RESUMEN
DNA-based molecular rulers enable scientists to determine important parameters across biology, from the measurement of protein binding interactions, to the study of membrane dynamics in cells. However, existing rulers can suffer from poor nanometre resolution due to the flexible nature of linkers used to tether to the DNA framework. We aimed to overcome this problem using zinc and free-base porphyrin chromophores attached via short and rigid acetylene linkers. This connectivity enables the distance and angle between the porphyrins to be fine-tuned along the DNA scaffold. The porphyrins undergo favorable energy transfer and chiral exciton coupling interactions to act as highly sensitive molecular ruler probes. To validate the system, we monitored the detection of small changes in DNA structure upon intercalation of ethidium bromide. CD spectroscopy showed the porphyrins undergo highly sensitive changes in excitation coupling to facilitate base pair resolution of the novel system.
RESUMEN
This study applies principles from the theory of household life cycles to the study of early childhood mortality in the population of the Northern Orkney Islands, Scotland. The primary hypothesis is that unfavorable household economic conditions resulting from changes in household demographic composition increase the risk of death for children under the age of 5 years because of limited resources and intra-household competition. We apply Cox proportional hazards models to nearly 5,000 linked birth and death records from the Northern Orkney Islands, Scotland, from the period 1855 to 2001. The dependent variable is the child's risk of death before age 5. Findings suggest that children in households with unfavorable age compositions face higher risk of death. This elevated risk of death continues once heterogeneity among children, islands, and households is controlled. Results also show differential risk of death for male children, children of higher birth orders, and twin births. The analyses present evidence for intra-household competition in this historic setting. The most convincing evidence of competition is found in the effects of household consumer/producer ratios and twinning on child mortality risks.
Asunto(s)
Composición Familiar , Mortalidad Infantil/historia , Mortalidad Infantil/tendencias , Antropología Física , Certificado de Nacimiento , Orden de Nacimiento , Preescolar , Certificado de Defunción , Femenino , Historia del Siglo XIX , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Lactante , Mortalidad Infantil/etnología , Masculino , Padres , Modelos de Riesgos Proporcionales , Factores de Riesgo , Escocia , Factores SocioeconómicosRESUMEN
OBJECTIVE: To investigate hypoestrogenic "inactive phases" (IP) in the follicular phase of the menstrual cycle, with respect to age, reproductive stage, and follicular depletion. DESIGN: Analysis of prospectively collected menstrual bleed and estrone-3-glucuronide data. SETTING: Center for Population and Health, Georgetown University. PATIENT(S): White women (n = 88, aged 25-59 years, mean = 44.7 years) from the population-based Biodemographic Models of Reproductive Aging (BIMORA) project. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The IP durations by age and reproductive stage. Estimated follicular depletion rate based on IP durations. RESULT(S): Mean IP duration and variability decreased and then increased with age/reproductive stage. The proportion of very short (≤ 1 day) IP durations increased and then decreased with age/stage. Long IPs occurred most, but not exclusively, in the oldest age/latest stage. Follicular depletion rate estimates were a plausible 2%-4% per year of age, but these models were a poor fit because IP durations did not consistently increase across ages/stages. CONCLUSION(S): Follicular depletion models alone do not explain the observed pattern of IPs. Our data suggest that IPs reflect both follicular depletion and hyperstimulation in premenopausal and perimenopausal women. Knowledge of underlying IP patterns in the menstrual cycle could inform decisions about hormone sampling and contraception during the perimenopause.
Asunto(s)
Envejecimiento/fisiología , Estrógenos/metabolismo , Ciclo Menstrual/fisiología , Modelos Biológicos , Modelos Estadísticos , Folículo Ovárico/fisiología , Reproducción , Adulto , Distribución por Edad , Factores de Edad , Envejecimiento/orina , Biomarcadores/orina , Estrógenos/orina , Estrona/análogos & derivados , Estrona/orina , Femenino , Fase Folicular/fisiología , Humanos , Ciclo Menstrual/orina , Persona de Mediana Edad , Folículo Ovárico/metabolismo , Estudios Prospectivos , Factores de Tiempo , Estados UnidosRESUMEN
Servants were an important part of the northwestern European household economy in the preindustrial past. This study examines household-level characteristics that are predictive of the presence of rural servants using data from Orkney, Scotland. The number of servants present in a household is related to household composition, landholding size, and the marital status of the household head. In addition, the sex of the particular servant hired reveals that the labor of male and female servants is not fungible. The sex of the servant hired is related to the ratio of male and female household members of working age, the occupation of the head, household composition, and the size of the household's landholding.
