RESUMO
As Caenorhabditis elegans hermaphrodites age, sperm become depleted, ovulation arrests, and oocytes accumulate in the gonad arm. Large ribonucleoprotein (RNP) foci form in these arrested oocytes that contain RNA-binding proteins and translationally masked maternal mRNAs. Within 65 min of mating, the RNP foci dissociate and fertilization proceeds. The majority of arrested oocytes with foci result in viable embryos upon fertilization, suggesting that foci are not deleterious to oocyte function. We have determined that foci formation is not strictly a function of aging, and the somatic, ceh-18, branch of the major sperm protein pathway regulates the formation and dissociation of oocyte foci. Our hypothesis for the function of oocyte RNP foci is similar to the RNA-related functions of processing bodies (P bodies) and stress granules; here, we show three orthologs of P body proteins, DCP-2, CAR-1 and CGH-1, and two markers of stress granules, poly (A) binding protein (PABP) and TIA-1, appear to be present in the oocyte RNP foci. Our results are the first in vivo demonstration linking components of P bodies and stress granules in the germ line of a metazoan. Furthermore, our data demonstrate that formation of oocyte RNP foci is inducible in non-arrested oocytes by heat shock, osmotic stress, or anoxia, similar to the induction of stress granules in mammalian cells and P bodies in yeast. These data suggest commonalities between oocytes undergoing delayed fertilization and cells that are stressed environmentally, as to how they modulate mRNAs and regulate translation.
Assuntos
Caenorhabditis elegans/fisiologia , Temperatura Alta , Hipóxia , Oócitos/fisiologia , Ovulação/fisiologia , Estresse Oxidativo , Ribonucleoproteínas/metabolismo , Animais , Caenorhabditis elegans/citologia , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Grânulos Citoplasmáticos/metabolismo , Feminino , Fertilização/fisiologia , Masculino , Oócitos/citologia , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Ribonucleoproteínas/genética , Espermatozoides/citologia , Espermatozoides/metabolismoRESUMO
OBJECTIVES: Children with underlying conditions remain at increased risk for invasive pneumococcal diseases (IPD). This study describes the epidemiology, serotype distribution, clinical presentations, and outcomes of IPD in children with and without comorbidity. METHODS: Cases of childhood IPD in Massachusetts were identified via enhanced surveillance from 2002 through 2014. Demographic and clinical data were collected via follow-up telephone interviews with parents and/or primary care providers. Underlying conditions were classified according to the 2012 Report of the Committee on Infectious Diseases and 2013 recommendations by the Advisory Committee on Immunization Practices. RESULTS: Among 1052 IPD cases in Massachusetts children <18 years old, 22.1% had at least 1 comorbidity. Immunocompromising conditions (32.7%) and chronic respiratory diseases (22.4%) were most common. Children with comorbidities were older at the time of IPD diagnosis (median 54 vs 23 months, P < .001), had higher hospitalization (odds ratio 2.5; 95% confidence interval 1.7-3.6) and case-fatality rates (odds ratio 3.7; 95% confidence interval 1.5-8.9) compared with children without known underlying conditions after adjusting for age, gender, year of diagnosis, and pneumococcal vaccination status. During the last 2 years of the study, IPD among children with comorbidities was caused by non-pneumococcal conjugate vaccine 13 serotypes in 23-valent polysaccharide pneumococcal vaccine (6/12, 50%) or serotypes that are not included in any of the vaccines (6/12; 50%). CONCLUSIONS: In children with comorbidity, IPD results in higher mortality, and a large proportion of disease is due to serotypes not included in current conjugate vaccines. Further research is needed, specifically to develop and evaluate additional strategies for prevention of IPD in the most vulnerable children.
Assuntos
Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas/farmacologia , Vigilância da População , Medição de Risco/métodos , Streptococcus pneumoniae/imunologia , Vacinação/métodos , Cápsulas Bacterianas , Criança , Pré-Escolar , Comorbidade , Feminino , Seguimentos , Humanos , Incidência , Lactente , Masculino , Massachusetts/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Vacinas ConjugadasRESUMO
Oxygen, an essential nutrient, is sensed by a multiple of cellular pathways that facilitate the responses to and survival of oxygen deprivation. The Caenorhabditis elegans embryo exposed to severe oxygen deprivation (anoxia) enters a state of suspended animation in which cell cycle progression reversibly arrests at specific stages. The mechanisms regulating interphase, prophase, or metaphase arrest in response to anoxia are not completely understood. Characteristics of arrested prophase blastomeres and oocytes are the alignment of condensed chromosomes at the nuclear periphery and an arrest of nuclear envelope breakdown. Notably, anoxia-induced prophase arrest is suppressed in mutant embryos lacking nucleoporin NPP-16/NUP50 function, indicating that this nucleoporin plays an important role in prophase arrest in wild-type embryos. Although the inactive form of cyclin-dependent kinase (CDK-1) is detected in wild-type-arrested prophase blastomeres, the inactive state is not detected in the anoxia exposed npp-16 mutant. Furthermore, we found that CDK-1 localizes near chromosomes in anoxia-exposed embryos. These data support the notion that NPP-16 and CDK-1 function to arrest prophase blastomeres in C. elegans embryos. The anoxia-induced shift of cells from an actively dividing state to an arrested state reveals a previously uncharacterized prophase checkpoint in the C. elegans embryo.