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1.
Fungal Syst Evol ; 5: 197-281, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32467924

RESUMO

To clarify the diversity of plant-parasitic Alternaria species in Japan, diseased samples were collected, and fungal isolates established in culture. We examined 85 isolates representing 23 species distributed in 14 known sections based on conidial morphology and DNA phylogeny. Three species were found to be new, A. cylindrica, A. paragomphrenae and A. triangularis. Furthermore, a lectotype was designated for A. gomphrenae, and epitypes for A. cinerariae, A. gomphrenae, A. iridicola, and A. japonica. Species boundaries of isolates were also clarified by studying phenotypes and determining host ranges. Alternaria gomphrenae and related species in sect. Alternantherae were recognized as distinct species owing to their host specificity. Among the species infecting Apiaceae, the pathogenicity of A. cumini and a novel species, A. triangularis ex Bupleurum, were confirmed as host specific. Another novel species, A. cylindrica, proved to be host specific to Petunia. Alternaria iridicola was recognized as a large-spored species in sect. Alternaria, being host specific to Iris spp. On the other hand, the experimental host ranges of three morphologically and phylogenetically distinct species infecting Brassicaceae (A. brassicae, A. brassicicola, and A. japonica) showed almost no differences. Alternaria brassicicola and A. porri were even found on non-host plants. In general, host ranges of Alternaria species correlated with morphology and molecular phylogeny, and combining these datasets resulted in clearer species boundaries.

3.
Sci Total Environ ; 618: 80-92, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29127871

RESUMO

This paper focuses on how a community of researchers under the COMET (CO-ordination and iMplementation of a pan European projecT for radioecology) project has improved the capacity of marine radioecology to understand at the process level the behaviour of radionuclides in the marine environment, uptake by organisms and the resulting doses after the Fukushima Dai-ichi nuclear accident occurred in 2011. We present new radioecological understanding of the processes involved, such as the interaction of waterborne radionuclides with suspended particles and sediments or the biological uptake and turnover of radionuclides, which have been better quantified and mathematically described. We demonstrate that biokinetic models can better represent radionuclide transfer to biota in non-equilibrium situations, bringing more realism to predictions, especially when combining physical, chemical and biological interactions that occur in such an open and dynamic environment as the ocean. As a result, we are readier now than we were before the FDNPP accident in terms of having models that can be applied to dynamic situations. The paper concludes with our vision for marine radioecology as a fundamental research discipline and we present a strategy for our discipline at the European and international levels. The lessons learned are presented along with their possible applicability to assess/reduce the environmental consequences of future accidents to the marine environment and guidance for future research, as well as to assure the sustainability of marine radioecology. This guidance necessarily reflects on why and where further research funding is needed, signalling the way for future investigations.


Assuntos
Acidente Nuclear de Fukushima , Radioisótopos/análise , Água do Mar/análise , Poluentes Radioativos da Água/análise , Biota , Ecossistema , Japão , Monitoramento de Radiação
4.
Neuroscience ; 318: 58-83, 2016 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-26772432

RESUMO

A sound interrupted by silence is perceived as discontinuous. However, when high-intensity noise is inserted during the silence, the missing sound may be perceptually restored and be heard as uninterrupted. This illusory phenomenon is called auditory induction. Recent electrophysiological studies have revealed that auditory induction is associated with the primary auditory cortex (A1). Although experimental evidence has been accumulating, the neural mechanisms underlying auditory induction in A1 neurons are poorly understood. To elucidate this, we used both experimental and computational approaches. First, using an optical imaging method, we characterized population responses across auditory cortical fields to sound and identified five subfields in rats. Next, we examined neural population activity related to auditory induction with high temporal and spatial resolution in the rat auditory cortex (AC), including the A1 and several other AC subfields. Our imaging results showed that tone-burst stimuli interrupted by a silent gap elicited early phasic responses to the first tone and similar or smaller responses to the second tone following the gap. In contrast, tone stimuli interrupted by broadband noise (BN), considered to cause auditory induction, considerably suppressed or eliminated responses to the tone following the noise. Additionally, tone-burst stimuli that were interrupted by notched noise centered at the tone frequency, which is considered to decrease the strength of auditory induction, partially restored the second responses from the suppression caused by BN. To phenomenologically mimic the neural population activity in the A1 and thus investigate the mechanisms underlying auditory induction, we constructed a computational model from the periphery through the AC, including a nonlinear dynamical system. The computational model successively reproduced some of the above-mentioned experimental results. Therefore, our results suggest that a nonlinear, self-exciting system is a key element for qualitatively reproducing A1 population activity and to understand the underlying mechanisms.


