RESUMO
Contemporary transgender youth in the U.S. today face increasing stigmatization as extraordinary legislative attacks intensify discrimination and exclusion of these young people in healthcare, recreation, and school life. These attacks reflect broader political, religious, and cultural ideologies embedded in systems of power that regulate the provision of healthcare for American transgender youth. We apply Foucauldian discourse analysis and a theory-driven conceptual framework for structural analysis of transgender health inequities-Intersectionality Research for Transgender Health Justice-to identify discourses youth encounter within healthcare practice. We analyzed data from interviews conducted in Western Washington State with youth ages 13-17 (n =11) and asked how transgender subjectivity was constructed in their accounts and in what ways youth made use of the discursive resources available to them when navigating systems of care. Three sets of discourses-discourses of normativity, discourses of temporality, and discourse of access-characterized participants' narratives. We discuss how participants negotiated discursively situated systems of power in order to ensure their safety and access to care.
Assuntos
Pessoas Transgênero , Adolescente , Acessibilidade aos Serviços de Saúde , Humanos , Menores de Idade , WashingtonRESUMO
PURPOSE: To describe behavior of children with periventricular brain injury (PBI) in a tethered-kicking intervention. METHODS: Sixteen infants with PBI were randomly assigned to exercise or no-training in a longitudinal pilot study. Frequencies of leg movements and interlimb coordination were described from videos at 2 and 4 months' corrected age (CA). RESULTS: Eight of the 13 children (62%) with longitudinal data increased the frequency of leg movements while tethered to a mobile between 2 and 4 months' CA. Movement frequency was correlated with scores on the Test of Infant Motor Performance, but no differences between experimental groups were found. Children with typical development at 12 months' CA increased the proportion of leg movements that were synchronous between 2 and 4 months, as did a child with cerebral palsy in the experimental group. CONCLUSIONS: The tethered-kicking intervention facilitates movement in infants with PBI, but effects on development remain to be demonstrated.
Assuntos
Lesões Encefálicas/reabilitação , Ventrículos Cerebrais , Movimento/fisiologia , Feminino , Cabeça/fisiopatologia , Humanos , Lactente , Perna (Membro)/fisiopatologia , Estudos Longitudinais , Masculino , Projetos PilotoRESUMO
PURPOSE: To determine whether motor outcomes of an exercise intervention beginning at 2 months corrected age (CA) in children with periventricular brain injury (PBI) are correlated with fractional anisotropy (FA) measures derived from diffusion tensor imaging (DTI) at 12 months CA. MATERIALS AND METHODS: DTI was performed in eight infants with PBI who were randomly assigned to kicking and treadmill stepping exercise or a no-training condition. Development was assessed using the Alberta Infant Motor Scale (AIMS) and the Gross Motor Function Classification System (GMFCS). FA values were derived from regions of interest (ROIs) in the middle third of the posterior limb of the internal capsule (PLIC) and the posterior thalamic radiation (PTR). RESULTS: Significant correlations were observed between motor development and FA measures. For PLIC, the correlation coefficients were 0.82 between FA and AIMS, and -0.92 between FA and GMFCS, while for PTR the corresponding correlation coefficients were 0.73 and -0.80, respectively. CONCLUSION: Results of this study suggest that quantitative evaluation of white matter tracts using DTI at 12 months CA may be useful for assessment of brain plasticity in children.
Assuntos
Lesões Encefálicas/complicações , Lesões Encefálicas/patologia , Ventrículos Cerebrais/lesões , Ventrículos Cerebrais/patologia , Imagem de Tensor de Difusão/métodos , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/etiologia , Anisotropia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Lactente , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como AssuntoRESUMO
Activating transcription factor 3 (ATF3) is a negative regulator of proinflammatory cytokine expression in macrophages, and ATF3-deficient mice are more susceptible to endotoxic shock. Here, we demonstrate that ATF3 interacts with a cis-regulatory element of the IFN-gamma gene in natural killer (NK) cells, and that ATF3null NK cells show increased transcription and secretion of IFN-gamma. NK cell-derived IFN-gamma has previously been demonstrated to be protective against murine cytomegalovirus (MCMV) infection, and we show here that ATF3null mice exhibit decreased hepatic viral load and reduced liver histopathology upon challenge with MCMV. Reconstitution of NK-deficient mice with ATF3null NK cells more effectively controlled MCMV infection than mice reconstituted with WT cells, indicating that ATF3 acts within NK cells to regulate antiviral responses.
