Characterization of genes encoding translation initiation factor eIF- 2gamma in mouse and human: sex chromosome localization, escape from X- inactivation and evolution

The Delta Sxrb interval of the mouse Y chromosome is critical for spermatogenesis and expression of the male-specific minor transplantation antigen H-Y. Several genes have been mapped to this interval and each has a homologue on the X chromosome. Four, Zfy1 , Zfy2 , Ube1y and Dffry , are expressed specifically in the testis and their X homologues are not transcribed from the inactive X chromosome. A further two, Smcy and Uty , are ubiquitously expressed and their X homologues escape X-inactivation. Here we report the identification of another gene from this region of the mouse Y chromosome. It encodes the highly conserved eukaryotic translation initiation factor eIF-2gamma. In the mouse this gene is ubiquitously expressed, has an X chromosome homologue which maps close to Dmd and escapes X-inactivation. The coding regions of the X and Y genes show 86% nucleotide identity and encode putative products with 98% amino acid identity. In humans, the eIF-2gamma structural gene is located on the X chromosome at Xp21 and this also escapes X-inactivation. However, there is no evidence of a Y copy of this gene in humans. We have identified autosomal retroposons of eIF-2gamma in both humans and mice and an additional retroposon on the X chromosome in some mouse strains. Ark blot analysis of eutherian and metatherian genomic DNA indicates that X-Y homologues are present in all species tested except simian primates and kangaroo and that retroposons are common to a wide range of mammals. These results shed light on the evolution of X-Y homologous genes.      

Daily social and physical activity increases slow-wave sleep and daytime neuropsychological performance in the elderly

Decreased levels of physical and social activity associated with aging can be particularly pronounced in residents of assisted living facilities. Reduced exposure to important behavioral and time-giving cues may contribute to the age-related changes in circadian rhythmicity and sleep. The present study was conducted to test the hypothesis that an enforced schedule of structured social and physical activity (0:900 to 10:30 and 19:00 to 20:30 daily for two weeks) can have beneficial effects on circadian rhythmicity, nocturnal sleep, daytime functioning, mood, and vigor. The subjects were 14 elderly residents of continued-care retirement facilities while a similar group of 9 elderly residents served as controls. The group exposed to structured activities had increased amounts of slow-wave sleep and demonstrated improvement in memory-oriented tasks following the intervention. Conversely, no significant changes were noted in the amplitude and phase of the body temperature rhythm or in subjective measures of vigor and mood. These results indicate that short-term exposure to structured social intervention and light physical activity can significantly improve memory performance and enhance slow-wave sleep in older adults without alterations to the circadian phase or amplitude of body temperature. This is the first report to demonstrate that low intensity activity in an elderly population can increase deep sleep and improve memory functioning. The high degree of interest in these activities paired with the simple nature of the tasks makes this a potentially practical intervention which can be adapted for both community dwelling and assisted-living elders.     

Local clinical guidelines: description and evaluation of a participative method for their development and implementation

BACKGROUND: National guidelines are rarely followed by immediate changein clinical behaviour. We present our experience of an activeeducational method for local development and implementationof a guideline. OBJECTIVE: To evaluate the effectiveness of a participative method fordeveloping local clinical guidelines. METHODS: A trial in a district of the effect of guideline developmentincorporating active participation of intended recipients onsubsequent relevant prescribing. It was carried out in WirralFamily Health Services Authority district (the Wirral peninsula)comprising 69 general practices covering a population of 345763. An exemplar guideline on ‘hypertension in the elderly’was developed by the method described. The principal recommendeddrug was bendrofluazide 2.5 mg once daily. The differences inprescribed daily doses (PDD) of bendrofluazide 2.5 mg tabletsper quarter per 1000 prescribing units (age-weighted population)between the intervention district and England as a whole wasmeasured. RESULTS: Comparison of the intervention district with England data demonstratesa median difference of 122.49 PDD before and 206.34 PDD afterguideline production, this change is statistically highly significant(Mann-Whitney two-tailed P < 0.0001; 95% CL = 36.51–104.77).Grouped regression analysis shows no significant difference(0.89) in slope gradients before guideline production (P = 0.35,95% CL = –3.97–5.76), but the difference in slopegradients after (12.95) is statistically highly significant(P < 0.0001; 95% CL = 8.17–17.73). The data suggeststhat the change in clinical behaviour persisted for at leasttwo years. CONCLUSION: Participation of intended recipient general practitioners andlocal specialists in the development of a guideline by an activeeducational method as described was followed by a favourablechange in clinical behaviour which persisted for at least twoyears. Keywords. Clinical guidelines, development, evaluation, implementation, participation.     

