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Objective: To understand the epidemiological characteristics of mpox epidemic in Guangzhou and provide scientific evidence for the prevention and control of the disease. Methods: Based on the mpox surveillance system in Guangzhou, suspected mpox cases with fever and rash were reported by local hospitals at all levels to centers for disease control and prevention in Guangzhou for sampling, investigation and diagnosis. Descriptive epidemiological analysis was conducted on the clinical characteristics and treatment of the mpox cases and positive detection rate reported in Guangzhou as of 24:00 on June 23. Whole genome sequencing of the virus isolates was performed using Illumina Miniseq high-throughput sequencing platform. Results: The first mpox case in Guangzhou was reported on June 10 in 2023. As of 24:00 on June 23, a total of 25 confirmed mpox cases were reported. All the mpox cases were men with a M(Q1,Q3) of 32 (26, 36) years, the majority of the cases were MSM (96.0%). The main clinical features were rash (100.0%, 25/25), lymphadenectasis (100.0%, 25/25) and fever (52.0%, 13/25). Rash usually occurred near the genitals (88.0%, 22/25). The close contacts, mainly family members (40.4%, 23/57), showed no similar symptoms, such as fever or rash. The positive rate of mpox virus in household environment samples was 30.5%. The analyses on 3 complete gene sequences of mpox virus indicated that the strains belonged to West African type â ¡b clade, B.1.3 lineage. Conclusions: Hidden transmission of mpox virus had occurred in MSM in Guangzhou. However, the size of affected population is relatively limited, and the possibility of wide spread of the virus is low.
Assuntos
Epidemias , Exantema , Mpox , Minorias Sexuais e de Gênero , Estados Unidos , Masculino , Humanos , Feminino , Homossexualidade Masculina , FebreRESUMO
Objective: To analyze the clinicopathological characteristics and prognosis of patients with small bowel tumors. Methods: This was a retrospective, observational study. We collected clinicopathological data of patients with primary jejunal or ileal tumors who had undergone small bowel resection in the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University between January 2012 and September 2017. The inclusion criteria included: (1) older than 18 years; (2) had undergone small bowel resection; (3) primary location at jejunum or ileum; (4) postoperative pathological examination confirmed malignancy or malignant potential; and (5) complete clinicopathological and follow-up data. Patients with a history of previous or other concomitant malignancies and those who had undergone exploratory laparotomy with biopsy but no resection were excluded. The clinicopathological characteristics and prognoses of included patients were analyzed. Results: The study cohort comprised 220 patients with small bowel tumors, 136 of which were classified as gastrointestinal stromal tumors (GISTs), 47 as adenocarcinomas, and 35 as lymphomas. The median follow-up for all patient was 81.0 months (75.9-86.1). GISTs frequently manifested as gastrointestinal bleeding (61.0%, 83/136) and abdominal pain (38.2%, 52/136). In the patients with GISTs, the rates of lymph node and distant metastasis were 0.7% (1/136) and 11.8% (16/136), respectively. The median follow-up time was 81.0 (75.9-86.1) months. The 3-year overall survival (OS) rate was 96.3%. Multivariate Cox regression-analysis results showed that distant metastasis was the only factor associated with OS of patients with GISTs (HR=23.639, 95% CI: 4.564-122.430, P<0.001). The main clinical manifestations of small bowel adenocarcinoma were abdominal pain (85.1%, 40/47), constipation/diarrhea (61.7%, 29/47), and weight loss (61.7%, 29/47). Rates of lymph node and distant metastasis in patients with small bowel adenocarcinoma were 53.2% (25/47) and 23.4% (11/47), respectively. The 3-year OS rate of patients with small bowel adenocarcinoma was 44.7%. Multivariate Cox regression-analysis results showed that distant metastasis (HR=4.018, 95%CI: 2.108-10.331, P<0.001) and adjuvant chemotherapy (HR=0.291, 95% CI: 0.140-0.609, P=0.001) were independently associated with OS of patients with small bowel adenocarcinoma. Small bowel lymphoma frequently manifested as abdominal pain (68.6%, 24/35) and constipation/diarrhea (31.4%, 11/35); 77.1% (27/35) of small bowel lymphomas were of B-cell origin. The 3-year OS rate of patients with small bowel lymphomas was 60.0%. T/NK cell lymphomas (HR= 6.598, 95% CI: 2.172-20.041, P<0.001) and adjuvant chemotherapy (HR=0.119, 95% CI: 0.015-0.925, P=0.042) were independently associated with OS of patients with small bowel lymphoma. Small bowel GISTs have a better prognosis than small intestinal adenocarcinomas (P<0.001) or lymphomas (P<0.001), and small bowel lymphomas have a better prognosis than small bowel adenocarcinomas (P=0.035). Conclusions: The clinical manifestations of small intestinal tumor are non-specific. Small bowel GISTs are relatively indolent and have a good prognosis, whereas adenocarcinomas and lymphomas (especially T/NK-cell lymphomas) are highly malignant and have a poor prognosis. Adjuvant chemotherapy would likely improve the prognosis of patients with small bowel adenocarcinomas or lymphomas.