Assuntos
Fator 3 Ativador da Transcrição/metabolismo , Infecções por Citomegalovirus/metabolismo , Interferon gama/metabolismo , Células Matadoras Naturais/metabolismo , Muromegalovirus/fisiologia , Fator 3 Ativador da Transcrição/deficiência , Fator 3 Ativador da Transcrição/genética , Animais , Infecções por Citomegalovirus/genética , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/virologia , Regulação da Expressão Gênica , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA Mensageiro/genéticaRESUMO
BACKGROUND: Hepatitis B vaccine provides a model for improving uptake and completion of multidose vaccinations in the drug-using community. METHODS: The Drugs, AIDS, STDs, and Hepatitis (DASH) project conducted a randomized controlled trial among not-in-treatment current drug users in 2 urban neighborhoods. Neighborhoods were cluster-randomized to receive a standard behavioral intervention (which provided information on human immunodeficiency virus [HIV]) or an enhanced behavioral intervention (designed to increase acceptance of or adherence to the hepatitis B vaccination protocol). Participants within clusters were randomized to a standard vaccination schedule (vaccines at 0, 1, and 6 months) or an accelerated vaccination schedule (vaccines at 0, 1, and 2 months). The outcomes were completion of the 3-dose vaccine and seroprotection against hepatitis B virus (HBV). RESULTS: Of participants with negative screening results for HIV and HBV, 77% accepted hepatitis B vaccination, and 75% of vaccinees received all 3 doses. Injection drug users (IDUs) on the accelerated schedule were significantly more likely to receive 3 doses (76%) than those on the standard schedule (66%; P = .04), although for drug users as a whole the corresponding adherence rates were 77% and 73%, respectively. No difference in adherence was observed between the behavioral intervention groups. Predictors of adherence were older age, African American race, stable housing, and alcohol use. Cumulative HBV seroprotection (≥10 mIU/mL) was gained within 12 months by 65% of those completing the schedule. Seroprotection at 6 months was greater for those on the accelerated schedule. CONCLUSION: The accelerated vaccination schedule improves hepatitis B vaccination adherence among IDUs.
Assuntos
Usuários de Drogas , Vacinas contra Hepatite B/administração & dosagem , Vírus da Hepatite B/imunologia , Hepatite B/prevenção & controle , Cooperação do Paciente , Vacinação , Adolescente , Adulto , Esquema de Medicação , Feminino , Antígenos de Superfície da Hepatite B/sangue , Humanos , Esquemas de Imunização , Masculino , Pessoa de Meia-Idade , Texas , Resultado do Tratamento , População UrbanaRESUMO
Oral food challenges are an integral part of an allergist's practice and are used to evaluate the presence or absence of allergic reactivity to foods. A work group within the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology was formed to update a previously published oral food challenge report. The intention of this document was to supplement the previous publication with additional focus on safety, treatment of IgE-mediated allergic reactions, guidance for challenges in infants and adults, psychosocial considerations for children and families participating in an oral food challenge, specific guidance for baked milk or baked egg challenges, masking agents and validated blinding recipes for common food allergens, and recommendations for conducting and interpreting challenges in patients with suspected food protein-induced enterocolitis syndrome. Tables and figures within the report and an extensive online appendix detail age-specific portion sizes, appropriate timing for antihistamine discontinuation, serum and skin test result interpretation, written consents, and instructional handouts that may be used in clinical practice.
