Phosphofructokinase 1 Glycosylation Regulates Cell Growth and Metabolism

Cancer cells must satisfy the metabolic demands of rapid cell growth within a continually changing microenvironment. We demonstrated that the dynamic posttranslational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAcylation) is a key metabolic regulator of glucose metabolism. O-GlcNAcylation was induced at serine 529 of phosphofructokinase 1 (PFK1) in response to hypoxia. Glycosylation inhibited PFK1 activity and redirected glucose flux through the pentose phosphate pathway, thereby conferring a selective growth advantage on cancer cells. Blocking glycosylation of PFK1 at serine 529 reduced cancer cell proliferation in vitro and impaired tumor formation in vivo. These studies reveal a previously uncharacterized mechanism for the regulation of metabolic pathways in cancer and a possible target for therapeutic intervention

Children's understandings of obesity, a thematic analysis

Childhood obesity is a major concern in today’s society. Research suggests the inclusion of the views and understandings of a target group facilitates strategies that have better efficacy. The objective of this study was to explore the concepts and themes that make up children’s understandings of the causes and consequences of obesity. Participants were selected from Reception (4-5 years old) and Year 6 (10-11 years old), and attended a school in an area of Sunderland, in North East England. Participants were separated according to age and gender, resulting in four focus groups, run across two sessions. A thematic analysis (Braun & Clarke, 2006) identified overarching themes evident across all groups, suggesting the key concepts that contribute to children’s understandings of obesity are ‘‘Knowledge through Education,’’ ‘‘Role Models,’’ ‘‘Fat is Bad,’’ and ‘‘Mixed Messages.’’ The implications of these findings and considerations of the methodology are discussed in full

Prospective Trial of CPAP in Community-Dwelling Adults with Down Syndrome and Obstructive Sleep Apnea Syndrome

Adults with Down syndrome (DS) are predisposed to obstructive sleep apnoea (OSA), but the effectiveness and acceptability of continuous positive airway pressure treatment (CPAP) in this group has rarely been formally assessed. This study was designed as a pilot randomised, parallel controlled trial for one month, continuing as an uncontrolled cohort study whereby the control group also received the intervention. Symptomatic, community-dwelling DS individuals exhibiting ≥10 apnoeas/hypopneas per hour in bed on a Type 3 home sleep study were invited to participate in this study, with follow-up at 1, 3, 6, and 12 months from baseline. Measurements of sleepiness, behaviour, cognitive function and general health were undertaken; the primary outcome was a change in the pictorial Epworth Sleepiness Scale (pESS) score. Twenty-eight participants (19 male) were enrolled: age 28 ± 9 year; body mass index 31.5 ± 7.9 kg/m2; 39.6 ± 32.2 apnoeas/hypopneas per hour in bed; pESS 11 ± 6/24. The pilot randomised controlled trial at one month demonstrated no change between the groups. At 12 months, participant (p = 0.001) pESS and Disruptive (p 0.0001), Anxiety/Antisocial (p = 0.024), and Depressive (p = 0.008) behaviour scores were reduced compared to baseline. Improvement was noted in verbal (p = 0.001) and nonverbal intelligence scores (p = 0.011). General health scores also improved (p = 0.02). At the end of the trial, 19 participants continued on treatment. Use of CPAP in adults with DS and OSA led to a number of significant, sustained improvements in sleepiness and behavioural/emotional outcomes at 12 months

Conceptualising quality of life for older people with aphasia

Background: There is an increasing need in speech and language therapy for clinicians to provide intervention in the context of the broader life quality issues for people with aphasia. However, there is no descriptive research that is explicitly focused on quality of life (QoL) from the perspectives of older people with aphasia. Aims: The current study explores how older people with chronic aphasia who are living in the community describe their QoL in terms of what contributes to and detracts from the quality in their current and future lives. The study is descriptive in nature, and the purpose is to conceptualize the factors that influence QoL. Methods & Procedures: Thirty older participants (16 women, 14 men) with mild to moderate aphasic impairment took part. All participants had adequate communication skills to participate: demonstrating reliable yes/no response and moderate auditory comprehension ability. Participants were interviewed in their own homes using six brief unprompted open questions about QoL, in a structured interview. The first five questions were drawn from previous gerontological research (Farquhar, 1995), and a sixth question specifically targeting communication was added. Content analysis was used, identifying discrete units of data and then coding these into concepts and factors. Additional demographic information was collected, and participants’ mood on day of interviewing was assessed using the Geriatric Depression Scale (Sheikh & Yesavage, 1986). Outcomes & Results: Activities, verbal communication, people, and body functioning were the core factors in QoL for these participants, and they described how these factors both contributed quality in life as well as detracted from life quality. Other factors that influenced QoL included stroke, mobility, positive personal outlook, in/dependence, home and health. Whilst the findings are limited by the lack of probing of participants’ responses, the study does present preliminary evidence for what is important in QoL to older people with aphasia. Conclusions: Quality of life for older people with predominantly mild to moderate chronic aphasia who are living in the community is multifactorial in nature. Some factors lie within the remit of speech and language therapy, some lie beyond the professional role, but all are relevant for consideration in rehabilitation and community practice. Further qualitative research is implicated to better understand QoL with aphasia, using in-depth interviewing with a broader range of people with aphasia

We are all one together : peer educators\u27 views about falls prevention education for community-dwelling older adults - a qualitative study

