866 research outputs found

    Selectins mediate macrophage infiltration in obstructive nephropathy in newborn mice11See Editorial by Kipari and Hughes, p. 760.

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    Selectins mediate macrophage infiltration in obstructive nephropathy in newborn mice.BackgroundUrinary tract obstruction during development leads to tubular atrophy and causes interstitial fibrosis. Macrophage infiltration into the interstitium plays a central role in this process. Selectins, a family of three adhesion molecules, are involved in leukocyte recruitment to sites of inflammation and immune activity. We investigated the role of selectins in obstructive nephropathy in newborn mice.MethodsTriple selectin-deficient mice (EPL-/-), L-selectin deficient mice (L-/-) and wild type mice (WT) were subjected to complete unilateral ureteral obstruction (UUO) or sham operation within the first 48 hours of life, and were sacrificed 5 and 12 days later. Kidneys were removed, and sections were stained for macrophage infiltration (mAb F4/80), apoptosis (TUNEL), tubular atrophy (periodic acid-Schiff) and interstitial fibrosis (Masson trichrome).ResultsSelectin deficient mice showed a marked reduction in macrophage infiltration into the obstructed kidney compared to WT at day 5 and day 12 after UUO. Tubular apoptosis was strongly reduced in EPL-/- at day 5 after UUO, and in EPL-/- and L-/- at day 12 after UUO when compared to WT. The number of apoptotic tubular cells was correlated with macrophage infiltration, suggesting that macrophages stimulate tubular apoptosis in obstructive nephropathy. In addition, tubular atrophy and interstitial fibrosis were significantly diminished in EPL-/- and L-/- compared to WT at day 12 after UUO.ConclusionFollowing UUO, selectins mediate macrophage infiltration into the obstructed kidney, which in turn may induce tubular apoptosis, tubular atrophy and interstitial fibrosis

    Remote Sensing analysis of the meanders migration in the Mamorecillo River between 1985 and 2012, Bolivia

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    The morphology of a channel, in a space-time resolution, suffers with sedimentological processes of erosion, transport and deposition. Processes that are more accentuated in meandering channels. In the present work the objective is to analyze, identify and discuss the changes occurred in spatial and temporal sequence in the form of the meanders and river bed of a section of the Mamorecillo River between the provinces of Cochabamba and Santa Cruz - Bolivia. Characterized by being an extensively meandering river - characteristic of the river basin in which it is inserted, the Amazon Basin, the present study, through remote sensing resources, seeks to discuss and correlate the changes occurred in the channel in a period of twenty-seven years (1985-2012). As well as understanding the processes of migration of the meanders that this section of the Mamorecillo River suffered through the sedimentological processes of erosion and deposition and consequently understand the processes in the Amazon basin. For the accomplishment of the work, the studied area was delimited and allied with geoprocessing tools such as software and aerial images, the main geomorphological features were identified and their changes discussed during the studied period. In this work, we intend to correlate and verify the inter-dependence (referring to the sedimentological and / or hydrological contribution) that exists between the Mamorecillo River and the Chimoreacute; and Ichilo rivers

    Identificação e resistĂȘncia a antibiĂłticos de gĂȘneros bacterianos presentes em surubins criados em tanques-rede.

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    O surubim Ă© uma espĂ©cie apreciada pelo mercado consumidor, entretanto, seu cultivo intensivo em tanques-rede pode trazer problemas de sanidade devido ao estresse dos peixes, caso nĂŁo sejam utilizadas boas prĂĄticas de manejo. Neste trabalho, objetivou-se identificar e verificar a resistĂȘncia aos antibiĂłticos de gĂȘneros bacterianos isolados de Pseudoplatystoma sp. criados em tanques-rede de baixo volume

    Targeting Neutrophil Adhesive Events to Address Vaso-Occlusive Crisis in Sickle Cell Patients

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    Neutrophils are essential to protect the host against invading pathogens but can promote disease progression in sickle cell disease (SCD) by becoming adherent to inflamed microvascular networks in peripheral tissue throughout the body. During the inflammatory response, leukocytes extravasate from the bloodstream using selectin adhesion molecules and migrate to sites of tissue insult through activation of integrins that are essential for combating pathogens. However, during vaso-occlusion associated with SCD, neutrophils are activated during tethering and rolling on selectins upregulated on activated endothelium that line blood vessels. Recently, we reported that recognition of sLex on L-selectin by E-selectin during neutrophil rolling initiates shear force resistant catch-bonds that facilitate tethering to endothelium and activation of integrin bond clusters that anchor cells to the vessel wall. Evidence indicates that blocking this important signaling cascade prevents the congestion and ischemia in microvasculature that occurs from neutrophil capture of sickled red blood cells, which are normally deformable ellipses that flow easily through small blood vessels. Two recently completed clinical trials of therapies targeting selectins and their effect on neutrophil activation in small blood vessels reveal the importance of mechanoregulation that in health is an immune adaption facilitating rapid and proportional leukocyte adhesion, while sustaining tissue perfusion. We provide a timely perspective on the mechanism underlying vaso-occlusive crisis (VOC) with a focus on new drugs that target selectin mediated integrin adhesive bond formation

