761 research outputs found
Depth-dependent ordering, two-length-scale phenomena and crossover behavior in a crystal featuring a skin-layer with defects
Structural defects in a crystal are responsible for the "two length-scale"
behavior, in which a sharp central peak is superimposed over a broad peak in
critical diffuse X-ray scattering. We have previously measured the scaling
behavior of the central peak by scattering from a near-surface region of a V2H
crystal, which has a first-order transition in the bulk. As the temperature is
lowered toward the critical temperature, a crossover in critical behavior is
seen, with the temperature range nearest to the critical point being
characterized by mean field exponents. Near the transition, a small two-phase
coexistence region is observed. The values of transition and crossover
temperatures decay with depth. An explanation of these experimental results is
here proposed by means of a theory in which edge dislocations in the
near-surface region occur in walls oriented in the two directions normal to the
surface. The strain caused by the dislocation lines causes the ordering in the
crystal to occur as growth of roughly cylindrically shaped regions. After the
regions have reached a certain size, the crossover in the critical behavior
occurs, and mean field behavior prevails. At a still lower temperature, the
rest of the material between the cylindrical regions orders via a weak
first-order transition.Comment: 12 pages, 8 figure
Mouse models for preeclampsia: disruption of redox-regulated signaling
The concept that oxidative stress contributes to the development of human preeclampsia has never been tested in genetically-defined animal models. Homozygous deletion of catechol-Omethyl transferase (Comt-/-) in pregnant mice leads to human preeclampsia-like symptoms (high
blood pressure, albuminurea and preterm birth) resulting from extensive vasculo-endothelial pathology, primarily at the utero-fetal interface where maternal cardiac output is dramatically increased during pregnancy. Comt converts estradiol to 2-methoxyestradiol 2 (2ME2) which
counters angiogenesis by depleting hypoxia inducible factor-1 alpha (HIF-1 alpha) at late pregnancy. We propose that in wild type (Comt++) pregnant mice, 2ME2 destabilizes HIF-1 alpha by inhibiting mitochondrial superoxide dismutase (MnSOD). Thus, 2ME2 acts as a pro-oxidant, disrupting
redox-regulated signaling which blocks angiogenesis in wild type (WT) animals in physiological pregnancy. Further, we suggest that a lack of this inhibition under normoxic conditions in mutant animals (Comt-/-) stabilises HIF-1 alpha by inactivating prolyl hydroxlases (PHD). We predict that a lack of inhibition of MnSOD, leading to persistent accumulation of HIF-1 alpha, would trigger
inflammatory infiltration and endothelial damage in mutant animals. Critical tests of this hypothesis would be to recreate preeclampsia symptoms by inducing oxidative stress in WT animals or to ameliorate by treating mutant mice with Mn-SOD-catalase mimetics or activators of PHD
A broad distribution of the alternative oxidase in microsporidian parasites
Microsporidia are a group of obligate intracellular parasitic eukaryotes that were considered to be amitochondriate until the recent discovery of highly reduced mitochondrial organelles called mitosomes. Analysis of the complete genome of Encephalitozoon cuniculi revealed a highly reduced set of proteins in the organelle, mostly related to the assembly of ironsulphur clusters. Oxidative phosphorylation and the Krebs cycle proteins were absent, in keeping with the notion that the microsporidia and their mitosomes are anaerobic, as is the case for other mitosome bearing eukaryotes, such as Giardia. Here we provide evidence opening the possibility that mitosomes in a number of microsporidian lineages are not completely anaerobic. Specifically, we have identified and characterized a gene encoding the alternative oxidase (AOX), a typically mitochondrial terminal oxidase in eukaryotes, in the genomes of several distantly related microsporidian species, even though this gene is absent from the complete genome of E. cuniculi. In order to confirm that these genes encode functional proteins, AOX genes from both A. locustae and T. hominis were over-expressed in E. coli and AOX activity measured spectrophotometrically using ubiquinol-1 (UQ-1) as substrate. Both A. locustae and T. hominis AOX proteins reduced UQ-1 in a cyanide and antimycin-resistant manner that was sensitive to ascofuranone, a potent inhibitor of the trypanosomal AOX. The physiological role of AOX microsporidia may be to reoxidise reducing equivalents produced by glycolysis, in a manner comparable to that observed in trypanosome
First principles simulations of liquid Fe-S under Earth's core conditions
First principles electronic structure calculations, based upon density
functional theory within the generalized gradient approximation and ultra-soft
