Noninvasive Stem Cell Labeling Using USPIO Technique and their Detection with MRI

Background: To date, several imaging techniques to track stem cells are used such as positron emission tomography (PET), single photon emission computed tomography (SPECT), Bioluminescence imaging (BLI), fluorescence imaging, CT scan and magnetic resonance imaging (MRI). Although, overall sensitivity of MRI compared to SPECT and Bioluminescence techniques are lower, but due to high spatial resolution (~100 mm), long term three-dimensional imaging capability, in vivo quick access to images in three different sections, and noninvasiveness it is being used as the method of choice. Methods: The present study is the search results for authors and sources of information in the field of molecular and cellular imaging to examine the problems and perspectives about stem cells labeling with Ultrasmall Super Paramagnetic Iron Oxide (USPIO) and their tracking by MRI. Results: With the advancement of technology, including quantum physics, chemistry, and computer software, MRI with an excellent spatial resolution and contrast, is surpasses other imaging modalities in the analysis of anatomical and pathological features and images of all body tissues. From the other side, advances in the astronomical science, chemistry and nanotechnology, high biocompatibility and cytotoxicity of nanoparticles, and due to analysis in the metabolic pathways of iron made the procedure easier; however, there are still several fundamental questions in understanding the mechanism of biological molecules in the living cells including: 1- How to detect not only the location but also the performance of the labeled cells? Probably combination of USPIO nanoparticles with other reporter genes as contrast agents for MRI and PET can simultaneously be used to overcome these limitations 2) How to trace stem cells from pre-clinical models to translate to humans? Up to now, due to issues of bioethics, little studies have been done in this area. 3) Whether the transplanted stem cells that have reached the target tissue, will remain or migrate? Despite the fact that cell proliferation and exocytosis are two main factors for long term protection of USPIO nanoparticles inside cells, their signals cannot be received for a long time. 4) What mechanisms cause stem cells reaching the target tissue to react with their environment? And 5) what is the number of transplanted cells in live tissue, and what is their half-life? Conclusion: This study showed that USPIO nanoparticles can enter the cell with a clear dose without any adverse biological effects and could be detected by SWI and T2* techniques under MRI (1.5 Tesla) scanner for almost one month. MRI as a secure mean can illustrate with optimal resolution the spatial-resolution and three-dimensional positions of the stem cells. Keywords: Ultrasmall Super Paramagnetic Iron Oxide (USPIO), labeled stem cell, in vivo tracking, MRI

A (re) organização espacial da Comunidade Tradicional de Antônio Maria Coelho, Corumbá/MS.

O estudo tem como propósito a compreensão da (re) organização da comunidade tradicional de Antônio Maria Coelho (AMC), bem como do potencial de ampliação do extrativismo agroecológico da bocaíuva. Utilizou-se a metodologia de diagnóstico rural participativo com técnicas de observação participante e entrevistas semi-estruturadas. A comunidade possui características rurais, com as moradias parcialmente dispersas em grupos. Observam-se constantes mudanças na dinâmica socioespacial da comunidade de AMC. Estas mudanças estão relacionadas com a pressão econômica proporcionada pela instalação de empresas mineradoras na região, provocando alteração no espaço e a busca de novas formas de organização social. The study has as purpose a understanding the (re) organization of traditional community by Antônio Maria Coelho (AMC) with a view to subsidize the potential of enlargement from extrativism agroecologic the bocaiúva. Being used the methodology to diagnosis participatory rural with observation techniques participant and semi-structured interviews The community has rural characteristics, with the housing partially dispersed in groups. Constant changes are observed in the dynamics of socio-community AMC. These changes are related to the economic pressure provided by the installation of mining companies in the region, causing changes in space and the search for new forms of social organization.Título em inglês: The spatial (re) organization of Traditional Community by Antônio Maria Coelho, Corumbá / MS

Phase Transitions in a Two-Component Site-Bond Percolation Model

A method to treat a N-component percolation model as effective one component model is presented by introducing a scaled control variable $p_{+}$. In Monte Carlo simulations on $16^{3}$, $32^{3}$, $64^{3}$ and $128^{3}$ simple cubic lattices the percolation threshold in terms of $p_{+}$ is determined for N=2. Phase transitions are reported in two limits for the bond existence probabilities $p_{=}$ and $p_{\neq}$. In the same limits, empirical formulas for the percolation threshold $p_{+}^{c}$ as function of one component-concentration, $f_{b}$, are proposed. In the limit $p_{=} = 0$ a new site percolation threshold, $f_{b}^{c} \simeq 0.145$, is reported.Comment: RevTeX, 5 pages, 5 eps-figure

