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Hermann Cuntz Friedrich Forstner Bettina Schnell Georg Ammer Shamprasad Varija Raghu Alexander Borst 《PloS one》2013,8(8)
Important brain functions need to be conserved throughout organisms of extremely varying sizes. Here we study the scaling properties of an essential component of computation in the brain: the single neuron. We compare morphology and signal propagation of a uniquely identifiable interneuron, the HS cell, in the blowfly (Calliphora) with its exact counterpart in the fruit fly (Drosophila) which is about four times smaller in each dimension. Anatomical features of the HS cell scale isometrically and minimise wiring costs but, by themselves, do not scale to preserve the electrotonic behaviour. However, the membrane properties are set to conserve dendritic as well as axonal delays and attenuation as well as dendritic integration of visual information. In conclusion, the electrotonic structure of a neuron, the HS cell in this case, is surprisingly stable over a wide range of morphological scales. 相似文献
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Cardiovascular disease (CVD) risk in India is currently assessed using the World Health Organization/International Society for Hypertension (WHO/ISH) risk prediction charts since no population-specific models exist. The WHO/ISH risk prediction charts have two versions—one with total cholesterol as a predictor (the high information (HI) model) and the other without (the low information (LI) model). However, information on the WHO/ISH risk prediction charts including guidance on which version to use and when, as well as relative performance of the LI and HI models, is limited. This article aims to, firstly, quantify the relative performance of the LI and HI WHO/ISH risk prediction (for WHO-South East Asian Region D) using data from rural India. Secondly, we propose a pre-screening (simplified) point-of-care (POC) test to identify patients who are likely to benefit from a total cholesterol (TC) test, and subsequently when the LI model is preferential to HI model. Analysis was performed using cross-sectional data from rural Andhra Pradesh collected in 2005 with recorded blood cholesterol measurements (N = 1066). CVD risk was computed using both LI and HI models, and high risk individuals who needed treatment(T
HR) were subsequently identified based on clinical guidelines. Model development for the POC assessment of a TC test was performed through three machine learning techniques: Support Vector Machine (SVM), Regularised Logistic Regression (RLR), and Random Forests (RF) along with a feature selection process. Disagreement in CVD risk predicted by LI and HI WHO/ISH models was 14.5% (n = 155; p<0.01) overall and comprised 36 clinically relevant T
HR patients (31% of patients identified as T
HR by using either model). Using two patient-specific parameters (age, systolic blood pressure), our POC assessment can pre-determine the benefit of TC testing and choose the appropriate risk model (out-of-sample AUCs:RF-0.85,SVM-0.84,RLR:0.82 and maximum sensitivity-98%). The identification of patients benefitting from a TC test for CVD risk stratification can aid planning for resource-allocation and save costs for large-scale screening programmes. 相似文献
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Patil Basavaprabhu L. Raghu Rajanna Dangwal Meenakshi Byregowda M. Voloudakis Andreas 《Journal of plant biochemistry and biotechnology.》2021,30(2):400-405
Journal of Plant Biochemistry and Biotechnology - Pigeonpea sterility mosaic emaraviruses (PPSMVs) cause sterility mosaic disease in pigeonpea which significantly reduce the crop yield. Currently... 相似文献
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Olusegun O. Osunkoya Christine Perrett Chandima Fernando Cameron Clark Sathyamurthy Raghu 《Population Ecology》2013,55(2):291-303
It is at the population level that an invasion either fails or succeeds. Lantana camara L. (Verbenaceae) is a weed of great significance in Queensland Australia and globally but its whole life-history ecology is poorly known. Here we used 3 years of field data across four land use types (farm, hoop pine plantation and two open eucalyptus forests, including one with a triennial fire regime) to parameterise the weed’s vital rates and develop size-structured matrix models. Lantana camara in its re-colonization phase, as observed in the recently cleared hoop pine plantation, was projected to increase more rapidly (annual growth rate, λ = 3.80) than at the other three sites (λ 1.88–2.71). Elasticity analyses indicated