138 research outputs found
European Dermatology Forum guidelines on topical photodynamic therapy 2019 Part 2: emerging indications â field cancerization, photorejuvenation and inflammatory/infective dermatoses
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Population-Wide Emergence of Antiviral Resistance during Pandemic Influenza
Background: The emergence of neuraminidase inhibitor resistance has raised concerns about the prudent use of antiviral drugs in response to the next influenza pandemic. While resistant strains may initially emerge with compromised viral fitness, mutations that largely compensate for this impaired fitness can arise. Understanding the extent to which these mutations affect the spread of disease in the population can have important implications for developing pandemic plans.
Methodology/Principal Findings: By employing a deterministic mathematical model, we investigate possible scenarios for the emergence of population-wide resistance in the presence of antiviral drugs. The results show that if the treatment level (the fraction of clinical infections which receives treatment) is maintained constant during the course of the outbreak, there is an optimal level that minimizes the final size of the pandemic. However, aggressive treatment above the optimal level can substantially promote the spread of highly transmissible resistant mutants and increase the total number of infections. We demonstrate that resistant outbreaks can occur more readily when the spread of disease is further delayed by applying other curtailing measures, even if treatment levels are kept modest. However, by changing treatment levels over the course of the pandemic, it is possible to reduce the final size of the pandemic below the minimum achieved at the optimal constant level. This reduction can occur with low treatment levels during the early stages of the pandemic, followed by a sharp increase in drug-use before the virus becomes widely spread.
Conclusions/Significance: Our findings suggest that an adaptive antiviral strategy with conservative initial treatment levels, followed by a timely increase in the scale of drug-use, can minimize the final size of a pandemic while preventing large outbreaks of resistant infections
In-Vitro Helix Opening of M. tuberculosis oriC by DnaA Occurs at Precise Location and Is Inhibited by IciA Like Protein
BACKGROUND: Mycobacterium tuberculosis (M.tb), the pathogen that causes tuberculosis, is capable of staying asymptomatically in a latent form, persisting for years in very low replicating state, before getting reactivated to cause active infection. It is therefore important to study M.tb chromosome replication, specifically its initiation and regulation. While the region between dnaA and dnaN gene is capable of autonomous replication, little is known about the interaction between DnaA initiator protein, oriC origin of replication sequences and their negative effectors of replication. METHODOLOGY/PRINCIPAL FINDINGS: By KMnO(4) mapping assays the sequences involved in open complex formation within oriC, mediated by M.tb DnaA protein, were mapped to position -500 to -518 with respect to the dnaN gene. Contrary to E. coli, the M.tb DnaA in the presence of non-hydrolysable analogue of ATP (ATPgammaS) was unable to participate in helix opening thereby pointing to the importance of ATP hydrolysis. Interestingly, ATPase activity in the presence of supercoiled template was higher than that observed for DnaA box alone. M.tb rRv1985c, a homologue of E.coli IciA (Inhibitor of chromosomal initiation) protein, could inhibit DnaA-mediated in-vitro helix opening by specifically binding to A+T rich region of oriC, provided the open complex formation had not initiated. rIciA could also inhibit in-vitro replication of plasmid carrying the M.tb origin of replication. CONCLUSIONS/SIGNIFICANCE: These results have a bearing on the functional role of the important regulator of M.tb chromosomal replication belonging to the LysR family of bacterial regulatory proteins in the context of latency
A Novel RSSI Prediction Using Imperialist Competition Algorithm (ICA), Radial Basis Function (RBF) and Firefly Algorithm (FFA) in Wireless Networks
This study aims to design a vertical handover prediction method to minimize unnecessary handovers for a mobile node (MN) during the vertical handover process. This relies on a novel method for the prediction of a received signal strength indicator (RSSI) referred to as IRBF-FFA, which is designed by utilizing the imperialist competition algorithm (ICA) to train the radial basis function (RBF), and by hybridizing with the firefly algorithm (FFA) to predict the optimal solution. The prediction accuracy of the proposed IRBFâFFA model was validated by comparing it to support vector machines (SVMs) and multilayer perceptron (MLP) models. In order to assess the modelâs performance, we measured the coefficient of determination (R2), correlation coefficient (r), root mean square error (RMSE) and mean absolute percentage error (MAPE). The achieved results indicate that the IRBFâFFA model provides more precise predictions compared to different ANNs, namely, support vector machines (SVMs) and multilayer perceptron (MLP). The performance of the proposed model is analyzed through simulated and real-time RSSI measurements. The results also suggest that the IRBFâFFA model can be applied as an efficient technique for the accurate prediction of vertical handover
BOD1 Is Required for Cognitive Function in Humans and <i>Drosophila</i>
Here we report a stop-mutation in the BOD1 (Biorientation Defective 1) gene, which co-segregates with intellectual disability in a large consanguineous family, where individuals that are homozygous for the mutation have no detectable BOD1 mRNA or protein. The BOD1 protein is required for proper chromosome segregation, regulating phosphorylation of PLK1 substrates by modulating Protein Phosphatase 2A (PP2A) activity during mitosis. We report that fibroblast cell lines derived from homozygous BOD1 mutation carriers show aberrant localisation of the cell cycle kinase PLK1 and its phosphatase PP2A at mitotic kinetochores. However, in contrast to the mitotic arrest observed in BOD1-siRNA treated HeLa cells, patient-derived cells progressed through mitosis with no apparent segregation defects but at an accelerated rate compared to controls. The relatively normal cell cycle progression observed in cultured cells is in line with the absence of gross structural brain abnormalities in the affected individuals. Moreover, we found that in normal adult brain tissues BOD1 expression is maintained at considerable levels, in contrast to PLK1 expression, and provide evidence for synaptic localization of Bod1 in murine neurons. These observations suggest that BOD1 plays a cell cycle-independent role in the nervous system. To address this possibility, we established two Drosophila models, where neuron-specific knockdown of BOD1 caused pronounced learning deficits and significant abnormalities in synapse morphology. Together our results reveal novel postmitotic functions of BOD1 as well as pathogenic mechanisms that strongly support a causative role of BOD1 deficiency in the aetiology of intellectual disability. Moreover, by demonstrating its requirement for cognitive function in humans and Drosophila we provide evidence for a conserved role of BOD1 in the development and maintenance of cognitive features
Cellular therapies for treating pain associated with spinal cord injury
Spinal cord injury leads to immense disability and loss of quality of life in human with no satisfactory clinical cure. Cell-based or cell-related therapies have emerged as promising therapeutic potentials both in regeneration of spinal cord and mitigation of neuropathic pain due to spinal cord injury. This article reviews the various options and their latest developments with an update on their therapeutic potentials and clinical trialing
Geomagnetic disturbances may be environmental risk factor for multiple sclerosis: an ecological study of 111 locations in 24 countries
Magnetic branes in GaussâBonnet gravity with nonlinear electrodynamics: correction of magnetic branes in EinsteinâMaxwell gravity
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