TLR-2/TLR-4 TREM-1 Signaling Pathway Is Dispensable in Inflammatory Myeloid Cells during Sterile Kidney Injury

Inflammatory macrophages are abundant in kidney disease, stimulating repair, or driving chronic inflammation and fibrosis. Damage associated molecules (DAMPs), released from injured cells engage pattern recognition receptors (PRRs) on macrophages, contributing to activation. Understanding mechanisms of macrophage activation during kidney injury may lead to strategies to alleviate chronic disease. We identified Triggering-Receptor-in-Myeloid-cells (TREM)-1, a regulator of TLR signaling, as highly upregulated in kidney inflammatory macrophages and tested the roles of these receptors in macrophage activation and kidney disease. Kidney DAMPs activated macrophages in vitro, independently of TREM-1, but partially dependent on TLR-2/−4, MyD88. In two models of progressive interstitial kidney disease, TREM-1 blockade had no impact on disease or macrophage activation in vivo, but TLR-2/−4, or MyD88 deficiency was anti-inflammatory and anti-fibrotic. When MyD88 was mutated only in the myeloid lineage, however, there was no bearing on macrophage activation or disease progression. Instead, TLR-2/−4 or MyD88 deficiency reduced activation of mesenchyme lineage cells resulting in reduced inflammation and fibrosis, indicating that these pathways play dominant roles in activation of myofibroblasts but not macrophages. To conclude, TREM-1, TLR2/4 and MyD88 signaling pathways are redundant in myeloid cell activation in kidney injury, but the latter appear to regulate activation of mesenchymal cells

Malignancy risk analysis in patients with inadequate fine needle aspiration cytology (FNAC) of the thyroid

Background Thyroid fine needle aspiration cytology (FNAC) is the standard diagnostic modality for thyroid nodules. However, it has limitations among which is the incidence of non-diagnostic results (Thy1). Management of cases with repeatedly non-diagnostic FNAC ranges from simple observation to surgical intervention. We aim to evaluate the incidence of malignancy in non-diagnostic FNAC, and the success rate of repeated FNAC. We also aim to evaluate risk factors for malignancy in patients with non-diagnostic FNAC. Materials and Methods Retrospective analyses of consecutive cases with thyroid non diagnostic FNAC results were included. Results Out of total 1657 thyroid FNAC done during the study period, there were 264 (15.9%) non-diagnostic FNAC on the first attempt. On repeating those, the rate of a non-diagnostic result on second FNAC was 61.8% and on third FNAC was 47.2%. The overall malignancy rate in Thy1 FNAC was 4.5% (42% papillary, 42% follicular and 8% anaplastic), and the yield of malignancy decreased considerably with successive non-diagnostic FNAC. Ultrasound guidance by an experienced head neck radiologist produced the lowest non-diagnostic rate (38%) on repetition compared to US guidance by a generalist radiologist (65%) and by non US guidance (90%). Conclusions There is a low risk of malignancy in patients with a non-diagnostic FNAC result, commensurate to the risk of any nodule. The yield of malignancy decreased considerably with successive non-diagnostic FNAC

Reversing Blood Flows Act through klf2a to Ensure Normal Valvulogenesis in the Developing Heart

Heart valve anomalies are some of the most common congenital heart defects, yet neither the genetic nor the epigenetic forces guiding heart valve development are well understood. When functioning normally, mature heart valves prevent intracardiac retrograde blood flow; before valves develop, there is considerable regurgitation, resulting in reversing (or oscillatory) flows between the atrium and ventricle. As reversing flows are particularly strong stimuli to endothelial cells in culture, an attractive hypothesis is that heart valves form as a developmental response to retrograde blood flows through the maturing heart. Here, we exploit the relationship between oscillatory flow and heart rate to manipulate the amount of retrograde flow in the atrioventricular (AV) canal before and during valvulogenesis, and find that this leads to arrested valve growth. Using this manipulation, we determined that klf2a is normally expressed in the valve precursors in response to reversing flows, and is dramatically reduced by treatments that decrease such flows. Experimentally knocking down the expression of this shear-responsive gene with morpholine antisense oligonucleotides (MOs) results in dysfunctional valves. Thus, klf2a expression appears to be necessary for normal valve formation. This, together with its dependence on intracardiac hemodynamic forces, makes klf2a expression an early and reliable indicator of proper valve development. Together, these results demonstrate a critical role for reversing flows during valvulogenesis and show how relatively subtle perturbations of normal hemodynamic patterns can lead to both major alterations in gene expression and severe valve dysgenesis

