170,826 research outputs found
The Jun family members, c-Jun and JunD, transactivate the human c-myb promoter via an Ap1-like element.
The c-myb protooncogene, which is preferentially expressed in hematopoietic cells at the G1/S boundary of the cell cycle, encodes a transcriptional activator that functions via DNA binding. The regulatory mechanisms governing this specific pattern of expression are not fully understood, although human c-myb expression appears to be positively autoregulated via myb-binding sites in the 5'-flanking region of the c-myb gene (Nicolaides, N. C., Gualdi, R., Casadevall, C., Manzella, L., and Calabretta, B. (1991) Mol. Cell. Biol. 11, 6166-6176). To determine the contribution of other transcription regulators such as JUN family members in the control of c-myb expression, transient expression assays were carried out which revealed a 6- to a 15-fold enhancement by c-Jun and JunD, but not JunB, in chloramphenicol acetyltransferase reporter gene expression driven by different segments of the human c-myb 5'-flanking region. An Ap1-like element located at nucleotide -149 from the c-myb initiation site appears to be required for this transactivation upon binding to a nuclear protein complex containing c-Jun and JunD, since site-directed mutations of this Ap1-like element abolished c-Jun and JunD binding and transactivation. Exposure of phytohemagglutinin-stimulated peripheral blood mononuclear cells to c-jun and junD antisense oligodeoxynucleotides resulted in a 46 and 43% inhibition of T-lymphocyte proliferation that was accompanied by a decrease in c-myb mRNA levels as compared with sense-treated cultures. Because T-lymphocytes induced to proliferate express c-jun and junD before c-myb, these data suggest a mechanism whereby c-Jun and JunD contribute to the transcriptional activation of c-myb that, in turn, is maintained at the G1/S transition and during S phase by positive autoregulation
Pastoral que el Ilmo. y Rmo. Sor. D. D. Luciano Casadevall Obispo de Vich dirige al venerable clero y demás fieles de su diocesis al empezar su pontificado
15 p. ; 20 c
Positive autoregulation of c-myb expression via myb binding sites in the 5' flanking region of the human c-myb gene
The nuclear proto-oncogene c-myb is preferentially expressed in lymphohematopoietic cells, in which it plays an important role in the processes of differentiation and proliferation. The mechanism(s) that regulates c-myb expression is not fully understood, although in mouse cells a regulatory mechanism involves a transcriptional block in the first intron. To analyze the contribution of the 5' flanking sequences in regulating the expression of the human c-myb gene, we isolated a genomic clone containing extensive 5' flanking sequences, the first exon, and a large portion of the first intron. Sequence analysis of a subcloned 1.3-kb BamHI insert corresponding to 687 nucleotides of the 5' flanking sequence, the entire first exon, and 300 nucleotides of the first intron revealed the presence of closely spaced putative Myb binding sites within a segment extending from nucleotides -616 to -575 upstream from the cap site. A 165-bp segment containing these putative Myb binding sites was linked to a human thymidine kinase (TK) cDNA driven by a low-activity proliferating cell nuclear antigen promoter and cotransfected into TK- ts13 cells with a plasmid in which a full-length human c-myb cDNA is driven by the early simian virus 40 promoter; Myb inducibility of TK mRNA expression was observed both in transient expression assays and in stable transformants. The highest level of inducibility was detected when the 165-bp fragment was placed 138 bp upstream of the proliferating cell nuclear antigen promoter-TK cDNA reporter unit or 3' of the TK cDNA. Mutation of the putative Myb binding sites greatly reduced c-myb transactivation of TK mRNA expression and specifically reduced the binding of in vitro-translated Myb protein at those sites. Finally, c-myb transactivated TK mRNA expression driven by a segment of the authentic c-myb 5' flanking region containing the Myb binding sites. These data suggest that human c-myb maintains high levels of Myb protein in cells that require this gene product for proliferation and/or differentiation by an autoregulatory mechanism involving Myb binding sites in the 5' flanking region
Variabilidade genética de Cryptococcus neoformans isolado de pacientes HIV positivos atendidos no Hospital Nereu Ramos de Florianópolis, Santa Catarina: (dissertação)
Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas. Programa de Pós-graduação em BiotecnologiaA criptococose é uma infecção fúngica de distribuição mundial causada pela levedura encapsulada Cryptococcus neoformans. Esta doença é de grande importância em pacientes imunocomprometidos, podendo também acometer indivíduos imunocompetentes. A infecção pelo C. neoformans resulta da inalação basidiósporos, conídios ou blastoconídios pouco capsulados (4 a 5µm) presentes no ambiente, podendo inicialmente causar infecção sintomática ou assintomática na área subpleural dos pulmões, ser erradicada ou ainda permanecer dentro de um granuloma em estado latente. Este patógeno pode ser classificado em três variedades: C. neoformans var grubii (sorotipo A), com distribuição mundial, C. neoformans var neoformans (sorotipo D) freqüentemente encontrado na Europa e América do Sul e C. neoformans var gattii (sorotipos B e C) regiões tropicais e subtropicais e o híbrido sorotipo AD. No Brasil, as três variedades são os agentes etiológicos da criptococose em humanos. O objetivo deste estudo foi avaliar a variabilidade genética de amostras de C. neoformans isoladas de pacientes HIV positivos atendidos no Hospital Nereu Ramos de Florianópolis, Santa Catarina. Os 35 isolados clínicos analisados foram caracterizados como C. neoformans var grubii, sorotipo A, através da metodologia de PCR-RFLP do fragmento de 597 pb do gene CAP59. A PCR-fingerprinting com o iniciador M13 agrupou 34 isolados clínicos no padrão molecular VNI e uma amostra apresentou perfil distinto. A caracterização das 35 amostras através da técnica de RAPD utilizando 4 iniciadores aleatórios 3303, 3304, 3306 e 3307 mostrou baixa variabilidade genética das amostras. O sequenciamento do fragmento de 597 pb do gene CAP59 de duas amostras representativas juntamente com o padrão sorotipo A LMM794, mostrou uma homologia de 96% na seqüência nucleotídica e de aminoácidos predita com as seqüências de sorotipo A e AD depositadas no GenBank. Nossos resultados adicionam novas informações sobre a Biologia Molecular do C. neoformans no Estado de Santa Catarina. Cryptococcus neoformans is an encapsulated yeast-like fungus of worldwide distribution and the etiologic agent of cryptococcosis. This disease is a common opportunistic infection among patients with immunosupression and in apparently immunocompetent individuals. The infection is acquired by the inhalation of infectious propagules present in the environment. Therefore, the primary settlement of the pathogens is in the lungs, a site from which dissemination may occur. This fungus is classified in three varieties C. neoformans var. grubii (serotype A) of worldwide distribution, C. neoformans var. neoformans (serotype D) isolated rather frequently in Europe and South America, C. neoformans var. gattii (serotypes B and C) isolated in tropical and subtropical regions and a hybrid serotype AD. In Brazil, these three distinct neoformans varieties are the main casual agents of human cryptococcosis. The main goal of this dissertation is to study the genetic variability of C. neoformans samples isolated from patients attended at the Hospital Nereu Ramos Hospital, Florianópolis, Santa Catarina state, Brazil. Thirty-five clinical isolates were characterized, based on morphological and molecular data. All 35 clinical isolates were identified as C. neoformans var. grubii, representing serotype A, by PCR-RFLP analysis of CAP59 gene 597pb restriction fragment. A PCR-fingerprinting with the microsatellite-specific primer M13 grouped 34 isolates into the molecular type VNI and one showed distinct profile. The genetic variability among C. neoformans isolates were studied using randomly amplified polymorphic DNA (RAPD) analysis. The four arbitrary polymerase chain reaction primers used in this study detected low genetic variability among the samples. The CAP59 nucleotide and predicted amino acid sequences analysis of two representative samples and serotype pattern A LMM794 of C. neoformans showed more than 96% similarity among serotype A and AD deposited in GenBank database. Our results add considerable new information to the available data on molecular biology of C. neoformans in the Santa Catarina State, Brazil
Restauració d’estucs i estucs de nova construcció
