39 research outputs found

    Selector function of MHC I molecules is determined by protein plasticity

    No full text
    The selection of peptides for presentation at the surface of most nucleated cells by major histocompatibility complex class I molecules (MHC I) is crucial to the immune response in vertebrates. However, the mechanisms of the rapid selection of high affinity peptides by MHC I from amongst thousands of mostly low affinity peptides are not well understood. We developed computational systems models encoding distinct mechanistic hypotheses for two molecules, HLA-B*44:02 (B*4402) and HLA-B*44:05 (B*4405), which differ by a single residue yet lie at opposite ends of the spectrum in their intrinsic ability to select high affinity peptides. We used <em>in vivo</em> biochemical data to infer that a conformational intermediate of MHC I is significant for peptide selection. We used molecular dynamics simulations to show that peptide selector function correlates with protein plasticity, and confirmed this experimentally by altering the plasticity of MHC I with a single point mutation, which altered <em>in vivo</em> selector function in a predictable way. Finally, we investigated the mechanisms by which the co-factor tapasin influences MHC I plasticity. We propose that tapasin modulates MHC I plasticity by dynamically coupling the peptide binding region and {\alpha}<sub>3</sub> domain of MHC I allosterically, resulting in enhanced peptide selector function

    Promoting climate-smart sustainable agroforestry to tackle social and environmental challenges: The case of macadamia agroforestry in Malawi

    Get PDF
    Our current global food system is understood to require a fundamental transformation based on a holistic approach to maintain long-term fertility, healthy biodiverse agroecosystems, and climate-proof/secure livelihoods. Recently, there has been a growing recognition of smallholder farmers’ contributions to addressing key global environmental and social development issues, including poverty, food security, climate change, and sustainable development. One specific approach is agroforestry-based agriculture, in which edible food and commercially important trees are grown on cropland, thereby improving the biodiversity of farming systems, enhancing agricultural productivity, and adding benefits such as nutrition and financial stability, not least climate resilience. In this context, we present lessons learned from an agroforestry system in Malawi that involves smallholder farmer cooperatives interplanting macadamia nut trees with annual crops such as groundnuts, maize, and soybeans. We review holistic advantages such as yield improvement, farmer perceptions, and challenges. We provide insights into what works in designing (Neno Macadami Trust and linkage with finance plan) and draw lessons that can be applied to other comparable programmes worldwide

    Systematic construction of anomaly detection benchmarks from real data

    Full text link
    Research in anomaly detection suffers from a lack of realis-tic and publicly-available problem sets. This paper discusses what properties such problem sets should possess. It then introduces a methodology for transforming existing classi-fication data sets into ground-truthed benchmark data sets for anomaly detection. The methodology produces data sets that vary along three important dimensions: (a) point diffi-culty, (b) relative frequency of anomalies, and (c) clustered-ness. We apply our generated datasets to benchmark several popular anomaly detection algorithms under a range of dif-ferent conditions. 1

    Effect of Harvesting Time and Drying Methods on Aflatoxin Contamination in Groundnut in Mozambique

    Get PDF
    The production and utilization of groundnut have increased tremendously across all provinces of Mozambique. However, the presence of aflatoxins has remained a critical food concern in the human diet. In this study, the effect of harvesting time and drying methods on aflatoxin contamination was examined in Northern Mozambique. A randomized complete block design in a split-split plot arrangement with four replications was used with groundnut varieties as the main plot and harvesting dates and drying methods as the subplots. Groundnut samples were analyzed for aflatoxin using the Mreader. In both locations, field observations indicated that on average, aflatoxin contamination levels were lower at physiological maturity (≤10 ppb) compared to harvesting 10 days before (≤15 ppb) and 10 days after physiological maturity (≥20 ppb). It was also observed that the two drying methods were effective in prevention of aflatoxin contamination on groundnut kernels to levels lower than 20 ppb. Aflatoxin contamination levels were significantly lower (≤12 ppb) as a result of the A-Frame than the tarpaulin method. The results of this study, therefore, have indicated that proper postharvest management of groundnuts, such as harvesting at physiological maturity and improved drying, gave lowest aflatoxin contamination levels

    Multiplexed single-cell proteomics using SCoPE2

    Get PDF
    Many biological systems are composed of diverse single cells. This diversity necessitates functional and molecular single-cell analysis. Single-cell protein analysis has long relied on affinity reagents, but emerging mass-spectrometry methods (either label-free or multiplexed) have enabled quantifying >1,000 proteins per cell while simultaneously increasing the specificity of protein quantification. Here we describe the Single Cell ProtEomics (SCoPE2) protocol, which uses an isobaric carrier to enhance peptide sequence identification. Single cells are isolated by FACS or CellenONE into multiwell plates and lysed by Minimal ProteOmic sample Preparation (mPOP), and their peptides labeled by isobaric mass tags (TMT or TMTpro) for multiplexed analysis. SCoPE2 affords a cost-effective single-cell protein quantification that can be fully automated using widely available equipment and scaled to thousands of single cells. SCoPE2 uses inexpensive reagents and is applicable to any sample that can be processed to a single-cell suspension. The SCoPE2 workflow allows analyzing ~200 single cells per 24 h using only standard commercial equipment. We emphasize experimental steps and benchmarks required for achieving quantitative protein analysis

    Climate suitability predictions for the cultivation of macadamia (<i>Macadamia integrifolia</i>) in Malawi using climate change scenarios

    Get PDF
    Climate change is altering suitable areas of crop species worldwide, with cascading effects on people reliant upon those crop species as food sources and for income generation. Macadamia is one of Malawi’s most important and profitable crop species; however, climate change threatens its production. Thus, this study’s objective is to quantitatively examine the potential impacts of climate change on the climate suitability for macadamia in Malawi. We utilized an ensemble model approach to predict the current and future (2050s) suitability of macadamia under two Representative Concentration Pathways (RCPs). We achieved a good model fit in determining suitability classes for macadamia (AUC = 0.9). The climatic variables that strongly influence macadamia’s climatic suitability in Malawi are suggested to be the precipitation of the driest month (29.1%) and isothermality (17.3%). Under current climatic conditions, 57% (53,925 km2) of Malawi is climatically suitable for macadamia. Future projections suggest that climate change will decrease the suitable areas for macadamia by 18% (17,015 km2) and 21.6% (20,414 km2) based on RCP 4.5 and RCP 8.5, respectively, with the distribution of suitability shifting northwards in the 2050s. The southern and central regions of the country will suffer the greatest losses (≥ 8%), while the northern region will be the least impacted (4%). We conclude that our study provides critical evidence that climate change will reduce the suitable areas for macadamia production in Malawi, depending on climate drivers. Therefore area-specific adaptation strategies are required to build resilience among producers
    corecore