that growth contributed more (64.6 %) to λ than fecundity (18.5 %) or survival (15.5 %), while across size groups, the contribution was of the order: juvenile (19–27 %) ≥ seed (17–28 %) ≥ seedling (16–25 %) > small adult (4–26 %) ≥ medium adult (7–20 %) > large adult (0–20 %). From a control perspective it is difficult to determine a single weak point in the life cycle of lantana that might be exploited to reduce growth below a sustaining rate. The triennial fire regime applied did not alter the population elasticity structure nor resulted in local control of the weed. However, simulations showed that, except for the farm population, periodic burning could work within 4–10 years for control of the weed, but fire frequency should increase to at least once every 2 years. For the farm, site-specific control may be achieved by 15 years if the biennial fire frequency is tempered with increased burning intensity. 相似文献
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Uma Shankar Sagaram Kaoutar El-Mounadi Garry W. Buchko Howard R. Berg Jagdeep Kaur Raghu S. Pandurangi Thomas J. Smith Dilip M. Shah 《PloS one》2013,8(12)
MtDef4 is a 47-amino acid cysteine-rich evolutionary conserved defensin from a model legume Medicago truncatula. It is an apoplast-localized plant defense protein that inhibits the growth of the ascomycetous fungal pathogen Fusarium graminearum in vitro at micromolar concentrations. Little is known about the mechanisms by which MtDef4 mediates its antifungal activity. In this study, we show that MtDef4 rapidly permeabilizes fungal plasma membrane and is internalized by the fungal cells where it accumulates in the cytoplasm. Furthermore, analysis of the structure of MtDef4 reveals the presence of a positively charged γ-core motif composed of β2 and β3 strands connected by a positively charged RGFRRR loop. Replacement of the RGFRRR sequence with AAAARR or RGFRAA abolishes the ability of MtDef4 to enter fungal cells, suggesting that the RGFRRR loop is a translocation signal required for the internalization of the protein. MtDef4 binds to phosphatidic acid (PA), a precursor for the biosynthesis of membrane phospholipids and a signaling lipid known to recruit cytosolic proteins to membranes. Amino acid substitutions in the RGFRRR sequence which abolish the ability of MtDef4 to enter fungal cells also impair its ability to bind PA. These findings suggest that MtDef4 is a novel antifungal plant defensin capable of entering into fungal cells and affecting intracellular targets and that these processes are mediated by the highly conserved cationic RGFRRR loop via its interaction with PA. 相似文献
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Jayashree Biswal Prajisha Jayaprakash Rayala Suresh Kumar Ganesh Venkatraman Saritha Poopandi Raghu Rangasamy 《Journal of biomolecular structure & dynamics》2020,38(1):13-31
Abstractp21-activated kinases (Paks) play an integral component in various cellular diverse processes. The full activation of Pak is dependent upon several serine residues present in the N-terminal region, a threonine present at the activation loop, and finally the phosphorylation of these residues ensure the complete activation of Pak1. The present study deals with the identification of novel potent candidates of Pak1 using computational methods as anti-cancer compounds. A diverse energy based pharmacophore (e-pharmacophore) was developed using four co-crystal inhibitors of Pak1 having pharmacophore features of 5 (DRDRR), 6 (DRHADR), and 7 (RRARDRP and DRRDADH) hypotheses. These models were used for rigorous screening against e-molecule database. The obtained hits were filtered using ADME/T and molecular docking to identify the high affinity binders. These hits were subjected to hierarchical clustering using dendritic fingerprint inorder to identify structurally diverse molecules. The diverse hits were scored against generated water maps to obtain WM/MM ΔG binding energy. Furthermore, molecular dynamics simulation and density functional theory calculations were performed on the final hits to understand the stability of the complexes. Five structurally diverse novel Pak1 inhibitors (4835785, 32198676, 32407813, 76038049, and 32945545) were obtained from virtual screening, water thermodynamics and WM/MM ΔG binding energy. All hits revealed similar mode of binding pattern with the hinge region residues replacing the unstable water molecules in the binding site. The obtained novel hits could be used as a platform to design potent drugs that could be experimentally tested against cancer patients having increased Pak1 expression. 相似文献