Assuntos
Neoplasias Intestinais , Humanos , Dor Abdominal , Adenocarcinoma/cirurgia , Constipação Intestinal , Neoplasias Duodenais , Tumores do Estroma Gastrointestinal , Neoplasias Intestinais/diagnóstico , Linfoma , Prognóstico , Estudos RetrospectivosAssuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos , Humanos , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do TratamentoRESUMO
The study was to investigate whether the application of checklist during ward rounds could improve the prognosis of critical ill patients.The results suggested that the checklist used during ward rounds could not improve the inhospital mortality of critically ill patients, but it increased the proportion of deep vein thrombosis prophylaxis, and shortened prophylaxis treatment of gastric stress ulcer.
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Lista de Checagem/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde/métodos , Visitas de Preceptoria , China , Estado Terminal/mortalidade , Estado Terminal/terapia , Mortalidade Hospitalar , Humanos , Prognóstico , Visitas de Preceptoria/métodos , Visitas de Preceptoria/normasRESUMO
OBJECTIVE: This study aimed to detect the expression of microRNA-378 in OSCC, and further studies its effects on clinicopathology and prognosis of OSCC patients. PATIENTS AND METHODS: Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) was used to detect the expression levels of microRNA-378 in 96 pairs of OSCC tissues and paracancerous tissues. The relationship between microRNA-378 expression and pathological parameters and prognosis of OSCC patients was analyzed. The expression level of microRNA-378 in OSCC cells was detected by RT-qPCR as well. Also, microRNA-378 knockdown expression model was constructed using small interfering RNA in OSCC cell lines CAL-27 and Tca8113. Biological functions of OSCC cells were determined using cell counting kit-8 (CCK-8), colony formation, and transwell assay. Western blot was conducted to detect the protein expression of FOXN3 in OSCC cells. RESULTS: RT-qPCR results showed that the expression level of microRNA-378 in OSCC tissues is remarkably higher than that in paracancerous tissues. Compared with OSCC patients with lower expression of microRNA-378, patients with higher expression of microRNA-378 had higher incidences of lymph node metastasis and distant metastasis, as well as shorter overall survival. MicroRNA-378 knockdown significantly decreased proliferative, invasive, and metastatic abilities of OSCC cells. Western blot results showed that microRNA-378 downregulates FOXN3 expression in OSCC cells. Rescue experiments found that microRNA-378 could regulate FOXN3, thus promoting the malignant progression of OSCC. CONCLUSIONS: MicroRNA-378 is highly expressed in OSCC, which is significantly associated with tumor staging, distant metastasis, and poor prognosis of OSCC. It is shown that microRNA-378 may promote malignant progression of OSCC by regulating FOXN3.
