49 research outputs found

    A network-based comparative framework to study conservation and divergence of proteomes in plant phylogenies

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    Comparative functional genomics offers a powerful approach to study species evolution. To date, the majority of these studies have focused on the transcriptome in mammalian and yeast phylogenies. Here, we present a novel multi-species proteomic dataset and a computational pipeline to systematically compare the protein levels across multiple plant species. Globally we find that protein levels diverge according to phylogenetic distance but is more constrained than the mRNA level. Module-level comparative analysis of groups of proteins shows that proteins that are more highly expressed tend to be more conserved. To interpret the evolutionary patterns of conservation and divergence, we develop a novel network-based integrative analysis pipeline that combines publicly available transcriptomic datasets to define co-expression modules. Our analysis pipeline can be used to relate the changes in protein levels to different species-specific phenotypic traits. We present a case study with the rhizobia-legume symbiosis process that supports the role of autophagy in this symbiotic association

    Targeting Iron Acquisition Blocks Infection with the Fungal Pathogens Aspergillus fumigatus and Fusarium oxysporum

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    Filamentous fungi are an important cause of pulmonary and systemic morbidity and mortality, and also cause corneal blindness and visual impairment worldwide. Utilizing in vitro neutrophil killing assays and a model of fungal infection of the cornea, we demonstrated that Dectin-1 dependent IL-6 production regulates expression of iron chelators, heme and siderophore binding proteins and hepcidin in infected mice. In addition, we show that human neutrophils synthesize lipocalin-1, which sequesters fungal siderophores, and that topical lipocalin-1 or lactoferrin restricts fungal growth in vivo. Conversely, we show that exogenous iron or the xenosiderophore deferroxamine enhances fungal growth in infected mice. By examining mutant Aspergillus and Fusarium strains, we found that fungal transcriptional responses to low iron levels and extracellular siderophores are essential for fungal growth during infection. Further, we showed that targeting fungal iron acquisition or siderophore biosynthesis by topical application of iron chelators or statins reduces fungal growth in the cornea by 60% and that dual therapy with the iron chelator deferiprone and statins further restricts fungal growth by 75%. Together, these studies identify specific host iron-chelating and fungal iron-acquisition mediators that regulate fungal growth, and demonstrate that therapeutic inhibition of fungal iron acquisition can be utilized to treat topical fungal infections

    Seven features of safety in maternity units: a framework based on multisite ethnography and stakeholder consultation

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    Background: Reducing avoidable harm in maternity services is a priority globally. As well as learning from mistakes, it is important to produce rigorous descriptions of ‘what good looks like’. Objective: We aimed to characterise features of safety in maternity units and to generate a plain language framework that could be used to guide learning and improvement. Methods: We conducted a multisite ethnography involving 401 hours of non-participant observations 33 semistructured interviews with staff across six maternity units, and a stakeholder consultation involving 65 semistructured telephone interviews and one focus group. Results: We identified seven features of safety in maternity units and summarised them into a framework, named For Us (For Unit Safety). The features include: (1) commitment to safety and improvement at all levels, with everyone involved; (2) technical competence, supported by formal training and informal learning; (3) teamwork, cooperation and positive working relationships; (4) constant reinforcing of safe, ethical and respectful behaviours; (5) multiple problem-sensing systems, used as basis of action; (6) systems and processes designed for safety, and regularly reviewed and optimised; (7) effective coordination and ability to mobilise quickly. These features appear to have a synergistic character, such that each feature is necessary but not sufficient on its own: the features operate in concert through multiple forms of feedback and amplification. Conclusions: This large qualitative study has enabled the generation of a new plain language framework—For Us—that identifies the behaviours and practices that appear to be features of safe care in hospital-based maternity units

