RESUMEN
Molecular lattice clocks enable the search for new physics, such as fifth forces or temporal variations of fundamental constants, in a manner complementary to atomic clocks. Blackbody radiation (BBR) is a major contributor to the systematic error budget of conventional atomic clocks and is notoriously difficult to characterize and control. Here, we combine infrared Stark-shift spectroscopy in a molecular lattice clock and modern quantum chemistry methods to characterize the polarizabilities of the Sr_{2} molecule from dc to infrared. Using this description, we determine the static and dynamic blackbody radiation shifts for all possible vibrational clock transitions to the 10^{-16} level. This constitutes an important step toward millihertz-level molecular spectroscopy in Sr_{2} and provides a framework for evaluating BBR shifts in other homonuclear molecules.
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The rising incidence of infection among youth in sub-Saharan Africa makes HIV-related research among younger people a top priority. There remains, however, a lack of consistent and unambiguous ethical principles and guidance for researchers wishing to conduct HIV studies with adolescents. The overarching aim of our research was to better understand youths' experiences with HIV studies. The present study explored four questions: (1) What strategies are effective for recruiting youth for HIV studies? (2) What motivates youth to participate in these studies? (3) How do study participants perceive HIV testing within the context of a research study? (4) What do participants understand about the risks of study participation? These data are essential to inform guidelines for the responsible conduct of research with young people. We interviewed 82 adolescents (aged 15-19) in Kenya taking part in a study examining ethical issues pertaining to their involvement in HIV-related research. Pursuant to our research questions, we found that direct study recruitment combined with encouragement from female relatives was the greatest facilitator to study enrolment among young people. Most young participants expressed that they were motivated to join the study in order to (1) learn their HIV status (n = 49) and (2) receive HIV-related education (n = 26), even though both are already free and widely available. Participants largely preferred testing in a place they deemed "private," although both the health clinic and home were regarded by adolescents as locations with greater privacy. Adolescents largely did not accurately perceive risks of the study two months after baseline, although they could remember the benefits with great clarity. This work can inform researchers, policymakers, and ethics review committees on approaches to maximize efficiency in recruitment and data collection, and to enhance understanding of risks and benefits in HIV-related research among adolescents. While further research is needed, these data may be used by others conducting HIV research in this region to improve recruitment strategies and more effectively engage and appeal to young people.
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Early B-cell factor 1 (EBF1) plays a central role in B-cell lineage specification and commitment. Loss of this critical transcription factor is strongly associated with high-risk, relapsed and therapy-resistant B-cell-acute lymphoblastic leukemia, especially in children. However, Ebf1 haploinsufficient mice exhibit a normal lifespan. To determine whether prolonged survival of B cells would enable tumorigenesis in Ebf1 haploinsufficient animals, we generated Ebf1+/-Bcl-xLTg mice, which express the anti-apoptotic factor Bcl-xL in B cells. Approximately half of Ebf1+/-Bcl-xLTg mice develop aggressive oligoclonal leukemia as they age, which engrafts in congenic wild-type recipients without prior conditioning. The neoplastic cells display a pre-B phenotype and express early developmental- and natural killer cell/myeloid-markers inappropriately. In addition, we found tumor cell-specific loss of several transcription factors critical for maintaining differentiation: EBF1, TCF3 and RUNX1. However, in the majority of tumors, loss of Ebf1 expression was not due to loss of heterozygosity. This is the first spontaneous mouse model of pre-B leukemia to demonstrate inappropriate expression of non-B-cell-specific genes associated with loss of Ebf1, Tcf3 and Runx1 expression.
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OBJECTIVE: This study examined the prevalence and correlates of exchanging sex for drugs or money among a nationally representative sample of 13,294 adolescents in the United States. METHODS: Data are from the National Longitudinal Study of Adolescent Health, waves I and II. The lifetime prevalence of exchanging sex was estimated and a cross sectional analysis of sociodemographic and behavioural correlates was conducted. Unadjusted odds ratios were obtained. RESULTS: 3.5% of adolescents had ever exchanged sex for drugs or money. Two thirds of these youths were boys. The odds of having exchanged sex were higher for youths who had used drugs, had run away from home, were depressed, and had engaged in various sexual risk behaviours. 15% of boys and 20% of girls who had exchanged sex reported they had ever been told they have HIV or another sexually transmitted infection (STI). CONCLUSIONS: Adolescents with a history of exchanging sex have engaged in other high risk behaviours and may experience poor health outcomes, including depression and HIV/STIs. These findings should help inform strategies to prevent this high risk sexual behaviour and its potential consequences.
