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1.
Aging Cell ; 22(9): e13907, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37415305

RESUMO

Amyloid-ß oligomers (Aßo) are the most pathologically relevant Aß species in Alzheimer's disease (AD), because they induce early synaptic dysfunction that leads to learning and memory impairments. In contrast, increasing VEGF (Vascular Endothelial Growth Factor) brain levels have been shown to improve learning and memory processes, and to alleviate Aß-mediated synapse dysfunction. Here, we designed a new peptide, the blocking peptide (BP), which is derived from an Aßo-targeted domain of the VEGF protein, and investigated its effect on Aß-associated toxicity. Using a combination of biochemical, 3D and ultrastructural imaging, and electrophysiological approaches, we demonstrated that BP strongly interacts with Aßo and blocks Aß fibrillar aggregation process, leading to the formation of Aß amorphous aggregates. BP further impedes the formation of structured Aßo and prevents their pathogenic binding to synapses. Importantly, acute BP treatment successfully rescues long-term potentiation (LTP) in the APP/PS1 mouse model of AD, at an age when LTP is highly impaired in hippocampal slices. Moreover, BP is also able to block the interaction between Aßo and VEGF, which suggests a dual mechanism aimed at both trapping Aßo and releasing VEGF to alleviate Aßo-induced synaptic damage. Our findings provide evidence for a neutralizing effect of the BP on Aß aggregation process and pathogenic action, highlighting a potential new therapeutic strategy.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Camundongos , Animais , Peptídeos beta-Amiloides/toxicidade , Peptídeos beta-Amiloides/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Doença de Alzheimer/metabolismo , Memória/fisiologia , Aprendizagem , Sinapses/metabolismo , Fragmentos de Peptídeos/farmacologia , Fragmentos de Peptídeos/metabolismo
2.
Sci Robot ; 5(48)2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239320

RESUMO

Knowing the displacement capacity and mobility patterns of industrially exploited (i.e., fished) marine resources is key to establishing effective conservation management strategies in human-impacted marine ecosystems. Acquiring accurate behavioral information of deep-sea fished ecosystems is necessary to establish the sizes of marine protected areas within the framework of large international societal programs (e.g., European Community H2020, as part of the Blue Growth economic strategy). However, such information is currently scarce, and high-frequency and prolonged data collection is rarely available. Here, we report the implementation of autonomous underwater vehicles and remotely operated vehicles as an aid for acoustic long-baseline localization systems for autonomous tracking of Norway lobster (Nephrops norvegicus), one of the key living resources exploited in European waters. In combination with seafloor moored acoustic receivers, we detected and tracked the movements of 33 tagged lobsters at 400-m depth for more than 3 months. We also identified the best procedures to localize both the acoustic receivers and the tagged lobsters, based on algorithms designed for off-the-shelf acoustic tags identification. Autonomous mobile platforms that deliver data on animal behavior beyond traditional fixed platform capabilities represent an advance for prolonged, in situ monitoring of deep-sea benthic animal behavior at meter spatial scales.


Assuntos
Pesqueiros , Nephropidae , Robótica/instrumentação , Acústica , Algoritmos , Animais , Comportamento Animal , Simulação por Computador , Conservação dos Recursos Naturais/métodos , Conservação dos Recursos Naturais/estatística & dados numéricos , Ecossistema , Desenho de Equipamento , Nephropidae/fisiologia , Oceanos e Mares , Tecnologia de Sensoriamento Remoto/instrumentação , Tecnologia de Sensoriamento Remoto/estatística & dados numéricos , Robótica/estatística & dados numéricos , Alimentos Marinhos
3.
Oncogene ; 37(35): 4901-4902, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30068941

RESUMO

Following the publication of this article the authors noted that two images were duplicated in Figure 2B. The corrected figure 2B is below. The authors wish to apologize for any inconvenience caused.

4.
Anaerobe ; 42: 74-77, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27544037

RESUMO

Up until now, Bacteroides faecis, a Gram-negative, anaerobic, non-motile, nonsporeforming rod has been principally described as a commensal microbe isolated from the feces of healthy adults. We report the first case of human Bacteroides faecis sepsis after removal of suspected post-colonic ischemia colonized epicardic electrodes. Electrodes and blood cultures both grew Gram-negative anaerobic rods but usual phenotypic methods and 16S rARN gene sequencing failed to ensure its species identification. B. faecis was finally identified using hsp60 gene sequencing. Because this species is not well-known and is difficult to identify, it may have been overlooked or misidentified in previous studies.