Assuntos
Córtex Auditivo/fisiologia , Percepção Auditiva/fisiologia , Potenciais Evocados Auditivos/fisiologia , Audição/fisiologia , Neurônios/fisiologia , Dinâmica não Linear , Estimulação Acústica/métodos , Animais , Masculino , Ruído , Ratos , Som
5.
J Environ Biol ; 37(4 Spec No): 685-95, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28779727

RESUMO

Seasonal variations of zooplankton community in terms of biomass and size-fractionated densities were studied in a tropical Sangga Kechil river, Matang, Perak from June 2010 to April 2011. Zooplankton and jellyfish (hydromedusae, siphonophores and ctenophores) samples were collected bimonthly from four sampling stations by horizontal towing of a 140-?m plankton net and 500 ?m bongo net, respectively. A total of 12 zooplankton groups consisting of six groups each of mesozooplankon (0.2 mm-2.0 mm) and macrozooplankton (2.0 mm-20.0 cm) were recorded. The total zooplankton density (12375?3339 ind m(-3)) and biomass (35.32?14.56 mg m(-3)) were highest during the northeast (NE) monsoon and southwest (SW) monsoon, respectively, indicating the presence of bigger individuals in the latter season. Mesozooplankton predominated (94%) over the macrozooplankton (6%) during all the seasons, and copepods contributed 84% of the total mesozooplankton abundance. Macrozooplankton was dominated by appendicularians during most of the seasons (43%-97%), except during the NE monsoon (December) when chaetognaths became the most abundant (89% of the total macrozooplankton). BIO-ENV analysis showed that total zooplankton density was correlated with turbidity, total nitrogen and total phosphorus, which in turn was positively correlated to chlorophyll a. Cluster analysis of the zooplankton community showed no significant temporal difference between the SW and NE monsoon season during the study period (> 90% similarity). The present study revealed that the zooplankton community in the tropical mangrove estuary in the Straits of Malacca was dominated by mesoplankton, especially copepods.


Assuntos
Biomassa , Clorofila , Animais , Clorofila A , Estuários , Estações do Ano , Zooplâncton
7.
Pharmazie ; 69(2): 142-7, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24640605

RESUMO

Certain physiological states and diseases can alter the expression and activity of cytochrome P450 s (CYPs), which have the potential to cause unexpected adverse effects. We previously demonstrated that lipopolysaccharide (LPS)-induced inflammation attenuates the induction of CYPs by xenobiotics in mouse liver. In this study, to investigate whether anaphylaxis-induced inflammation affects the hepatic CYPs' expression, we examined the effects of ovalbumin (OVA)-induced anaphylaxis on constitutive CYP mRNA and protein expressions. We also compared these effects with those obtained with LPS treatment. In addition, we examined the tumor necrosis factor (TNF) alpha and interleukin (IL)-113 mRNA levels, because these cytokines are known to be induced by LPS treatment and anaphylactic reactions. LPS treatment decreased the constitutively expressed Cyp1a2, Cyp2c29, and Cyp3al 1 mRNAs, and increased the TNFalpha and IL-1beta mRNAs. LPS treatment also decreased the CYP1A2 and CYP3A protein levels. Anaphylaxis, on the other hand, did not change the levels of the constitutively expressed Cyp1a2, Cyp2c29, or Cyp3a1 1 mRNAs, although it increased the TNFalpha and IL-1beta mRNAs, as observed in the LPS-treated mice. These results suggest that anaphylaxis-induced inflammation had less effect than LPS-induced inflammation on these CYPs in the liver. In contrast, we observed that the expressions of Cyp2b10 mRNA and its protein were quite different from those of the other CYPs in both the anaphylactic and LPS-treated mice. Our findings strongly suggest that the alteration of the constitutive CYPs' expression levels during inflammation varies according to the immunostimulation pathway.


