Multi-modal hydrogel-based platform to deliver and monitor cardiac progenitor/stem cell engraftment

Retention and survival of transplanted cells are major limitations to the efficacy of regenerative medicine, with short-term paracrine signals being the principal mechanism underlying current cell therapies for heart repair. Consequently, even improvements in short-term durability may have a potential impact on cardiac cell grafting. We have developed a multimodal hydrogel-based platform comprised of a poly(ethylene glycol) network cross-linked with bioactive peptides functionalized with Gd(III) in order to monitor the localization and retention of the hydrogel in vivo by magnetic resonance imaging. In this study, we have tailored the material for cardiac applications through the inclusion of a heparin-binding peptide (HBP) sequence in the cross-linker design and formulated the gel to display mechanical properties resembling those of cardiac tissue. Luciferase-expressing cardiac stem cells (CSC-Luc2) encapsulated within these gels maintained their metabolic activity for up to 14 days in vitro. Encapsulation in the HBP hydrogels improved CSC-Luc2 retention in the mouse myocardium and hind limbs at 3 days by 6.5- and 12- fold, respectively. Thus, this novel heparin-binding based, Gd(III)-tagged hydrogel and CSC-Luc2 platform system demonstrates a tailored, in vivo detectable theranostic cell delivery system that can be implemented to monitor and assess the transplanted material and cell retention

CTLA-4 Activation of Phosphatidylinositol 3-Kinase (PI 3-K) and Protein Kinase B (PKB/AKT) Sustains T-Cell Anergy without Cell Death

The balance of T-cell proliferation, anergy and apoptosis is central to immune function. In this regard, co-receptor CTLA-4 is needed for the induction of anergy and tolerance. One central question concerns the mechanism by which CTLA-4 can induce T-cell non-responsiveness without a concurrent induction of antigen induced cell death (AICD). In this study, we show that CTLA-4 activation of the phosphatidylinositol 3-kinase (PI 3-K) and protein kinase B (PKB/AKT) sustains T-cell anergy without cell death. CTLA-4 ligation induced PI 3K activation as evidenced by the phosphorylation of PKB/AKT that in turn inactivated GSK-3. The level of activation was similar to that observed with CD28. CTLA-4 induced PI 3K and AKT activation also led to phosphorylation of the pro-apoptotic factor BAD as well as the up-regulation of BcL-XL. In keeping with this, CD3/CTLA-4 co-ligation prevented apoptosis under the same conditions where T-cell non-responsiveness was induced. This effect was PI 3K and PKB/AKT dependent since inhibition of these enzymes under conditions of anti-CD3/CTLA-4 co-ligation resulted in cell death. Our findings therefore define a mechanism by which CTLA-4 can induce anergy (and possibly peripheral tolerance) by preventing the induction of cell death

Heritability of longevity in Large White and Landrace sows using continuous time and grouped data models

<p>Abstract</p> <p>Background</p> <p>Using conventional measurements of lifetime, it is not possible to differentiate between productive and non-productive days during a sow's lifetime and this can lead to estimated breeding values favoring less productive animals. By rescaling the time axis from continuous to several discrete classes, grouped survival data (discrete survival time) models can be used instead.</p> <p>Methods</p> <p>The productive life length of 12319 Large White and 9833 Landrace sows was analyzed with continuous scale and grouped data models. Random effect of herd*year, fixed effects of interaction between parity and relative number of piglets, age at first farrowing and annual herd size change were included in the analysis. The genetic component was estimated from sire, sire-maternal grandsire, sire-dam, sire-maternal grandsire and animal models, and the heritabilities computed for each model type in both breeds.</p> <p>Results</p> <p>If age at first farrowing was under 43 weeks or above 60 weeks, the risk of culling sows increased. An interaction between parity and relative litter size was observed, expressed by limited culling during first parity and severe risk increase of culling sows having small litters later in life. In the Landrace breed, heritabilities ranged between 0.05 and 0.08 (s.e. 0.014-0.020) for the continuous and between 0.07 and 0.11 (s.e. 0.016-0.023) for the grouped data models, and in the Large White breed, they ranged between 0.08 and 0.14 (s.e. 0.012-0.026) for the continuous and between 0.08 and 0.13 (s.e. 0.012-0.025) for the grouped data models.</p> <p>Conclusions</p> <p>Heritabilities for length of productive life were similar with continuous time and grouped data models in both breeds. Based on these results and because grouped data models better reflect the economical needs in meat animals, we conclude that grouped data models are more appropriate in pig.</p

The feasibility of canine rabies elimination in Africa: dispelling doubts with data