Assuntos
Carcinoma de Células Escamosas/patologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , MicroRNAs/genética , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Estadiamento de Neoplasias , Prognóstico , Regulação para CimaRESUMO
Objective: Pancreatic enzymes may spread into the injured intestine, bloodstream,and cause the cascade of inflammatory reactions.Our objective was to explore trypsin expression in serum and vital organs in septic rats. Methods: Trypsin levels in serum,heart,lung and jejunum were tested and compared between Escherichia coli endotoxin injected rats(SS), SS treated with a protease inhibitor(ulinastatin) and control group(SHAM).The correlations between serum trypsin,intestinal proteins and inflammation indices were assessed.Two components of mucosal barrier, i.e. mucin-2 and E-cadherin,were measured to evaluate the intestinal mucosal barrier function.The levels of tumor necrosis factor alpha (TNFα),interleukin-6(IL-6) and neutrophil elastase(NE) were measured to determine the inflammation indices. Results: Compared to SHAM group, trypsin levels in serum[(73.71±9.14) ng/ml vs. (12.12±2.36) ng/ml],heart[(51.60±15.06) ng/ml vs. (6.39±3.53) ng/ml],lung [(54.73±5.57) ng/ml vs. (5.24±3.08) ng/ml] and jejunum(1.19±0.48 vs. 0.40±0.12) were significantly higher in SS group (all P<0.05). The level of serum trypsin had negative correlation with mucin-2 and E-cadherin, and positive correlation with TNFα, IL-6 and NE (all P<0.05). In rats treated with ulinastatin, trypsin levels were significantly decreased compared with those in SS group including in serum [(65.79±4.88)ng/ml]], heart [(26.33±12.03)ng/ml], lung [(28.73±14.46) ng/ml] and jejunum (0.80±0.20) (all P<0.05).Serum TNFα[(247.34±16.97)ng/L vs. (178.78±40.81)ng/L] revealed similar changes in ulinastatin and SS group,whereas mucin-2 (0.58±0.14 vs. 0.89±0.17) and E-cadherin (0.11±0.04 vs. 0.23±0.06) were both significantly elevated after administration of ulinastatin (both P<0.05) . Conclusion: Serum and tissue trypsin is elevated in septic rats. Protease inhibitor ulinastatin protects intestinal function by reducing inflammatory reaction.
Assuntos
Anti-Inflamatórios/farmacologia , Glicoproteínas/farmacologia , Sepse/prevenção & controle , Inibidores da Tripsina/farmacologia , Tripsina/sangue , Animais , Modelos Animais de Doenças , Inflamação , Interleucina-6 , Intestinos , Ratos , Ratos Sprague-Dawley , Sepse/sangue , Sepse/imunologia , Tripsina/metabolismo , Fator de Necrose Tumoral alfaRESUMO
Objective: To study the willingness and influence factors related to "centralized slaughtering, fresh poultry listing and marketing" strategy, among the household chefs, and provide reference for government to adjust and optimize the strategy on avian influenza prevention. Methods: According to the geographical characteristics and regional functions, 6 'monitoring stations' were selected from 12 residential districts of Guangzhou, respectively. Another 21 meat markets which selling live poultry, were selected in each station and 5 household chefs of each market were invited to attend a face to face interview. Basic information, personal cognitive, willingness and influencing factors to the policy were under study. Univariate and multivariate logistic regression methods were used. Results: A total of 664 household chefs underwent the survey and results showed that the rate of support to the "centralized slaughtering, fresh poultry listing and marketing" strategy was 44.6% (296/664). Results from the multi-factor logistic regression showed that those household chefs who were males (OR=1.618, 95% CI: 1.156-2.264, P=0.005), having received higher education (OR=1.814, 95% CI: 1.296-2.539, P=0.001), or believing that the existence of live poultry stalls was related to the transmission of avian influenza (OR=1.918, 95% CI: 1.341-2.743, P<0.001) were factors at higher risk. These household chefs also intended to avoid the use of live poultry stalls (OR=1.666, 95%CI: 1.203-2.309, P=0.002) and accept the "centralized slaughtering, fresh poultry listing and marketing" strategy. Conclusion: Detailed study on this subject and, setting up pilot project in some areas as well as prioritizing the education programs for household chefs seemed helpful to the implementation of the 'freezing-fresh poultry' policy.