Hysteresis at low Reynolds number: the onset of 2D vortex shedding

Hysteresis has been observed in a study of the transition between laminar flow and vortex shedding in a quasi-two dimensional system. The system is a vertical, rapidly flowing soap film which is penetrated by a rod oriented perpendicular to the film plane. Our experiments show that the transition from laminar flow to a periodic K\'arm\'an vortex street can be hysteretic, i.e. vortices can survive at velocities lower than the velocity needed to generate them.Comment: RevTeX file 4 pages + 5 (encapsulated postscript) figures. to appear in Phys.Rev.E, Rapid Communicatio

Statistical Models of Nuclear Fragmentation

A method is presented that allows exact calculations of fragment multiplicity distributions for a canonical ensemble of non-interacting clusters. Fragmentation properties are shown to depend on only a few parameters. Fragments are shown to be copiously produced above the transition temperature. At this transition temperature, the calculated multiplicity distributions broaden and become strongly super-Poissonian. This behavior is compared to predictions from a percolation model. A corresponding microcanonical formalism is also presented.Comment: 12 pages, 5 figure

Association of systemic anaplastic large cell lymphoma and active toxoplasmosis in a child

Introduction: Anaplastic large cell lymphoma is a subset of non-Hodgkin lymphoma and an unusual disease in children. Case Presentation: Herein we have reported a 7- year- old girl with a large necrotic skin ulcer on the chest caused by systemic form of anaplastic large-cell lymphoma and simultaneous active toxoplasmosis diagnosed by PCR on lymph node specimen. There were few reports showing a role for toxoplasma infection to cause some malignancies such as lymphoma in adults. Conclusions: Based to our knowledge, this has been the first report of simultaneous systemic anaplastic large cell lymphoma and active toxoplasmosis, documented by positive PCR on tissue biopsy in a child. This case report has suggested more attention to the accompanying Toxoplasma gondii infection as a probable cause of some types of lymphomas. © 2015, Iranian Journal of Cancer Prevention

Cysteine oxidation targets peroxiredoxins 1 and 2 for exosomal release through a novel mechanism of redox-dependent secretion

Non-classical protein secretion is of major importance as a number of cytokines and inflammatory mediators are secreted via this route. Current evidence indicates that there are several mechanistically distinct methods of non-classical secretion. We have recently shown that peroxiredoxin (Prdx) 1 and Prdx2 are released by various cells upon exposure to inflammatory stimuli such as LPS or TNF-α. The released Prdx then acts to induce production of inflammatory cytokines. However, Prdx1 and 2 do not have signal peptides and therefore must be secreted by alternative mechanisms as has been postulated for the inflammatory mediators IL-1β and HMGB1. We show here that circulating Prdx1 and 2 are present exclusively as disulphide-linked homodimers. Inflammatory stimuli also induce in vitro release of Prdx1 and 2 as disulfide-linked homodimers. Mutation of cysteines Cys51 or Cys172 (but not Cys70) in Prdx2, and Cys52 or Cys173 (but not Cys71 or Cys83) in Prdx1 prevented dimer formation and this was associated with inhibition of their TNF-α-induced release. Thus, the presence and oxidation of key cysteine residues in these proteins are a prerequisite for their secretion in response to TNF-α and this release can be induced with an oxidant. In contrast, the secretion of the nuclear-associated danger signal HMGB1 is independent of cysteine oxidation, as shown by experiments with a cysteine-free HMGB1 mutant. Release of Prdx1 and 2 is not prevented by inhibitors of the classical secretory pathway; instead, both Prdx1 and 2 are released in exosomes from both HEK cells and monocytic cells. Serum Prdx1 and 2 are also associated with the exosomes. These results describe a novel pathway of protein secretion mediated by cysteine oxidation that underlines the importance of redox-dependent signalling mechanisms in inflammation