Assuntos
Proteínas de Bactérias/genética , Infecções por Bacteroides/microbiologia , Bacteroides/isolamento & purificação , Chaperonina 60/genética , Sepse/microbiologia , Idoso , Antibacterianos/uso terapêutico , Proteínas de Bactérias/química , Bacteroides/classificação , Bacteroides/efeitos dos fármacos , Bacteroides/genética , Infecções por Bacteroides/diagnóstico , Infecções por Bacteroides/tratamento farmacológico , Infecções por Bacteroides/patologia , Chaperonina 60/química , Evolução Fatal , Expressão Gênica , Humanos , Masculino , Testes de Sensibilidade Microbiana , Filogenia , Sepse/diagnóstico , Sepse/tratamento farmacológico , Sepse/patologia , Análise de Sequência de DNA , Falha de Tratamento
5.
Clin Microbiol Infect ; 22(7): 644.e7-644.e12, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27108966

RESUMO

The clinical course of a case of infant botulism was characterized by several relapses despite therapy with amoxicillin and metronidazole. Botulism was confirmed by identification of botulinum toxin and Clostridium botulinum in stools. A C. botulinum A2 strain resistant to penicillins and with heterogeneous resistance to metronidazole was isolated from stool samples up to 110 days after onset. Antibiotic susceptibility was tested by disc agar diffusion and MICs were determined by Etest. Whole genome sequencing allowed detection of a gene cluster composed of blaCBP for a novel penicillinase, blaI for a regulator, and blaR1 for a membrane-bound penicillin receptor in the chromosome of the C. botulinum isolate. The purified recombinant penicillinase was assayed. Resistance to ß-lactams was in agreement with the kinetic parameters of the enzyme. In addition, the ß-lactamase gene cluster was found in three C. botulinum genomes in databanks and in two of 62 genomes of our collection, all the strains belonging to group I C. botulinum. This is the first report of a C. botulinum isolate resistant to penicillins. This stresses the importance of antibiotic susceptibility testing for adequate therapy of botulism.


Assuntos
Antibacterianos/farmacologia , Botulismo/diagnóstico , Botulismo/microbiologia , Clostridium botulinum/efeitos dos fármacos , Clostridium botulinum/isolamento & purificação , Farmacorresistência Bacteriana , Metronidazol/farmacologia , Penicilinas/farmacologia , Toxinas Botulínicas/análise , Botulismo/tratamento farmacológico , Botulismo/patologia , Fezes/química , Fezes/microbiologia , Feminino , Genes Reguladores , Genoma Bacteriano , Humanos , Lactente , Proteínas de Membrana Transportadoras/genética , Testes de Sensibilidade Microbiana , Família Multigênica , Penicilinase/genética , Penicilinase/isolamento & purificação , Penicilinase/metabolismo , Análise de Sequência de DNA
7.
Oncogene ; 26(26): 3878-91, 2007 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-17237827

RESUMO

The p53 tumor suppressor is a nucleocytoplasmic shuttling protein that is found predominantly in the nucleus of cells. In addition to mutation, abnormal p53 cellular localization is one of the mechanisms that inactivate p53 function. To further understand features of p53 that contribute to the regulation of its trafficking within the cell, we analysed the subnuclear localization of wild-type and mutant p53 in human cells that were either permeabilized with detergent or treated with the proteasome inhibitor MG132. We, here, show that either endogenously expressed or exogenously added p53 protein localizes to the nucleolus in detergent-permeabilized cells in a concentration- and ATP hydrolysis-dependent manner. Two discrete regions within the carboxyl terminus of p53 are essential for nucleolar localization in permeabilized cells. Similarly, localization of p53 to the nucleolus after proteasome inhibition in unpermeabilized cells requires sequences within the carboxyl terminus of p53. Interestingly, genotoxic stress markedly decreases the association of p53 with the nucleolus, and phosphorylation of p53 at S392, a site that is modified by such stress, partially impairs its nucleolar localization. The possible significance of these findings is discussed.