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Trabajo Sexual/estadística & datos numéricos , Adolescente , Femenino , Humanos , Masculino , Pronóstico , Factores Socioeconómicos , Trastornos Relacionados con Sustancias/epidemiología , Estados Unidos/epidemiología , Sexo Inseguro/estadística & datos numéricosRESUMEN
OBJECTIVE: This study uses a cluster analysis of adolescents, based on their substance use and sexual risk behaviors, to 1) examine associations between risk behavior patterns and depressive symptoms, stratified by gender, and 2) examine gender differences in risk for depression. METHODS: Data are from a nationally representative survey of over 20,000 U.S. adolescents. Logistic regression was used to examine the associations between 16 risk behavior patterns and current depressive symptoms by gender. RESULTS: Compared to abstention, involvement in common adolescent risk behaviors (drinking, smoking, and sexual intercourse) was associated with increased odds of depressive symptoms in both sexes. However, sex differences in depressive symptoms vary by risk behavior pattern. There were no differences in odds for depressive symptoms between abstaining male and female adolescents (OR = 1.07, 95% CI 0.70-1.62). There were also few sex differences in odds of depressive symptoms within the highest-risk behavior profiles. Among adolescents showing light and moderate risk behavior patterns, females experienced significantly more depressive symptoms than males. CONCLUSIONS: Adolescents who engage in risk behaviors are at increased risk for depressive symptoms. Girls engaging in low and moderate substance use and sexual activity experience more depressive symptoms than boys with similar behavior. Screening for depression is indicated for female adolescents engaging in even experimental risk behaviors.
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Trastorno Depresivo/epidemiología , Asunción de Riesgos , Conducta Sexual , Trastornos Relacionados con Sustancias/complicaciones , Adolescente , Análisis por Conglomerados , Estudios Transversales , Trastorno Depresivo/prevención & control , Femenino , Humanos , Modelos Logísticos , Masculino , Factores de Riesgo , Distribución por Sexo , Factores Sexuales , Trastornos Relacionados con Sustancias/psicología , Estados Unidos/epidemiologíaRESUMEN
The Mad family comprises four basic-helix-loop-helix/leucine zipper proteins, Mad1, Mxi1, Mad3, and Mad4, which heterodimerize with Max and function as transcriptional repressors. The balance between Myc-Max and Mad-Max complexes has been postulated to influence cell proliferation and differentiation. The expression patterns of Mad family genes are complex, but in general, the induction of most family members is linked to cell cycle exit and differentiation. The expression pattern of mad3 is unusual in that mad3 mRNA and protein were found to be restricted to proliferating cells prior to differentiation. We show here that during murine development mad3 is specifically expressed in the S phase of the cell cycle in neuronal progenitor cells that are committed to differentiation. To investigate mad3 function, we disrupted the mad3 gene by homologous recombination in mice. No defect in cell cycle exit and differentiation could be detected in mad3 homozygous mutant mice. However, upon gamma irradiation, increased cell death of thymocytes and neural progenitor cells was observed, implicating mad3 in the regulation of the cellular response to DNA damage.
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Apoptosis/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/fisiología , Proteínas Proto-Oncogénicas c-myc/antagonistas & inhibidores , Proteínas Represoras , Fase S/genética , Fase S/fisiología , Animales , Apoptosis/fisiología , Apoptosis/efectos de la radiación , Secuencia de Bases , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Diferenciación Celular , División Celular , Cartilla de ADN/genética , Rayos gamma , Expresión Génica , Marcación de Gen , Linfocitos/citología , Linfocitos/efectos de la radiación , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neuronas/citología , Neuronas/efectos de la radiación , Tolerancia a Radiación/efectos de los fármacos , Tolerancia a Radiación/fisiologíaRESUMEN
Lnk is an SH2 domain-containing adaptor protein expressed preferentially in lymphocytes. To illuminate the importance of Lnk, we generated lnk(-/-) mice. Whereas T cell development was unaffected, pre-B and immature B cells accumulated in the spleens. In the bone marrow, B-lineage cells were proportionately increased, reflecting enhanced production of pro-B cells that resulted in part from hypersensitivity of precursors to SCF, the ligand for c-kit. Hence, Lnk ordinarily acts to regulate B cell production. Further characterization of lnk(-/-) mice also revealed that full-length Lnk is a 68 kDa protein containing a conserved proline-rich region and a PH domain. Lnk is a representative of a multigene adaptor protein family whose members act, by analogy with Lnk, to modulate intracellular signaling.
