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991.
Rossello A Nuti E Orlandini E Carelli P Rapposelli S Macchia M Minutolo F Carbonaro L Albini A Benelli R Cercignani G Murphy G Balsamo A 《Bioorganic & medicinal chemistry》2004,12(9):2441-2450
New N-arylsulfonyl-substituted alkoxyaminoaceto hydroxamic acid derivatives of types 8 and 10 designed as oxa-analogues of known sulfonamide-based MMPi of types 2 and 7 were synthesized and tested for their inhibitory activities on some matrix metalloproteinases. The combination of a biphenylsulfonamide group with oxyamino oxygen in the pharmacophoric central skeleton of sulfonamide-based MMPi obtained in the new sulfonamides 10 seems to be able to give selectivity for MMP-2 over MMP-1. The most potent derivative of this type, 10a, shows similar anti-invasive properties to the analogue reference drug CGS27023A, 2, in an in vitro model of invasion on matrigel, carried out on cellular lines of fibrosarcoma HT1080 (tumoural cells over-expressing MMP-2 and MMP-9). 相似文献
992.
993.
Octavian Stephan Stephanie Cottier Sara Fahlén Adriana Montes-Rodriguez Jia Sun D. Magnus Eklund Ulrich Klahre Benedikt Kost 《The Plant cell》2014,26(11):4426-4447
RAC/ROP GTPases coordinate actin dynamics and membrane traffic during polar plant cell expansion. In tobacco (Nicotiana tabacum), pollen tube tip growth is controlled by the RAC/ROP GTPase RAC5, which specifically accumulates at the apical plasma membrane. Here, we describe the functional characterization of RISAP, a RAC5 effector identified by yeast (Saccharomyces cerevisiae) two-hybrid screening. RISAP belongs to a family of putative myosin receptors containing a domain of unknown function 593 (DUF593) and binds via its DUF593 to the globular tail domain of a tobacco pollen tube myosin XI. It also interacts with F-actin and is associated with a subapical trans-Golgi network (TGN) compartment, whose cytoplasmic position at the pollen tube tip is maintained by the actin cytoskeleton. In this TGN compartment, apical secretion and endocytic membrane recycling pathways required for tip growth appear to converge. RISAP overexpression interferes with apical membrane traffic and blocks tip growth. RAC5 constitutively binds to the N terminus of RISAP and interacts in an activation-dependent manner with the C-terminal half of this protein. In pollen tubes, interaction between RAC5 and RISAP is detectable at the subapical TGN compartment. We present a model of RISAP regulation and function that integrates all these findings. 相似文献
994.
995.
María-Jesús Navarro Francisco-José Gea L. Adriana Escudero-Colomar 《Experimental & applied acarology》2010,50(4):309-316
The myceliophagous mite Microdispus lambi has become a veritable plague since 1996, when it was first observed in Spanish mushroom crops, and is now causing substantial
economic losses, particulary in spring and summer. This study looks at seasonal variation of the pest, its distribution on
commercial farms and the population development during the crop cycle of the common white mushroom, Agaricus bisporus. Over a period of 18 months, 24 consecutive mushroom crop cycles were monitored and a total of 24 spawn and 960 substrate
samples were analysed. We found that it is usually the substrates in the growing rooms that are infested, most commonly the
compost. In many cases, the pest can be detected when the first ‘flush’—i.e., mushroom growth surge, with weekly periodicity—is
harvested, although damage does not become evident until the third flush. Mites were detected at the back of the mushroom
growing room and, to a lesser extent, near the access door. 相似文献
996.
Sainz B Barretto N Martin DN Hiraga N Imamura M Hussain S Marsh KA Yu X Chayama K Alrefai WA Uprichard SL 《Nature medicine》2012,18(2):281-285
Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. With ~170 million individuals infected and current interferon-based treatment having toxic side effects and marginal efficacy, more effective antivirals are crucially needed. Although HCV protease inhibitors were just approved by the US Food and Drug Administration (FDA), optimal HCV therapy, analogous to HIV therapy, will probably require a combination of antivirals targeting multiple aspects of the viral lifecycle. Viral entry represents a potential multifaceted target for antiviral intervention; however, to date, FDA-approved inhibitors of HCV cell entry are unavailable. Here we show that the cellular Niemann-Pick C1-like 1 (NPC1L1) cholesterol uptake receptor is an HCV entry factor amendable to therapeutic intervention. Specifically, NPC1L1 expression is necessary for HCV infection, as silencing or antibody-mediated blocking of NPC1L1 impairs cell culture-derived HCV (HCVcc) infection initiation. In addition, the clinically available FDA-approved NPC1L1 antagonist ezetimibe potently blocks HCV uptake in vitro via a virion cholesterol-dependent step before virion-cell membrane fusion. Moreover, ezetimibe inhibits infection by all major HCV genotypes in vitro and in vivo delays the establishment of HCV genotype 1b infection in mice with human liver grafts. Thus, we have not only identified NPC1L1 as an HCV cell entry factor but also discovered a new antiviral target and potential therapeutic agent. 相似文献
997.