Assuntos
Enterocolite , Hipersensibilidade Alimentar , Adulto , Alérgenos , Animais , Criança , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/epidemiologia , Humanos , Imunoglobulina E , Lactente , Testes CutâneosRESUMO
There is widespread evidence that individuals select information that supports their convictions and worldviews. This behavior yields the formation of echo chambers - environments in which an individual's own political beliefs are repeated and amplified and dissenting opinions are screened out. Recent research demonstrates that social networking sites (SNS) such as Facebook or Twitter can facilitate this selection into homogenous networks. Using data from a representative nationwide online survey, we consider the degree to which respondents' social media networks resemble virtual echo chambers. We then analyze the effect of these social media echo chambers on satisfaction with democracy among Democrats and Republicans in the aftermath of the 2016 U.S. elections. Our findings reveal that virtual echo chambers boost democratic satisfaction among Republicans but they do not have an effect on system support by self-identified Democrats. Our paper therefore adds to a growing literature linking online behaviors to mass attitudes about politics.
RESUMO
Results from the Learning Early About Peanut trial and its follow-up study suggest that early peanut introduction in the diets of high-risk infants may prevent the development of peanut allergy. Allergy organizations around the world released a unified statement, the Consensus Communication on Early Peanut Introduction and the Prevention of Peanut Allergy in High Risk Infants, in response to results from the Learning Early About Peanut trial, which recommends early introduction of peanut into the diet of those children at greatest risk of development of peanut allergy. As a result, it is expected that practicing allergists will experience an increased demand to perform an oral food challenge (OFC) in infants. Allergists often perform OFCs; however, conducting an OFC in an infant creates unique circumstances that have not been considered in previously published OFC guideline documents. The purpose of this workgroup report is to provide guidance to practitioners regarding the proper approach for conducting a peanut challenge in an infant.
Assuntos
Alérgenos/imunologia , Arachis/imunologia , Imunização/métodos , Hipersensibilidade a Amendoim/imunologia , Hipersensibilidade a Amendoim/prevenção & controle , Administração Oral , Conferências de Consenso como Assunto , Dieta , Humanos , Lactente , Recém-NascidoRESUMO
The genetic basis of hyper-IgE syndrome (HIES), also known as Job syndrome, a primary immunodeficiency associated with recurrent skin and pulmonary infections, is unknown. We hypothesized that HIES is due to a defect in the Toll-like receptor signaling pathway. We used a whole blood cytokine assay to compare inflammatory responses to stimulation with specific Toll-like receptor (TLR) pathway agonists in four individuals with HIES and nine healthy controls. Production of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and IL-12 was not impaired in response to stimulation with lipopolysaccharide, peptidoglycan, zymosan, lipoteichoic acid, Staphylococcus aureus, Escherichia coli, or Streptococcus pneumoniae. Interferon (IFN)-gamma was reduced in HIES subjects in response to each of these stimuli. We sequenced several candidate genes from the TLR pathway in HIES individuals to determine whether any mutations were associated with this syndrome. No novel mutations or polymorphisms were found in the coding regions of TLR1, TLR2, TLR6, MyD88, or TRAF6. In summary, although HIES individuals had an IFN-gamma secretion defect, they also produced normal levels of several TLR-regulated proinflammatory cytokines. No unique mutations or polymorphisms were observed in several candidate genes from the TLR pathway. Our studies do not support a role for a defective TLR response in HIES individuals.
