Infection of Human Endothelial Cells by Japanese Encephalitis Virus: Increased Expression and Release of Soluble HLA-E

Japanese encephalitis virus (JEV) is a single stranded RNA virus that infects the central nervous system leading to acute encephalitis in children. Alterations in brain endothelial cells have been shown to precede the entry of this flavivirus into the brain, but infection of endothelial cells by JEV and their consequences are still unclear. Productive JEV infection was established in human endothelial cells leading to IFN-beta and TNF-alpha production. The MHC genes for HLA-A, -B, -C and HLA-E antigens were upregulated in human brain microvascular endothelial cells, the endothelial-like cell line, ECV 304 and human foreskin fibroblasts upon JEV infection. We also report the release/shedding of soluble HLA-E (sHLA-E) from JEV infected human endothelial cells for the first time. This shedding of sHLA-E was blocked by an inhibitor of matrix metalloproteinases (MMP). In addition, MMP-9, a known mediator of HLA solubilisation was upregulated by JEV. In contrast, human fibroblasts showed only upregulation of cell-surface HLA-E. Addition of UV inactivated JEV-infected cell culture supernatants stimulated shedding of sHLA-E from uninfected ECV cells indicating a role for soluble factors/cytokines in the shedding process. Antibody mediated neutralization of TNF-alpha as well as IFNAR receptor together not only resulted in inhibition of sHLA-E shedding from uninfected cells, it also inhibited HLA-E and MMP-9 gene expression in JEV-infected cells. Shedding of sHLA-E was also observed with purified TNF-alpha and IFN-beta as well as the dsRNA analog, poly (I:C). Both IFN-beta and TNF-alpha further potentiated the shedding when added together. The role of soluble MHC antigens in JEV infection is hitherto unknown and therefore needs further investigation.

RNA-dependent RNA polymerase of Japanese encephalitis virus binds the initiator nucleotide GTP to form a mechanistically important pre-initiation state

Flaviviral RNA-dependent RNA polymerases (RdRps) initiate replication of the single-stranded RNA genome in the absence of a primer. The template sequence 5'-CU-3' at the 3'-end of the flaviviral genome is highly conserved. Surprisingly, flaviviral RdRps require high concentrations of the second incoming nucleotide GTP to catalyze de novo template-dependent RNA synthesis. We show that GTP stimulates de novo RNA synthesis by RdRp from Japanese encephalitis virus (jRdRp) also. Crystal structures of jRdRp complexed with GTP and ATP provide a basis for specific recognition of GTP. Comparison of the jRdRp(GTP) structure with other viral RdRp-GTP structures shows that GTP binds jRdRp in a novel conformation. Apo-jRdRp structure suggests that the conserved motif F of jRdRp occupies multiple conformations in absence of GTP. Motif F becomes ordered on GTP binding and occludes the nucleotide triphosphate entry tunnel. Mutational analysis of key residues that interact with GTP evinces that the jRdRp(GTP) structure represents a novel pre-initiation state. Also, binding studies show that GTP binding reduces affinity of RdRp for RNA, but the presence of the catalytic Mn2+ ion abolishes this inhibition. Collectively, these observations suggest that the observed pre-initiation state may serve as a check-point to prevent erroneous template-independent RNA synthesis by jRdRp during initiation.

Infection of human amniotic and endothelial cells by Japanese encephalitis virus: Increased expression of HLA-F

Productive infection of human amniotic and endothelial cell lines with Japanese encephalitis virus (JEV) was established leading to the induction of NF kappa B and HLA-F, a non-classical MHC molecule. Induction of the HLA-F gene and protein in JEV-infected cells was shown to be NF kappa B dependent since it was blocked by inhibitors of NF kappa B activation. ShRNA targeting lentivirus-mediated stable knockdown of the p65 subunit of NF kappa B inhibited JEV-mediated induction of HLA-F both in the amniotic cell line, AV-3 as well as the human brain microendothelial cell line, HBMEC. The induction of HLA-F by treatment of AV-3 with TNF-alpha was also inhibited by ShRNA mediated knockdown of NF kappa B. TNF-alpha treatment of HEK293T cells that were transfected with reporter plasmids under the control of HLA-F enhancer A elements resulted in significant transactivation of the luciferase reporter gene. NF kappa B-mediated induction of HLA-F following JEV infection and TNF-alpha exposure is being suggested for the first time. (C) 2014 Elsevier Inc. All rights reserved.