    Virulent Shigella flexneri subverts the host innate immune response through manipulation of antimicrobial peptide gene expression

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    Antimicrobial factors are efficient defense components of the innate immunity, playing a crucial role in the intestinal homeostasis and protection against pathogens. In this study, we report that upon infection of polarized human intestinal cells in vitro, virulent Shigella flexneri suppress transcription of several genes encoding antimicrobial cationic peptides, particularly the human ÎČ-defensin hBD-3, which we show to be especially active against S. flexneri. This is an example of targeted survival strategy. We also identify the MxiE bacterial regulator, which controls a regulon encompassing a set of virulence plasmid-encoded effectors injected into host cells and regulating innate signaling, as being responsible for this dedicated regulatory process. In vivo, in a model of human intestinal xenotransplant, we confirm at the transcriptional and translational level, the presence of a dedicated MxiE-dependent system allowing S. flexneri to suppress expression of antimicrobial cationic peptides and promoting its deeper progression toward intestinal crypts. We demonstrate that this system is also able to down-regulate additional innate immunity genes, such as the chemokine CCL20 gene, leading to compromised recruitment of dendritic cells to the lamina propria of infected tissues. Thus, S. flexneri has developed a dedicated strategy to weaken the innate immunity to manage its survival and colonization ability in the intestine

    VIP: An Experiment to Search for a Violation of the Pauli Exclusion Principle

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    The Pauli Exclusion Principle is a basic principle of Quantum Mechanics, and its validity has never been seriously challenged. However, given its fundamental standing, it is very important to check it as thoroughly as possible. Here we describe the VIP (VIolation of the Pauli exclusion principle) experiment, an improved version of the Ramberg and Snow experiment (E. Ramberg and G. Snow, {\it Phys. Lett. B} {\bf 238}, 438 (1990)); VIP has just completed the installation at the Gran Sasso underground laboratory, and aims to test the Pauli Exclusion Principle for electrons with unprecedented accuracy, down to ÎČ2/2≈10−30−10−31\beta^2/2 \approx 10^{-30} - 10^{-31}. We report preliminary experimental results and briefly discuss some of the implications of a possible violation.Comment: Plenary talk presented by E. Milotti at Meson 2006, Cracow, 9-13 June 200

    New experimental limit on the Pauli Exclusion Principle violation by electrons

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    The Pauli Exclusion Principle (PEP) is one of the basic principles of modern physics and, even if there are no compelling reasons to doubt its validity, it is still debated today because an intuitive, elementary explanation is still missing, and because of its unique stand among the basic symmetries of physics. The present paper reports a new limit on the probability that PEP is violated by electrons, in a search for a shifted Kα_\alpha line in copper: the presence of this line in the soft X-ray copper fluorescence would signal a transition to a ground state already occupied by 2 electrons. The obtained value, 1/2ÎČ2≀4.5×10−28{1/2} \beta^{2} \leq 4.5\times 10^{-28}, improves the existing limit by almost two orders of magnitude.Comment: submitted to Phys. Lett.

    New experimental limit on Pauli Exclusion Principle violation by electrons (the VIP experiment)

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    The Pauli Exclusion Principle is one of the basic principles of modern physics and is at the very basis of our understanding of matter: thus it is fundamental importance to test the limits of its validity. Here we present the VIP (Violation of the Pauli Exclusion Principle) experiment, where we search for anomalous X-rays emitted by copper atoms in a conductor: any detection of these anomalous X-rays would mark a Pauli-forbidden transition. ] VIP is currently taking data at the Gran Sasso underground laboratories, and its scientific goal is to improve by at least four orders of magnitude the previous limit on the probability of Pauli violating transitions, bringing it into the 10**-29 - 10**-30 region. First experimental results, together with future plans, are presented.Comment: To appear in proceedings of the XLVI International Winter Meeting on Nuclear Physics, Bormio, Italy, January 20-26, 200

    Testing the Pauli Exclusion Principle for Electrons

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    One of the fundamental rules of nature and a pillar in the foundation of quantum theory and thus of modern physics is represented by the Pauli Exclusion Principle. We know that this principle is extremely well fulfilled due to many observations. Numerous experiments were performed to search for tiny violation of this rule in various systems. The experiment VIP at the Gran Sasso underground laboratory is searching for possible small violations of the Pauli Exclusion Principle for electrons leading to forbidden X-ray transitions in copper atoms. VIP is aiming at a test of the Pauli Exclusion Principle for electrons with high accuracy, down to the level of 10−29^{-29} - 10−30^{-30}, thus improving the previous limit by 3-4 orders of magnitude. The experimental method, results obtained so far and new developments within VIP2 (follow-up experiment at Gran Sasso, in preparation) to further increase the precision by 2 orders of magnitude will be presented.Comment: Proceedings DISCRETE 2012-Third Symposium on Prospects in the Physics of Discrete Symmetries, Lisbon, December 3-7, 201
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