646 research outputs found
Recombinant 60-kda Heat Shock Protein From Paracoccidioides Brasiliensis: Is It A Good Antigen For Serological Diagnosis Of Paracoccidioidomycosis?
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Paracoccidioides brasiliensis and P. lutzii are fungi that cause paracoccidioidomycosis (PCM), the most prevalent systemic mycosis in South America. For serological diagnosis, although 43-kDa glycoprotein (gp43) is regarded as highly specific for PCM, the occurrence of false negative reactions in sera from patients infected with P. lutzii suggests that preparation with only one antigen is not recommended. Heat shock proteins are feasible alternatives as a second antigen because they are often highly immunogenic. In this study, we evaluated the usefulness of recombinant 60-kDa heat shock protein from P. brasiliensis (rPbHsp60) for the serological diagnosis of PCM. Using western blotting assay, we observed that 77.3% of the sera from PCM patients were positive to rPbHsp60, with 90.9% positivity to recombinant gp43 (rgp43). More importantly, sera from healthy subjects had 27% positivity to rPbHsp60 and none to rgp43. When rPbHsp60 was used in ELISA, we did not observe significant differences between the reactions with sera from PCM patients and healthy subjects, while the difference was clearly evident when the antigen was rgp43. Furthermore, rPbHsp60 was recognized by sera from patients with histoplasmosis, aspergillosis, sporotrichosis or tuberculosis in an ELISA test. These results show that rPbHsp60 is not a good antigen for PCM diagnosis.504Sao Paulo Research Foundation (FAPESP) [2013/12278-3]FAPESP [2012/07924-0, 2009/03235-3, 2012/08552-0]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP
Steady drainage in emulsions: corrections for surface Plateau borders and a model for high aqueous volume fraction
We compare extensive experimental results for the
gravity-driven steady drainage of oil-in-water emulsions with two
theoretical predictions, both based on the assumption of Poiseuille flow.
The first is from standard foam drainage theory,
applicable at low aqueous volume fractions, for which a
correction is derived to account for the effects
of the confinement of the emulsion. The second arises
from considering the permeability of a model porous
medium consisting of solid sphere packings, applicable
at higher aqueous volume fractions. We find quantitative
agreement between experiment and the foam drainage theory at low
aqueous volume fractions. At higher aqueous volume
fractions, the reduced flow rate calculated from the
permeability theory approaches the master curve
of the experimental data. Our experimental data
demonstrates the analogy between the problem of electrical flow and liquid
flow through foams and emulsions
Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and regeneration
Type 2 diabetes (T2D) is a disease characterized by impaired insulin secretion. The Wnt signaling transcription factor Tcf7l2 is to date the T2D-associated gene with the largest effect on disease susceptibility. However, the mechanisms by which TCF7L2 variants affect insulin release from β-cells are not yet fully understood. By taking advantage of a tcf7l2 zebrafish mutant line, we first show that these animals are characterized by hyperglycemia and impaired islet development. Moreover, we demonstrate that the zebrafish tcf7l2 gene is highly expressed in the exocrine pancreas, suggesting potential bystander effects on β-cell growth, differentiation and regeneration. Finally, we describe a peculiar vascular phenotype in tcf7l2 mutant larvae, characterized by significant reduction in the average number and diameter of pancreatic islet capillaries. Overall, the zebrafish Tcf7l2 mutant, characterized by hyperglycemia, pancreatic and vascular defects, and reduced regeneration proves to be a suitable model to study the mechanism of action and the pleiotropic effects of Tcf7l2, the most relevant T2D GWAS hit in human populations. © 2017 The Author(s)
A GFP-Tagged Gross Deletion on Chromosome 1 Causes Malignant Peripheral Nerve Sheath Tumors and Carcinomas in Zebrafish
Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft-tissue sarcomas, characterized by complex karyotypes. The molecular bases of such malignancy are poorly understood and efficient targeted molecular therapies are currently lacking. Here we describe a novel zebrafish model of MPNSTs, represented by the transgenic mutant line Tg(-8.5nkx2.2a:GFP)ia2. ia2 homozygous animals displayed embryonic lethality by 72 hpf, while the heterozygotes develop visible tumor masses with high frequency in adulthood. Histological and immunohistochemical examination revealed aggressive tumors with either mesenchymal or epithelial features. The former (54% of the cases) arose either in the abdominal cavity, or as intrathecal/intraspinal lesions and is composed of cytokeratin-negative spindle cells with fascicular/storiform growth pattern consistent with zebrafish MPNSTs. The second histotype was composed by polygonal or elongated cells, immunohistochemically positive for the pan-cytokeratin AE1/AE3. The overall histologic and immunohistochemical features were consistent with a malignant epithelial neoplasm of possible gastrointestinal/pancreatic origin. With an integrated approach, based on microsatellite (VNTR) and STS markers, we showed that ia2 insertion, in Tg(-8.5nkx2.2a:GFP)ia2 embryos, is associated with a deletion of 15.2 Mb in the telomeric portion of chromosome 1. Interestingly, among ia2 deleted genes we identified the presence of the 40S ribosomal protein S6 gene that may be one of the possible drivers for the MPNSTs in ia2 mutants.Thanks to the peculiar features of zebrafish as animal model of human cancer (cellular and genomic similarity, transparency and prolificacy) and the GFP tag, the Tg(-8.5nkx2.2a:GFP)ia2 line provides a manageable tool to study in vivo with high frequency MPNST biology and genetics, and to identify, in concert with the existing zebrafish MPNST models, conserved relevant mechanisms in zebrafish and human cancer development
Spectral Theory of Sparse Non-Hermitian Random Matrices
Sparse non-Hermitian random matrices arise in the study of disordered
physical systems with asymmetric local interactions, and have applications
ranging from neural networks to ecosystem dynamics. The spectral
characteristics of these matrices provide crucial information on system
stability and susceptibility, however, their study is greatly complicated by
the twin challenges of a lack of symmetry and a sparse interaction structure.
In this review we provide a concise and systematic introduction to the main
tools and results in this field. We show how the spectra of sparse
non-Hermitian matrices can be computed via an analogy with infinite dimensional
operators obeying certain recursion relations. With reference to three
illustrative examples --- adjacency matrices of regular oriented graphs,
adjacency matrices of oriented Erd\H{o}s-R\'{e}nyi graphs, and adjacency
matrices of weighted oriented Erd\H{o}s-R\'{e}nyi graphs --- we demonstrate the
use of these methods to obtain both analytic and numerical results for the
spectrum, the spectral distribution, the location of outlier eigenvalues, and
the statistical properties of eigenvectors.Comment: 60 pages, 10 figure
Clumping and X-Rays in cooler B supergiant stars
B supergiants (BSGs) are evolved stars with effective temperatures between 10
to 30 kK and are important to understand massive star evolution. Located on the
edge of the line-driven wind regime, the study of their atmospheres is helpful
to understand phenomena such as the bi-stability jump. Key UV features of their
spectra have so far not been reproduced by models for types later than B1.
Here, we aim to remedy this situation via spectral analysis that accounts for
wind clumping and X-rays. In addition, we investigate the evolutionary status
of our sample stars based on the obtained stellar parameters. We determined
parameters via quantitative spectroscopy using CMFGEN and PoWR codes. The
models were compared to UV and optical data of four BSGs: HD206165, HD198478,
HD53138, and HD164353. We also study the evolutionary status of our sample
using GENEC and MESA tracks. When including clumping and X-rays, we find good
agreements between synthetic and observed spectra for our sample stars. For the
first time, we reproduced key lines in the UV. For that, we require a
moderately clumped wind (f_infty > ~0.5). We also infer relative X-ray
luminosities of ~10^-7.5 to 10^-8 -- lower than the typical ratio of 10^-7.
