774 research outputs found

    Detrended fluctuation analysis on the correlations of complex networks under attack and repair strategy

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    We analyze the correlation properties of the Erdos-Renyi random graph (RG) and the Barabasi-Albert scale-free network (SF) under the attack and repair strategy with detrended fluctuation analysis (DFA). The maximum degree k_max, representing the local property of the system, shows similar scaling behaviors for random graphs and scale-free networks. The fluctuations are quite random at short time scales but display strong anticorrelation at longer time scales under the same system size N and different repair probability p_re. The average degree , revealing the statistical property of the system, exhibits completely different scaling behaviors for random graphs and scale-free networks. Random graphs display long-range power-law correlations. Scale-free networks are uncorrelated at short time scales; while anticorrelated at longer time scales and the anticorrelation becoming stronger with the increase of p_re.Comment: 5 pages, 4 figure

    Papillorenal Syndrome-Causing Missense Mutations in PAX2/Pax2 Result in Hypomorphic Alleles in Mouse and Human

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    Papillorenal syndrome (PRS, also known as renal-coloboma syndrome) is an autosomal dominant disease characterized by potentially-blinding congenital optic nerve excavation and congenital kidney abnormalities. Many patients with PRS have mutations in the paired box transcription factor gene, PAX2. Although most mutations in PAX2 are predicted to result in complete loss of one allele's function, three missense mutations have been reported, raising the possibility that more subtle alterations in PAX2 function may be disease-causing. To date, the molecular behaviors of these mutations have not been explored. We describe a novel mouse model of PRS due to a missense mutation in a highly-conserved threonine residue in the paired domain of Pax2 (p.T74A) that recapitulates the ocular and kidney findings of patients. This mutation is in the Pax2 paired domain at the same location as two human missense mutations. We show that all three missense mutations disrupt potentially critical hydrogen bonds in atomic models and result in reduced Pax2 transactivation, but do not affect nuclear localization, steady state mRNA levels, or the ability of Pax2 to bind its DNA consensus sequence. Moreover, these mutations show reduced steady-state levels of Pax2 protein in vitro and (for p.T74A) in vivo, likely by reducing protein stability. These results suggest that hypomorphic alleles of PAX2/Pax2 can lead to significant disease in humans and mice

    Profiling the serum protein corona of fibrillar human islet amyloid polypeptide

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    Amyloids may be regarded as native nanomaterials that form in the presence of complex protein mixtures. By drawing an analogy with the physicochemical properties of nanoparticles in biological fluids, we hypothesized that amyloids should form a protein corona in vivo that would imbue the underlying amyloid with a modified biological identity. To explore this hypothesis we characterized the protein corona of human islet amyloid polypeptide (IAPP) fibrils in FBS using two complementary methodologies developed herein; quartz crystal microbalance and ‘centrifugal capture’, coupled with nano-liquid chromatography tandem mass spectroscopy. Clear evidence for a significant protein corona was obtained. No trends were identified for amyloid corona proteins based on their physicochemical properties, while strong binding with IAPP fibrils occurred for linear proteins or multi-domain proteins with structural plasticity. Proteomic analysis identified amyloid-enriched proteins that are known to play significant roles in mediating cellular machinery and processing, potentially leading to pathological outcomes and therapeutic targets

    Star polymers reduce IAPP toxicity via accelerated amyloid aggregation

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    Protein aggregation into amyloid fibrils is a ubiquitous phenomenon across the spectrum of neurodegenerative disorders and type 2 diabetes. A common strategy against amyloidogenesis is to minimize the populations of toxic oligomers and protofibrils by inhibiting protein aggregation with small molecules or nanoparticles. However, melanin synthesis in nature is realized by accelerated protein fibrillation to circumvent accumulation of toxic intermediates. Accordingly, we designed and demonstrated the use of star-shaped poly(2-hydroxyethyl acrylate) (PHEA) nanostructures for promoting the aggregation while ameliorating the toxicity of human islet amyloid polypeptide (IAPP), the peptide involved in glycemic control and the pathology of type 2 diabetes. The binding of PHEA elevated the beta-sheet content in IAPP aggregates while rendered a new morphology of ‘stelliform’ amyloids originating from the polymers. Atomistic molecular dynamics simulations revealed that the PHEA arms served as rod-like scaffolds for IAPP binding and subsequently accelerated IAPP aggregation by increased local peptide concentration. The tertiary structure of the star nanoparticles was found to be essential to drive the specific interactions required to impel the accelerated IAPP aggregation. This study shed new light on the structure-toxicity relationship of IAPP and points to the potential of exploiting star polymers as a new class of therapeutic agents against amyloidogenesis