Assuntos
Síndrome de Job/genética , Transdução de Sinais/genética , Receptores Toll-Like/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Antígenos de Diferenciação/genética , Bactérias/imunologia , Feminino , Humanos , Interferon gama/sangue , Interleucinas/metabolismo , Síndrome de Job/sangue , Lipopolissacarídeos/farmacologia , Masculino , Pessoa de Meia-Idade , Fator 88 de Diferenciação Mieloide , Peptidoglicano/farmacologia , Polimorfismo Genético/genética , Receptores Imunológicos/genética , Transdução de Sinais/efeitos dos fármacos , Fator 6 Associado a Receptor de TNF/genética , Ácidos Teicoicos/farmacologia , Receptor 1 Toll-Like/genética , Receptor 2 Toll-Like/genética , Receptor 6 Toll-Like/genética , Receptores Toll-Like/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Zimosan/farmacologiaAssuntos
Alérgenos/administração & dosagem , Culinária , Dessensibilização Imunológica , Hipersensibilidade a Ovo/terapia , Proteínas do Ovo/administração & dosagem , Administração Oral , Alérgenos/efeitos adversos , Criança , Pré-Escolar , Hipersensibilidade a Ovo/sangue , Hipersensibilidade a Ovo/imunologia , Proteínas do Ovo/efeitos adversos , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Lactente , MasculinoRESUMO
Building on the previous work of Robinson and Jackson(1), this study addresses the extent to which interpersonal trust in America is changing due to age, period, or cohort effects (APC). The importance of APC in explaining variations in trust stems from the understanding that the specific source of change can have important - albeit different and possibly, negative - consequences on society. Moreover, 3years after the previous study concluded, the country experienced the largest concerted terrorist attacks on US soil. Little is known about how the attacks affected the dynamics of interpersonal trust relative to the processes of birth, aging, and historical change - such an investigation has important implications for our understanding of the sources and consequences of interpersonal trust. Two analysis techniques for disentangling APC effects are used: constrained generalized linear models and intrinsic estimator models. The results show that while period effects are an important contributor to declining trust, the attacks exert little influence over one's decision to trust others. Also, the investigation provides further confirmation that trust in others has fallen dramatically in the US with the scarcity being led by individuals coming of age in the late 1940s, after which, trust falls with each successive cohort. If this trend continues, through the process of cohort replacement, we will become a society of "distrusters".
RESUMO
As food allergies become increasingly prevalent and testing methods to identify "food allergy" increase in number, the importance of careful diagnosis has become even more critical. Misdiagnosis of food allergy and inappropriate use of unproven testing modalities may lead to a harmful food-elimination diet. This case is an example of an infant who was placed on an overly restrictive elimination diet at the recommendation of her health care providers, resulting in kwashiorkor and acquired acrodermatitis enteropathica.
Assuntos
Acrodermatite/etiologia , Erros de Diagnóstico , Hipersensibilidade Alimentar/dietoterapia , Hipersensibilidade Alimentar/diagnóstico , Kwashiorkor/etiologia , Acrodermatite/diagnóstico , Acrodermatite/dietoterapia , Terapias Complementares , Comportamento Cooperativo , Feminino , Alimentos Formulados , Humanos , Imunoglobulina E/sangue , Lactente , Comunicação Interdisciplinar , Testes Intradérmicos , Kwashiorkor/diagnóstico , Kwashiorkor/dietoterapia , Nutrição Parenteral Total , Zinco/deficiênciaRESUMO
BACKGROUND: Preterm infants with periventricular brain injury (PBI) have a high incidence of atypical development and leg movements. OBJECTIVE: Determine whether kicking and treadmill stepping intervention beginning at 2 months corrected age (CA) in children with PBI improves motor function at 12 months CA when compared with control subjects. METHOD: In a multi-center pilot study for a controlled clinical trial, sixteen infants with PBI were randomly assigned to home exercise consisting of kicking and treadmill stepping or a no-training control condition. Development was assessed at 2, 4, 6, 10, and 12 months CA with the Alberta Infant Motor Scale (AIMS). At 12 months children were classified as normal, delayed, or with cerebral palsy (CP). RESULTS: At 12 months CA 3 of 7 (43%) of the exercise group children walked alone or with one hand held versus 1 of 9 (11%) in the control group (p=0.262), but no significant differences in AIMS scores were found at any age. Half of the subjects had CP or delay; the outcomes of these infants were not improved by exercise. Compliance with the home program was lower than requested and may have affected results. CONCLUSION: Although not statistically significant with a small sample size, self-produced kicking and treadmill exercise may lower age at walking in infants with normal development following PBI, but improvements of the protocol to increase and document compliance are needed before a larger study is implemented.
