Insights into battles between Mycobacterium tuberculosis and macrophages

As the first line of immune defense for Mycobacterium tuberculosis (Mtb), macrophages also provide a major habitat for Mtb to reside in the host for years. The battles between Mtb and macrophages have been constant since ancient times. Triggered upon Mtb infection, multiple cellular pathways in macrophages are activated to initiate a tailored immune response toward the invading pathogen and regulate the cellular fates of the host as well. Toll-like receptors (TLRs) expressed on macrophages can recognize pathogen-associated-molecular patterns (PAMPs) on Mtb and mediate the production of immune-regulatory cytokines such as tumor necrosis factor (TNF) and type I Interferons (IFNs). In addition, Vitamin D receptor (VDR) and Vitamin D-1-hydroxylase are up-regulated in Mtb-infected macrophages, by which Vitamin D participates in innate immune responses. The signaling pathways that involve TNF, type I IFNs and Vitamin D are inter-connected, which play critical roles in the regulation of necroptosis, apoptosis, and autophagy of the infected macrophages. This review article summarizes current knowledge about the interactions between Mtb and macrophages, focusing on cellular fates of the Mtb-infected macrophages and the regulatory molecules and cellular pathways involved in those processes

Novel genome polymorphisms in BCG vaccine strains and impact on efficacy

Bacille Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis currently used as a vaccine against tuberculosis. Global distribution and propagation of BCG has contributed to the in vitro evolution of the vaccine strain and is thought to partially account for the different outcomes of BCG vaccine trials. Previous efforts by several molecular techniques effectively identified large sequence polymorphisms among BCG daughter strains, but lacked the resolution to identify smaller changes. In this study, we have used a NimbleGen tiling array for whole genome comparison of 13 BCG strains. Using this approach, in tandem with DNA resequencing, we have identified six novel large sequence polymorphisms including four deletions and two duplications in specific BCG strains. Moreover, we have uncovered various polymorphisms in the phoP-phoR locus. Importantly, these polymorphisms affect genes encoding established virulence factors including cell wall complex lipids, ESX secretion systems, and the PhoP-PhoR two-component system. Our study demonstrates that major virulence factors are different among BCG strains, which provide molecular mechanisms for important vaccine phenotypes including adverse effect profile, tuberculin reactivity and protective efficacy. These findings have important implications for the development of a new generation of vaccines

NRAV, a Long Noncoding RNA, Modulates Antiviral Responses through Suppression of Interferon-Stimulated Gene Transcription

SummaryLong noncoding RNAs (lncRNAs) modulate various biological processes, but their role in host antiviral responses is largely unknown. Here we identify a lncRNA as a key regulator of antiviral innate immunity. Following from the observation that a lncRNA that we call negative regulator of antiviral response (NRAV) was dramatically downregulated during infection with several viruses, we ectopically expressed NRAV in human cells or transgenic mice and found that it significantly promotes influenza A virus (IAV) replication and virulence. Conversely, silencing NRAV suppressed IAV replication and virus production, suggesting that reduction of NRAV is part of the host antiviral innate immune response to virus infection. NRAV negatively regulates the initial transcription of multiple critical interferon-stimulated genes (ISGs), including IFITM3 and MxA, by affecting histone modification of these genes. Our results provide evidence for a lncRNA in modulating the antiviral interferon response

Synergetic treatment of dye contaminated wastewater using microparticles functionalized with carbon nanotubes/titanium dioxide nanocomposites

This journal is © The Royal Society of Chemistry. The highly efficient treatment of azo dye contaminated wastewater from the textile industry is an important but challenging problem. Herein, polydimethylsiloxane (PDMS) microparticles, incorporating multiple-walled carbon nanotubes/titanium dioxide (MWCNTs/TiO2) nanocomposites, were successfully synthesized to treat wastewater containing Rhodamine B (RhB) dyes in a synergetic approach, by combining sorption and photocatalytic degradation. The surfactant wrapping sol-gel method was applied to synthesize MWCNTs/TiO2 nanocomposites with TiO2 nanoparticles evenly distributed on the surface of the MWCNTs. The PDMS microparticles were fabricated with an oil-in-water (O/W) single emulsion template, using needle-based microfluidic devices. MWCNTs/TiO2 nanocomposites (at a weight ratio of 1%, and 2%, respectively) were mixed with the PDMS precursor as the dispersed phase, and an aqueous solution of polyvinyl alcohol (PVA) was used as the continuous phase. Highly monodispersed microparticles, with average diameters of 692.7 μm (Coefficient of Variation, CV = 0.74%) and 678.3 μm (CV = 1.04%), were formed at an applied flow rate of the dispersed and continuous phase of 30 and 200 μL min-1, respectively. The fabricated hybrid microparticles were employed for the treatment of RhB, involving a dark equilibrium for 5 hours and UV irradiation for 3 hours. The experimental conditions of applied PDMS type, mass loading amount, treatment duration, photodegradation kinetics, initial concentration of pollutants and environmental pH values were investigated in this work. The PDMS microparticles with 2 wt% MWCNTs/TiO2 nanocomposites can exhibit a removal efficiency of 85%. Remarkably, an efficiency of 70% can be retained after the microparticles have been recycled and reused for 3 cycles. The PDMS-MWCNTs/TiO2 microparticles possess a superior performance over conventional treatment approaches for dye contaminated wastewater, especially in recyclability and the prevention of secondary pollution. This work provides a feasible and eco-friendly route for developing an efficient and low-cost microfluidic method for treating complicated water environmental systems

Genetic Variation of SARS Coronavirus in Beijing Hospital

To characterize genetic variation of severe acute respiratory syndrome–associated coronavirus (SARS-CoV) transmitted in the Beijing area during the epidemic outbreak of 2003, we sequenced 29 full-length S genes of SARS-CoV from 20 hospitalized SARS patients on our unit, the Beijing 302 Hospital. Viral RNA templates for the S-gene amplification were directly extracted from raw clinical samples, including plasma, throat swab, sputum, and stool, during the course of the epidemic in the Beijing area. We used a TA-cloning assay with direct analysis of nested reverse transcription–polymerase chain reaction products in sequence. One hundred thirteen sequence variations with nine recurrent variant sites were identified in analyzed S-gene sequences compared with the BJ01 strain of SARS-CoV. Among them, eight variant sites were, we think, the first documented. Our findings demonstrate the coexistence of S-gene sequences with and without substitutions (referred to BJ01) in samples analyzed from some patients

Polypyrrole/TiO2 nanotube arrays with coaxial heterogeneous structure as sulfur hosts for lithium sulfur batteries

The lithium-sulfur cell has shown great prospects for future energy conversion and storage systems due to the high theoretical specific capacity of sulfur, 1675 mAh g−1. However, it has been hindered by rapid capacity decay and low energy efficiency. In this work, polypyrrole (PPy)/TiO2 nanotubes with coaxial heterogeneous structure as the substrate of the cathode is prepared and used to improve the electrochemical performance of sulfur electrodes. TiO2 nanotubes decorated with PPy provide a highly ordered conductive framework for Li+ ion diffusion and reaction with sulfur. This architecture also is helpful for trapping the produced polysulfides, and as a result attenuates the capacity decay. Furthermore, the heat treatment temperature used in the sulfur loading process has been confirmed to have an important impact on the overall performance of the resultant cell. The as-designed S/PPy/TiO2 nanotube cathode using an elevated heating temperature shows excellent cycling stability with a high discharge capacity of 1150 mAh g−1 and average coulombic efficiency of 96% after 100 cycles

Polluted dust promotes new particle formation and growth

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