Assuntos
Atitude Frente a Saúde , Subtipo H7N9 do Vírus da Influenza A , Influenza Humana/prevenção & controle , Marketing , Indústria de Embalagem de Carne , Aves Domésticas/virologia , Animais , China , Humanos , Influenza Aviária , Masculino , Análise Multivariada , Projetos Piloto , Inquéritos e QuestionáriosRESUMO
In this study, the expression of DNA excision repair cross-complementing gene 1 (ERCC1) in local advanced nasopharyngeal carcinoma has been correlated with the efficacy of concurrent chemoradiotherapy. A total of 76 patients diagnosed with undifferentiated nasopharyngeal carcinoma diagnosed by nasopharyngeal biopsy and undergoing single-agent cisplatin chemotherapy (80 mg/m(2)) with concurrent radiotherapy (on the first, twenty-second, and forty-third day, 5 times per week, mean dose 74 Gy, range 70-78 Gy) at the Affiliated Cancer Hospital of Guangxi Medical University between January and December 2010 were included. After chemoradiotherapy, outcomes and long-term survival were evaluated. Immunohistochemistry was used to detect expression of ERCC1 protein in nasopharyngeal carcinoma. The relationship between the expression of ERCC1 and efficacy of concurrent chemoradiotherapy and long-term survival were analyzed. ERCC1 was expressed in 42.1% of cases. The expression of ERCC1 was correlated with T stage and clinical staging (P < 0.05), but not with gender, age, or N stage. The response rate in the ERCC1-positive and ERCC1-negative groups was 75.0% and 97.7%, respectively (P < 0.05). In the 72 cases with follow-up available, 1-, 2-, and 3-year survival rates were 91.0, 83.3, and 79.0%; they were 92.4, 87.8, 80.5%, respectively, in the ERCC1-positive group, and 87.9, 77.4, 77.4%, respectively, in the ERCC1-negative group. The expression of ERCC1 may be a sensitive prognostic indicator of concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma.
Assuntos
Proteínas de Ligação a DNA/biossíntese , Endonucleases/biossíntese , Neoplasias Nasofaríngeas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Adulto , Quimiorradioterapia , Cisplatino/administração & dosagem , Proteínas de Ligação a DNA/genética , Intervalo Livre de Doença , Endonucleases/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapiaRESUMO
As an essential member of the HSP70 family, heat shock cognate 70 (Hsc70) is a constitutively expressed molecular chaperone involved in protein metabolism. In this paper, turbot Hsc70 was cloned and the expression profile was also analyzed. The full-length cDNA of the turbot Hsc70 was 2,292 bp in length, including a 113-bp 5' UTR, a 223-bp 3' UTR and a 1,956-bp open reading frame coding a protein with 651 amino acid residues. Comparison of amino acid sequence revealed the existence of three classical HSP70 family signature motifs, a signature nonapeptide and one repeat of tetrapeptide in turbot Hsc70. The turbot Hsc70-deduced amino acids sequence exhibited 75.4-96.8 % homology with Hsp70s/Hsc70s of 24 other known sequences. In particular, the strongest homology was found with the cognate members of Hsc70 subfamily and the highest identity was found with Japanese flounder Hsc70. Semi-quantitative RT-PCR revealed that turbot Hsc70 transcripts were stably expressed in all tested tissues under normal physiological condition, while the expression levels also increased (~1.5-fold to ~threefold) after heat shock and bacterial infection. In addition, Hsc70 transcripts were detected throughout embryonic development and in turbot embryonic cell line (TEC) in the absence of any stress. Meanwhile, it was also heat inducible, but not cold inducible in TEC. These results suggest that Hsc70 gene may be involved in embryogenesis and cellular protection events under normal and stress condition.
Assuntos
Linguados/genética , Proteínas de Choque Térmico HSC70/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Desenvolvimento Embrionário , Linguados/crescimento & desenvolvimento , Linguados/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Choque Térmico HSC70/metabolismo , Dados de Sequência Molecular , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosRESUMO
Sixty novel simple sequence repeat (SSR) markers were developed from expressed sequence tags (EST) of half-smooth tongue sole Cynoglossus semilaevis exploited in the laboratory. The number of alleles, observed and expected heterozygosity per locus ranged from two to 16, from 0·0833 to 1·0000 and from 0·0816 to 0·913, respectively. Of these SSRs, 20 had significant homology to known genes by BLASTx (basic local alignment search tool x) search. For cross-species amplification, there are 53 positive amplifications in Japanese flounder Paralichthys olivaceus with 12 polymorphic loci and 51 positive amplifications in Senegalese sole Solea senegalensis with 11 polymorphic loci. These new EST-SSR markers will be useful for genetic studies and genome mapping of C. semilaevis and its closely related fishes.
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Etiquetas de Sequências Expressas , Linguados/genética , Repetições Minissatélites , Animais , Polimorfismo GenéticoRESUMO
We study the effects of global noise on waves in heterogeneous, spatially clustered, reaction-diffusion systems with possible applications to calcium signaling. We first discuss how clustering of the excitability determines the dynamics by shifting bifurcation points and creating new oscillatory solutions. We then consider the specific situation, where intrinsic noise, due to the smallness of the excitable patches, destroys the global oscillatory state. We show that additional small global fluctuations, however, can partially restore temporal and spatial coherence of the oscillatory signal.