    Nanotoxicology and nanomedicine: The Yin and Yang of nano-bio interactions for the new decade

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    Nanotoxicology and nanomedicine are two sub-disciplines of nanotechnology focusing on the phenomena, mechanisms, and engineering at the nano-bio interface. For the better part of the past three decades, these two disciplines have been largely developing independently of each other. Yet recent breakthroughs in microbiome research and the current COVID-19 pandemic demonstrate that holistic approaches are crucial for solving grand challenges in global health. Here we show the Yin and Yang relationship between the two fields by highlighting their shared goals of making safer nanomaterials, improved cellular and organism models, as well as advanced methodologies. We focus on the transferable knowledge between the two fields as nanotoxicological research is moving from pristine to functional nanomaterials, while inorganic nanomaterials - the main subjects of nanotoxicology - have become an emerging source for the development of nanomedicines. We call for a close partnership between the two fields in the new decade, to harness the full potential of nanotechnology for benefiting human health and environmental safety

    A novel technique for detoxification of phenol from wastewater: Nanoparticle Assisted Nano Filtration (NANF)

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    © 2016 Naidu et al. Background: Phenol is one of the most versatile and important organic compound. It is also a growing concern as water pollutants due to its high persistence and toxicity. Removal of Phenol from wastewaters was investigated using a novel nanoparticle adsorption and nanofiltration technique named as Nanoparticle Assisted Nano Filtration (NANF). Methods: The nanoparticle used for NANF study were silver nanoparticles and synthesized to three distinct average particle sizes of 10 nm, 40 nm and 70 nm. The effect of nanoparticle size, their concentrations and their tri and diparticle combinations upon phenol removal were studied. Results: Total surface areas (TSA) for various particle size and concentrations have been calculated and the highest was 4710 × 1012 nm2 for 10 nm particles and 180 ppm concentration while the lowest was for 2461 × 1011 for 70 nm and 60 ppm concentrations. Tri and diparticle studies showed more phenol removal % than that of their individual particles, particularly for using small particles on large membrane pore size and large particles at low concentrations. These results have also been confirmed with COD and toxicity removal studies. Conclusions: The combination of nanoparticles adsorption and nanofiltration results in high phenol removal and mineralization, leading to the conclusion that NANF has very high potential for treating toxic chemical wastewaters

    q-Form fields on p-branes

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    In this paper, we give one general method for localizing any form (q-form) field on p-branes with one extra dimension, and apply it to some typical p-brane models. It is found that, for the thin and thick Minkowski branes with an infinite extra dimension, the zero mode of the q-form fields with q<(p-1)/2 can be localized on the branes. For the thick Minkowski p-branes with one finite extra dimension, the localizable q-form fields are those with q<p/2, and there are also some massive bound Kaluza-Klein modes for these q-form fields on the branes. For the same q-form field, the number of the bound Kaluza-Klein modes (but except the scalar field (q=0)) increases with the dimension of the p-branes. Moreover, on the same p-brane, the q-form fields with higher q have less number of massive bound KK modes. While for a family of pure geometrical thick p-branes with a compact extra dimension, the q-form fields with q<p/2 always have a localized zero mode. For a special pure geometrical thick p-brane, there also exist some massive bound KK modes of the q-form fields with q<p/2, whose number increases with the dimension of the p-brane.Comment: 14 pages, 2 figures, published versio
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