Genetic association and altered gene expression of mir-155 in multiple sclerosis patients

Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system characterized by chronic inflammation, demyelination, and axonal damage. As microRNA (miRNA)-dependent alterations in gene expression in hematopoietic cells are critical for mounting an appropriate immune response, miRNA deregulation may result in defects in immune tolerance. In this frame, we sought to explore the possible involvement of miRNAs in MS pathogenesis by monitoring the differential expression of 22 immunity-related miRNAs in peripheral blood mononuclear cells of MS patients and healthy controls, by using a microbead-based technology. Three miRNAs resulted >2 folds up-regulated in MS vs controls, whereas none resulted down-regulated. Interestingly, the most up-regulated miRNA (mir-155; fold change = 3.30; P = 0.013) was previously reported to be up-regulated also in MS brain lesions. Mir-155 up-regulation was confirmed by qPCR experiments. The role of mir-155 in MS susceptibility was also investigated by genotyping four single nucleotide polymorphisms (SNPs) mapping in the mir-155 genomic region. A haplotype of three SNPs, corresponding to a 12-kb region encompassing the last exon of BIC (the B-cell Integration Cluster non-coding RNA, from which mir-155 is processed), resulted associated with the disease status (P = 0.035; OR = 1.36, 95% CI = 1.05-1.77), suggesting that this locus strongly deserves further investigations.     

What are the impacts of living in social housing? New evidence from Australia

Abstract

In this paper, we apply statistical matching methods to a national longitudinal dataset of Australians facing housing insecurity to estimate the impacts of social housing on employment, education, health, incarceration and homelessness. We find social housing in Australia provides an important `safety net’ protecting people from homelessness. However, at least in the short run, individuals in social housing have similar outcomes in terms of employment, education, physical and mental health, and incarceration to other comparable individuals not in social housing. These are the first estimates of causal impacts of social housing, simultaneously estimating impacts on a range of shelter and non-shelter outcomes highlighted as important by the broader social housing literature. They also provide an interesting contrast with the existing US estimates. These results are potentially due to strict targeting of individuals into social housing and that they represent the average effect across individuals who may experience substantially different impacts.     

Close relationships and adjustments to a life crisis: The case of breast cancer.

When life crises occur significant others are thought to help alleviate distress and resolve practical problems. Yet life crises may overwhelm significant others, eroding their ability to provide effective support. The accuracy of these contrasting accounts of relationship functioning was evaluated in a study of 102 breast cancer patients and their significant others, interviewed at 4 and 10 months after diagnosis. Results largely confirmed the negative account of relationship functioning. Although significant others provided support in response to patients' physical impairment, they withdrew support in response to patients' emotional distress. Moreover, support from significant others did not alleviate patients' distress or promote physical recovery. These results reveal limits to the effectiveness of close relationships in times of severe stress. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

New Anti-Nodal Monoclonal Antibodies Targeting the Nodal Pre-Helix Loop Involved in Cripto-1 Binding

Nodal is a potent embryonic morphogen belonging to the TGF-β superfamily. Typically, it also binds to the ALK4/ActRIIB receptor complex in the presence of the co-receptor Cripto-1. Nodal expression is physiologically restricted to embryonic tissues and human embryonic stem cells, is absent in normal cells but re-emerges in several human cancers, including melanoma, breast, and colon cancer. Our aim was to obtain mAbs able to recognize Nodal on a major CBR (Cripto-Binding-Region) site and to block the Cripto-1-mediated signalling. To achieve this, antibodies were raised against hNodal(44–67) and mAbs generated by the hybridoma technology. We have selected one mAb, named 3D1, which strongly associates with full-length rhNodal (K_D 1.4 nM) and recognizes the endogenous protein in a panel of human melanoma cell lines by western blot and FACS analyses. 3D1 inhibits the Nodal-Cripto-1 binding and blocks Smad2/3 phosphorylation. Data suggest that inhibition of the Nodal-Cripto-1 axis is a valid therapeutic approach against melanoma and 3D1 is a promising and interesting agent for blocking Nodal-Cripto mediated tumor development. These findings increase the interest for Nodal as both a diagnostic and prognostic marker and as a potential new target for therapeutic intervention.     

Hybrid optimal control: Case study of a car with gears

The purpose of this paper is to show the use of some analytical tools for hybrid optimal control. We illustrate both the hybrid maximum principle and the hybrid necessary principle at work on a simple example of a car with gears. The model is sufficiently rich to generate non-trivial optimization problems and the obtained results match with intuition. Finally, computer simulations confirm the theoretical analysis.     

Master equations for two qubits coupled via a nonlinear mode

A microscopic master equation describing the dynamics of two qubits coupled via a nonlinear mediator is constructed supposing that the two qubits, as well as the nonlinear mode, interact, each with its own independent bosonic bath. Generally speaking the master equation derived in this way represents a more appropriate tool for studying the dynamics of open quantum systems. Indeed we show that it is more complex than the phenomenological master equation, constructed simply adding ad hoc dissipative terms.     

Microfluidic devices modulate tumor cell line susceptibility to NK cell recognition

This study aims to adoptively reduce the major histocompatibility complex class I (MHC-I) molecule surface expression of cancer cells by exposure to microfluid shear stress and a monoclonal antibody. A microfluidic system is developed and tumor cells are injected at different flow rates. The bottom surface of the microfluidic system is biofunctionalized with antibodies (W6/32) specific for the MHC-I molecules with a simple method based on microfluidic protocols. The antibodies promote binding between the bottom surface and the MHC-I molecules on the tumor cell membrane. The cells are injected at an optimized flow rate, then roll on the bottom surface and are subjected to shear stress. The stress is localized and enhanced on the part of the membrane where MHC-I proteins are expressed, since they stick to the antibodies of the system. The localized stress allows a stripping effect and consequent reduction of the MHC-I expression. It is shown that it is possible to specifically treat and recover eukaryotic cells without damaging the biological samples. MHC-I molecule expression on treated and control cell surfaces is measured on tumor and healthy cells. After the cell rolling treatment a clear reduction of MHC-I levels on the tumor cell membrane is observed, whereas no changes are observed on healthy cells (monocytes). The MHC-I reduction is investigated and the possibility that the developed system could induce a loss of these molecules from the tumor cell surface is addressed. The percentage of living tumor cells (viability) that remain after the treatment is measured. The changes induced by the microfluidic system are analyzed by fluorescence-activated cell sorting and confocal microscopy. Cytotoxicity tests show a relevant increased susceptibility of natural killer (NK) cells on microchip-treated tumor cells.