RESUMEN
Although investigations of medieval plague victims have identified Yersinia pestis as the putative etiologic agent of the pandemic, methodological limitations have prevented large-scale genomic investigations to evaluate changes in the pathogen's virulence over time. We screened over 100 skeletal remains from Black Death victims of the East Smithfield mass burial site (1348-1350, London, England). Recent methods of DNA enrichment coupled with high-throughput DNA sequencing subsequently permitted reconstruction of ten full human mitochondrial genomes (16 kb each) and the full pPCP1 (9.6 kb) virulence-associated plasmid at high coverage. Comparisons of molecular damage profiles between endogenous human and Y. pestis DNA confirmed its authenticity as an ancient pathogen, thus representing the longest contiguous genomic sequence for an ancient pathogen to date. Comparison of our reconstructed plasmid against modern Y. pestis shows identity with several isolates matching the Medievalis biovar; however, our chromosomal sequences indicate the victims were infected with a Y. pestis variant that has not been previously reported. Our data reveal that the Black Death in medieval Europe was caused by a variant of Y. pestis that may no longer exist, and genetic data carried on its pPCP1 plasmid were not responsible for the purported epidemiological differences between ancient and modern forms of Y. pestis infections.
Asunto(s)
ADN Bacteriano/genética , Peste/microbiología , Plásmidos/genética , Yersinia pestis/genética , Adulto , Técnicas de Tipificación Bacteriana , Secuencia de Bases , Huesos/metabolismo , Huesos/microbiología , ADN Bacteriano/química , ADN Mitocondrial/química , ADN Mitocondrial/genética , Europa (Continente)/epidemiología , Femenino , Variación Genética , Historia Medieval , Humanos , Masculino , Datos de Secuencia Molecular , Pandemias/historia , Peste/epidemiología , Peste/genética , Análisis de Secuencia de ADN , Homología de Secuencia de Ácido Nucleico , Especificidad de la Especie , Diente/metabolismo , Diente/microbiología , Virulencia/genética , Yersinia pestis/clasificación , Yersinia pestis/patogenicidadRESUMEN
Was the mortality associated with the deadliest known epidemic in human history, the Black Death of 1347-1351, selective with respect to preexisting health conditions ("frailty")? Many researchers have assumed that the Black Death was so virulent, and the European population so immunologically naïve, that the epidemic killed indiscriminately, irrespective of age, sex, or frailty. If this were true, Black Death cemeteries would provide unbiased cross-sections of demographic and epidemiological conditions in 14th-century Europe. Using skeletal remains from medieval England and Denmark, new methods of paleodemographic age estimation, and a recent multistate model of selective mortality, we test the assumption that the mid-14th-century Black Death killed indiscriminately. Skeletons from the East Smithfield Black Death cemetery in London are compared with normal, nonepidemic cemetery samples from two medieval Danish towns (Viborg and Odense). The results suggest that the Black Death did not kill indiscriminately-that it was, in fact, selective with respect to frailty, although probably not as strongly selective as normal mortality.