En totes les ciutats i pobles existeixen edificis emblemàtics i històrics, dignes de recordar i conservar. La seva recuperació i manteniment requereix una tècnica especialitzada per tornar la llum i la vida a aquestes joies arquitectòniques, i en això n’és especialista C. Casadevall - Estucs 1881 SL. La dilatada trajectòria de 120 anys ens ha fet desenvolupar diferents tècniques que dominem com els estucs tradicionals, esgrafiats, relleus, revestiments tipus venecià, els planxats al foc o la recuperació i restauració de vells estucs, pintures o pedra
Selectivity study in the functionalization of organic compounds promoted by radical and radical-like species
Oxidative C-H functionalization of organic substrates promoted by cheap, eco-friendly, and selective systems has received a great attention in recent years, since it allows to convert relatively unreactive bonds, ubiquitous in organic molecules, into functional groups suitable for further transformations. Oxidation of sulfides to sulfoxides is another important process due to the presence of sulfinyl functional group in many natural products and biologically active compounds, like anti-inflammatory or antibiotic drugs. Moreover, sulfoxides are important reagents in organic synthesis: in fact, chiral sulfoxides have been used as auxiliaries in asymmetric synthesis. In this thesis, the use of biomimetic nonheme iron complexes and N-hydroxyphthalimide (NHPI) as efficient and selective catalysts for the oxidation of alkylaromatic compounds, alcohols, and sulfides by hydrogen atom transfer (HAT) or S-oxidative processes has been described. Concerning the former systems, elucidation of mechanism and reactivity patterns of [(N4Py)FeII]2+ complex have been investigated in detail with respect to the generation of the iron-oxo and iron-peroxo active species both in common organic solvents and in non-common fluorinated solvents. For the N-hydroxyphthalimide catalyst, reactivity, and selectivity patterns of the corresponding N-oxyl radical (PINO) in S-oxidation from sulfur compounds have been analysed by kinetic and product studies.
In addition, the two systems can be used together in a mediated system, in which NHPI acts as efficient mediator in the oxidations of organic compounds promoted by the nonheme iron(IV)-oxo complex, enhancing its reactivity and expanding its oxidizing ability. In the mediated system, the increase of reactivity is associated to the oxidation of the mediator to the corresponding phthalimide-N-oxyl radical, which efficiently abstracts hydrogen atoms from the substrates regenerating the mediator NHPI. The possibility of a change of selectivity in the C-H functionalization of alkylaromatic compounds and alcohols has been studied in the presence of the NHPI mediator as a result of the different polar effects operating in the HAT processes promoted by [(N4Py)FeIV=O]2+ and PINO radical. Furthermore, a change of chemoselectivity in the competitive oxidation of sulfides, alkylaromatic compounds and alcohols by effect of variation of the oxidizing species in the absence or in the presence of the NHPI mediator has been investigated
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Distribution and impact of yeast thermal tolerance permissive for mammalian infection
Background: From the viewpoint of fungal virulence in mammals, thermal tolerance can be defined as the ability to grow in the 35 degrees C to 40 degrees C range, which is essential for inhabiting these hosts.
Results: We used archival information in a fungal collection to analyze the relationship between thermal tolerance and genetic background for over 4,289 yeast strains belonging to 1,054 species. Fungal genetic relationships were inferred from hierarchical trees based on pairwise alignments using the rRNA internal transcribed spacer and large subunit rDNA (LSU) sequences. In addition, we searched for correlations between thermal tolerance and other archival information including antifungal susceptibility, carbon sources, and fermentative capacity. Thermal tolerance for growth at mammalian temperatures was not monophyletic, with thermally tolerant species being interspersed among families that include closely related species that are not thermal tolerant. Thermal tolerance and resistance to antifungal drugs were not correlated, suggesting that these two properties evolved independently. Nevertheless, the ability to grow at higher temperatures did correlate with origin from lower geographic latitudes, capacity for fermentation and assimilation of certain carbon sources.