Assuntos
Paralisia Cerebral , Técnicas de Exercício e de Movimento/métodos , Terapia por Exercício/métodos , Recém-Nascido Prematuro/crescimento & desenvolvimento , Leucomalácia Periventricular , Caminhada , Fatores Etários , Paralisia Cerebral/diagnóstico , Paralisia Cerebral/etiologia , Paralisia Cerebral/fisiopatologia , Paralisia Cerebral/terapia , Desenvolvimento Infantil , Feminino , Humanos , Lactente , Recém-Nascido , Leucomalácia Periventricular/complicações , Leucomalácia Periventricular/diagnóstico , Leucomalácia Periventricular/fisiopatologia , Leucomalácia Periventricular/terapia , Masculino , Monitorização Fisiológica/métodos , Destreza Motora , Projetos Piloto , Resultado do TratamentoRESUMO
Ferret systemic coronavirus (FRSCV) infection is associated with an emerging, highly fatal disease of ferrets. Enhanced macrophage tropism and the resulting induction of pyogranulomatous lesions are shared with feline infectious peritonitis virus (FIPV) infection in cats, but are not features of ferret enteric coronavirus (FRECV) infection. Comparative sequence analysis of the distal one-third of the genomes of one FRSCV and one FRECV strain showed that these two ferret coronaviruses share >96% nucleotide sequence identities in the membrane (M), nucleocapsid (N) and non-structural protein genes (partial polymerase, open reading frames [ORFs] 3 and 7b). The envelope (E) protein gene showed a moderate nucleotide sequence similarity of 91.6%. In contrast, nucleotide and amino acid sequence similarities observed with the spike (S) protein were only 79.5 and 79.6%, respectively. Twenty-one amino acid differences within a 195-199-amino acid C-terminal portion of the S protein were conserved between 3 strains each of FRSCV and FRECV. Both systemic and enteric strains were found to carry a single ORF 3 gene with truncated proteins observed in two out of three FRSCV strains examined. The two enteric strains analyzed each contained an intact ORF 3 gene. Phylogenetically, FRSCV is more closely related to FRECV than to other group 1 coronaviruses.
Assuntos
Coronavirus/genética , Furões/virologia , Genoma Viral , Polimorfismo Genético , RNA Viral/genética , Análise de Sequência de DNA , Substituição de Aminoácidos/genética , Animais , Análise por Conglomerados , Coronavirus/isolamento & purificação , Coronavirus/patogenicidade , Dados de Sequência Molecular , Filogenia , Homologia de Sequência do Ácido Nucleico , Proteínas Virais/genéticaRESUMO
Commensal flora and pathogenic microbes influence the incidence of diabetes in animal models yet little is known about the mechanistic basis of these interactions. We hypothesized that Myd88, an adaptor molecule in the Toll-like-receptor (TLR) pathway, regulates pancreatic beta-cell function and homeostasis. We first examined beta-cells histologically and found that Myd88-/- mice have smaller islets in comparison to C57Bl/6 controls. Myd88-/- mice were nonetheless normoglycemic both at rest and after an intra-peritoneal glucose tolerance test (IPGTT). In contrast, after low-dose streptozotocin (STZ) challenge, Myd88-/-mice had an abnormal IPGTT relative to WT controls. Furthermore, Myd88-/- mice suffer enhanced beta-cell apoptosis and have enhanced hepatic damage with delayed recovery upon low-dose STZ treatment. Finally, we treated WT mice with broad-spectrum oral antibiotics to deplete their commensal flora. In WT mice, low dose oral lipopolysaccharide, but not lipotichoic acid or antibiotics alone, strongly promoted enhanced glycemic control. These data suggest that Myd88 signaling and certain TLR ligands mediate a homeostatic effect on beta-cells primarily in the setting of injury.
