243 research outputs found

    Analysis of multiple incidence angle SIR-B data for determining forest stand characteristics

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    For the first time in the U.S. space program, digital synthetic aperture radar (SR) data were obtained from different incidence angles during Space Shuttle Mission 41-G. Shuttle Imaging Radar-B (SIR-B) data were obtained at incidence angles of 58 deg., 45 deg., and 28 deg., on October 9, 10, and 11, 1984, respectively, for a predominantly forested study area in northern Florida. Cloud-free LANDSAT Thematic Mapper (T.M.) data were obtained over the same area on October 12. The SIR-B data were processed and then digitally registered to the LANDSAT T.M. data by scientists at the Jet Propulsion Laboratory. This is the only known digitally registered SIR-B and T.M. data set for which the data were obtained nearly simultaneously. The data analysis of this information is discussed

    4-Octyl itaconate reduces influenza A replication by targeting the nuclear export protein CRM1

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    In recent years, especially since the outbreak of the severe acute respiratory syndrome coronavirus 2 pandemic, the cell-permeable itaconate derivative 4-octyl itaconate (4-OI) has gained traction as a potential antiviral agent. Here, we demonstrate that 4-OI inhibits replication of multiple influenza A viruses (IAV) by restricting nuclear export of viral ribonucleoproteins, a key step in the IAV replication cycle. This nuclear retention is achieved by deactivation and subsequent degradation of chromosomal maintenance 1 protein (CRM1), also known as exportin 1 (XPO1), a host cell protein exploited by IAV during replication. 4-OI-mediated deactivation of CRM1 resulted in the accumulation of the IAV nucleoprotein, the Rev protein of feline immunodeficiency virus, as well as the natural CRM1 cargos p53 and p65, in the nucleus of treated cells. Further mechanism of action studies revealed that, similar to known CRM1 inhibitors, 4-OI modifies a key cysteine in the cargo binding pocket of CRM1 at position 528 through an alkylation reaction called 2,3-dicarboxypropylation. Subsequent studies in a cell line in which the cysteine at position 528 in CRM1 protein was substituted by a serine confirmed that modification of this residue was indeed the cause for the observed inhibitory effect induced by 4-OI on CRM1 function. Overall, this study demonstrated a mechanism through which 4-OI directly interferes with the replication cycle of CRM1-dependent viruses, which contributes to the understanding of the antiviral and anti-inflammatory properties of this multifaceted immuno-metabolite. IMPORTANCE Itaconate derivates, as well as the naturally produced metabolite, have been proposed as antivirals against influenza virus. Here, the mechanism behind the antiviral effects of exogenous 4-octyl itaconate (4-OI), a derivative of itaconate, against the influenza A virus replication is demonstrated. The data indicate that 4-OI targets the cysteine at position 528 of the CRM1 protein, resulting in inhibition of the nuclear export of viral ribonucleoprotein complexes in a similar manner as previously described for other selective inhibitors of nuclear export. These results postulate a mechanism not observed before for this immuno-metabolite derivative. This knowledge is helpful for the development of derivatives of 4-OI as potential antiviral and anti-inflammatory therapeutics.</p

    Curative Chemoradiotherapy of Primary Pancreatic Lymphoma with Vertebral Metastasis: Palliation of Persistent Biliary Stricture by Roux-en-Y Hepaticojejunostomy

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    Primary pancreatic lymphoma (PPL) is a rare tumor that usually presents with the clinical picture of advanced adenocarcinoma but has a much better prognosis. A 38-year-old man was referred after percutaneous transhepatic external biliary drainage for obstructive jaundice. Abdominal magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography had revealed a 5-cm pancreatic head mass that caused biliary tract dilation. Computed tomography angiography showed that the mass encased the celiac trunk as well as the common hepatic and splenic arteries. MRI also revealed a metastatic lesion at the third lumbar vertebra. Serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels were within normal range. The initial diagnosis was inoperable pancreatic adenocarcinoma; however, Tru-Cut pancreatic biopsy showed a large B cell lymphoma. After 6 sessions of chemotherapy and 21 sessions of radiotherapy, both the pancreatic mass and the vertebral metastasis had disappeared. However, he had persistent distal common bile duct stricture that could not be negotiated by either the endoscopic or percutaneous route. A Roux-en-Y hepaticojejunostomy was performed. The patient stayed alive without recurrence for 52 months after the initial diagnosis and 45 months after completion of oncologic treatment. In conclusion, a large pancreatic mass with grossly involved peripancreatic lymph nodes, without ascites, liver or splenic metastasis, should alert the clinician to the possibility of PPL. Cure is possible by chemoradiotherapy even in the presence of vertebral metastasis. Persistent stricture in the distal common bile duct may require a biliodigestive anastomosis

    BRIEF CHARACTERISTIC OF EUROPEAN GENOTYPE TICK-BORNE ENCEPHALITIS VIRUS STRAINS IDENTIFIED IN SIBERIAN REGION

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    The molecular-genetic analysis of 13 strains of Western genotype TBEV isolated in Western and Eastern Siberia demonstrated two groups of strains differed geneticallyfrom each other and had a high level of E gene sequences homology within each group. Nevertheless, the heterogeneity of biological propertiesfor some strains within a group was observed

    Psychological Stress-Induced, IDO1-Dependent Tryptophan Catabolism: Implications on Immunosuppression in Mice and Humans

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    It is increasingly recognized that psychological stress influences inflammatory responses and mood. Here, we investigated whether psychological stress (combined acoustic and restraint stress) activates the tryptophan (Trp) catabolizing enzyme indoleamine 2,3-dioxygenase 1(IDO1) and thereby alters the immune homeostasis and behavior in mice. We measured IDO1 mRNA expression and plasma levels of Trp catabolites after a single 2-h stress session and in repeatedly stressed (4.5-days stress, 2-h twice a day) naïve BALB/c mice. A role of cytokines in acute stress-induced IDO1 activation was studied after IFNγ and TNFα blockade and in IDO1−/− mice. RU486 and 1-Methyl-L-tryptophan (1-MT) were used to study role of glucocorticoids and IDO1 on Trp depletion in altering the immune and behavioral response in repeatedly stressed animals. Clinical relevance was addressed by analyzing IDO1 activity in patients expecting abdominal surgery. Acute stress increased the IDO1 mRNA expression in brain, lung, spleen and Peyer's patches (max. 14.1±4.9-fold in brain 6-h after stress) and resulted in a transient depletion of Trp (−25.2±6.6%) and serotonin (−27.3±4.6%) from the plasma measured 6-h after stress while kynurenine levels increased 6-h later (11.2±9.3%). IDO1 mRNA up-regulation was blocked by anti-TNFα and anti-IFNγ treatment. Continuous IDO1 blockade by 1-MT but not RU486 treatment normalized the anti-bacterial defense and attenuated increased IL-10 inducibility in splenocytes after repeated stress as it reduced the loss of body weight and behavioral alterations. Moreover, kynurenic acid which remained increased in 1-MT treated repeatedly stressed mice was identified to reduce the TNFα inducibility of splenocytes in vitro and in vivo. Thus, psychological stress stimulates cytokine-driven IDO1 activation and Trp depletion which seems to have a central role for developing stress-induced immunosuppression and behavioral alteration. Since patients showed Trp catabolism already prior to surgery, IDO is also a possible target enzyme for humans modulating immune homeostasis and mood
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