1,017 research outputs found
A novel function for the Caenorhabditis elegans torsin OOC-5 in nucleoporin localization and nuclear import.
Torsin proteins are AAA+ ATPases that localize to the endoplasmic reticular/nuclear envelope (ER/NE) lumen. A mutation that markedly impairs torsinA function causes the CNS disorder DYT1 dystonia. Abnormalities of NE membranes have been linked to torsinA loss of function and the pathogenesis of DYT1 dystonia, leading us to investigate the role of the Caenorhabditis elegans torsinA homologue OOC-5 at the NE. We report a novel role for torsin in nuclear pore biology. In ooc-5-mutant germ cell nuclei, nucleoporins (Nups) were mislocalized in large plaques beginning at meiotic entry and persisted throughout meiosis. Moreover, the KASH protein ZYG-12 was mislocalized in ooc-5 gonads. Nups were mislocalized in adult intestinal nuclei and in embryos from mutant mothers. EM analysis revealed vesicle-like structures in the perinuclear space of intestinal and germ cell nuclei, similar to defects reported in torsin-mutant flies and mice. Consistent with a functional disruption of Nups, ooc-5-mutant embryos displayed impaired nuclear import kinetics, although the nuclear pore-size exclusion barrier was maintained. Our data are the first to demonstrate a requirement for a torsin for normal Nup localization and function and suggest that these functions are likely conserved
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Contribution of Calcium Oxalate to Soil-Exchangeable Calcium
Acid deposition and repeated biomass harvest have decreased
soil calcium (Ca) availability in many temperate forests worldwide, yet
existing methods for assessing available soil Ca do not fully characterize
soil Ca forms. To account for discrepancies in ecosystem Ca budgets, it
has been hypothesized that the highly insoluble biomineral Ca oxalate
might represent an additional soil Ca pool that is not detected in standard
measures of soil-exchangeable Ca. We asked whether several standard
method extractants for soil-exchangeable Ca could also access Ca held in
Ca oxalate crystals using spike recovery tests in both pure solutions and
soil extractions. In solutions of the extractants ammonium chloride, ammonium
acetate, and barium chloride, we observed 2% to 104% dissolution
of Ca oxalate crystals, with dissolution increasing with both solution molarity
and ionic potential of cation extractant. In spike recovery tests using
a low-Ca soil, we estimate that 1 M ammonium acetate extraction dissolved
sufficient Ca oxalate to contribute an additional 52% to standard measurements
of soil-exchangeable Ca. However, in a high-Ca soil, the amount
of Ca oxalate spike that would dissolve in 1 M ammonium acetate extraction
was difficult to detect against the large pool of exchangeable
Ca. We conclude that Ca oxalate can contribute substantially to standard
estimates of soil-exchangeable Ca in acid forest soils with low soil-exchangeable
Ca. Consequently, measures of exchangeable Ca are unlikely
to fully resolve discrepancies in ecosystem Ca mass balance unless the
contribution of Ca oxalate to exchangeable Ca is also assessed.Keywords: Exchangeable Ca, Soil calcium extraction, Soil analysis, Calcium oxalat
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Calcium oxalate contribution to calcium cycling in forests of contrasting nutrient status
Calcium oxalate (Ca oxalate) is an insoluble biomineral that forms in plants and fungi, and occurs in soils
across many types of ecosystems. Assessing how Ca oxalate may shape ecosystem Ca cycling requires
information on the distribution of Ca oxalate among plant biomass, detritus, and mineral soil, and how
it varies with ecosystem Ca status. We compared two Douglas-fir forests of contrasting ecosystem Ca
availability, and found that Ca oxalate was partitioned similarly among plant biomass, detritus and mineral
soil major ecosystem compartments at both sites, and total pools of Ca oxalate were greater in the
high-Ca forest. However, the proportional importance of Ca oxalate was greater in the low-Ca than
high-Ca forest (18% versus 4% of actively cycling ecosystem Ca, respectively). And calcium oxalate in mineral
soil, which is of particular interest as a potential long-term Ca reservoir, was a larger portion of total
available Ca (exchangeable Ca plus Ca oxalate Ca) in the low-Ca site than the high-Ca site (9% versus 1% of
available soil Ca, respectively). Calcium oxalate was the dominant form of Ca returned from plants to soil
as leaf litterfall at the high-Ca site, yet calcium oxalate disappeared rapidly from decomposing litter
(0.28 yr⁻¹ or faster) at both sites. We conclude that accumulation of Ca oxalate in forest ecosystems
appears most closely related to overall Ca supply for live biomass pools, and that the accumulation of
Ca oxalate in forest floor and mineral soil is limited by rapid microbial degradation of putatively unavailable
Ca oxalate.Keywords: Leaf litter decomposition, Calcium cycling, Exchangeable calcium, Soil nutrients, Microbial degradation, Calcium oxalateKeywords: Leaf litter decomposition, Calcium cycling, Exchangeable calcium, Soil nutrients, Microbial degradation, Calcium oxalat
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P10. Concomitant gemcitabine therapy negatively affects DC vaccine-induced CD8+ T cell and B cell responses but improves clinical efficacy in a murine pancreatic carcinoma model
A full scale comparative study of methods for generation of functional Dendritic cells for use as cancer vaccines