Inhibition of ERK and proliferation in NK cell lines by soluble HLA-E released from Japanese encephalitis virus infected cells

Productive infection of human endothelial cells with Japanese encephalitis virus (JEV), a single stranded RNA virus induces shedding of sHLA-E. We show here that sHLA-E that is released upon infection with this flavivirus can inhibit IL-2 and PMA mediated ERK 1/2 phosphorylation in two NK cell lines, Nishi and NKL. Virus infected or IFN-gamma treated cell culture supernatants containing sHLA-E were found to partially inhibit IL-2 mediated induction of CD25 molecules on NKL cells. It was also found that sHLA-E could inhibit IL-2 induced H-3]-thymidine incorporation suggesting that, similar to cell surface expressed HLA-E, sHLA-E could also inhibit NK cell responses. Hence JEV-induced shedding of sHLA-E needs further investigation to better understand immune responses in JEV infections since it may have a role in viral evasion of NK cell responses. (C) 2014 Elsevier B.V. All rights reserved.

The Comovement between Monetary and Fiscal Policy Instruments during the Post-War Period in the U.S.

This paper empirically studies the dynamic relationship between monetary and fiscal policies by analyzing the comovements between the Fed funds rate and the primary deficit/output ratio. Simple economic thinking establishes that a negative correlation between Fed rate and deficit arises whenever the two policy authorities share a common stabilization objective. However, when budget balancing concerns lead to a drastic deficit reduction the Fed may reduce the Fed rate in order to smooth the impact of fiscal policy, which results in a positive correlation between these two policy instruments. The empirical results show (i) a significant negative comovement between Fed rate and deficit and (ii) that deficit and output gap Granger-cause the Fed funds rate during the post-Volcker era, but the opposite is not true.

Markov Switching Risk Premium and the term structure of interest rates. Empirical evidence from US post-war interest rates

This paper considers the basic present value model of interest rates under rational expectations with two additional features. First, following McCallum (1994), the model assumes a policy reaction function where changes in the short-term interest rate are determined by the long-short spread. Second, the short-term interest rate and the risk premium processes are characterized by a Markov regime-switching model. Using US post-war interest rate data, this paper finds evidence that a two-regime switching model fits the data better than the basic model. The estimation results also show the presence of two alternative states displaying quite different features.

The changing behaviour of the term structure of post-war US

Using U.S. interest rate data covering the period 1950:1-1992:7, this paper tests the rational expectations model of the term structure of interest rates. We show evidence that the rational expectations model of the term structure is supported by the data during the seventies and a period lasting from the mid-eighties to the end of the sample. However, during the …fties, sixties and a period that covers most of the Volcker’s office term (from September 1979 to April 1986) the term structure model is rejected by the data. Moreover, wefind evidence of regime changes in the short-term rate process and the term structure of interest rates. These regime switches roughly coincide with changes in the Federal Reserve chairman. The switches in monetary policy taking place when the chairmanship of the Federal Reserve changes therefore seem to play an important role in characterizing the term structure of interest rates.

Switching Regimes in the Term Structure of Interest Rates During U.S. Post-War: A case for the Lucas proof equilibrium?

Published as an article in: Studies in Nonlinear Dynamics & Econometrics, 2004, vol. 8, issue 1, pages 5.

Canal diggers in Panama, 1904 to 1928

Leonard Carpenter Panama Canal Collection. Publication: The Canal Diggers in Panama 1904 to 1928 [Box 1] from the Special Collections & Area Studies Department, George A. Smathers Libraries, University of Florida. (10 page document)

Size composition of catches of Yellowfin tuna in the Japanese long-line fishery in the eastern tropical Pacific east of 130°W