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Linfocitos B/fisiología , Proteínas/fisiología , Proteínas Adaptadoras Transductoras de Señales , Secuencia de Aminoácidos , Animales , Linfocitos B/citología , Diferenciación Celular/fisiología , Regulación del Desarrollo de la Expresión Génica/inmunología , Péptidos y Proteínas de Señalización Intracelular , Proteínas de la Membrana , Ratones , Ratones Noqueados , Datos de Secuencia Molecular , Alineación de Secuencia , Transducción de Señal , Dominios Homologos srcRESUMEN
Members of the myc family of nuclear protooncogenes play roles in cell proliferation, differentiation, and apoptosis. Moreover, inappropriate expression of c-myc genes contributes to the development of many types of cancers, including B cell lymphomas in humans. Although Myc proteins have been shown to function as transcription factors, their immediate effects on the cell have not been well defined. Here we have utilized a murine model of lymphomagenesis (Emu-myc mice) to show that constitutive expression of a c-myc transgene under control of the Ig heavy-chain enhancer (Emu) results in an increase in cell size of normal pretransformed B lymphocytes at all stages of B cell development. Furthermore, we show that c-Myc-induced growth occurs independently of cell cycle phase and correlates with an increase in protein synthesis. These results suggest that Myc may normally function by coordinating expression of growth-related genes in response to mitogenic signals. Deregulated c-myc expression may predispose to cancer by enhancing cell growth to levels required for unrestrained cell division.
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Linfocitos B/citología , Tamaño de la Célula/fisiología , Proteínas Proto-Oncogénicas c-myc/fisiología , Animales , Ciclo Celular , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas Proto-Oncogénicas c-myc/biosíntesis , TransgenesRESUMEN
Successful in-frame rearrangement of immunoglobulin heavy chain genes or T cell antigen receptor (TCR) beta chain genes in lymphocyte progenitors results in formation of pre-BCR and pre-TCR complexes. These complexes signal progenitor cells to mature, expand in cell number, and suppress further rearrangements at the immunoglobulin heavy chain or TCRbeta chain loci, thereby ensuring allelic exclusion. We used transgenic expression of a constitutively active form of c-Raf-1 (Raf-CAAX) to demonstrate that activation of the Map kinase pathway can stimulate both maturation and expansion of B and T lymphocytes, even in the absence of pre-TCR or pre-BCR formation. However, the same Raf signal did not mediate allelic exclusion. We conclude that maturation of lymphocyte progenitors and allelic exclusion require distinct signals.
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Alelos , Subgrupos Linfocitarios/inmunología , Transducción de Señal/inmunología , Células Madre/inmunología , Transferasas Alquil y Aril/biosíntesis , Transferasas Alquil y Aril/genética , Diferenciación Celular/inmunología , Proteínas de Unión al ADN , Activación Enzimática/inmunología , Reordenamiento Génico de Cadena Pesada de Linfocito B/inmunología , Reordenamiento Génico de la Cadena beta de los Receptores de Antígenos de los Linfocitos T/inmunología , Subgrupos Linfocitarios/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos , Proteínas Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-raf/biosíntesis , Proteínas Proto-Oncogénicas c-raf/genética , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/genética , Transducción de Señal/genética , Células Madre/metabolismo , Transgenes/inmunologíaRESUMEN
Mice deficient for the pre-TCR alpha (pT alpha) chain cannot form a pre-T cell receptor (TCR) and exhibit a severe defect in early T cell development, characterized by lack of "beta selection" and impaired generation of double-positive (DP) thymocytes. Here, we demonstrate that intraperitoneal injection of CD3epsilon-specific antibodies into pT alpha-/- x RAG-/- mice or introduction of an activated p56(lck) transgene in pT alpha-/- mice fully restores the number of DP thymocytes, and that expression of a transgenic pT alpha chain lacking its cytoplasmic portion can overcome all developmental defects associated with pT alpha deficiency. These results allow a better definition of the role of pT alpha in pre-TCR signal transduction and provide conclusive evidence that the cytoplasmic tail of pT alpha is not essential for pre-TCR signaling.