Assuntos
Nucléolo Celular/metabolismo , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/metabolismo , Trifosfato de Adenosina/metabolismo , Western Blotting , Células Cultivadas , Inibidores de Cisteína Proteinase/farmacologia , Dano ao DNA/efeitos dos fármacos , Detergentes/farmacologia , Imunofluorescência , Humanos , Técnicas In Vitro , Leupeptinas/farmacologia , Permeabilidade , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Estrutura Terciária de Proteína , Transporte Proteico/efeitos dos fármacos , Transporte Proteico/fisiologia , Transfecção
8.
Epidemiol Infect ; 134(1): 171-8, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16409665

RESUMO

A total of 1873 strains from human origin and 4283 strains from non-human origin of Salmonella enterica serotypes Typhimurium, Enteritidis, Heidelberg, Hadar and Virchow, collected over three years 1993, 1997 and 2000, were examined in order to determine the rate of antimicrobial resistance to 12 antimicrobial drugs. The objective of the study was to describe and to compare the evolution of the main resistance types in human and non-human isolates, focusing on the poultry sector. The evolution and the rates of antimicrobial resistances for the five serotypes, with the exception of Virchow, were almost comparable in strains isolated from human and non-human sources over the period studied. The most striking result concerning single resistance was the spectacular increase of the resistance frequency to nalidixic acid for the strains belonging to serotypes Hadar and Virchow, especially in the poultry food sector (14% in 1993 vs. 72% in 2000 for Salmonella Virchow, 4% in 1993 vs. 70% in 2000 for Salmonella Hadar) and also in human isolates (24% in 1997 vs. 48% in 2000 for S. Virchow, 31% in 1997 vs. 78% in 2000 for S. Hadar). In addition to the classical resistance to ampicillin, streptomycin, sulphonamide, chloramphenicol and tetracycline (ASSuCT resistance type), which stabilized between 1997 and 2000, the emergence of a new resistance type was observed.


Assuntos
Salmonelose Animal/tratamento farmacológico , Infecções por Salmonella/tratamento farmacológico , Salmonella enterica/efeitos dos fármacos , Salmonella enterica/patogenicidade , Animais , Evolução Biológica , Farmacorresistência Bacteriana , França/epidemiologia , Humanos , Fenótipo , Aves Domésticas , Salmonella enterica/classificação , Sorotipagem
9.
Euro Surveill ; 8(7): 151-6, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12941980

RESUMO

Salmonelloses are one are the main causes of foodborne infections in industrialised countries. In France, the incidence of human salmonellosis recorded by the National Reference Centre for Salmonella and Shigella (CNRSS) in 2001 was 21 cases per 100,000 inhabitants, and Salmonella serotype Enteritidis represented 39% of cases (1). This article reports the investigation results of two community outbreaks of salmonellosis that occurred simultaneously in the south west of France, and which were linked to the consumption of cheese made from raw milk.


Assuntos
Queijo/microbiologia , Surtos de Doenças , Intoxicação Alimentar por Salmonella/epidemiologia , Fagos de Salmonella/classificação , Salmonella enteritidis/classificação , Salmonella enteritidis/virologia , Animais , Tipagem de Bacteriófagos , Estudos de Casos e Controles , Bovinos , Monitoramento Ambiental/métodos , Monitoramento Epidemiológico , Gastroenterite/epidemiologia , Gastroenterite/microbiologia , Humanos , Leite/microbiologia , Salmonelose Animal/diagnóstico , Salmonella enteritidis/isolamento & purificação , Sepse/epidemiologia
10.
Biochem Biophys Res Commun ; 301(1): 152-8, 2003 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-12535655

RESUMO

Nucleolar segregation is the most striking cellular phenotypic feature of cold-acclimatized carp and depicts the cyclical reprogramming that the physiology of the fish undergoes between summer and winter, where a clear differential expression of some nucleolar related genes occurs. We characterized carp nucleolin, a nucleolar protein involved in multiple steps of ribosome biogenesis, and evaluated its expression upon fish acclimatization. We show that the carp cDNA deduced amino acid sequence exhibits the same tripartite structural organization found in other species. Nevertheless, we observed that nucleolin mRNA expression was strongly induced in the cold-adapted carp as was the nuclear protein content, assessed by immunocytochemistry in liver sections. The physiological up-regulation of nucleolin in the cold-acclimatized carp, where rRNA transcription and processing are depressed concomitantly with the nucleolus segregation, is consistent with the notion that nucleolin plays a fundamental role in repressing rRNA synthesis.