Assuntos
Anafilaxia/metabolismo , Sistema Enzimático do Citocromo P-450/biossíntese , Inflamação/induzido quimicamente , Inflamação/metabolismo , Lipopolissacarídeos , Fígado/enzimologia , Animais , Western Blotting , Sistema Enzimático do Citocromo P-450/genética , Expressão Gênica/genética , Interleucina-1beta/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microssomos Hepáticos/enzimologia , Microssomos Hepáticos/metabolismo , RNA/biossíntese , RNA/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Fator de Necrose Tumoral alfa/biossíntese
8.
Dis Esophagus ; 27(1): 50-4, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23442212

RESUMO

Endoscopic submucosal dissection (ESD) is an accepted standard treatment for early gastric cancer but is not widely used in the esophagus because of technical difficulties. To increase the safety of esophageal ESD, we used a scissors-type device called the stag beetle (SB) knife. The aim of this study was to determine the efficacy and safety of ESD using the SB knife. We performed a single-center retrospective, uncontrolled trial. A total of 38 lesions were excised by ESD from 35 consecutive patients who were retrospectively divided into the following two groups according to the type of knife used to perform ESD: the hook knife (hook group) was used in 20 patients (21 lesions), and the SB knife (SB group) was used in 15 patients (17 lesions). We evaluated and compared the operative time, lesion size, en bloc resection rate, pathological margins free rate, and complication rate in both groups. The operative time was shorter in the SB group (median 70.0 minutes [interquartile range, 47.5-87.0]) than in the hook group (92.0 minutes [interquartile range, 63.0-114.0]) (P = 0.019), and the rate of complications in the SB group was 0% compared with 45.0% in the hook group (P = 0.004). However, the lesion size, en bloc resection rate, and pathological margins free rate did not differ significantly between the two groups. In conclusion, ESD using the SB knife was safer than that using a conventional knife for superficial esophageal neoplasms.


Assuntos
Carcinoma in Situ/cirurgia , Carcinoma de Células Escamosas/cirurgia , Dissecação/instrumentação , Neoplasias Esofágicas/cirurgia , Esofagoscopia/instrumentação , Esôfago/cirurgia , Mucosa/cirurgia , Idoso , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Esôfago/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Instrumentos Cirúrgicos , Resultado do Tratamento
9.
Stud Mycol ; 75(1): 115-70, 2013 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-24014899

RESUMO

The genus Cercospora contains numerous important plant pathogenic fungi from a diverse range of hosts. Most species of Cercospora are known only from their morphological characters in vivo. Although the genus contains more than 5 000 names, very few cultures and associated DNA sequence data are available. In this study, 360 Cercospora isolates, obtained from 161 host species, 49 host families and 39 countries, were used to compile a molecular phylogeny. Partial sequences were derived from the internal transcribed spacer regions and intervening 5.8S nrRNA, actin, calmodulin, histone H3 and translation elongation factor 1-alpha genes. The resulting phylogenetic clades were evaluated for application of existing species names and five novel species are introduced. Eleven species are epi-, lecto- or neotypified in this study. Although existing species names were available for several clades, it was not always possible to apply North American or European names to African or Asian strains and vice versa. Some species were found to be limited to a specific host genus, whereas others were isolated from a wide host range. No single locus was found to be the ideal DNA barcode gene for the genus, and species identification needs to be based on a combination of gene loci and morphological characters. Additional primers were developed to supplement those previously published for amplification of the loci used in this study. TAXONOMIC NOVELTIES: New species - Cercospora coniogrammes Crous & R.G. Shivas, Cercospora delaireae C. Nakash., Crous, U. Braun & H.D. Shin, Cercospora euphorbiae-sieboldianae C. Nakash., Crous, U. Braun & H.D. Shin, Cercospora pileicola C. Nakash., Crous, U. Braun & H.D. Shin, Cercospora vignigena C. Nakash., Crous, U. Braun & H.D. Shin. Typifications: epitypifications - Cercospora alchemillicola U. Braun & C.F. Hill, Cercospora althaeina Sacc., Cercospora armoraciae Sacc., Cercospora corchori Sawada, Cercospora mercurialis Pass., Cercospora olivascens Sacc., Cercospora violae Sacc.; neotypifications - Cercospora fagopyri N. Nakata & S. Takim., Cercospora sojina Hara.

