Decreased T cell reactivity to Epstein–Barr virus infected lymphoblastoid cell lines in multiple sclerosis

Objective: To investigate T cell and antibody immunity to Epstein-Barr virus (EBV) in multiple sclerosis (MS)

Immunology of multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) leading to demyelination, axonal damage, and progressive neurologic disability. The development of MS is influenced by environmental factors, particularly the Epstein-Barr virus (EBV), and genetic factors, which include specific HLA types, particularly DRB1*1501-DQA1*0102-DQB1*0602, and a predisposition to autoimmunity in general. MS patients have increased circulating T-cell and antibody reactivity to myelin proteins and gangliosides. It is proposed that the role of EBV is to infect autoreactive B cells that then seed the CNS and promote the survival of autoreactive T cells there. It is also proposed that the clinical attacks of relapsing-remitting MS are orchestrated by myelin-reactive T cells entering the white matter of the CNS from the blood, and that the progressive disability in primary and secondary progressive MS is caused by the action of autoantibodies produced in the CNS by ­meningeal lymphoid follicles with germinal centers

Dynamics of levitated nanospheres: towards the strong coupling regime

The use of levitated nanospheres represents a new paradigm for the optomechanical cooling of a small mechanical oscillator, with the prospect of realising quantum oscillators with unprecedentedly high quality factors. We investigate the dynamics of this system, especially in the so-called self-trapping regimes, where one or more optical fields simultaneously trap and cool the mechanical oscillator. The determining characteristic of this regime is that both the mechanical frequency $\omega_M$ and single-photon optomechanical coupling strength parameters $g$ are a function of the optical field intensities, in contrast to usual set-ups where $\omega_M$ and $g$ are constant for the given system. We also measure the characteristic transverse and axial trapping frequencies of different sized silica nanospheres in a simple optical standing wave potential, for spheres of radii $r=20-500$\,nm, illustrating a protocol for loading single nanospheres into a standing wave optical trap that would be formed by an optical cavity. We use this data to confirm the dependence of the effective optomechanical coupling strength on sphere radius for levitated nanospheres in an optical cavity and discuss the prospects for reaching regimes of strong light-matter coupling. Theoretical semiclassical and quantum displacement noise spectra show that for larger nanospheres with $r \gtrsim 100$\,nm a range of interesting and novel dynamical regimes can be accessed. These include simultaneous hybridization of the two optical modes with the mechanical modes and parameter regimes where the system is bistable. We show that here, in contrast to typical single-optical mode optomechanical systems, bistabilities are independent of intracavity intensity and can occur for very weak laser driving amplitudes

Assessment of Demyelination in Glycol Methacrylate Sections: a New Protocol for Cresyl Fast Violet Staining

A simple staining technique for nervous tissue is described. Tissue perfused with glutaraldehyde and formaldehyde and postfixed with osmium tetroxide is embedded in glycol methacrylate. One-micrometer sections are stained with 0.05% cresyl fast violet aqueous solution at 60 C for 5 min, washed with tap water and air dried. With this method the details of all nervous tissue elements are clearly demonstrated. The technique is particularly useful for assessing demyelination because the staining of the axoplasm allows demyelinated axons to be well visualised

Decreased CD8+ T cell response to Epstein-Barr virus infected B cells in multiple sclerosis is not due to decreased HLA class I expression on B cells or monocytes

Background: Patients with multiple sclerosis (MS) have a decreased frequency of CD8(+) T cells reactive to their own Epstein-Barr virus (EBV) infected B cells. We have proposed that this might predispose to the development of MS by allowing EBV-infected autoreactive B cells to accumulate in the central nervous system. The decreased CD8(+) T cell response to EBV results from a general CD8(+) T cell deficiency and also a decreased proportion of EBV-specific T cells within the total CD8(+) T cell population. Because decreased HLA class I expression on monocytes and B cells has been reported in MS and could influence the generation and effector function of EBV-specific CD8(+) T cells, the present study was undertaken to measure the expression of HLA molecules on B cells and monocytes in patients with MS