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Complejo CD3/fisiología , Receptores de Antígenos de Linfocitos T alfa-beta/química , Linfocitos T/citología , Familia-src Quinasas/fisiología , Animales , Diferenciación Celular , Citoplasma , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Eliminación de Secuencia , Transducción de Señal , Relación Estructura-Actividad , Timo/citología , TransgenesRESUMEN
Cell fate commitment in a variety of lineages requires signals conveyed via p21ras. To examine the role of p21ras in the development of B lymphocytes, we generated transgenic mice expressing a dominant-negative form of Ras in B lymphocyte progenitors, using a novel transcriptional element consisting of the Emu enhancer and the lck proximal promoter. Expression of dominant-negative Ras arrests B cell development at a very early stage, prior to formation of the pre-B cell receptor. Furthermore, an activated form of Raf expressed in the same experimental system could both drive the maturation of normal pro-B cells and rescue development of progenitors expressing dominant-negative Ras. Hence p21ras normally regulates early development of B lymphocytes by a mechanism that involves activation of the serine/threonine kinase Raf.
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Linfocitos B/fisiología , Hematopoyesis , Células Madre Hematopoyéticas/fisiología , Proteínas Proto-Oncogénicas c-raf/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Animales , Subgrupos de Linfocitos B , Células de la Médula Ósea/citología , Diferenciación Celular , Linaje de la Célula , Regulación de la Expresión Génica , Depleción Linfocítica , Ratones , Ratones Transgénicos , Modelos Biológicos , Proteínas Proto-Oncogénicas p21(ras)/genética , Transducción de Señal , Bazo/citología , Linfocitos T/fisiologíaRESUMEN
The literature on family predictors of substance use for the general population is reviewed and compared to findings for three specific ethnic groups: black, white and Asian Americans. Rates of substance use initiation are examined in a sample of 919 urban 5th-grade students. Ethnic differences on measures of family predictors are examined and significant ethnic differences are found on several of these factors. Finally, separate regressions for black, white and Asian American youths of family factors on the variety of substances initiated examine ethnic similarities and differences in predictors. The results demonstrate significant differences by ethnicity in family management practices, involvement in family activity, sibling deviance, parental disapproval of children's drinking and family structure. The regression equations identified unique as well as common predictors of the variety of substances initiated by the end of 5th grade. Implications of the results are discussed.
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Alcoholismo/etnología , Hijo de Padres Discapacitados/psicología , Desarrollo de la Personalidad , Psicotrópicos , Medio Social , Trastornos Relacionados con Sustancias/etnología , Alcoholismo/prevención & control , Alcoholismo/psicología , Niño , Familia/psicología , Femenino , Humanos , Masculino , Factores de Riesgo , Socialización , Factores Socioeconómicos , Trastornos Relacionados con Sustancias/prevención & control , Trastornos Relacionados con Sustancias/psicologíaRESUMEN
This article examines racial differences in self-reported delinquency, school trouble, antisocial attitudes, and toughness and in teacher-rated aggressive and inattentive behaviors among fifth grade black, white, and Asian American subjects. Also examined are the relationships of these variables to substance initiation within each racial group. Controlling for socio-economic status, racial groups differed from one another in self-reported delinquency, school trouble and toughness, and in teacher-rated aggressiveness and inattention. Antisocial behavior and attitudes were stronger predictors of substance initiation for Asian American than for black and white children. For white children both self-reported and teacher-rated behavior were significantly related to substance initiation. For black children, only self-reported antisocial behavior, and for Asian American children only self-reported delinquent behavior and attitudes predicted substance initiation. Implications for prevention and research are discussed.
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Trastorno de Personalidad Antisocial/epidemiología , Actitud , Negro o Afroamericano/estadística & datos numéricos , Comparación Transcultural , Hispánicos o Latinos/estadística & datos numéricos , Delincuencia Juvenil/estadística & datos numéricos , Trastornos Relacionados con Sustancias/epidemiología , Adolescente , Negro o Afroamericano/psicología , Trastorno de Personalidad Antisocial/prevención & control , Trastorno de Personalidad Antisocial/psicología , Niño , Femenino , Hispánicos o Latinos/psicología , Humanos , Delincuencia Juvenil/prevención & control , Delincuencia Juvenil/psicología , Estudios Longitudinales , Masculino , Análisis de Regresión , Factores de Riesgo , Factores Sexuales , Valores Sociales , Factores Socioeconómicos , Trastornos Relacionados con Sustancias/prevención & control , Trastornos Relacionados con Sustancias/psicologíaRESUMEN
This paper examines differences among three racial groups in exposure to three risk factors for drug use (availability of drugs, acceptability of drug use, and peer alcohol use), and the relationship of these factors to drug use initiation in a sample of preadolescent urban youths. Tobacco and alcohol initiation rates were highest among Whites, lower among Blacks, and lowest among Asian-Americans. Paralleling these differences, White youths reported the greatest access to marijuana, greatest parental tolerance of substance use, and greatest intentions to use drugs as adults. Blacks somewhat less, and Asian-Americans the least. No racial differences appear in the proportion who reported that their peers used alcohol. Marijuana availability and peer use predicted substance initiation for all three racial groups. However, intentions to use substances as an adult and perceived parental tolerance of substance use predicted drug use only for White and Asian-American youths, while the expectation of punishment for drug use predicted lower drug use only among Black youths. Implications for prevention are discussed.
