Eleanor Bantry White

Human nuclear Dicer restricts the deleterious accumulation of endogenous double-stranded RNA

Dicer is a central enzymatic player in RNA-interference pathways that acts to regulate gene expression in nearly all eukaryotes. Although the cytoplasmic function of Dicer is well documented in mammals, its nuclear function remains obscure. Here we show that Dicer is present in both the nucleus and cytoplasm, and its nuclear levels are tightly regulated. Dicer interacts with RNA polymerase II (Pol II) at actively transcribed gene loci. Loss of Dicer causes the appearance of endogenous double-stranded RNA (dsRNA), which in turn leads to induction of the interferon-response pathway and consequent cell death. Our results suggest that Pol II–associated Dicer restricts endogenous dsRNA formation from overlapping noncoding-RNA transcription units. Failure to do so has catastrophic effects on cell function.

Electronic Tracking for People with Dementia Who Get Lost outside the Home: A Study of the Experience of Familial Carers

Purpose: The study aimed to elicit a description of GPS (global positioning system) tracking use in the care of people with dementia in domestic settings and to generate hypotheses about impact. Procedures: Users were recruited through a commercial provider. Qualitative interviews with 10 carers were completed to generate an in-depth description of how the devices were used and the perceived impact. A questionnaire was administered to ascertain sample characteristics. Findings: Most carers preferred to use tracking as a back-up to other strategies of management, particularly supervision by a carer and locked doors. In cases where the carers perceived the risk of harm from getting lost to be low, tracking was used to preserve the independence of the person with dementia. The carers reported that tracking gave them reassurance and also enhanced the sense of independence both for themselves and for the person with dementia. The poor reliability of the device was identified as a substantial limitation. Conclusion: Larger studies are needed to assess the safety and clinical value of GPS tracking. These should explore the views of people with dementia. Assessment tools are needed to assess suitability. Occupational therapy can play a pivotal role in this process of intervention design, assessment and evaluation.

Electronic tracking for people with dementia: An exploratory study of the ethical issues experienced by carers in making decisions about usage

Electronic tracking through GPS (global positioning system) is being used to monitor and locate people with dementia who are vulnerable to becoming lost. Through a review of the literature and an original study, this article examined ethical issues associated with use in a domestic setting. The qualitative study consisted of in-depth interviews with 10 carers who were using electronic tracking. The study explored the values, beliefs and contextual factors that motivated carers to use electronic tracking. It examined the extent of involvement of the person with dementia in decision-making and it explored the various ethical dilemmas encountered by carers when introducing the tracking system. As an issue that emerged from the interviews, specific attention was paid to exploring covert usage. From the study findings, recommendations have been made for research and practice about the use of electronic tracking in dementia care.

Dementia, walking outdoors and getting lost: incidence, risk factors and consequences from dementia-related police missing-person reports

Objectives: To estimate incidence, identify consequences and potential risk factors for harm in people with dementia who got lost in one UK policing region. Methods: In a retrospective observational study, data were extracted from missing-person records over a four-year period in one UK policing region (population of 2.1 million). Results: Two hundred and eighty-one incidents of getting lost were identified. Incidence of getting lost was estimated at 0.5% of the regional dementia population. Fifty-nine percent of reports came from domestic settings, 29% from care homes/hospitals, and 12% on excursions from home. Five percent (n = 15) sustained significant harm, including two deaths. Average age was 78 years (SD 8.3). Harm was associated with older age (mean difference 6.16 years, CI 1.86 to 10.46, p = 0.005, t = 2.82), length of time missing (Mdn time 2.48 hours; IQR 0.97 to 9.45, p = 0.02), and season (9% winter, 2% summer, p = 0.006). The length of time missing increased with delays in reporting to police (r = 0.15, p = 0.018), getting lost at night (Mdn time 1.70 hours, IQR 0.52–3.32, p = 0.028), driving themselves (Mdn time 2.45 hours, IQR 0.42–2.00, p = 0.001), and using public transport (Mdn 1.78 hours, IQR 1.07–3.92, p = 0.001). Conclusion: Incidence in this study suggests getting lost is a low-frequency event for people with dementia but for a small minority, the risks are considerable. Exploratory analyses suggest individual and environmental factors increase the risk of harm. Suitable methods need to be developed to replicate these findings in larger prospective samples. A focus on the predictors of harm may aid development of assessment protocols to ensure intervention is proportionate.