Assuntos
Homeostase , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Fator 88 de Diferenciação Mieloide/metabolismo , Transdução de Sinais/fisiologia , Receptores Toll-Like/metabolismo , Animais , Antibacterianos/administração & dosagem , Glicemia/metabolismo , Células Cultivadas , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Teste de Tolerância a Glucose , Humanos , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/efeitos dos fármacos , Lipopolissacarídeos/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/genética , Estreptozocina/farmacologia , Receptores Toll-Like/genéticaRESUMO
We recently demonstrated the pivotal role of the transcription factor (TF) activating TF 3 (ATF3) in dampening inflammation. We demonstrate that ATF3 also ameliorates allergen-induced airway inflammation and hyperresponsiveness in a mouse model of human asthma. ATF3 expression was increased in the lungs of mice challenged with ovalbumin allergen, and this was associated with its recruitment to the promoters of genes encoding Th2-associated cytokines. ATF3-deficient mice developed significantly increased airway hyperresponsiveness, pulmonary eosinophilia, and enhanced chemokine and Th2 cytokine responses in lung tissue and in lung-derived CD4(+) lymphocytes. Although several TFs have been associated with enhanced inflammatory responses in the lung, ATF3 attenuates the inflammatory responses associated with allergic airway disease.
Assuntos
Fator 3 Ativador da Transcrição/imunologia , Asma/imunologia , Hiper-Reatividade Brônquica/imunologia , Pneumonia/imunologia , Fator 3 Ativador da Transcrição/genética , Alérgenos/imunologia , Animais , Líquido da Lavagem Broncoalveolar , Linfócitos T CD4-Positivos/imunologia , Quimiocinas/genética , Quimiocinas/imunologia , Regulação da Expressão Gênica , Humanos , Interleucina-13/genética , Interleucina-13/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Interleucina-5/genética , Interleucina-5/imunologia , Pulmão/citologia , Pulmão/imunologia , Pulmão/patologia , Camundongos , Camundongos Knockout , Ovalbumina/imunologia , Pneumonia/patologia , Regiões Promotoras Genéticas , Eosinofilia Pulmonar/imunologia , Células Th2/imunologiaRESUMO
We sought to determine the prevalence of HIV conspiracy beliefs in patients with HIV and how those beliefs correlate with access and adherence to HIV care and health outcomes. From March to December 2005, 113 patients at four public facilities in Houston, Texas, diagnosed with HIV for 3 years or less, participated in a cross-sectional survey. Conspiracy beliefs were assessed with five items that dealt with HIV origin, cure, and vaccine. Medical records were reviewed for CD4 cell counts, HAART use, and appointment dates. Statistical analyses (including analysis of variance [ANOVA], chi(2) testing, and regression) determined the predictors of conspiracy beliefs and correlated them with outcomes. Sixty-three percent of the participants endorsed 1 or more conspiracy beliefs. African American patients more often held HIV conspiracy beliefs than white and other/mixed race patients (73%, 52%, 47%; p = 0.045). Persons holding 1 or more conspiracy beliefs had higher CD4 cell counts at diagnosis (254 cells/mm(3) versus 92, p = 0.03); and similar rates of highly active antiretroviral therapy (HAART) use (73% versus 71%), 100% adherence to HAART by self-report (53% versus 45%,), mean adherence by pharmacy refill (83% versus 87%), and gaps in care greater than 120 days (49% versus 53%), compared to subjects who did not hold any conspiracy beliefs (all p > 0.40). Since recruitment focused on patients in care, patients with extreme conspiracy beliefs may be underrepresented. Despite this, more than 50% of the study population endorsed 1 or more conspiracy belief. However, these beliefs did not negatively impact access or adherence to HIV care. Efforts to improve adherence to HIV care may not need to focus on eliminating conspiracy beliefs.
Assuntos
Atitude Frente a Saúde , Infecções por HIV/psicologia , Entrevistas como Assunto , Cooperação do Paciente , Adolescente , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Estudos Transversais , Etnicidade/psicologia , Feminino , Infecções por HIV/tratamento farmacológico , Homossexualidade , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Comportamento Sexual , Classe Social , Texas , Confiança/psicologiaRESUMO
Macrophages respond to Salmonella typhimurium infection via Ipaf, a NACHT-leucine-rich repeat family member that activates caspase-1 and secretion of interleukin 1beta. However, the specific microbial salmonella-derived agonist responsible for activating Ipaf is unknown. We show here that cytosolic bacterial flagellin activated caspase-1 through Ipaf but was independent of Toll-like receptor 5, a known flagellin sensor. Stimulation of the Ipaf pathway in macrophages after infection required a functional salmonella pathogenicity island 1 type III secretion system but not the flagellar type III secretion system; furthermore, Ipaf activation could be recapitulated by the introduction of purified flagellin directly into the cytoplasm. These observations raise the possibility that the salmonella pathogenicity island 1 type III secretion system cannot completely exclude 'promiscuous' secretion of flagellin and that the host capitalizes on this 'error' by activating a potent host-defense pathway.