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Asiático/estadística & datos numéricos , Negro o Afroamericano/estadística & datos numéricos , Comparación Transcultural , Trastornos Relacionados con Sustancias/etnología , Adolescente , Niño , Estudios Transversales , Femenino , Humanos , Incidencia , Estudios Longitudinales , Masculino , Factores de Riesgo , Trastornos Relacionados con Sustancias/epidemiología , Washingtón/epidemiologíaRESUMEN
A group C latex agglutination reagent, included as the negative control in the PathoDx Strep A latex agglutination test (Diagnostic Products Corp., Los Angeles, Calif), was compared with culture for rapid detection of group C streptococci (Streptococcus equi, S. equisimilis, S. zooepidemicus, and S. dysgalactiae) from swabs of veterinary specimens. The overall sensitivity of the latex test was 78%, and specificity was 97.6%. Only 25% of S. dysgalactiae isolates were detected, thereby accounting for the relatively low sensitivity. Ninety-three percent of the group C streptococci other than S. dysgalactiae were isolated from horses. When the latex test was evaluated for detection of group C streptococci other than S. dysgalactiae from horses, the sensitivity and specificity were 95.3 and 100%, respectively. We found the group C latex agglutination test to be a rapid and accurate method for the detection of the major pathogenic group C streptococci from swabs of equine specimens.
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Caballos/microbiología , Pruebas de Fijación de Látex/veterinaria , Streptococcus/aislamiento & purificación , Animales , Antígenos Bacterianos/análisis , Errores DiagnósticosRESUMEN
Lipooligosaccharides (LOSs) from four strains of "Haemophilus somnus" were purified and their electrophoretic profile, composition, endotoxic activity, and antigenic properties were analyzed. The LOSs were most efficiently purified by enzyme digestion, hot aqueous phenol extraction, and ultracentrifugation. Each LOS could be separated into two to six distinct bands with apparent Mrs of 3280 to 4960, following electrophoresis in polyacrylamide gels. Each LOS contained dodecanoic, tetradecanoic, and 3-hydroxytetradecanoic fatty acids; a high proportion of hexose, 3-deoxy-D-manno-octulosonic acid, and phosphate; and a small amount of heptose; glucosamine was present in both the oligosaccharide and the lipid A. Each "H. somnus" LOS demonstrated endotoxic activity, as determined by gelation of Limulus ameobocyte lysate, the dermal Schwartzman reaction, and mouse lethality. Antiserum to purified "H. somnus" LOS cross-reacted with all strains of "H. somnus" tested by enzyme-linked immunosorbent assay (ELISA), but not to any Enterobacteriaceae, Pseudomonas, or Pasteurella species tested. "H. somnus" LOS was a poor immunogen, but inhibition, dot blot, and sandwich ELISA data indicated that antibodies made to LOS were predominantly, though not exclusively, to lipid A. Monoclonal antibodies directed to "H. somnus" LOS confirmed that lipid A and non-lipid A determinants were present.
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Haemophilus/análisis , Lipopolisacáridos/aislamiento & purificación , Animales , Anticuerpos Antibacterianos/inmunología , Antígenos Bacterianos/análisis , Bovinos , Electroforesis , Endotoxinas/análisis , Ensayo de Inmunoadsorción Enzimática , Haemophilus/inmunología , Lipopolisacáridos/inmunologíaRESUMEN
Three hundred sixty-six isolates of gram-negative, oxidase-negative bacteria from veterinary specimens were tested by a tube test for identification as Escherichia coli by production within 60 min of indole, beta-galactosidase, and beta-glucuronidase. The test correctly identified 255 of 269 isolates of E. coli (95% sensitivity) and correctly indicated that 97 of 97 isolates were not E. coli (100% specificity). We conclude that production of indole, beta-galactosidase, and beta-glucuronidase as measured by a rapid tube test is useful for identification of E. coli from veterinary specimens.