Background: Falls are common in older people. Despite strong evidence for effective falls prevention strategies, there appears to be limited translation of these strategies from research to clinical practice. Use of peers in delivering falls prevention education messages has been proposed to improve uptake of falls prevention strategies and facilitate translation to practice. Volunteer peer educators often deliver educational presentations on falls prevention to community-dwelling older adults. However, research evaluating the effectiveness of peer-led education approaches in falls prevention has been limited and no known study has evaluated such a program from the perspective of peer educators involved in delivering the message. The purpose of this study was to explore peer educators’ perspective about their role in delivering peer-led falls prevention education for community-dwelling older adults. Methods: A two-stage qualitative inductive constant comparative design was used.In stage one (core component) focus group interviews involving a total of eleven participants were conducted. During stage two (supplementary component) semi-structured interviews with two participants were conducted. Data were analysed thematically by two researchers independently. Key themes were identified and findings were displayed in a conceptual framework. Results: Peer educators were motivated to deliver educational presentations and importantly, to reach an optimal peer connection with their audience. Key themes identified included both personal and organisational factors that impact on educators’ capacity to facilitate their peers’ engagement with the message. Personal factors that facilitated message delivery and engagement included peer-to-peer connection and perceived credibility, while barriers included a reluctance to accept the message that they were at risk of falling by some members in the audience. Organisational factors, including ongoing training for peer educators and formative feedback following presentations, were perceived as essential because they affect successful message delivery. Conclusions: Peer educators have the potential to effectively deliver falls prevention education to older adults and influence acceptance of the message as they possess the peer-to-peer connection that facilitates optimal engagement. There is a need to consider incorporating learnings from this research into a formal large scale evaluation of the effectiveness of the peer education approach in reducing falls in older adults

High-resolution temporal profiling of transcripts during Arabidopsis leaf senescence reveals a distinct chronology of processes and regulation

Leaf senescence is an essential developmental process that impacts dramatically on crop yields and involves altered regulation of thousands of genes and many metabolic and signaling pathways, resulting in major changes in the leaf. The regulation of senescence is complex, and although senescence regulatory genes have been characterized, there is little information on how these function in the global control of the process. We used microarray analysis to obtain a highresolution time-course profile of gene expression during development of a single leaf over a 3-week period to senescence. A complex experimental design approach and a combination of methods were used to extract high-quality replicated data and to identify differentially expressed genes. The multiple time points enable the use of highly informative clustering to reveal distinct time points at which signaling and metabolic pathways change. Analysis of motif enrichment, as well as comparison of transcription factor (TF) families showing altered expression over the time course, identify clear groups of TFs active at different stages of leaf development and senescence. These data enable connection of metabolic processes, signaling pathways, and specific TF activity, which will underpin the development of network models to elucidate the process of senescence

Large-scale features of Pliocene climate: results from the Pliocene Model Intercomparison Project

Climate and environments of the mid-Pliocene warm period (3.264 to 3.025 Ma) have been extensively studied. Whilst numerical models have shed light on the nature of climate at the time, uncertainties in their predictions have not been systematically examined. The Pliocene Model Intercomparison Project quantifies uncertainties in model outputs through a coordinated multi-model and multi-model/data intercomparison. Whilst commonalities in model outputs for the Pliocene are clearly evident, we show substantial variation in the sensitivity of models to the implementation of Pliocene boundary conditions. Models appear able to reproduce many regional changes in temperature reconstructed from geological proxies. However, data/model comparison highlights that models potentially underestimate polar amplification. To assert this conclusion with greater confidence, limitations in the time-averaged proxy data currently available must be addressed. Furthermore, sensitivity tests exploring the known unknowns in modelling Pliocene climate specifically relevant to the high latitudes are essential (e.g. palaeogeography, gateways, orbital forcing and trace gasses). Estimates of longer-term sensitivity to CO2 (also known as Earth System Sensitivity; ESS), support previous work suggesting that ESS is greater than Climate Sensitivity (CS), and suggest that the ratio of ESS to CS is between 1 and 2, with a "best" estimate of 1.5

A Social Model for Health Promotion for an Aging Population: Initial Evidence on the Experience Corps Model

This report evaluates whether a program for older volunteers, designed for both generativity and health promotion, leads to short-term improvements in multiple behavioral risk factors and positive effects on intermediary risk factors for disability and other morbidities. The Experience Corps® places older volunteers in public elementary schools in roles designed to meet schools\u27 needs and increase the social, physical, and cognitive activity of the volunteers. This article reports on a pilot randomized trial in Baltimore, Maryland. The 128 volunteers were 60-86 years old; 95% were African American. At follow-up of 4-8 months, physical activity, strength, people one could turn to for help, and cognitive activity increased significantly, and walking speed decreased significantly less, in participants compared to controls. In this pilot trial, physical, cognitive, and social activity increased, suggesting the potential for the Experience Corps to improve health for an aging population and simultaneously improve educational outcomes for children

Air Pollution–Associated Changes in Lung Function among Asthmatic Children in Detroit

In a longitudinal cohort study of primary-school–age children with asthma in Detroit, Michigan, we examined relationships between lung function and ambient levels of particulate matter ≤ 10 μm and ≤ 2.5 μm in diameter (PM(10) and PM(2.5)) and ozone at varying lag intervals using generalized estimating equations. Models considered effect modification by maintenance corticosteroid (CS) use and by the presence of an upper respiratory infection (URI) as recorded in a daily diary among 86 children who participated in six 2-week seasonal assessments from winter 2001 through spring 2002. Participants were predominantly African American from families with low income, and > 75% were categorized as having persistent asthma. In both single-pollutant and two-pollutant models, many regressions demonstrated associations between higher exposure to ambient pollutants and poorer lung function (increased diurnal variability and decreased lowest daily values for forced expiratory volume in 1 sec) among children using CSs but not among those not using CSs, and among children reporting URI symptoms but not among those who did not report URIs. Our findings suggest that levels of air pollutants in Detroit, which are above the current National Ambient Air Quality Standards, adversely affect lung function of susceptible asthmatic children