Moreover, we find a possible mismatch between evolutionary and spectroscopic
masses, which could be related to the mass-discrepancy problem present in other
OB stars. Our results provide evidence that X-rays and clumping are needed to
describe the winds of cool BSGs. However, their winds seem less structured than
in earlier type stars. This aligns with observational X-rays and clumping
constraints as well as recent hydrodynamical simulations. The BSGs'
evolutionary status appears diverse: some objects are potentially post-red
supergiants or merger products. The wind parameters provide evidence for a
moderate mass-loss rate increase around the bi-stability jump. Abstract
abridgedComment: 27 pages, 22 figures, accepted for publication in A&
Effect of a polyphenol-rich dietary pattern on intestinal permeability and gut and blood microbiomics in older subjects: study protocol of the MaPLE randomised controlled trial.
BACKGROUND:
During aging, alterations of the intestinal microbial ecosystem can occur contributing to immunosenescence, inflamm-aging and impairment of intestinal barrier function (increased intestinal permeability; IP). In the context of a diet-microbiota-IP axis in older subjects, food bioactives such as polyphenols may play a beneficial modulatory role.
METHODS:
MaPLE is a project centered on a randomized, controlled cross-over dietary intervention trial [polyphenol-rich diet (PR-diet) versus control diet (C-diet)] targeted to older people ( 65 60 y) living in a well-controlled setting (i.e. nursing home). The 8-week interventions are separated by an 8-week wash-out period. Three small portions per day of selected polyphenol-rich foods are consumed during intervention in substitution of other comparable products within the C-diet. Biological samples are collected before and after each treatment period to evaluate markers related to IP, inflammation, vascular function, oxidative stress, gut and blood microbiomics, metabolomics. A sample size of 50 subjects was defined based on IP as primary outcome.
DISCUSSION:
Evidence that increasing the consumption of polyphenol-rich food products can positively affect intestinal microbial ecosystem resulting in reduced IP and decreased translocation of inflammogenic bacterial factors into the bloodstream will be provided. The integration of data from gut and blood microbiomics, metabolomics and other IP-related markers will improve the understanding of the beneficial effect of the intervention in the context of polyphenols-microbiota-IP interactions. Finally, findings obtained will provide a proof of concept of the reliability of the dietary intervention, also contributing to future implementations of dietary guidelines directed to IP management in the older and other at risk subjects.
TRIAL REGISTRATION:
The trial is registered at (ISRCTN10214981); April 28, 2017
Ferramentas moleculares para garantir a qualidade de alimentos produzidos à base de mamão.
bitstream/item/164102/1/CT130-ferramentas-moleculares-mamao.pd
Lymphangioleiomyomatosis, multifocal micronodular pneumocyte hyperplasia, and sarcoidosis : More pathological findings in the same chest CT, or a single pathological pathway?
Background: Autoimmune hepatitis/primary biliary cirrhosis overlap syndrome, lymphangioleiomyomatosis/tuberous sclerosis complex (LAM-TSC), and sarcoidosis are three rare diseases. Here we present, to the best of our knowledge, the first description of a patient with the coexistence of these three diseases. Case presentation: A 47-year-old woman affected by LAM-TSC and primary biliary cirrosis/autoimmune hepatitis overlap syndrome. During her follow up a high resolution chest CT scan (HRTC) confirmed the presence of both multiple cysts and micronodular opacities consistent with multifocal micronodular pneumocytes hyperlasia (MMPH), and revealed multiple hilar-mediastinal symmetrical lymphadenopathies suggestive of sarcoidosis. Simultaneously, subcutaneous nodules appeared on her forearm bilaterally. Cutaneous biopsy showed granulomatous dermatitis with sarcoid-like granulomas. A diagnosis of stage I pulmonary sarcoidosis was made. No treatment for sarcoidosis was initiated since the patient had neither systemic involvement, nor respiratory impairment. Conclusions: The presence of more than one rare disease should challenge the concept of a potential common underlying mechanism, since the a priori probability of the concomitant presence of different conditions with different pathogenic mechanisms - especially if rare diseases - is low. We speculate that the dysregulation of the pathway involving mTOR and MAPK and their interaction might play a role in the pathogenesis of other diseases, including sarcoidosis
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