Asunto(s)
Brotes de Enfermedades/historia , Peste/historia , Dinamarca , Inglaterra , Salud , Historia Medieval , Humanos , Inmunidad , Paleopatología , Peste/inmunología , Peste/mortalidad , EsqueletoRESUMEN
OBJECTIVE: This study describes age-related changes in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in a 5-year prospective study of reproductive aging. DESIGN: Participants (n = 156 college-educated, white, US women; 25 to 58 y) were recruited from the TREMIN Research Program on Women's Health. They collected daily urine specimens for 6 months in each of 5 consecutive years. Specimens were assayed for LH and FSH. Aggregate changes were calculated in LH and FSH with age, and multilevel models were used to estimate individual hormone trajectories and within-woman and between-woman variances by age. RESULTS: Aggregate LH levels increased beginning after age 45; FSH increased at all ages, accelerating after age 45. Individual-level patterns with age included the following: reproductive-age LH and FSH levels, with increasing FSH and increasing or decreasing LH (ages 20 to 49); rapidly increasing LH and FSH (ages 40 to 59); and increasing or steady postmenopausal LH and FSH (ages 46 to 62). FSH levels were consistently high in the latter category, but LH levels overlapped with levels found in younger women (<45 y). Individual LH patterns showed more variability (5% to 35% of total variance) than FSH (3% to 22% of total variance). Both hormones had relatively low variation within individuals compared with between-woman differences (65% to 97% of total variance). CONCLUSIONS: Aggregate-level data do not reflect differences across women and oversimplify the age-related increases and variability in LH and FSH. Individual FSH levels are not distinguishable from reproductive-age levels until after rapid perimenopausal increases in FSH occur; individuals vary in whether their postmenopausal LH levels are distinguishable from reproductive-age levels.
Asunto(s)
Envejecimiento/fisiología , Fertilidad/fisiología , Hormona Folículo Estimulante/orina , Hormona Luteinizante/orina , Adulto , Femenino , Humanos , Persona de Mediana Edad , Ovario/fisiología , Estudios ProspectivosRESUMEN
Native Americans have higher rates of alcohol use, frequency of use, and increased rates of fetal alcohol syndrome, compared with other ethnic groups (J. Hisnanick, 1992; P. A. May, 1996; J. M. Wallace et al., 2003). High prevalence rates of alcohol misuse among Native Americans must be understood in light of their unique history, which has resulted in trauma and exposure to many risk factors for problem alcohol use. Many risk factors have been identified in the general population; however, only some of these risk factors have been examined among Native American populations. The unique history and world view of Native Americans mean that, often, risk factors operate differently from the way they do in other populations. The authors discuss interventions and promising treatments.
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Alcoholismo/etnología , Indígenas Norteamericanos/etnología , Alcohólicos Anónimos , Alcoholismo/epidemiología , Alcoholismo/psicología , Alcoholismo/rehabilitación , Femenino , Trastornos del Espectro Alcohólico Fetal/epidemiología , Trastornos del Espectro Alcohólico Fetal/etnología , Trastornos del Espectro Alcohólico Fetal/prevención & control , Trastornos del Espectro Alcohólico Fetal/psicología , Humanos , Indígenas Norteamericanos/psicología , Indígenas Norteamericanos/estadística & datos numéricos , Recién Nacido , Acontecimientos que Cambian la Vida , Masculino , Medicina Tradicional , Embarazo , Prejuicio , Factores de Riesgo , Medio Social , Estados UnidosRESUMEN
OBJECTIVE: We describe a 5-year prospective study of reproductive aging, and present analyses of steroid hormone and menstrual cycle changes with age. DESIGN: Participants were college-educated white women, primarily of northern European ancestry, recruited from the Tremin Research Program on Women's Health (n = 156, 25-58 years). In each of 5 consecutive years, they collected daily urine specimens for 6 months and recorded menstrual bleeds for all months. Urine specimens were assayed for estrone-3-glucuronide (E1G) and pregnanediol-3-glucuronide (PDG), urinary metabolites of estradiol and progesterone. Using multilevel models, we estimated hormone and cycle-length trajectories for individual women and within- and between-woman variance by age. RESULTS: At the aggregate level, PDG declined beginning in the 30s, E1G increased into the 40s before declining, and cycle length became more variable with age. Individual-level models revealed substantial hormonal variation across women, in both absolute levels and rates of change. Most women showed declining E1G by the late 40s, declining PDG in the 30s, and increasing mean cycle length in the 40s. Hormonal variation decreased with age; cycle length variation decreased and then increased. Within individual women, cycle lengths were highly variable while hormone levels were more stable. Women differed more from each other in hormone levels than for cycle lengths. CONCLUSIONS: Aggregate-level analyses show general changes in steroid hormones and cycle length but cannot show variation within and across women. Individuals' cycle lengths were too variable to predict hormone levels. Clinicians should obtain more data on individual women's hormonal patterns when determining fertility or menopause treatments.