<Emphasis Type="Italic">In vivo</Emphasis> activity of <Emphasis Type="Italic">Sapindus saponaria</Emphasis> against azole-susceptible and -resistant human vaginal <Emphasis Type="Italic">Candida</Emphasis> species

Background  

Study of in vivo antifungal activity of the hydroalcoholic extract (HE) and n-BuOH extract (BUTE) of Sapindus saponaria against azole-susceptible and -resistant human vaginal Candida spp.     

Changes in insulin secretion and action in adults with familial risk for type 2 diabetes who curtail their sleep

OBJECTIVE

Experimental sleep deprivation is accompanied by changes in glucose regulation. However, the effects of chronic sleep insufficiency on insulin secretion and action in populations at high risk for type 2 diabetes are not known. This study examined the relationship between objectively documented habitual sleep curtailment and measures of insulin sensitivity, insulin secretion, and oral glucose tolerance in free-living adults with parental history of type 2 diabetes.

RESEARCH DESIGN AND METHODS

A total of 47 healthy participants with parental history of type 2 diabetes (26 female/21 male, mean [SD] age 26 [4] years and BMI 23.8 [2.5] kg/m²) completed 13 (SD = 2) days of sleep and physical activity monitoring by wrist actigraphy and waist accelerometry while following their usual lifestyle at home. Laboratory polysomnography was used to screen for sleep disorders. Indices of diabetes risk based on oral glucose tolerance tests were compared between participants with habitual short sleep and those with usual sleep duration >6 h/day.

RESULTS

Consistent with a behavioral pattern of habitual sleep curtailment, short sleepers obtained an average of 1.5 h less sleep per night and showed signs of increased sleep pressure. Participants who habitually curtailed their sleep had considerably higher indices of insulin resistance and increased insulin secretion but maintained normal glucose tolerance similar to that of subjects who slept more.

CONCLUSIONS

Young lean adults with parental history of type 2 diabetes who habitually curtail their sleep have increased insulin resistance and compensatory hyperinsulinemia—a pattern that has been associated with higher risk of developing diabetes in such susceptible individuals.Driven by the demands and opportunities of modern life, many Americans today sleep <6 h/day (1). Self-reports of such short sleep have been associated with increased incidence of diabetes (2), which raises the possibility that chronic sleep insufficiency may affect factors involved in the pathogenesis of type 2 diabetes. Indeed, studies of healthy volunteers in the laboratory indicate that short-term sleep deprivation can modify systemic glucose tolerance, insulin secretion, or insulin action (3–8). However, the importance of these experimentally induced changes in insulin secretion or action for the association of self-reported short sleep with incident diabetes in free-living adults is not well defined. Furthermore, the impact of chronic sleep insufficiency on measures of glucose tolerance, pancreatic β-cell function, and insulin sensitivity in individuals with high preexisting risk of type 2 diabetes has not been studied. There is also concern that the relationship between self-reported short sleep and diabetes risk in epidemiological studies may harbor residual confounding by factors such as undiagnosed sleep problems (e.g., sleep apnea and insomnia), poor physical or emotional health, and systemic biases in the subjective recall of sleep and physical activity (1,9,10).Healthy adults with parental history of type 2 diabetes have a high risk for developing the disease and exhibit changes in insulin secretion and action long before the onset of diabetes (11–16). Understanding whether objectively documented chronic sleep insufficiency can aggravate the preexisting defects in insulin sensitivity and β-cell function in such high-risk individuals may inform the development of improved behavioral strategies for metabolic risk reduction. The goal of this exploratory study was to collect objective measures of habitual sleep duration and free-living physical activity and test the hypothesis that healthy adults with parental history of type 2 diabetes who curtail their sleep will show signs of increased insulin resistance. Secondary end points included measures of insulin secretion and oral glucose tolerance.