Assuntos
Aclimatação/fisiologia , Carpas/fisiologia , Nucléolo Celular/metabolismo , Regulação da Expressão Gênica , Fosfoproteínas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Encéfalo/citologia , Encéfalo/metabolismo , Temperatura Baixa , DNA Complementar/genética , Fígado/citologia , Fígado/metabolismo , Masculino , Dados de Sequência Molecular , Fosfoproteínas/genética , Estrutura Terciária de Proteína , RNA Nucleolar Pequeno/genética , RNA Nucleolar Pequeno/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Estações do Ano , Nucleolina
12.
J Mol Biol ; 309(3): 763-75, 2001 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-11397095

RESUMO

Nucleolin is an abundant nucleolar protein which is essential for ribosome biogenesis. The first two of its four tandem RNA-binding domains (RBD12) specifically recognize a stem-loop structure containing a conserved UCCCGA sequence in the loop called the nucleolin-recognition element (NRE). We have determined the structure of the consensus SELEX NRE (sNRE) by NMR spectroscopy. In both the free and bound RNA the top part of the stem forms a loop E (or S-turn) motif. In the absence of protein, the structure of the hairpin loop is not well defined due to conformational heterogeneity, and appears to be in equilibrium between two families of conformations. Titrations of RBD1, RBD2, and RBD12 with the sNRE show that specific binding requires RBD12. In complex with RBD12, the hairpin loop interacts specifically with the protein and adopts a well-defined structure which shares some of the features of the free form. The loop E motif also has specific interactions with the protein. Implications of these findings for the mechanism of recognition of RNA structures by modular proteins are discussed.


Assuntos
Conformação de Ácido Nucleico , Fosfoproteínas/química , Fosfoproteínas/metabolismo , RNA Ribossômico/química , RNA Ribossômico/metabolismo , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/metabolismo , Animais , Pareamento de Bases , Sequência de Bases , Sítios de Ligação , Sequência Consenso/genética , Humanos , Camundongos , Modelos Moleculares , Mutação/genética , Ressonância Magnética Nuclear Biomolecular , Nucleotídeos/química , Nucleotídeos/genética , Nucleotídeos/metabolismo , Maleabilidade , Ligação Proteica , Estrutura Terciária de Proteína , Precursores de RNA/química , Precursores de RNA/genética , Precursores de RNA/metabolismo , Estabilidade de RNA , RNA Ribossômico/genética , Sequências Reguladoras de Ácido Nucleico/genética , Especificidade por Substrato , Termodinâmica , Titulometria , Nucleolina
14.
Nucleic Acids Res ; 29(11): 2223-33, 2001 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-11376140

RESUMO

Numerous RNA-binding proteins have modular structures, comprising one or several copies of a selective RNA-binding domain generally coupled to an auxiliary domain that binds RNA non-specifically. We have built and compared homology-based models of the cold-shock domain (CSD) of the Xenopus protein, FRGY2, and of the third RNA recognition motif (RRM) of the ubiquitous nucleolar protein, nucleolin. Our model of the CSD(FRG)-RNA complex constitutes the first prediction of the three-dimensional structure of a CSD-RNA complex and is consistent with the hypothesis of a convergent evolution of CSD and RRM towards a related single-stranded RNA-binding surface. Circular dichroism spectroscopy studies have revealed that these RNA-binding domains are capable of orchestrating similar types of RNA conformational change. Our results further show that the respective auxiliary domains, despite their lack of sequence homology, are functionally equivalent and indispensable for modulating the properties of the specific RNA-binding domains. A comparative analysis of FRGY2 and nucleolin C-terminal domains has revealed common structural features representing the signature of a particular type of auxiliary domain, which has co-evolved with the CSD and the RRM.


Assuntos
Proteínas de Ligação a RNA/metabolismo , RNA/metabolismo , Proteínas de Xenopus , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação , Dicroísmo Circular , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Molecular , Oligonucleotídeos/genética , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Fosfoproteínas/química , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Ligação Proteica , Conformação Proteica , Estrutura Terciária de Proteína , RNA/genética , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/genética , Homologia de Sequência de Aminoácidos , Fatores de Transcrição/química , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Xenopus , Nucleolina
15.
J Biol Chem ; 276(17): 14338-43, 2001 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-11278842