Asunto(s)
Envejecimiento/fisiología , Estrona/análogos & derivados , Ciclo Menstrual/fisiología , Pregnanodiol/análogos & derivados , Adulto , Estrona/orina , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Pregnanodiol/orina , Estudios ProspectivosRESUMEN
Recent research has questioned whether the European Black Death of 1347-1351 could possibly have been caused by the bubonic plague bacillus Yersinia pestis, as has been assumed for over a century. Central to the arguments both for and against involvement of Y. pestis has been a comparison of the temporal dynamics observed in confirmed outbreaks of bubonic plague in early-20th-century India, versus those reconstructed for the Black Death from English church records--specifically, from lists of institutions (appointments) to vacated benefices contained in surviving bishops' registers. This comparison is, however, based on a statistical error arising from the fact that most of the bishops' registers give only the dates of institution and not the dates of death. Failure to correct for a distributed (as opposed to constant) lag time from death to institution has made it look as if the Black Death passed slowly through specific localities. This error is compounded by a failure to disaggregate the information from the bishops' registers to a geographical level that is genuinely comparable to the modern data. A sample of 235 deaths from the bishop's register of Coventry and Lichfield, the only English register to list both date of death and date of institution, shows that the Black Death swept through local areas much more rapidly than has previously been thought. This finding is consistent with those of earlier studies showing that the Black Death spread too rapidly between locales to have been a zoonosis such as bubonic plague. A further analysis of the determinants of the lag between death and institution, designed to provide a basis for reexamining other bishops' registers that do not provide information on date of death, shows that the distribution of lags could vary significantly by time and space even during a single epidemic outbreak.
Asunto(s)
Brotes de Enfermedades/historia , Peste/historia , Inglaterra/epidemiología , Historia del Siglo XX , Historia Medieval , Humanos , Peste/epidemiología , Peste/transmisión , Sistema de Registros/estadística & datos numéricos , Factores de TiempoRESUMEN
BACKGROUND: Monitoring of reproductive steroid hormones at the population level requires frequent measurements, hormones or metabolites that remain stable under less than ideal collection and storage conditions, a long-term supply of antibodies, and assays useful for a range of populations. We developed enzyme immunoassays for urinary pregnanediol 3-glucuronide (PDG) and estrone conjugates (E1Cs) that meet these criteria. METHODS: Enzyme immunoassays based on monoclonal antibodies were evaluated for specificity, detection limit, parallelism, recovery, and imprecision. Paired urine and serum specimens were analyzed throughout menstrual cycles of 30 US women. Assay application in different populations was examined with 23 US and 42 Bangladeshi specimens. Metabolite stability in urine was evaluated for 0-8 days at room temperature and for 0-10 freeze-thaw cycles. RESULTS: Recoveries were 108% for the PDG assay and 105% for the E1C assay. Serially diluted specimens exhibited parallelism with calibration curves in both assays. Inter- and intraassay CVs were <11%. Urinary and serum concentrations were highly correlated: r = 0.93 for E1C-estradiol; r = 0.98 for PDG-progesterone. All Bangladeshi and US specimens were above detection limits (PDG, 21 nmol/L; E1C, 0.27 nmol/L). Bangladeshi women had lower follicular phase PDG and lower luteal phase PDG and E1Cs than US women. Stability experiments showed a maximum decrease in concentration for each metabolite of <4% per day at room temperature and no significant decrease associated with number of freeze-thaw cycles. CONCLUSIONS: These enzyme immunoassays can be used for the field conditions and population variation in hormone metabolite concentrations encountered in cross-cultural research.