A model analysis of static stress in the vestibular membranes

<p>Abstract</p> <p>Background</p> <p>The scheme of the core vestibular membranes, consisting of serially connected utricle, ampulla and semicircular canal, first appeared hundreds of millions of years ago in primitive fish and has remained largely unchanged during the subsequent course of evolution. The labyrinths of higher organisms build on this core structure, with the addition of the phylogenetically newer membrane structures, namely, saccule, lagena and cochlea. An analysis of static stress in these core vestibular membranes may contribute to a better understanding of the role of stress in the evolution of derivative membrane structures over the long term as well as the short-term membrane distortions seen in Meniere's disease.</p> <p>Methods</p> <p>A model of these core vestibular membranes is proposed in order to analyze the distribution of stress in the walls of the component chambers. The model uses basic geometrical elements of hollow cylinders and spheres to emulate the actual structures. These model elements lend themselves to a mathematical analysis of static stress in their membranes.</p> <p>Results</p> <p>Hoop stress, akin to the stress in hoops used to reinforce barrel walls, is found to be the predominant stress in the model membranes. The level of hoop stress depends not only on pressure but as well on a geometric stress factor that incorporates membrane shape, thickness and curvature. This result implies that hoop stress may be unevenly distributed in the membranes of the several vestibular chambers due to variations in these dimensional parameters. These results provide a theoretical framework for appraising hoop stress levels in any vestibular labyrinth whose dimensions are known.</p> <p>Conclusion</p> <p>Static hoop stress disparities are likely to exist in the vestibular membranes given their complex physical configurations. Such stress disparities may contribute to the development of membrane pathologies as seen in Meniere's Disease. They may also factor in the evolutionary development of other derivative membrane structures such as the saccule, the lagena, and the cochlea found in higher animals.</p

Efficient Genotyping of KRAS Mutant Non-Small Cell Lung Cancer Using a Multiplexed Droplet Digital PCR Approach

© 2015 Pender et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Droplet digital PCR (ddPCR) can be used to detect low frequency mutations in oncogenedriven lung cancer. The range of KRAS point mutations observed in NSCLC necessitates a multiplex approach to efficient mutation detection in circulating DNA. Here we report the design and optimisation of three discriminatory ddPCR multiplex assays investigating nine different KRAS mutations using PrimePCRddPCRMutation Assays and the Bio-Rad QX100 system. Together these mutations account for 95% of the nucleotide changes found in KRAS in human cancer. Multiplex reactions were optimised on genomic DNA extracted from KRAS mutant cell lines and tested on DNA extracted from fixed tumour tissue from a cohort of lung cancer patients without prior knowledge of the specific KRAS genotype. The multiplex ddPCR assays had a limit of detection of better than 1 mutant KRAS molecule in 2,000 wild-type KRAS molecules, which compared favourably with a limit of detection of 1 in 50 for next generation sequencing and 1 in 10 for Sanger sequencing. Multiplex ddPCR assays thus provide a highly efficient methodology to identify KRAS mutations in lung adenocarcinoma

Health-Promoting Lifestyles of English-Speaking and Spanish-Speaking Mexican-American Migrant Farm Workers

This study was conducted with 62 Mexican-American migrant farm workers at four different sites in northern Illinois. An established English and a newly developed pilot Spanish version of the health-promoting lifestyle profile was used. The concept of health-promoting lifestyle appeared to be culturally relevant to study participants. English-speaking migrant workers scored significantly lower than Spanish-speaking workers on the dimensions of self-actualization, exercise, and stress management. Patterns of scores among both groups were highest in self-actualization and interpersonal support, and lowest in health responsibility and exercise. Further research in health-promoting behaviors with all cultural groups and socioeconomic levels of society will contribute to achievement of the World Health Organization's goal, health for all by the year 2000.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75750/1/j.1525-1446.1990.tb00616.x.pd

Long-lived photoexcited states in polydiacetylenes with different molecular and supramolecular organization

With the aim of determining the importance of the molecular and supramolecular organization on the excited states of polydiacetylenes, we have studied the photoinduced absorption spectra of the red form of poly[1,6-bis(3,6-didodecyl-N-carbazolyl)-2,4-hexadiyne] (polyDCHD-S) and the results compared with those of the blue form of the same polymer. An interpretation of the data is given in terms of both the conjugation length and the interbackbone separation also in relation to the photoinduced absorption spectra of both blue and red forms of poly[1,6-bis(N-carbazolyl)-2,4-hexadiyne] (polyDCHD), which does not carry the alkyl substituents on the carbazolyl side groups. Information on the above properties is derived from the analysis of the absorption and Raman spectra of this class of polydiacetylenes