RESUMO

Nucleolin is an abundant nucleolar protein involved in several steps of ribosome biogenesis. The protein is highly conserved through evolution and possesses four RNA-binding domains (RBD), which are likely to determine its RNA binding specificity. Previous studies have shown that nucleolin interacts with two different RNA targets. The first is a small stem-loop structure, the nucleolin recognition element (NRE), found all along the pre-ribosomal RNA. The second is a short single-stranded RNA sequence, the evolutionary conserved motif (ECM), located five nucleotides downstream of the first processing site in the pre-ribosomal RNA 5' external transcribed spacer. Biochemical, genetic, and structural studies have shown that the first two RBD of nucleolin are necessary and sufficient for the specific interaction of nucleolin with the NRE motif. In this work, we have studied the interaction of nucleolin with the ECM sequence. Deletion and mutational analyses showed that all four RBDs of hamster nucleolin were required for the interaction with the ECM sequence. This RNA binding specificity is conserved between hamster and Xenopus laevis, whereas the Xenopus protein does not interact with the NRE. Nucleolin is the first example of a protein that requires four RBDs for its interaction with an RNA target, demonstrating that a single protein can use different combinations of RBD to interact specifically with several RNA sequences.


Assuntos
Fosfoproteínas/química , Fosfoproteínas/metabolismo , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/metabolismo , RNA/metabolismo , Animais , Sequência de Bases , Sequência Conservada , Cricetinae , Análise Mutacional de DNA , Relação Dose-Resposta a Droga , Deleção de Genes , Cinética , Dados de Sequência Molecular , Mutação , Fosfoproteínas/genética , Plasmídeos/metabolismo , Ligação Proteica , Conformação Proteica , Estrutura Terciária de Proteína , RNA Ribossômico/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas Recombinantes/metabolismo , Transcrição Gênica , Raios Ultravioleta , Xenopus , Nucleolina
16.
J Clin Microbiol ; 39(2): 618-21, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11158117

RESUMO

From September 1997 to November 1998, the French National Center for Salmonella and Shigella received 22 Shigella isolates recovered from 22 different patients suffering from dysentery. None of these isolates reacted with any of the antisera used to identify established Shigella serotypes, but all of them agglutinated in the presence of antisera to a previously described potentially new Shigella dysenteriae serotype (represented by strain 96-204) primarily isolated from stool cultures of imported diarrheal cases in Japan. All French isolates, as well as strain 96-204, showed biochemical reactions typical of S. dysenteriae and gave positive results in a PCR assay for detection of the plasmid ipaH gene coding for invasiveness. No Shiga toxin gene was detected by PCR. These isolates were indistinguishable by molecular analysis of ribosomal DNA (ribotyping) and seemed to be related to S. dysenteriae serotypes 3 and 12. However, further characterization by restriction of the amplified O-antigen gene cluster clearly distinguished this new serotype from all other Shigella or Escherichia coli serotypes.


Assuntos
Disenteria Bacilar/diagnóstico , Shigella dysenteriae/classificação , Diarreia/microbiologia , Disenteria Bacilar/microbiologia , França , Humanos , Japão , Fenótipo , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição , Ribotipagem , Sorotipagem/métodos , Toxina Shiga/genética , Shigella dysenteriae/genética , Shigella dysenteriae/isolamento & purificação
17.
EMBO J ; 19(24): 6870-81, 2000 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-11118222

RESUMO

The structure of the 28 kDa complex of the first two RNA binding domains (RBDs) of nucleolin (RBD12) with an RNA stem-loop that includes the nucleolin recognition element UCCCGA in the loop was determined by NMR spectroscopy. The structure of nucleolin RBD12 with the nucleolin recognition element (NRE) reveals that the two RBDs bind on opposite sides of the RNA loop, forming a molecular clamp that brings the 5' and 3' ends of the recognition sequence close together and stabilizing the stem-loop. The specific interactions observed in the structure explain the sequence specificity for the NRE sequence. Binding studies of mutant proteins and analysis of conserved residues support the proposed interactions. The mode of interaction of the protein with the RNA and the location of the putative NRE sites suggest that nucleolin may function as an RNA chaperone to prevent improper folding of the nascent pre-rRNA.