11.
Allergy ; 68(7): 953-6, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23742077

RESUMO

Eotaxins and their receptor CCR3 have a definitive role for tissue accumulation of eosinophils both under homeostatic and pathologic conditions. However, physiological stimuli that can up-regulate CCR3 in blood-derived human eosinophils have not been recognized. As a prior gene microarray study revealed up-regulation of CCR3 in eosinophils stimulated with retinoic acids (RAs), the expression of functional CCR3 was examined. We found that 9-cis RA and all-trans RA (ATRA) significantly induced surface CCR3 expression regardless of the presence of IL-3 or IL-5. Pharmacological manipulations with receptor-specific agonists and antagonists indicated that retinoic acid receptor-α activation is critical for CCR3 up-regulation. RA-induced CCR3 was associated with its functional capacity, in terms of the calcium mobilization and chemotactic response to eotaxin-1 (CCL11). Our study suggests an important role of vitamin A derivatives in the tissue accumulation of eosinophils.


Assuntos
Quimiotaxia de Leucócito/efeitos dos fármacos , Dermatite Atópica/sangue , Eosinófilos/efeitos dos fármacos , Receptores CCR3/genética , Tretinoína/farmacologia , Células Cultivadas , Quimiocina CCL24/genética , Quimiocina CCL24/metabolismo , Fatores Quimiotáticos de Eosinófilos/genética , Fatores Quimiotáticos de Eosinófilos/metabolismo , Quimiotaxia de Leucócito/genética , Dermatite Atópica/genética , Eosinófilos/imunologia , Regulação da Expressão Gênica , Humanos , Receptores CCR3/metabolismo , Sensibilidade e Especificidade , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Regulação para Cima
13.
Pharmacogenomics J ; 13(1): 60-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21912425

RESUMO

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe, cutaneous adverse drug reactions that are rare but life threatening. Genetic biomarkers for allopurinol-related SJS/TEN in Japanese were examined in a genome-wide association study in which Japanese patients (n=14) were compared with ethnically matched healthy controls (n=991). Associations between 890 321 single nucleotide polymorphisms and allopurinol-related SJS/TEN were analyzed by the Fisher's exact test (dominant genotype mode). A total of 21 polymorphisms on chromosome 6 were significantly associated with allopurinol-related SJS/TEN. The strongest association was found at rs2734583 in BAT1, rs3094011 in HCP5 and GA005234 in MICC (P=2.44 × 10(-8); odds ratio=66.8; 95% confidence interval, 19.8-225.0). rs9263726 in PSORS1C1, also significantly associated with allopurinol-related SJS/TEN, is in absolute linkage disequilibrium with human leukocyte antigen-B*5801, which is in strong association with allopurinol-induced SJS/TEN. The ease of typing rs9263726 makes it a useful biomarker for allopurinol-related SJS/TEN in Japanese.


Assuntos
Alopurinol/efeitos adversos , Síndrome de Stevens-Johnson/genética , Idoso , Idoso de 80 Anos ou mais , Alopurinol/uso terapêutico , Povo Asiático/genética , Biomarcadores/metabolismo , Cromossomos Humanos Par 6/efeitos dos fármacos , Cromossomos Humanos Par 6/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Estudo de Associação Genômica Ampla/métodos , Antígenos HLA/genética , Antígenos HLA/metabolismo , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Síndrome de Stevens-Johnson/induzido quimicamente , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/metabolismo
15.
Isotopes Environ Health Stud ; 45(3): 208-19, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19507080

RESUMO

Overgrazing often lowers species richness and productivity of grassland communities. For Mongolian grassland ecosystems, a lack of detailed information about food-web structures makes it difficult to predict the effects of overgrazing on species diversity and community composition. We analysed the delta13C and delta15N signatures of herbaceous plants, arthropods (grouped by feeding habit), wild and domestic mammals, and humans in central Mongolia to understand the predominant food-web pathways in this grassland ecosystem. The delta13C and delta15N values of mammals showed little variation within species, but varied considerably with slope position for arthropods. The apparent isotopic discrimination between body tissue and hair of mammals was estimated as 2.0 per thousand for delta13C and 2.1 per thousand for delta15N, which was large enough to cause overestimation of the trophic level of mammals if not taken into account when using hair samples to measure isotopic enrichment.