Vanderbilt pseudopotentials, have been used to simulate a liquid alloy of iron
and sulfur at Earth's core conditions. We have used a sulfur concentration of
wt, in line with the maximum recent estimates of the sulfur
abundance in the Earth's outer core. The analysis of the structural, dynamical
and electronic structure properties has been used to report on the effect of
the sulfur impurities on the behavior of the liquid. Although pure sulfur is
known to form chains in the liquid phase, we have not found any tendency
towards polymerization in our liquid simulation. Rather, a net S-S repulsion is
evident, and we propose an explanation for this effect in terms of the
electronic structure. The inspection of the dynamical properties of the system
suggests that the sulfur impurities have a negligible effect on the viscosity
of Earth's liquid core.Comment: 24 pages (including 8 figures
Relationship between tooth loss and mortality in 80-year-old Japanese community-dwelling subjects
<p>Abstract</p> <p>Background</p> <p>Findings from several studies suggest associations between tooth loss and health outcomes, including malnutrition, poor quality of life, and mortality, in older individuals. However, limited information is available regarding whether those associations remain true in very elderly subjects after adequately considering confounding factors such as sex and smoking status. Herein, we determined whether the number of teeth in 80-year-old subjects is an independent predictor of mortality.</p> <p>Methods</p> <p>We initially contacted 1282 80-year-old community-dwelling individuals born in 1917, of whom 697 responded and participated in a baseline study, with follow-up examinations conducted 4 and 5.5 years later. Data from interviews and medical and oral examinations were obtained, and oral health was determined according to the number of teeth remaining in the oral cavity.</p> <p>Results</p> <p>A total of 108 and 157 subjects died in 4 years and 5.5 years, respectively, after the baseline study. Tooth loss was significantly associated with mortality at age 85.5, but not at age 84, after adjusting for potential confounders. When the analysis was stratified by sex, we found a stronger association in females in follow-up examinations conducted at both 4- and 5.5 years. On the other hand, the effect of tooth loss on mortality was not significantly different between smokers and non-smokers.</p> <p>Conclusion</p> <p>Tooth loss is a significant predictor of mortality independent of health factors, socio-economic status, and lifestyle in octogenarians, with a stronger association in females.</p
Clinical and immunohistochemical study of eight cases with thymic carcinoma
BACKGROUND: Thymic carcinoma is a rare neoplasm with extremely poor prognosis. To evaluate the biological characteristics of thymic carcinoma, we reviewed 8 patients. METHODS: There were 2 men and 6 women: ages ranged from 19 to 67 years old (mean 54.8 years). None of these patients had concomitant myasthenia gravis and pure red cell aplasia. No patient had stage I disease, 1 stage II, 5 stage III, and 2 stage IV. The pathologic subtypes of thymic carcinoma included 5 squamous cell carcinomas, 1 adenosquamous cell carcinomas, 1 clear cell carcinoma, and 1 small cell carcinoma. Immunohistochemical study was performed using antibodies against p53, bcl-2, Ki-67, carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), nm23-H1, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2) and factor VIII. RESULTS: Curative resection could be done in 4 patients (50%). Our data indicates a trend toward an association between complete resection and patient survival. Expression of p53, bcl-2, CEA, EMA, nm23-H1, VEGF and FGF-2 was detected in 5/8, 3/8, 4/8, 5/8, 6/8, 5/8 and 3/8, respectively. Mean Ki-67 labeling index and microvessel density was 7.01 and 34.36 (per 200× field), respectively. When compared with our previous studies, immunohistochemical staining of these proteins in thymomas, the expression rates of these proteins in thymic carcinomas were higher than those in thymomas. CONCLUSIONS: In this small series, it is suggested that a complete resection suggests a favorable result. Immunohistochemical results reveal that the expression of these proteins might indicate the aggressiveness of thymic carcinoma
NOX4-dependent ROS production by stromal mammary cells modulates epithelial MCF-7 cell migration
BACKGROUND: The influence of the stromal microenvironment on the progression of epithelial cancers has been demonstrated.
Unravelling the mechanisms by which stromal cells affect epithelial behaviour will contribute in understanding cellular malignancy.
It has been proposed that redox environment has a role in the acquisition of malignancy. In this work, we studied the influence
of epithelial cells on the stromal redox status and the consequence of this phenomenon on MCF-7 cell motility.
