NS1 Specific CD8(+) T-Cells with Effector Function and TRBV11 Dominance in a Patient with Parvovirus B19 Associated Inflammatory Cardiomyopathy

Background: Parvovirus B19 (B19V) is the most commonly detected virus in endomyocardial biopsies (EMBs) from patients with inflammatory cardiomyopathy (DCMi). Despite the importance of T-cells in antiviral defense, little is known about the role of B19V specific T-cells in this entity. Methodology and Principal Findings: An exceptionally high B19V viral load in EMBs (115,091 viral copies/mg nucleic acids), peripheral blood mononuclear cells (PBMCs) and serum was measured in a DCMi patient at initial presentation, suggesting B19V viremia. The B19V viral load in EMBs had decreased substantially 6 and 12 months afterwards, and was not traceable in PBMCs and the serum at these times. Using pools of overlapping peptides spanning the whole B19V proteome, strong CD8(+) T-cell responses were elicited to the 10-amico-acid peptides SALKLAIYKA (19.7% of all CD8(+) cells) and QSALKLAIYK (10%) and additional weaker responses to GLCPHCINVG (0.71%) and LLHTDFEQVM (0.06%). Real-time RT-PCR of IFN gamma secretion-assay-enriched T-cells responding to the peptides, SALKLAIYKA and GLCPHCINVG, revealed a disproportionately high T-cell receptor Vbeta (TRBV) 11 expression in this population. Furthermore, dominant expression of type-1 (IFN gamma, IL2, IL27 and Tbet) and of cytotoxic T-cell markers (Perforin and Granzyme B) was found, whereas gene expression indicating type-2 (IL4, GATA3) and regulatory T-cells (FoxP3) was low. Conclusions: Our results indicate that B19V Ag-specific CD8(+) T-cells with effector function are involved in B19V associated DCMi. In particular, a dominant role of TRBV11 and type-1/CTL effector cells in the T-cell mediated antiviral immune response is suggested. The persistence of B19V in the endomyocardium is a likely antigen source for the maintenance of CD8(+) T-cell responses to the identified epitopes

Association of treatment satisfaction and psychopathological sub-syndromes among involuntary patients with psychotic disorders

Publisher's version: http://www.springerlink.com/content/rx24036274667t10

The role of nutrient loading and eutrophication in estuarine ecology.

Eutrophication is a process that can be defined as an increase in the rate of supply of organic matter (OM) to an ecosystem. We provide a general overview of the major features driving estuarine eutrophication and outline some of the consequences of that process. The main chemical constituent of OM is carbon (C), and therefore rates of eutrophication are expressed in units of C per area per unit time. OM occurs in both particulate and dissolved forms. Allochthonous OM originates outside the estuary, whereas autochthonous OM is generated within the system, mostly by primary producers or by benthic regeneration of OM. The supply rates of limiting nutrients regulate phytoplankton productivity that contributes to inputs of autochthonous OM. The trophic status of an estuary is often based on eutrophication rates and can be categorized as oligotrophic (<100 g C m(-2) y(-1), mesotrophic (100-300 g C m(-2) y(-1), eutrophic (300-500 g C m(-2) y(-1), or hypertrophic (>500 g C m(-2) y(-1). Ecosystem responses to eutrophication depend on both export rates (flushing, microbially mediated losses through respiration, and denitrification) and recycling/regeneration rates within the estuary. The mitigation of the effects of eutrophication involves the regulation of inorganic nutrient (primarily N and P) inputs into receiving waters. Appropriately scaled and parameterized nutrient and hydrologic controls are the only realistic options for controlling phytoplankton blooms, algal toxicity, and other symptoms of eutrophication in estuarine ecosystems

The effectiveness of public health interventions to reduce the health impact of climate change:a systematic review of systematic reviews

Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases

Localisation of RNAs into the germ plasm of vitellogenic xenopus oocytes

We have studied the localisation of mRNAs in full-grown Xenopus laevis oocytes by injecting fluorescent RNAs, followed by confocal microscopy of the oocyte cortex. Concentrating on RNA encoding the Xenopus Nanos homologue, nanos1 (formerly Xcat2), we find that it consistently localised into aggregated germ plasm ribonucleoprotein (RNP) particles, independently of cytoskeletal integrity. This implies that a diffusion/entrapment-mediated mechanism is active, as previously reported for previtellogenic oocytes. Sometimes this was accompanied by localisation into scattered particles of the “late”, Vg1/VegT pathway; occasionally only late pathway localisation was seen. The Xpat RNA behaved in an identical fashion and for neither RNA was the localisation changed by any culture conditions tested. The identity of the labelled RNP aggregates as definitive germ plasm was confirmed by their inclusion of abundant mitochondria and co-localisation with the germ plasm protein Hermes. Further, the nanos1/Hermes RNP particles are interspersed with those containing the germ plasm protein Xpat. These aggregates may be followed into the germ plasm of unfertilized eggs, but with a notable reduction in its quantity, both in terms of injected molecules and endogenous structures. Our results conflict with previous reports that there is no RNA localisation in large oocytes, and that during mid-oogenesis even germ plasm RNAs localise exclusively by the late pathway. We find that in mid oogenesis nanos1 RNA also localises to germ plasm but also by the late pathway. Late pathway RNAs, Vg1 and VegT, also may localise into germ plasm. Our results support the view that mechanistically the two modes of localisation are extremely similar, and that in an injection experiment RNAs might utilise either pathway, the distinction in fates being very subtle and subject to variation. We discuss these results in relation to their biological significance and the results of others

Theories for influencer identification in complex networks

In social and biological systems, the structural heterogeneity of interaction networks gives rise to the emergence of a small set of influential nodes, or influencers, in a series of dynamical processes. Although much smaller than the entire network, these influencers were observed to be able to shape the collective dynamics of large populations in different contexts. As such, the successful identification of influencers should have profound implications in various real-world spreading dynamics such as viral marketing, epidemic outbreaks and cascading failure. In this chapter, we first summarize the centrality-based approach in finding single influencers in complex networks, and then discuss the more complicated problem of locating multiple influencers from a collective point of view. Progress rooted in collective influence theory, belief-propagation and computer science will be presented. Finally, we present some applications of influencer identification in diverse real-world systems, including online social platforms, scientific publication, brain networks and socioeconomic systems.Comment: 24 pages, 6 figure

History of climate modeling

The history of climate modeling begins with conceptual models, followed in the 19th century by mathematical models of energy balance and radiative transfer, as well as simple analog models. Since the 1950s, the principal tools of climate science have been computer simulation models of the global general circulation. From the 1990s to the present, a trend toward increasingly comprehensive coupled models of the entire climate system has dominated the field. Climate model evaluation and intercomparison is changing modeling into a more standardized, modular process, presenting the potential for unifying research and operational aspects of climate science. WIREs Clim Change 2011 2 128–139 DOI: 10.1002/wcc.95 For further resources related to this article, please visit the WIREs websitePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79438/1/95_ftp.pd