Felipe S. Gallardo Adriana Crdova-Casanova Enrique Brandan 《Journal of cell communication and signaling》2021,15(3):317
Muscular dystrophies (MDs) are a diverse group of severe disorders characterized by increased skeletal muscle feebleness. In many cases, respiratory and cardiac muscles are also compromised. Skeletal muscle inflammation and fibrosis are hallmarks of several skeletal muscle diseases, including MDs. Until now, several keys signaling pathways and factors that regulate inflammation and fibrosis have been identified. However, no curative treatments are available. Therefore, it is necessary to find new therapeutic targets to fight these diseases and improve muscle performance. Lysophosphatidic acid (LPA) is an active glycerophospholipid mainly synthesized by the secreted enzyme autotaxin (ATX), which activates six different G protein-coupled receptors named LPA1 to LPA6 (LPARs). In conjunction, they are part of the ATX/LPA/LPARs axis, involved in the inflammatory and fibrotic response in several organs-tissues. This review recapitulates the most relevant aspects of inflammation and fibrosis in MDs. It analyzes experimental evidence of the effects of the ATX/LPA/LPARs axis on inflammatory and fibrotic responses. Finally, we speculate about its potential role as a new therapeutic pharmacological target to treat these diseases. 相似文献
998.
Martínez de Villarreal L Pérez JZ Vázquez PA Herrera RH Campos Mdel R López RA Ramírez JL Sánchez JM Villarreal JJ Garza MT Limón A López AG Bárcenas M García JR Domínguez AS Nuñez RH Ayala JL Martínez JG González MT Alvarez CG Castro RN 《Teratology》2002,66(5):249-256
BACKGROUND: Nuevo León is a state in northeastern Mexico, near the border of Texas. Mean mortality rate from 1996-98 due to anencephaly cases was 0.6/1,000. In 1999 a surveillance program for the registry and prevention of neural tube defects (NTD) cases was initiated. METHODS: Cases were obtained from hospitals and OB-GYN clinics by immediate notification, death certificates, or fetal death registries. Only isolated cases of NTD were included. In August 1999 a folic acid campaign was initiated with the free distribution of the vitamin to low-income women with a recommendation to take a 5.0-mg pill once a week. Number of cases and rates from 1999 to 2001 were compared (chi(2) test). RESULTS: After 2 years there has been a significant reduction in the number of cases and rates. In 1999 there were 95 NTD cases and in the years 2000 and 2001 there were only 59 and 55 respectively (P < 0.001). NTD rate decreased from 1.04/1,000 in 1999 to 0.58/1,000 in 2001. Anencephaly and spina bifida rates decreased from 0.55/1,000 to 0.29/1,000 and from 0.47/1,000 to 0.22/1,000 respectively, from 1999-2001. Decrease of female cases was higher than male cases for both phenotypes. CONCLUSION: After 2 years there was a 50% decrease in the incidence of anencephaly and spina bifida cases with a significant reduction of infant mortality and disability. These results encourage us to propose the use of a single tablet of 5.0-mg of folic acid per week as an alternative to supplementation on a daily basis. 相似文献
999.
José Rodrigues Coura Pedro Albajar Vi?as Lucia Maria Brum-Soares Andréa Silvestre de Sousa Sérgio Salles Xavier 《Memórias do Instituto Oswaldo Cruz》2013,108(8):1009-1013
A case-control study on the morbidity of Chagas heart disease was carried out in the
municipality of Barcelos in the microregion of the Rio Negro, state of Amazonas. One
hundred and six individuals, who were serologically positive for Trypanosoma
cruzi infection, as confirmed by at least two techniques with different
principles, were matched according to age and sex with an equal number of
seronegative individuals. The cases and controls were evaluated using an
epidemiological questionnaire and clinical, electrocardiograph and echocardiograph
examinations. In the seroepidemiological evaluation, 62% of the interviewees
recognised triatomines and most of them confirmed that they had seen these insects in
the piassava plantations of the riverside communities of the Negro River tributaries.
Of the seropositive patients, 25.8% affirmed that they had been stung by the
triatomines and 11.7% denied having been stung. The principal clinical manifestations
of the seropositive individuals were palpitations, chest pain and dyspnoea upon
effort. Cardiac auscultation revealed extrasystoles, bradycardia and systolic
murmurs. The electrocardiographic alterations were ventricular extrasystoles, left
and right bundle branch block, atrioventricular block and primary T wave alterations.
The echocardiogram was altered in 22.6% of the seropositive individuals and in 8.5%
of the seronegative individuals. 相似文献
1000.