ENGLISH (pgs. 267-283): In the spring of 1963, the senior author, who is a member of the staff of the Nankai Regional Fisheries Research. Laboratory, Fisheries Agency, Japanese Government, came to the Institute of Marine Resources of the University of California as a visiting investigator, bringing with him catch statistical data from the fishery in the eastern Pacific, which had been collected at the Nankai Regional Fisheries Research Laboratory (NRFRL) through September 1962, in order to conduct studies of these data in collaboration with the junior author, and with investigators of the InterAmerican Tropical Tuna Commission. A general review of the long-line fishery, based on the catch statistics of the commercial fishing fleet has been published by Suda and Schaefer (1965). In this paper we present an analysis of data respecting the size-composition of yellowfin tuna taken on long-line gear throughout the eastern Pacific between 1958 and 1962, and make some comparisons with data on size-composition of yellowfin tuna taken in the near-surface fishery, by bait boats and purse-seiners, in waters adjacent to the American coast. As has been shown by Suda and Schaefer (1965), the long-line fishery in the eastern Pacific is primarily directed toward the capture of bigeye tuna. However, considerable quantities of yellowfin tuna are also taken on this gear, and, in addition, there are substantial catches of albacore and of several species of spearfishes in some parts of the range of this fishery. Information respecting the catch rates of yellowfin tuna, and information respecting the size-composition of the stock of yellowfin tuna being exploited by the long-line fishery, is of particular interes~" because the yellowfin tuna population of the eastern Pacific is also subject to an intensive fishery by baitboats and purse-seiners which capture this species, together with skipjack, near the surface along the coast of the Americas, and around the outlying islands, in the region of California to northern Chile. SPANISH (pgs. 311-329): En la primavera de 1963, el autor principal, quien es miembro del personal del Nankai Regional Fisheries Research Laboratory, Fisheries Agency del gobierno japonés, vino al Institute of Marine Resources de la Universidad de California en calidad de investigador visitante y trajo consigo datos estadísticos de las capturas de la pesquería en el Pacífico oriental, que habían sido recolectados en el Nankai Regional Fisheries Research Laboratory (NRFRL) hasta septiembre de 1962, con el fin de hacer estudios de esos datos en colaboración con el coautor y con investigadores de la Comisión Interamericana del Atún Tropical. Una revisión general de la pesquería con palangre, basada sobre las estadísticas de captura de la flota pesquera comercial, ha sido publicada por Suda y Schaefer (1965). En este trabajo presentamos un análisis de los datos correspondientes a la composición de tamaños del atún aleta amarilla capturado con equipo palangrero en todo el Pacífico oriental, entre 1958 y 1962, y hacemos algunas comparaciones con los datos sobre la composición de tamaños del atún aleta amarilla cogido en la pesquería superficial cercana, por barcos de carnada y rederos en aguas adyacentes a la costa americana. Como ha sido demostrado por Suda y Schaefer (1965) la pesquería con palangre en el Pacífico oriental tiene como principal objeto la captura del atún ojo grande. Sin embargo, considerables cantidades de atún aleta amarilla son capturadas también por este equipo y, además, hay también considerables capturas de albacora y de diversas especies de peces-espada en algunas partes de la región que abarca esta pesquería. La información respecto a las tasas de captura del atún aleta amarilla, y la relativa a la composición de tamaños del stock de esta especie que explota la pesquería con palangre, es de particular interés, a causa de que la población de atún aleta amarilla del Pacífico oriental es también objeto de una pesca intensiva por barcos de carnada y rederos que capturan esta especie, junto con el barrilete, cerca de la superficie a 10 largo de la costa de las Américas y alrededor de las islas mar afuera, en la región desde California hasta el norte de Chile.

Collecção das Leis da República dos Estados Unidos do Brazil de 1904

Parte 1 - Atos do Poder Legislativo.

Collecção das Leis da Republica dos Estados Unidos do Brazil de 1905

Parte 1 - Atos do Poder Legislativo

Voyages and travels into Brasil and east-Indies : containing an exact description of the dutch Brasil and divers parts of the east-Indies, their provinces, cities, living creatures, and products, the manners, customs, habits and religion the inhabitants : with a particular account of all the remarkable passages that happened during the author's stay of nine years in Brasil, especially in relation to the revolt of the portugueses, and the intestine war carried on there from 1640 to 1649 : as also a most ample description of the most famous city of batavia in the east-Indies

Joan Nieuhoff, viajante alemão, nasceu em Usen, Vesfália, em 1618, e morreu em Madagascar, em 1672. Trabalhou na Companhia das Índias Orientais, foi nomeado agente em Batávia, em 1654. Em 1655, foi à China tratar da abertura dos portos daquele país ao comércio holandês. Governou o Ceilão de 1662 a 1667. Em 1672, desembarcando em Madagascar, foi morto pelos nativos.