Assuntos
Sinalização do Cálcio/fisiologia , Modelos Biológicos , Periodicidade , Algoritmos , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Espaço Intracelular/metabolismo , Processos EstocásticosRESUMO
Twenty-one microsatellite markers were studied in three meiogynogenetic families of Cynoglossus semilaevis gunther for centromere mapping using half-tetrad analysis. Among the 13 mapped loci, 10 were estimated to be located in the telomeric region, one in the centromeric region, and two in the intermediate region of the chromosome. This study provides a basis for constructing a linkage map of C. semilaevis.
Assuntos
Centrômero/genética , Mapeamento Cromossômico , Linguados/genética , Repetições de Microssatélites/genética , Espermatozoides , Animais , Diploide , Feminino , Pesqueiros/métodos , Genótipo , MasculinoRESUMO
The human CD81 (hCD81) molecule has been identified as a putative receptor for hepatitis C virus (HCV). HCV envelope glycoprotein 2 (E2) most likely plays a pivotal role in binding to host cells by interacting with the hCD81 molecule. In this study, a phage-displayed peptide library was used to select small peptides with anti-hCD81 monoclonal antibody JS-81. The output/input ratio of phages increased about 91 fold after the third round of selection. Eight of the 30 phage clones selected from the phage library showed specific binding to the anti-hCD81 by enzyme linked immunosorbent assay (ELISA). Competitive inhibition test further demonstrated that HCV E2 could significantly inhibit the binding of a positive phage clone to anti-hCD81 JS-81. Exogenous small peptide ATWVCGPCT contained by the positive phage clones showed aligned with the hCD81 sequence from 153-161 by sequence analyses. These results suggest that the selected ATWVCGPCT is a novel hCD81-like small peptide, which can block the binding site of HCV E2 for hCD81. It may be of further application on development of antiviral agents targeting the stage of HCV entry.
Assuntos
Anticorpos Monoclonais/imunologia , Antígenos CD/metabolismo , Biblioteca de Peptídeos , Peptídeos/imunologia , Proteínas do Envelope Viral/metabolismo , Sequência de Aminoácidos , Anticorpos Monoclonais/metabolismo , Antígenos CD/química , Antígenos CD/imunologia , Sítios de Ligação/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Hepacivirus , Humanos , Dados de Sequência Molecular , Peptídeos/química , Peptídeos/farmacologia , Tetraspanina 28 , Proteínas do Envelope Viral/imunologiaRESUMO
Scterotinia scterotiorum (Lib.) de by is a world-wide disease, which seriously decreases the yield and the quality of oil of rapeseed. Mapping resistance genes of S. scterotiorum is of vital effect to breed new elite cultivars resisting the disease. In this paper, we reported that a RAPD linkage map was constructed, including 193 RAPD markers, 19 linkage groups and covering 1,324 cM, by using Mapmaker 3.0. On the basis of map, and resistance genes, Sc1, Sc2 and Sc3, were located in 4th, 8th and 18th linkage groups. Among three QTLs, Sc2 has the characteristics of major gene with explained 29%. The three QTLs together explained about 56% of phenotypic variation.
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Brassica/genética , Mapeamento Cromossômico , Ligação Genética , Doenças das Plantas/genética , Característica Quantitativa Herdável , Técnica de Amplificação ao Acaso de DNA PolimórficoRESUMO
AIM: To study the effects of morphine on active oxygen free radicals. METHOD: Chemiluminescence method was used to measure (a) active oxygen generation induced by respiratory burst of neutrophils from human blood stimulated with phorbol myristate acetate (PMA), (b) Superoxide anion (O2.-) induced by xanthine-xanthine oxidase system, (c) hydroxyl radical (.OH) generated by ascorbic acid (AA)-Cu(2+)-zymosan, and (d) the release of H2O2. RESULTS: The (a), (b), (c), and (d) were scavenged by morphine and their median inhibitory concentrations (IC50 and 95% confidence limits) were 21.1 (13.0-34.0), 54.1 (50.0-58.5), 224.0 (128.2-390.8), and 66.9 (62.9-71.0), nmol L-1, respectively. CONCLUSION: The immunosuppressant effect of morphine was related to its free radicals scavenging action.
