Biochemical studies of P97 AAA ATPase

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CD28 costimulation in T cells: requirements, outcomes and regulation

The costimulatory receptor CD28 and its inhibitory counterpart CTLA-4 share the same ligands and comprise a crucial checkpoint in T cell activation. CTLA-4 removes its ligands from antigen presenting cells by trans-endocytosis, which reduces the availability of costimulatory ligands for CD28 engagement to regulate T cell activation. This project examined the functional implications of reducing the availability of costimulatory molecules for CD4 T cell responses, and investigated the use of trans-endocytosis by other T cell receptors. Surprisingly, it was revealed that PD-1 and OX40 can also internalise their ligands, although perhaps not via the same mechanism as CTLA-4 trans-endocytosis. It was also shown that altering the availability of CD28 ligands affects the extent of T cell proliferation, suggesting that CTLA-4 trans-endocytosis can finely tune the T cell response. Furthermore, it was observed that CD28 costimulation is not always required for T cell activation and proliferation, but CD28 engagement is required for the optimal upregulation of a number of effector proteins and for TH2 cytokine production. Interestingly, T cells activated in the absence of CD28 signalling were not classically anergic. Strikingly, it was also found that memory T cells are dependent on CD28 costimulation

How can character education programmes support young people to develop their character to promote wellbeing?

DAppEdPsy ThesisDeveloping young people’s character is believed to promote their wellbeing, helping them to weigh competing priorities in complex situations and act in ways which uphold the interests of themselves and others. There is currently disagreement about the theoretical underpinnings of Character Education and the best way to support young people to develop their character. This thesis aims to explore these issues in more detail. Chapter 1 This chapter reports on a systematic literature review, synthesising six papers. It explores Character Education programmes, outlining their theoretical underpinnings and reporting their effects on participants’ moral virtues and practical wisdom. The majority of interventions were based on mixed theoretical underpinnings but commonly cited trait theories of virtue. Four studies demonstrated improvement in some aspects of moral virtue as a result of Character Education interventions. Chapter 2 This chapter is a bridging document which links Chapters 1 and 3. It outlines the reasons for choosing Character Education as a topic of study and discusses key considerations informing the design of the empirical research, including philosophical stance, methodology and ethics. Chapter 3 This chapter reports on an empirical research project which involved 18 secondary school students discussing the process they undergo when making moral decisions. It provides a qualitative exploration of how participants’ personal beliefs about the meaning of good character interact with situational factors to influence their moral decision-making. Findings suggest that young people’s moral decision-making is influenced by a range of situational factors which are integrated to produce the best possible outcome for self and others. Implications for the design of Character Education programmes and the potential role of educational psychologists in supporting this are explored in more detail

Glucocorticoid-Induced Bone Loss Is Associated with Abnormal Intravertebral Areal Bone Mineral Density Distribution

Individuals with glucocorticoid-induced osteoporosis experience vertebral fractures at an increased rate and at higher vertebral areal bone mineral density (aBMD) than individuals with primary osteoporosis. Standard posteroanterior- (PA-) projection dual energy X-ray absorptiometry (DXA) lacks the diagnostic sensitivity required for reliable estimation of vertebral fracture risk in individuals. Assessment of subregional vertebral aBMD using lateral-projection DXA may improve the predictive value of DXA parameters for fracture. One hundred and four individuals were recruited and grouped for this study: primary osteoporosis with no history of vertebral fracture (n = 43), glucocorticoid-induced bone loss (n = 13), and healthy controls (n = 48). Standard PA-projection and supine-lateral scans were performed, and lateral scans were analysed according to an established protocol to measure aBMD within 6 subregions. Main effects for subregion and group were assessed and observed, by ANCOVA. Ratios were calculated between subregions and compared between groups, to overcome the potentially confounding influence of variability in subregional geometry. Significantly lower values were observed in the glucocorticoid group for the ratios of (i) anterior subregion: whole vertebral body and (ii) posterior: whole vertebral body when compared to the primary osteoporosis and control groups (P < 0.0 5). Lower anterior subregional aBMD in individuals on glucocorticoid therapy may help to explain the increased vertebral fracture risk in this patient group