<p/> <p>Background</p> <p>Dendritic cells (DCs) are professional antigen-presenting cells with the ability to induce primary T-cell responses and are commonly produced by culturing monocytes in the presence of IL-4 and GM-CSF for 5–7 days (Standard DC). Recently, Dauer and co-workers presented a modified protocol for differentiation of human monocytes into mature DCs within 48 hours (Fast DC). Here we report a functional comparison of the two strategies for generation of DCs from human monocytes with adaptions for large-scale clinical use.</p> <p>Methods</p> <p>The Elutra Cell Selection System was used to isolate monocytes after collection of leukapheresis product. The enriched monocytes were cultured in gas permeable Teflon bags with IL-4 and GM-CSF for 24 hours (Fast DC) or 5 days (Standard DC) to obtain immature DCs. The cells were then transfected with mRNA from the leukemia cell line Jurkat E6 by electroporation and incubated for additional 24 h or 2 days in the presence of pro-inflammatory cytokines (TNFα, IL-1β, IL-6 and PGE<sub>2</sub>) to obtain mature DCs.</p> <p>Results</p> <p>Mature Fast DC and Standard DC displayed comparable levels of many markers expressed on DC, including HLA-DR, CD83, CD86, CD208 and CCR7. However, compared to Standard DC, mature Fast DC was CD14<sup>high </sup>CD209<sup>low</sup>. Fast DC and Standard DC transfected with Jurkat E6-cell mRNA were equally able to elicit T cell specifically recognizing transfected DCs in vitro. IFNγ-secreting T cells were observed in both the CD4+ and CD8+ subsets.</p> <p>Conclusion</p> <p>Our results indicate that mature Fast DC are functional antigen presenting cells (APCs) capable of inducing primary T-cell responses, and suggest that these cells may be valuable for generation of anti-tumor vaccines.</p
A peroxisome proliferator-activated receptor-δ agonist provides neuroprotection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease
Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.Peer reviewedPublisher PD
Alpha-synuclein fibrils amplified from multiple system atrophy and Parkinson's disease patient brain spread after intracerebral injection into mouse brain
Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB) are neurodegenerative disorders with alpha-synuclein (& alpha;-syn) aggregation pathology. Different strains of & alpha;-syn with unique properties are suggested to cause distinct clinical and pathological manifestations resulting in PD, MSA, or DLB. To study individual & alpha;-syn spreading patterns, we injected & alpha;-syn fibrils amplified from brain homogenates of two MSA patients and two PD patients into the brains of C57BI6/J mice. Antibody staining against pS129-& alpha;-syn showed that & alpha;-syn fibrils amplified from the brain homogenates of the four different patients caused different levels of & alpha;-syn spreading. The strongest & alpha;-syn pathology was triggered by & alpha;-syn fibrils of one of the two MSA patients, followed by comparable pS129-& alpha;-syn induction by the second MSA and one PD patient material. Histological analysis using an antibody against Iba1 further showed that the formation of pS129-& alpha;-syn is associated with increased microglia activation. In contrast, no differences in dopaminergic neuron numbers or co-localization of & alpha;-syn in oligodendrocytes were observed between the different groups. Our data support the spreading of & alpha;-syn pathology in MSA, while at the same time pointing to spreading heterogeneity between different patients potentially driven by individual patient immanent factors
Assessing the Health of Richibucto Estuary with the Latent Health Factor Index
The ability to quantitatively assess the health of an ecosystem is often of
great interest to those tasked with monitoring and conserving ecosystems. For
decades, research in this area has relied upon multimetric indices of various
forms. Although indices may be numbers, many are constructed based on
procedures that are highly qualitative in nature, thus limiting the
quantitative rigour of the practical interpretations made from these indices.
The statistical modelling approach to construct the latent health factor index
(LHFI) was recently developed to express ecological data, collected to
construct conventional multimetric health indices, in a rigorous quantitative
model that integrates qualitative features of ecosystem health and preconceived
ecological relationships among such features. This hierarchical modelling
approach allows (a) statistical inference of health for observed sites and (b)
prediction of health for unobserved sites, all accompanied by formal
uncertainty statements. Thus far, the LHFI approach has been demonstrated and
validated on freshwater ecosystems. The goal of this paper is to adapt this
approach to modelling estuarine ecosystem health, particularly that of the
previously unassessed system in Richibucto in New Brunswick, Canada. Field data
correspond to biotic health metrics that constitute the AZTI marine biotic
index (AMBI) and abiotic predictors preconceived to influence biota. We also
briefly discuss related LHFI research involving additional metrics that form
the infaunal trophic index (ITI). Our paper is the first to construct a
scientifically sensible model to rigorously identify the collective explanatory
capacity of salinity, distance downstream, channel depth, and silt-clay content
--- all regarded a priori as qualitatively important abiotic drivers ---
towards site health in the Richibucto ecosystem.Comment: On 2013-05-01, a revised version of this article was accepted for
publication in PLoS One. See Journal reference and DOI belo
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