    A constitutive model for thermoplastics based on two temperatures

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    Posed within a two-temperature thermodynamic framework, our aim is to propose a unified glass-rubber constitutive model for thermo-rheologically simple thermoplastic polymers. This modelling set-up usually applies to phenomena wherein sub-macroscopic processes involving different time scales occur and accordingly the thermodynamic system may be interpreted as comprising of two subsystems. The configurational subsystem contains the slower states, while the kinetic-vibrational subsystem comprises of the faster moving states. The two subsystems fail to equilibrate within experimental timescales in the glassy regime (low temperature or high strain rate) due to low structural relaxation rates. As transition to the rubbery regime commences at temperatures higher than glass transition or at sufficiently low loading rates, the two subsystems equilibrate within microscopic timescales. The model exploits physically inspired prescriptions for the free energies due to different underlying mechanisms-elastic stretching, localised shear transformations and infra-molecular straightening of chains. A simple temperature dependent formulation for structural relaxation in terms of heat transfer between the subsystems is used to capture transition between these mechanisms. The model is then validated against experimental results of uniaxial compression tests for various strain rates and temperatures establishing its ability to seamlessly transit between the glassy and rubbery regimes. Also demonstrated is the model's efficacy in capturing the key features of physical ageing and mechanical rejuvenation

    A constitutive model for block-copolymers based on effective temperature

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    Phase segregated copolymers such as elastomeric copolymers find myriad applications especially in impact resistant structures. When domains with varying relaxation characteristics are present, these polymers exhibit thermorheologically complex behaviour. The multiple relaxation processes are herein captured using the effective temperature based thermodynamics, used extensively in modelling thermo-mechanical response of metals and polymers. Specifically, we use two slowly evolving configurational subsystems and a fast evolving kinetic-vibration (K-V) subsystem. The two configurational subsystems represent the inter-molecular and intra-molecular meso-scale configurational transformations occurring within the two domains. The K-V subsystem represents the faster atomic vibrations. The configurational subsystems are weakly coupled with the K-V through heat exchange which accounts for structural relaxations of the individual domains towards the equilibrium microstructure. Based on this, we are able to capture strain rate dependence and strain induced softening of these materials under cyclic loads. In comparison with the existing formulations for such copolymers, ours is perhaps a more transparent approach, as it uses quantities such as volume fraction, glass transition temperatures of individual domains as material parameters. Indeed, our formulation could be readily adapted for non-elastomeric copolymers. It should also be potentially useful as a design tool for copolymers with increased glass transition range

    Screening of Elite Mungbean Genotypes (Vigna radiata (L.) Wilczek) through Multivariate Analysis for Food and Nutritional Security

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    The ever-increasing urbanization to accommodate the growing population reduces substantially the agricultural land but poses a threat to meeting the requirement of proper nutrition for human health. Mungbean [Vigna radiata (L.) Wilczek] is a unique gift bestowed by nature to mankind, which has the potency to make up the gap of protein shortage with an inexpensive cost, but due to its low level of production as well as productivity, which in a roundabout way influences the nutritional status of people resulting in malnutrition. Therefore, enhancement of the total area under mungbean cultivation is not permissible, and an increase in the total productivity per unit area is necessary. In this manner, screening and evaluation of improved genotypes for high yield are necessary to ensure food security. But at the same time seed yield being a complex character governed by several other contributing traits, selection for the characters proves to be quite challenging. As a prerequisite for any breeding program aimed at yield enhancement presence of significant genetic diversity in a given population is highly important. In the present investigation principal component analysis was performed and the results revealed two principal components contributing to the total variance in the population. While the PC1 was predominated by yield and its attributing traits, the PC2 was mainly comprised of growth-related traits. The hierarchical (UPGMA) cluster analysis using standardized data classified the fifty-two mungbean genotypes into 4 clusters, which showed 2 major, 1 minor and one outlier. Among them, cluster II is the most fascinating, as its individual had high seed yield plant–1 and related traits. The present work concluded that the identification of promising high-yielding mungbean genotypes through multivariate analysis has a good promise for future breeding programs with a view of food and nutritional security
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