Within-trial cost and 1-year cost-effectiveness of the DiRECT/Counterweight-Plus weight-management programme to achieve remission of type 2 diabetes

No abstract available

The Iowa Homemaker vol.3, no.10

Table of Contents Activities of the Merrill Palmer School by Edna E. Walls, page 1 Specific Helps on Everyday Teaching Problems by Florence E. Busse, page 2 Winter Diets and the Elusive Meal by Lucile Barta, page 2 Modern Women and Floriculture by E. C. Volz, page 3 Historic Costume the Mother of Modern Vogue by Clara Jordan, page 4 Feeding the Multitude by Gertrude E. Murray, page 5 Our Travels in France by Josephine Arnquist, page 6 The Evolution of Home Economics at Iowa State by Ruth Elaine Wilson, page 8 The Power of Music by Oscar Hatch Hawley, page 9 To Judge of a Bargain by Mildred Briggs, page 9 Who is Responsible for the Child? by Louise Crawford, page 1

Estimating the global burden of endemic canine rabies

Background: Rabies is a notoriously underreported and neglected disease of lowincome countries. This study aims to estimate the public health and economic burden of rabies circulating in domestic dog populations, globally and on a country-by-country basis, allowing an objective assessment of how much this preventable disease costs endemic countries.&lt;p&gt;&lt;/p&gt; Methodology/Principal Findings: We established relationships between rabies mortality and rabies prevention and control measures, which we incorporated into a model framework. We used data derived from extensive literature searches and questionnaires on disease incidence, control interventions and preventative measures within this framework to estimate the disease burden. The burden of rabies impacts on public health sector budgets, local communities and livestock economies, with the highest risk of rabies in the poorest regions of the world. This study estimates that globally canine rabies causes approximately 59,000 (95% Confidence Intervals: 25- 159,000) human deaths, over 3.7 million (95% CIs: 1.6-10.4 million) disability-adjusted life years (DALYs) and 8.6 billion USD (95% CIs: 2.9-21.5 billion) economic losses annually. The largest component of the economic burden is due to premature death (55%), followed by direct costs of post-exposure prophylaxis (PEP, 20%) and lost income whilst seeking PEP (15.5%), with only limited costs to the veterinary sector due to dog vaccination (1.5%), and additional costs to communities from livestock losses (6%).&lt;p&gt;&lt;/p&gt; Conclusions/Significance: This study demonstrates that investment in dog vaccination, the single most effective way of reducing the disease burden, has been inadequate and that the availability and affordability of PEP needs improving. Collaborative investments by medical and veterinary sectors could dramatically reduce the current large, and unnecessary, burden of rabies on affected communities. Improved surveillance is needed to reduce uncertainty in burden estimates and to monitor the impacts of control efforts.&lt;p&gt;&lt;/p&gt

Sinking Organic Particles in the Ocean—Flux Estimates From in situ Optical Devices

Optical particle measurements are emerging as an important technique for understanding the ocean carbon cycle, including contributions to estimates of their downward flux, which sequesters carbon dioxide (CO2) in the deep sea. Optical instruments can be used from ships or installed on autonomous platforms, delivering much greater spatial and temporal coverage of particles in the mesopelagic zone of the ocean than traditional techniques, such as sediment traps. Technologies to image particles have advanced greatly over the last two decades, but the quantitative translation of these immense datasets into biogeochemical properties remains a challenge. In particular, advances are needed to enable the optimal translation of imaged objects into carbon content and sinking velocities. In addition, different devices often measure different optical properties, leading to difficulties in comparing results. Here we provide a practical overview of the challenges and potential of using these instruments, as a step toward improvement and expansion of their applications