Assuntos
Isótopos de Carbono/análise , Cadeia Alimentar , Isótopos de Nitrogênio/análise , Plantas/química , Poaceae , Animais , Animais Domésticos/metabolismo , Animais Selvagens/metabolismo , Artrópodes/química , Artrópodes/metabolismo , Cabelo/química , Cabelo/metabolismo , Mamíferos/metabolismo , Mongólia , Plantas/metabolismo , Poaceae/química
16.
Aquat Toxicol ; 85(1): 57-66, 2007 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-17875330

RESUMO

The imposex phenomenon in female prosobranch gastropods provides one of the best documented examples of endocrine disruption in wildlife. While many field studies have demonstrated the negative impact of tributyltin (TBT) upon female gastropods, the mechanism(s) underlying imposex development has not yet been fully clarified. Over the years several hypotheses have been raised to determine the biochemical and molecular determinants of this process. Nevertheless, the interplay between the different suggested pathways (neuroendocrine, steroid and retinoid) is still unknown. Hence, through a combination of exposure experiments, we show that the 9-cis-retinoic acid (9cisRA), the proposed natural ligand of the retinoic X receptor (RXR), induces imposex in females of Nucella lapillus to the same degree as tributyltin, when administered at similar concentrations (1 microg/g body weight). Methoprene acid, a selective ligand for RXR, also induces imposex, albeit to a lower degree than that of the positive control. In contrast, testosterone significantly induced imposex, but had no effect on female penis induction, while the neuropeptide APGWamide had no effect on imposex development. These results clearly demonstrate that imposex induction in N. lapillus is mediated through the modulation of the RXR signalling pathways. In addition to the effects reported in female dogwhelks, both TBT and RA significantly increased male penis length, thus suggesting that TBT may also impact male secondary sex organs through the RXR signalling pathways. As a step for future studies, we have cloned the orthologue of N. lapillus RXR and provide experimental evidence that it binds 9cisRA. Finally, the basal expression level of RXR in several tissues of N. lapillus was determined through real-time PCR, thus showing that RXR is ubiquitously expressed in mollusc tissues, with the highest expression levels being recorded in female and male gonads. The mechanistic impacts of the overall findings to the imposex process are discussed.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Receptores X de Retinoides/metabolismo , Caracteres Sexuais , Caramujos/efeitos dos fármacos , Tretinoína/toxicidade , Alitretinoína , Sequência de Aminoácidos , Animais , Sequência de Bases , Primers do DNA/química , Escherichia coli/genética , Feminino , Perfilação da Expressão Gênica/veterinária , Genitália/efeitos dos fármacos , Ligantes , Masculino , Metoprene/toxicidade , Dados de Sequência Molecular , Receptores X de Retinoides/química , Receptores X de Retinoides/genética , Alinhamento de Sequência , Caramujos/genética , Caramujos/fisiologia , Testosterona/toxicidade , Distribuição Tecidual , Compostos de Trialquitina/toxicidade
18.
Science ; 311(5758): 194, 2006 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-16410516

RESUMO

Here we report successful interferometric coupling of two large telescopes with single-mode fibers. Interference fringes were obtained in the 2- to 2.3-micrometer wavelength range on the star 107 Herculis by using the two Keck 10-meter telescopes, each feeding their common interferometric focus with 300 meters of single-mode fibers. This experiment demonstrates the potential of fibers for future kilometric arrays of telescopes and is the first step toward the 'OHANA (Optical Hawaiian Array for Nanoradian Astronomy) interferometer at the Mauna Kea observatory in Hawaii. It opens the way to sensitive optical imagers with resolutions below 1 milli-arc second. Our experimental setup can be directly extended to large telescopes separated by many hundreds of meters.