Conclusions: Thermal tolerance was significantly more common among ascomycetous than basidiomycetous yeasts, suggesting an explanation for the preponderance of ascomycetous yeasts among human pathogenic fungi. Analysis of strain maximum tolerable temperature as a function of collection time suggested that basidiomycetous yeasts are rapidly adapting to global warming. The analysis identified genera with a high prevalence of the thermal-tolerant species that could serve as sources of emerging pathogenic fungi
Mitomycin C in highly myopic eyes - Author reply
Ophthalmology. 2005 Feb;112(2):208-18; discussion 219.
Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes.
Gambato C, Ghirlando A, Moretto E, Busato F, Midena E.
SourceRefractive Surgery Service and Antimetabolite Therapy Research Unit, Department of Ophthalmology, University of Padova, Padova, Italy.
Abstract
PURPOSE: To evaluate the role of topical mitomycin C in corneal wound healing (CWH) after photorefractive keratectomy (PRK) in highly myopic eyes.
DESIGN: Prospective, double-masked, randomized clinical trial.
PARTICIPANTS: Seventy-two eyes of 36 patients affected by high (>7 diopters) myopia.
METHODS: In each patient, one eye was randomly assigned to PRK with intraoperative topical 0.02% mitomycin C application, and the fellow eye was treated with a placebo. Postoperatively, mitomycin C-treated eyes received artificial tears (3 times daily, tapered in 3 months), whereas the fellow eye was treated with fluorometholone sodium 2% and artificial tears (3 times daily, tapered in 3 months).
MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), contrast sensitivity, manifest refraction, and biomicroscopy. Contrast sensitivity was determined using the Pelli-Robson chart. Corneal confocal microscopy documented CWH.
RESULTS: Mean follow-up was 18 months (range, 12-36). No side effects or toxic effects were documented. At 12-month follow-up examination, UCVAs (logarithm of the minimum angle of resolution) were 0.4+/-0.48 and 0.5+/-0.53 (P = .03) in mitomycin C-treated eyes and corticosteroid-treated eyes, respectively. At 1 year, corneal haze developed in 20% of corticosteroid-treated eyes, versus 0% of mitomycin C-treated eyes. At 12, 24, and 36 months, corneal confocal microscopy showed activated keratocytes and extracellular matrix significantly more evident in untreated eyes (Ps = 0.004, 0.024, and 0.046, respectively).
CONCLUSION: Topical intraoperative application of 0.02% mitomycin C can reduce haze formation in highly myopic eyes undergoing PRK.
Comment in
Ophthalmology. 2006 Feb;113(2):357; author reply 357-8
Cryptococcus neoformans capsular glucuronoxylomannan induces expression of fas ligand in macrophages.
The major component of capsular material of Cryptococcus neoformans is glucuronoxylomannnan (GXM), a polysaccharide that exhibits potent immunosuppressive properties in vitro and in vivo. The results reported here show that 1) soluble purified GXM induces a prompt, long-lasting, and potent up-regulation of Fas ligand (FasL) on macrophages, 2) the up-regulation of FasL is related to induced synthesis and increased mobilization to the cellular surface, 3) this effect is largely mediated by interaction between GXM and TLR4, 4) FasL up-regulation occurs exclusively in GXM-loaded macrophages, 5) macrophages that show up-regulation of FasL induce apoptosis of activated T cells expressing Fas and Jurkat cells that constitutively express Fas, and 6) anti-Fas Abs rescue T cells from apoptosis induced by GXM. Collectively our results reveal novel aspects of the immunoregulatory properties of GXM and suggest that this nontoxic soluble compound could be used to dampen the immune response, to promote or accelerate the death receptor, and to fix FasL expression in a TLR/ligand-dependent manner. In the present study, we delineate potential new therapeutic applications for GXM that exploit death receptors as key molecular targets in regulating cell-mediated cytotoxicity, immune homeostasis, and the immunopathology of diseases
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