicans, and provides evidence of a cross-talk between mitochondrial lipid homeostasis, CW integrity and azole tolerance

Synthetic Nanoparticles for Vaccines and Immunotherapy

The immune system plays a critical role in our health. No other component of human physiology plays a decisive role in as diverse an array of maladies, from deadly diseases with which we are all familiar to equally terrible esoteric conditions: HIV, malaria, pneumococcal and influenza infections; cancer; atherosclerosis; autoimmune diseases such as lupus, diabetes, and multiple sclerosis. The importance of understanding the function of the immune system and learning how to modulate immunity to protect against or treat disease thus cannot be overstated. Fortunately, we are entering an exciting era where the science of immunology is defining pathways for the rational manipulation of the immune system at the cellular and molecular level, and this understanding is leading to dramatic advances in the clinic that are transforming the future of medicine.1,2 These initial advances are being made primarily through biologic drugs– recombinant proteins (especially antibodies) or patient-derived cell therapies– but exciting data from preclinical studies suggest that a marriage of approaches based in biotechnology with the materials science and chemistry of nanomaterials, especially nanoparticles, could enable more effective and safer immune engineering strategies. This review will examine these nanoparticle-based strategies to immune modulation in detail, and discuss the promise and outstanding challenges facing the field of immune engineering from a chemical biology/materials engineering perspectiveNational Institutes of Health (U.S.) (Grants AI111860, CA174795, CA172164, AI091693, and AI095109)United States. Department of Defense (W911NF-13-D-0001 and Awards W911NF-07-D-0004

Computational Identification of Transcriptional Regulators in Human Endotoxemia

One of the great challenges in the post-genomic era is to decipher the underlying principles governing the dynamics of biological responses. As modulating gene expression levels is among the key regulatory responses of an organism to changes in its environment, identifying biologically relevant transcriptional regulators and their putative regulatory interactions with target genes is an essential step towards studying the complex dynamics of transcriptional regulation. We present an analysis that integrates various computational and biological aspects to explore the transcriptional regulation of systemic inflammatory responses through a human endotoxemia model. Given a high-dimensional transcriptional profiling dataset from human blood leukocytes, an elementary set of temporal dynamic responses which capture the essence of a pro-inflammatory phase, a counter-regulatory response and a dysregulation in leukocyte bioenergetics has been extracted. Upon identification of these expression patterns, fourteen inflammation-specific gene batteries that represent groups of hypothetically ‘coregulated’ genes are proposed. Subsequently, statistically significant cis-regulatory modules (CRMs) are identified and decomposed into a list of critical transcription factors (34) that are validated largely on primary literature. Finally, our analysis further allows for the construction of a dynamic representation of the temporal transcriptional regulatory program across the host, deciphering possible combinatorial interactions among factors under which they might be active. Although much remains to be explored, this study has computationally identified key transcription factors and proposed a putative time-dependent transcriptional regulatory program associated with critical transcriptional inflammatory responses. These results provide a solid foundation for future investigations to elucidate the underlying transcriptional regulatory mechanisms under the host inflammatory response. Also, the assumption that coexpressed genes that are functionally relevant are more likely to share some common transcriptional regulatory mechanism seems to be promising, making the proposed framework become essential in unravelling context-specific transcriptional regulatory interactions underlying diverse mammalian biological processes