AT-rich sequence elements promote nascent transcript cleavage leading to RNA polymerase II termination

RNA Polymerase II (Pol II) termination is dependent on RNA processing signals as well as specific terminator elements located downstream of the poly(A) site. One of the two major terminator classes described so far is the Co-Transcriptional Cleavage (CoTC) element. We show that homopolymer A/T tracts within the human β-globin CoTC-mediated terminator element play a critical role in Pol II termination. These short A/T tracts, dispersed within seemingly random sequences, are strong terminator elements, and bioinformatics analysis confirms the presence of such sequences in 70% of the putative terminator regions (PTRs) genome-wide.

A Review of “Wandering” Instruments for People With Dementia Who Get Lost

Objectives: This study is the first review to be conducted to evaluate measures of wandering behavior for identifying people with dementia at risk of getting lost. Method: Drawing upon systematic review search strategies, the relevant literature was reviewed for wandering instruments using MEDLINE, Embase, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature. The psychometric properties of these were evaluated with reference to establishing the risk of getting lost. Results: The search yielded 34 instruments. Of these, one wandering-specific measure and four measures of behavioral change in dementia met inclusion criteria. The ability of these to confidently evaluate the risk of getting lost remains uncertain. Conclusion: Further research is required to more fully evaluate the psychometric properties of the retrieved instruments. This process is made complex by difficulties in defining wandering and getting lost and methodologically, by the absence of a criterion reference. Methodological developments are required to enhance assessment-focused reviews in the psychosocial intervention field.

Perceptions, Expectations, and Informal Supports Influence Exercise Activity in Frail Older Adults

This study aims to explore frail older adults’ perceptions of what influences their exercise behaviors. A qualitative descriptive design was used. Semi-structured, open-ended interviews were conducted with 29 frail older adults. Thematic content analysis established the findings. Frail older adults perceive exercise as a by-product of other purposeful activities such as manual work or social activities. Progression into frailty appears to be associated with a decline in non-family support, changing traditional roles within family support networks, and lower baseline activity levels. Frail older adults perceive exercise as incidental to more purposeful activities rather than an endpoint in itself. Therefore, exercise programs concentrating on functional outcomes may be more relevant for this population. Strategies that educate and promote social support networks may also benefit frail older adults.

Transcriptional Activation of the General Amino Acid Permease Gene per1 by the Histone Deacetylase Clr6 Is Regulated by Oca2 Kinase

ABSTRACT Expression of nitrogen metabolism genes is regulated by the quality of the nitrogen supply. Here, we describe a mechanism for the transcriptional regulation of the general amino acid permease gene per1 in Schizosaccharomyces pombe. We show that when ammonia is used as the nitrogen source, low levels of per1 are transcribed and histones in the coding and surrounding regions of per1 are acetylated. In the presence of proline, per1 transcription is upregulated and initiates from a more upstream site, generating 5′-extended mRNAs. Concomitantly, histones at per1 are deacetylated in a Clr6-dependent manner, suggesting a positive role for Clr6 in transcriptional regulation of per1. Upstream initiation and histone deactylation of per1 are constitutive in cells lacking the serine/threonine kinase oca2, indicating that Oca2 is a repressor of per1. Oca2 interacts with a protein homologous to the Saccharomyces cerevisiae transcriptional activator Cha4 and with Ago1. Loss of Cha4 or Ago1 causes aberrant induction of per1 under noninducing conditions, suggesting that these proteins are also involved in per1 regulation and hence in nitrogen utilization.