19.
Int J Gastrointest Cancer ; 37(4): 133-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-18080789

RESUMO

BACKGROUND: With the development of endoscopic submucosal dissection, an expansion of the criteria for local treatment was suggested for lesions with ulcerous changes or undifferentiated-type adenocarcinoma. AIM OF THE STUDY: To determine the efficacy of endoscopic ultrasonography for such lesions, we retrospectively analyzed factors that influenced accurate diagnosis by endoscopic ultrasonography of the depth of tumor invasion. METHODS: We investigated 267 gastric adenocarcinomas for which histopathological results were obtained by endoscopic mucosal resection or gastrectomy. The lesions were divided into four groups by histological type and the presence of ulcerous changes. Five clinicopathological factors were assessed for their possible associations with incorrect diagnosis. RESULTS: The positive predictive value (PPV) for cancer limited within the mucosa (endoscopic ultrasonography, EUS-M) and cancer invaded into the submucosal layer (EUS-SM) were 88.0% (125 of 142 lesions) and 60.0% (30 of 50 lesions), respectively. The lesions diagnosed as EUS-M/SM borderline (37 lesions) included 19 lesions (51.4%) of M cancer and 17 lesions (45.9%) of SM cancer. In logistic analysis, ulcerous changes (p < 0.0001) and macroscopic classification (p = 0.0284) were factors that caused incorrect diagnosis by endoscopic ultrasonography. In the group having differentiated-type adenocarcinoma with ulcerous changes, the PPV of EUS-SM was 25% (3 of 12), and there was a significant difference (p < 0.05) between the EUS-SM of this group and that of the differentiated-type adenocarcinoma without ulcerous changes. CONCLUSION: The accuracy of endoscopic ultrasonography tumor staging was not sufficient for the lesions with ulcerous changes in our study. Therefore, we should be careful to perform endoscopic submucosal dissection for lesions with ulcerous changes.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Diagnóstico Diferencial , Endossonografia , Neoplasias Gástricas/diagnóstico por imagem , Úlcera Gástrica/diagnóstico por imagem , Adenocarcinoma/patologia , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/patologia , Humanos , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Estômago/diagnóstico por imagem , Estômago/patologia , Estômago/cirurgia , Neoplasias Gástricas/patologia , Úlcera Gástrica/complicações
20.
Oncogene ; 23(53): 8563-70, 2004 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-15378026

RESUMO

SAP is an adaptor molecule with one SH2 domain and it is expressed in activated T and NK cells, where it is required for the appropriate signaling from the SLAM family of surface receptors. Deleted or mutated SAP genes that encode functionally defective protein are associated with the X-linked lymphoproliferative disease (XLP). This primary immunodeficiency is characterized by extreme sensitivity to Epstein-Barr virus (EBV) infection, dysgammaglobulinemia and a high rate of lymphoma development. The vigorous T- and B-cell proliferation that follows EBV infection and the high incidence of lymphomas (30%) in XLP patients might reflect functional defects in cell cycle and/ or apoptosis control. Our experiments show that SAP is a target of p53. In Burkitt lymphoma (BL) lines transfected with a temperatur-sensitive (ts) p53, SAP mRNA and protein expression was dependent on wild-type (wt) p53. Activation of endogenous wt p53 in BLs and lymphoblastoid cell lines led to the induction of SAP and this was inhibited by the specific p53 inhibitor pifithrin-alpha. Cell lines that carried mutant p53 did not express SAP under similar conditions. Moreover, we have shown binding of wt p53 to the promoter region of SAP by ChIP assay. Our results suggest that SAP contributes to the execution of some p53 functions.


Assuntos
Regulação da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Linfócitos/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Sequência de Bases , Linfoma de Burkitt , Linhagem Celular Tumoral , Dano ao DNA , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/patologia , Linfócitos/efeitos da radiação , Dados de Sequência Molecular , Mutação/genética , Fito-Hemaglutininas/farmacologia , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Elementos de Resposta/genética , Proteína Associada à Molécula de Sinalização da Ativação Linfocitária , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Linfócitos T/efeitos da radiação , Temperatura , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/genética , Regulação para Cima/efeitos dos fármacos
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