IFN-α/β and autophagy: tug-of-war between HCV and the host

Hepatitis C virus (HCV) infects approximately 130 million people worldwide. The clinical sequelae of this chronic disease include cirrhosis, functional failure and carcinoma of the liver. HCV induces autophagy, a fundamental cellular process for maintaining homeostasis and mediating innate immune response, and also inhibits autophagic protein degradation and suppresses antiviral immunity. In addition to this ploy, the HCV serine protease composed of the viral non-structural proteins 3/4A (NS3/4A) can enzymatically digest two cellular proteins, mitochondria-associated anti-viral signaling protein (MAVS) and Toll/interleukin-1 receptor domain containing adaptor inducing IFN-β (TRIF). Since these two proteins are the adaptor molecules in the retinoic acid-inducible gene I (RIG-I) and TLR3 pathways, respectively, their cleavage has been suggested as a pivotal mechanism by which HCV blunts the IFN-α/β signaling and antiviral responses. Thus far, how HCV perturbs autophagy and copes with IFN-α/β in the liver remains unclear.     

The Drosophila segmentation gene runt has an extended cis-regulatory region that is required for vital expression at other stages of development.

The Drosophila runt gene functions in several developmental pathways during embryogenesis. This gene was initially characterized due to the pivotal role that it plays in the genetic regulatory network that establishes the segmented body pattern. Recently it was found that this X-chromosome-linked gene is one of several dosage-sensitive, X-linked components that is involved in activating the Sex-lethal gene in blastoderm stage female embryos. Finally, this gene is also extensively re-expressed in later stages of embryogenesis in the developing nervous system where it plays an important role in the development of specific neural lineages. We have initiated an analysis of the runt cis-regulatory region in order to investigate runt's roles in these (and other) developmental pathways. Analysis of both the function and the expression patterns of runt genes with truncated cis-regulatory regions indicates that there are multiple elements that make quantitative contributions to runt regulation during segmentation. We find that sequences that are more than 8.5 kb upstream of the runt promoter are necessary for normal expression during the post-blastoderm stages of embryogenesis. Genetic experiments indicate that the post-blastoderm expression of runt is vital to the organism.     

Mammalian microtubule P-body dynamics are mediated by nesprin-1

Nesprins are a multi-isomeric family of spectrin-repeat (SR) proteins, predominantly known as nuclear envelope scaffolds. However, isoforms that function beyond the nuclear envelope remain poorly examined. Here, we characterize p50^Nesp1, a 50-kD isoform that localizes to processing bodies (PBs), where it acts as a microtubule-associated protein capable of linking mRNP complexes to microtubules. Overexpression of dominant-negative p50^Nesp1 caused Rck/p54, but not GW182, displacement from microtubules, resulting in reduced PB movement and cross talk with stress granules (SGs). These cells disassembled canonical SGs induced by sodium arsenite, but not those induced by hydrogen peroxide, leading to cell death and revealing PB–microtubule attachment is required for hydrogen peroxide-induced SG anti-apoptotic functions. Furthermore, p50^Nesp1 was required for miRNA-mediated silencing and interacted with core miRISC silencers Ago2 and Rck/p54 in an RNA-dependent manner and with GW182 in a microtubule-dependent manner. These data identify p50^Nesp1 as a multi-functional PB component and microtubule scaffold necessary for RNA granule dynamics and provides evidence for PB and SG micro-heterogeneity.     

Spin trapping in biological systems. Oxidation of the spin trap 5,5-dimethyl-1-pyrroline-1-oxide by a hydroperoxide-hematin-system.

We have used the spin trap 5,5-dimethyl-1-pyrroline-1-oxide to determine if primary free radicals are involved in the hematin-cumene hydroperoxide system which has been shown to oxidize N-hydroxy-2-acetylaminofluorene into the nitroxyl free radical form of this carcinogen. We have found that the spin trap was oxidized itself rather than trapping either primary free radicals or carcinogen free radicals.     

Modulation of dendritic cell function by Leishmania parasites

The interactions between Leishmania parasites and dendritic cells (DCs) are complex and involve paradoxical functions that can stimulate or halt T cell responses, leading to the control of infection or progression of disease. The magnitude and profile of DC activation vary greatly, depending upon the Leishmania species/strains, developmental stages, DC subsets, serum opsonization, and exogenous DC stimuli involved in the study. In general, the uptake of Leishmania parasites alone can trigger relatively weak and transient DC activation; however, the intracellular parasites (amastigotes) are capable of down-modulating LPS/IFN-gamma-stimulated DC activation via multiple mechanisms. This review will highlight current data regarding the initial interaction of DC subsets with invading parasites, the alterations of DC signaling pathways and function by amastigotes, and the impact of DC functions on protective immunity and disease pathogenesis. Available information provides insight into the mechanisms by which DCs discriminate between the types of pathogens and regulate appropriate immune responses.     

Gel electrophoretic mobility evaluation of a necklace-like DNA nanostructure

DNA nanotechnologies have been highlighted as a promising synthetic tool for the creation of new shaped materials. They have developed a variety of materials in different shapes and sizes [1]. Inspired by these advancements, we sought to design a ring-shaped DNA nanostructure connected by X-DNA blocks. Six XDNA blocks were ligated together to form a circular nanostructure with a diameter of approximately 30 nm. Each DNA block possesses different overhang sequences in its terminal. It was sequentially built up onto each block platform in the line and later clipped into a necklace shape via enzymatic ligation. It was finally evaluated by a gel electrophoretic migration shift assay. It was concluded that the complete set of the necklace shaped DNA nanostructure was the most slowly retarded relative to other forms of incompleteness.     

Mesenchymal stem cell transplantation ameliorates motor function deterioration of spinocerebellar ataxia by rescuing cerebellar Purkinje cells

Background  

Spinocerebellar ataxia (SCA) refers to a disease entity in which polyglutamine aggregates are over-produced in Purkinje cells (PCs) of the cerebellum as well as other neurons in the central nervous system, and the formation of intracellular polyglutamine aggregates result in the loss of neurons as well as deterioration of motor functions. So far there is no effective neuroprotective treatment for this debilitating disease although numerous efforts have been made. Mesenchymal stem cells (MSCs) possess multi-lineage differentiation potentials as well as immuno-modulatory properties, and are theoretically good candidates for SCA treatment. The purpose of this study is to investigate whether transplantation of human MSCs (hMSCs) can rescue cerebellar PCs and ameliorate motor function deterioration in SCA in a pre-clinical animal model.