Assuntos
Sequestradores de Radicais Livres/farmacologia , Imunossupressores/farmacologia , Morfina/farmacologia , Neutrófilos/fisiologia , Explosão Respiratória/efeitos dos fármacos , Adulto , Humanos , Medições LuminescentesRESUMO
To address the mechanisms that underlie splice site selection and splice site partner assignment, we analyzed the splicing of yeast (Saccharomyces cerevisiae) transcripts containing splice site region duplications. When the 5'-splice site region was duplicated, both sites were utilized to the same extent, indicating little or no influence of proximity on 5'-splice site choice. However, the effect of a 5'-mutant site was greatly enhanced by the presence of an adjacent wild-type site, and this effect was reversed by the restoration of base-pairing with U1 snRNA. 3'-Splice site choice was apparently influenced by proximity, as the site closest to the 5'-splice site was greatly preferred. Studies with strains carrying some U1 snRNA mutations showed an increase in the use of the distal 3'-splice site, indicating a role for U1 snRNP in 3'-splice site selection. The data are compared with those from mammalian splice site choice experiments and suggest mechanisms that influence differential splice site choice as well as exon skipping.
Assuntos
Splicing de RNA , RNA Nuclear Pequeno/genética , Ribonucleoproteínas/genética , Saccharomyces cerevisiae/genética , Transcrição Gênica , Sequência de Bases , Calorimetria , Deleção Cromossômica , Genes Fúngicos , Íntrons , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Conformação de Ácido Nucleico , Plasmídeos , Ribonucleoproteínas Nucleares Pequenas , beta-Galactosidase/genética , beta-Galactosidase/metabolismoRESUMO
To study the contribution of the large, 568-nucleotide yeast (Saccharomyces cerevisiae) U1 snRNA to pre-mRNA splicing, we generated mutations in two regions of the molecule and introduced each mutant gene back into yeast as the sole copy of the U1 snRNA gene. We mutagenized the "A loop," a subregion highly conserved in primary sequence in all U1 snRNA molecules analyzed to date. We also mutagenized a portion of the yeast core subdomain, a region conserved in primary and secondary structure among several yeast species but absent from the much smaller metazoan U1 molecule. Surprisingly, mutations in these two regions had little or no effect on growth rate, yet several of them affected an inefficiently spliced reporter gene construct. In addition, combinations of mutants in both regions gave rise to reduced growth rates. Using the latter assay, we confirmed some of the proposed secondary structure of the yeast core domain. The experiments indicate that both regions contribute to U1 snRNP activity but that mutations in a single region do not have a substantial effect on growth rate because U1 snRNP activity is not rate-limiting for growth.
Assuntos
RNA Fúngico/genética , RNA Nuclear Pequeno/genética , Ribonucleoproteínas/fisiologia , Saccharomyces cerevisiae/genética , Sequência de Bases , Proteínas Fúngicas/genética , Dados de Sequência Molecular , Mutação/genética , Conformação de Ácido Nucleico , Fenótipo , Plasmídeos/genética , Splicing de RNA/genética , RNA Fúngico/isolamento & purificação , RNA Mensageiro/genética , Ribonucleoproteínas/genética , Ribonucleoproteínas Nucleares PequenasRESUMO
Diethylcarbamazine citrate (DEC) at 180-300 mg/kg ip or 560 mg/kg ig inhibited hind paw swelling induced by sc 0.15 ml of carrageenan in normal and adrenalectomized rats. DEC ip 300 mg/kg also inhibited the same swelling induced by sc 2.5% formaldehyde in rats. The proliferation of granuloma induced by cotton-pellets tended to be inhibited by DEC, although not significantly. It inhibited the swelling of mouse ear induced by xylene and the increased vascular permeability induced by ip 0.7% HAC. DEC neither prolonged the survival time in adrenalectomized rats nor increased the weight of the adrenal or plasma cortisol levels in normal rats. DEC decreased the prostaglandin E content in inflammatory tissue, although less than the extent in the indomethacin group. These results indicate that the anti-inflammatory action of DEC is presumably due to the inhibition of synthesis or the release of prostaglandin E, in addition to a possible action mediated by its leukotriene synthesis inhibitor action.