Assuntos
Fosfoproteínas/química , Fosfoproteínas/metabolismo , Precursores de RNA/química , Precursores de RNA/metabolismo , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação , Calorimetria , Cricetinae , Processamento de Imagem Assistida por Computador , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Ressonância Magnética Nuclear Biomolecular , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Conformação de Ácido Nucleico , Conformação Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Termodinâmica , Nucleolina
18.
J Mol Biol ; 303(2): 227-41, 2000 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-11023788

RESUMO

Nucleolin is an abundant 70 kDa nucleolar protein involved in many aspects of ribosomal RNA biogenesis. The central region of nucleolin contains four tandem consensus RNA-binding domains (RBD). The two most N-terminal domains (RBD12) bind with nanomolar affinity to an RNA stem-loop containing the consensus sequence UCCCGA in the loop. We have determined the solution structure of nucleolin RBD12 in its free form and have studied its interaction with a 22 nt RNA stem-loop using multidimensional NMR spectroscopy. The two RBDs adopt the expected beta alpha beta beta alpha beta fold, but the position of the beta 2 strand in both domains differs from what was predicted from sequence alignments. RBD1 and RBD2 are significantly different from each others and this is likely important in their sequence specific recognition of the RNA. RBD1 has a longer alpha-helix 1 and a shorter beta 2-beta 3 loop than RBD2, and differs from most other RBDs in these respects. The two RBDs are separated by a 12 amino acid flexible linker and do not interact with one another in the free protein. This linker becomes ordered when RBD12 binds to the RNA. Analysis of the observed NOEs between the protein and the RNA indicates that both RBDs interact with the RNA loop via their beta-sheet. Each domain binds residues on one side of the loop; specifically, RBD2 contacts the 5' side and RBD1 contacts the 3'.


Assuntos
Ressonância Magnética Nuclear Biomolecular , Fosfoproteínas/química , Fosfoproteínas/metabolismo , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/metabolismo , RNA/química , RNA/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação , Modelos Moleculares , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Maleabilidade , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , RNA/genética , Sequências Reguladoras de Ácido Nucleico/genética , Alinhamento de Sequência , Soluções , Especificidade por Substrato , Nucleolina
19.
Clin Infect Dis ; 31(2): 488-92, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10987710

RESUMO

To determine risk factors for the occurrence of sporadic Salmonella typhimurium infections among children in France, we conducted a matched case-control study. Cases were identified between 15 June and 30 September 1996. We interviewed 101 pairs of case patients and control subjects, matched for age and place of residence. The risk of illness was greater for children who ate undercooked ground beef than for those who did not (odds ratio [OR], 5.0; 95% confidence interval [CI], 1.9-13.1). Case patients were more likely than control subjects to have taken antibiotics during the month before onset of disease (OR, 2.2; 95% CI, 1.0-4.9). Case patients <5 years of age were more likely to have been in contact with a household member with diarrhea 3-10 days before onset (P=.05). Consumption of undercooked ground beef is a risk factor for the sporadic occurrence of S. typhimurium infection among children, and antibiotics may facilitate the occurrence of illness. The possibility of person-to-person transmission among young children needs to be considered.


Assuntos
Infecções por Salmonella/epidemiologia , Salmonella typhimurium , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Ingestão de Alimentos , França/epidemiologia , Humanos , Lactente , Produtos da Carne/microbiologia , Fatores de Risco , Infecções por Salmonella/etiologia , Infecções por Salmonella/microbiologia
20.
Am J Epidemiol ; 152(2): 171-7, 2000 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-10909954

RESUMO

Despite control measures, foodborne outbreaks of non-typhi Salmonella infection continue to occur in developed countries. The authors aimed to assess the number of foodborne Salmonella outbreaks that occurred in France in 1995 using a capture-recapture approach. Data from three sources--the National Public Health Network (NPHN), the Ministry of Agriculture (MA), which receives mandatory notification, and the National Salmonella and Shigella Reference Center (NRC)-were collected. Matching algorithms permitted identification of matched outbreaks. The total number of outbreaks was estimated by log-linear modeling taking into account source dependencies and the variable catchability. The final estimate was adjusted for the positive predictive value (66%) of the NRC case definition. The dependence between the NPHN and the MA was also evaluated by means of a qualitative survey. A total of 716 foodborne Salmonella outbreaks were reported to the three sources, and 108 matches were identified. The best-fitting model, taking into account a positive dependence between the NPHN and MA sources, gave an estimate of 757 outbreaks. The sensitivity was 15% for the NPHN, 10% for the MA, and 50% for the NRC. In France, routine mandatory reporting of foodborne Salmonella outbreaks is very incomplete, and it is not representative of the serotype and the type of outbreak.


Assuntos
Surtos de Doenças , Intoxicação Alimentar por Salmonella/epidemiologia , França/epidemiologia , Humanos , Vigilância da População/métodos
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