Assuntos
Proteínas Reguladoras de Apoptose/fisiologia , Proteínas de Ligação ao Cálcio/fisiologia , Caspase 1/metabolismo , Flagelina/imunologia , Interleucina-1/metabolismo , Infecções por Salmonella/imunologia , Salmonella typhimurium/patogenicidade , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Proteínas de Ligação ao Cálcio/genética , Citoplasma/metabolismo , Citoplasma/microbiologia , Ativação Enzimática , Flagelina/genética , Macrófagos/enzimologia , Macrófagos/imunologia , Macrófagos/microbiologia , Camundongos , Camundongos Mutantes , Mutação , Transporte Proteico , Infecções por Salmonella/enzimologia , Infecções por Salmonella/genética , Salmonella typhimurium/genética , Salmonella typhimurium/imunologia , Receptor 5 Toll-Like/genética , Receptor 5 Toll-Like/fisiologiaRESUMO
The eukaryotic flagellum is one of the most complex macromolecular structures found in cells, containing more than 250 proteins. One unique structure in the flagella of trypanomastids is the paraflagellar rod (PFR). The PFR constitutes a lattice of cytoskeletal filaments that lies alongside the axoneme in the flagella. This unique and complex structure is critical for cell motility, though little is known about its molecular assembly or its role in the lifecycle of trypanosomatids. These proteins are of particular importance in Trypanosoma cruzi, as purified or recombinant PFR proteins have been demonstrated to be immunogenic, protecting mice from a lethal challenge with the parasite. We have searched the T. cruzi databases and discovered two novel genes containing PFR domains. Both these genes are transcribed in vivo and are significantly larger than the previously described PFR genes identified in T. cruzi (>2 Kb). Real-time PCR was used to examine the relative expression levels of six PFR genes, including the two we describe here, in all three stages of T. cruzi's lifecycle. Database searches have further provided EST and genomic sequence support for the presence of these genes in two other pathogenic trypanosomatids, Trypanosoma brucei and Leishmania spp. One of these genes, designated PFR5 contains a carboxy terminal SH3 domain not previously seen in PFR family genes. We propose that this proline-binding SH3 domain may play an important role in the assembly of the PFR.
Assuntos
Genes de Protozoários , Proteínas de Protozoários/genética , Trypanosoma cruzi/genética , Sequência de Aminoácidos , Animais , Expressão Gênica , Dados de Sequência Molecular , Filogenia , Estrutura Terciária de Proteína/genética , Alinhamento de Sequência , Homologia de SequênciaRESUMO
Environmental pollution that renders waters along the coastline and beaches unsatisfactory for use by the general public has become a global health problem. This study was conducted to examine the effects of pollution of beach waters and sediment at seven selected locations receiving land drainage along a 45-km stretch of the east coast near Visakhapatnam, India. Pathogenic bacteria were identified using standard methods of culturing on selective media. The Pollution Index (PI) was determined as the ratio of fecal coliform/fecal streptococci. Protozoan cysts and helminth ova were also identified by microscopic examination of water after appropriate staining. The results suggested that the beach waters in Visakhapatnam are hygienically poor. A high PI of the water in Lawson's Bay indicated that the water was unsuitable even for noncontact recreation (boating, etc.). Pathogen densities dissipated considerably from the source to the low tide mark. Sediments had significantly higher bacterial and protozoan populations but pathogen concentrations were low except in heavily used areas. The general distribution pattern suggests that the nature of the sediment has a significant role in the retention of bacteria, protozoan cysts, and soil-transmitted helminths.