Estimation of expected number of rare alleles of a locus and calculation of mutation rate

An approach is described for the estimation of the number of rare variants in the population from the number in a sample drawn at random from the population. This quantity is used to derive an estimate of the mutation rate. The data required are the number of rare variants in the sample and the distribution of offspring within a population of well-defined size with little or no immigration. Application of this approach to data on 28 loci assayed in the Yanamamo, a tribe of South American Indians, yields an average mutation rate of 0.1 ~ 0.2 × 10^-5. Determination of this figure is subject to several assumptions concerning the nature of the rare variants and the structure of the population. Violation of these assumptions will generally result in the underestimate of the true mutation rate.     

Lactate rise detected by 1H NMR in human visual cortex during physiologic stimulation.

Brain lactate concentration is usually assumed to be stable except when pathologic conditions cause a mismatch between glycolysis and respiration. Using newly developed 1H NMR spectroscopic techniques that allow measurement of lactate in vivo, we detected lactate elevations of 0.3-0.9 mM in human visual cortex during physiologic photic stimulation. The maximum rise appeared in the first few minutes; thereafter lactate concentration declined while stimulation continued. The results are consistent with a transient excess of glycolysis over respiration in the visual cortex, occurring as a normal response to stimulation in the physiologic range.     

Pregnancy,birth and risk: an introduction

In this introduction, I use my nearly 40 years of work in the area to reflect on the total medicalisation of pregnancy and childbirth that informs even the critical sociology that purports to examine the issue. The risks that are faced in pregnancy and birth are not only the inherent dangers that midwives have worked with across time and space but also those particular risks introduced by medicalisation itself. Medicalisation blinds us to those risks on the one hand, while it blinds us to the skills and knowledge that midwives and birthing women themselves have on the other. The women and midwives researched in these articles show us that in pregnancy and birth, as in most of life, it is not just a matter of ‘real risk’ versus ‘perceived risk’ as risk theorists (too) often describe it. There is rather an intelligent balancing of risks, weighing of risks and contextualising of risks. What we see in this issue is a glimpse into the ways in which people intelligently, creatively and determinedly balance risks.     

Prospective Associations between Bilingualism and Executive Function in Latino Children: Sustained Effects While Controlling for Biculturalism

The study purpose was to test 1-year prospective associations between English–Spanish bilingualism and executive function in 5th to 6th grade students while controlling for biculturalism. Participants included 182 US Latino students (50 % female). Self-report surveys assessed biculturalism, bilingualism, and executive function (i.e., working memory, organizational skills, inhibitory control, and emotional control, as well as a summary executive function score). General linear model regressions demonstrated that bilingualism significantly predicted the summary executive function score as well as working memory such that bilingual proficiency was positively related to executive function. Results are the first to demonstrate (a) prospective associations between bilingualism to executive function while controlling for the potential third variable of biculturalism, and (b) a principal role for working memory in this relationship. Since executive function is associated with a host of health outcomes, one implication of study findings is that bilingualism may have an indirect protective influence on youth development.     

Estrogen Replacement Reduces Hearing Threshold Shifts and Cochlear Hair Cell Loss After Acoustic Overexposure in Ovariectomized Rats

Objectives.The relationship of estrogen (the primary female sex hormone) with hearing function has been studied in both humans and animals. However, whether estrogen levels affect hearing remains uncertain. Therefore, in this study, we investigated changes in the vulnerability of hearing to acoustic overexposure in ovariectomized female rats.Methods.Eighteen 8-week-old female Sprague-Dawley rats were separated into four groups as follows: sham ovariectomy (OP), OP only, and OP treated with low (10 µg/kg) or high doses (100 µg/kg) of estrogen. Rats in the estrogen replacement groups were given two intraperitoneal injections. Hearing thresholds were measured before noise exposure, and at 1 day and 2 weeks after exposure.Results.The hearing thresholds of the sham OP and OP-only groups were not significantly different. However, both estrogen groups showed a lower threshold shift than the OP-only group. Histological immunostaining analyses showed that hair cell loss in the 32 kHz region was more severe in the sham OP group than in the OP-only group. Furthermore, there was little or no hair cell loss in either estrogen replacement group and significantly more hair cell loss in the OP-only group.Conclusion.These results suggest that estrogen replacement may reduce the vulnerability of hearing to noise exposure in menopausal women.     

The pathogenesis and treatment of large granular lymphocyte leukemia

Large granular lymphocyte (LGL) leukemia is a spectrum of rare lymphoproliferative diseases of T lymphocytes and natural killer cells. These diseases frequently present with splenomegaly, neutropenia, and autoimmune diseases like rheumatoid arthritis. LGL leukemia is more commonly of a chronic, indolent nature; however, rarely, they have an aggressive course. LGL leukemia is thought to arise from chronic antigen stimulation, which drives long-term cell survival through the activation of survival signaling pathways and suppression of pro-apoptotic signals. These include Jak-Stat, Mapk, Pi3k-Akt, sphingolipid, and IL-15/Pdgf signaling. Treatment traditionally includes immunosuppression with low dose methotrexate, cyclophosphamide, and other immunosuppressive agents; however, prospective and retrospective studies reveal very limited success. New studies surrounding Jak-Stat signaling suggest this may reveal new avenues for LGL leukemia therapeutics.