METHODS: We analysed in a co-culture system, the effect of RMF-EG mammary stromal cells on the migratory capacity of MCF-7 cell
line. To test whether the NOX-dependent stromal redox environment influences the epithelial migratory behaviour, we knocked
down the expression of NOX4 using siRNA strategy. The effect of TGF-b1 on NOX4 expression and activity was analysed by qPCR,
and intracellular ROS production was measured by a fluorescent method.
RESULTS: Migration of MCF-7 breast epithelial cells was stimulated when co-cultured with RMF-EG cells. This effect depends on
stromal NOX4 expression that, in turn, is enhanced by epithelial soluble factors. Pre-treatment of stromal cells with TGF-b1
enhanced this migratory stimulus by elevating NOX4 expression and intracellular ROS production. TGF-b1 seems to be a major
component of the epithelial soluble factors that stimulate NOX4 expression.
CONCLUSIONS: Our results have identified that an increased stromal oxidative status, mainly provided by an elevated NOX4
expression, is a permissive element in the acquisition of epithelial migratory properties. The capacity of stromal cells to modify their
intracellular ROS production, and accordingly, to increase epithelial motility, seems to depend on epithelial soluble factors among
which TGF-b1 have a decisive role.This work was supported by the grant (1080196 to JM) from the
Fondo Nacional de Ciencia y Tecnologı´a (FONDECYT) of Chile
Identification of excreted iron superoxide dismutase for the diagnosis of Phtytomonas
An excreted iron superoxide dismutase (FeSODe) of pI 3.6 with a molecular weight of 28-30 kDa was detected in the in vitro culture of Phytomonas isolated from Euphorbia characias (SODeCHA) and from Lycopersicon esculentum (SODeTOM), in Grace's medium without serum. These FeSODe excreted into the medium had immunogenic capacity: the positivity of the anti-SODeCHA serum persisted to a dilution of 1/30,000, and for the anti-SODeTOM to 1/10,000 by Western blot. In addition, cross reaction was detected between the anti-SODe serum of Phytomonas isolated from E. characias against SODeTOM, and the anti-SODe serum from L. esculentum with SODeCHA. This characteristic offers the possibility of its use to diagnose plant trypanosomatids. The validation of the test was confirmed by experimental inoculation of tomato fruits with Phytomonas isolated from L. esculentum. At 7, 10, 15, and 21 days post infection, it was possible to detect the presence of the parasites with the anti-SODe serum of Phytomonas isolated from L. esculentum at a dilution of 1/250. These serological results were confirmed by visualization of the parasites by optical microscopy. The data of this study confirm that the SOD is sufficient to identify a trypanosomatid isolated from plants as belonging to the genus Phytomonas.Finacial support: ATP 2002/03: Circulation of Trypanosomatidae Project (CIRAD, France), grant BIO-2000-1429 (University of Granada, Spain)
The Temporal Winner-Take-All Readout
How can the central nervous system make accurate decisions about external stimuli
at short times on the basis of the noisy responses of nerve cell populations? It
has been suggested that spike time latency is the source of fast decisions.
Here, we propose a simple and fast readout mechanism, the temporal
Winner-Take-All (tWTA), and undertake a study of its accuracy. The tWTA is
studied in the framework of a statistical model for the dynamic response of a
nerve cell population to an external stimulus. Each cell is characterized by a
preferred stimulus, a unique value of the external stimulus for which it
responds fastest. The tWTA estimate for the stimulus is the preferred stimulus
of the cell that fired the first spike in the entire population. We then pose
the questions: How accurate is the tWTA readout? What are the parameters that
govern this accuracy? What are the effects of noise correlations and baseline
firing? We find that tWTA sensitivity to the stimulus grows algebraically fast
with the number of cells in the population, N, in contrast to
the logarithmic slow scaling of the conventional rate-WTA sensitivity with
N. Noise correlations in first-spike times of different
cells can limit the accuracy of the tWTA readout, even in the limit of large
N, similar to the effect that has been observed in
population coding theory. We show that baseline firing also has a detrimental
effect on tWTA accuracy. We suggest a generalization of the tWTA, the
n-tWTA, which estimates the stimulus by the identity of the
group of cells firing the first n spikes and show how this
simple generalization can overcome the detrimental effect of baseline firing.
Thus, the tWTA can provide fast and accurate responses discriminating between a
small number of alternatives. High accuracy in estimation of a continuous
stimulus can be obtained using the n-tWTA
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