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Canine rabies causes many thousands of human deaths every year in Africa, and continues to increase throughout much of the continent.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology/Principal Findings:&lt;/b&gt; This paper identifies four common reasons given for the lack of effective canine rabies control in Africa: (a) a low priority given for disease control as a result of lack of awareness of the rabies burden; (b) epidemiological constraints such as uncertainties about the required levels of vaccination coverage and the possibility of sustained cycles of infection in wildlife; (c) operational constraints including accessibility of dogs for vaccination and insufficient knowledge of dog population sizes for planning of vaccination campaigns; and (d) limited resources for implementation of rabies surveillance and control. We address each of these issues in turn, presenting data from field studies and modelling approaches used in Tanzania, including burden of disease evaluations, detailed epidemiological studies, operational data from vaccination campaigns in different demographic and ecological settings, and economic analyses of the cost-effectiveness of dog vaccination for human rabies prevention.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions/Significance:&lt;/b&gt; We conclude that there are no insurmountable problems to canine rabies control in most of Africa; that elimination of canine rabies is epidemiologically and practically feasible through mass vaccination of domestic dogs; and that domestic dog vaccination provides a cost-effective approach to the prevention and elimination of human rabies deaths.&lt;/p&gt

Dimensions of professional competences for interventions towards sustainability

This paper investigates sustainability competences through the eyes of professional practitioners in the field of sustainability and presents empirical data that have been created using an action research approach. The design of the study consists of two workshops, in which professional practitioners in interaction with each other and the facilitators are invited to explore and reflect on the specific knowledge, skills, attitudes and behaviours necessary to conduct change processes successfully towards sustainability in a variety of business and professional contexts. The research focuses on the competences associated with these change processes to devise, propose and conduct appropriate interventions that address sustainability issues. Labelled ‘intervention competence’, this ability comprises an interlocking set of knowledge, skills, attitudes and behaviours that include: appreciating the importance of (trying to) reaching decisions or interventions; being able to learn from lived experience of practice and to connect such learning to one’s own scientific knowledge; being able to engage in political-strategic thinking, deliberations and actions, related to different perspectives; the ability for showing goal-oriented, adequate action; adopting and communicating ethical practices during the intervention process; being able to cope with the degree of complexity, and finally being able to translate stakeholder diversity into collectively produced interventions (actions) towards sustainability. Moreover, this competence has to be practised in contexts of competing values, non-technical interests and power relations. The article concludes with recommendations for future research and practice

PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis

PICH is a SNF2 family DNA translocase that binds to ultra-fine DNA bridges (UFBs) in mitosis. Numerous roles for PICH have been proposed from protein depletion experiments, but a consensus has failed to emerge. Here, we report that deletion of PICH in avian cells causes chromosome structural abnormalities, and hypersensitivity to an inhibitor of Topoisomerase II (Topo II), ICRF-193. ICRF-193-treated PICH-/- cells undergo sister chromatid non-disjunction in anaphase, and frequently abort cytokinesis. PICH co-localises with Topo IIα on UFBs and at the ribosomal DNA locus, and the timely resolution of both structures depends on the ATPase activity of PICH. Purified PICH protein strongly stimulates the catalytic activity of Topo II in vitro. Consistent with this, a human PICH-/- cell line exhibits chromosome instability and chromosome condensation and decatenation defects similar to those of ICRF-193-treated cells. We propose that PICH and Topo II cooperate to prevent chromosome missegregation events in mitosis

Can Healthcare Assistant Training (CHAT) improve the relational care of older people? Study protocol for a pilot cluster-randomised controlled trial

Background People aged 75 years and over account for one in four of all hospital admissions. There has been increasing recognition of problems in the care of older people, particularly in hospitals. Evidence suggests that older people judge the care they receive in terms of kindness, empathy, compassion, respectful communication and being seen as a person not just a patient. These are aspects of care to which we refer when we use the term 'relational care'. Healthcare assistants deliver an increasing proportion of direct care to older people, yet their training needs are often overlooked. Methods/design This study will determine the acceptability and feasibility of a cluster randomised controlled trial of 'Older People's Shoes' a two-day training intervention for healthcare assistants caring for older people in hospital. Within this pilot, two-arm, parallel, cluster randomised controlled trial, healthcare assistants within acute hospital wards are randomised to either the two-day training intervention or training as usual. Registered nurses deliver 'Older People's Shoes' over two days, approximately one week apart. It contains three components: experiential learning about ageing, exploration of older people's stories, and customer care. Outcomes will be measured at the level of patient (experience of emotional care and quality of life during their hospital stay), healthcare assistant (empathy and attitudes towards older people), and ward (quality of staff/patient interaction). Semi-structured interviews of a purposive sample of healthcare assistants receiving the intervention, and all trainers delivering the intervention, will be undertaken to gain insights into the experiences of both the intervention and the trial, and its perceived impact on practice. Trial registration The study was registered as an International Standard Randomised Contolled Trial (ISRCTN10385799) on 29 December 2014

The plasticity of Plasmodium falciparum gametocytaemia in relation to age in Burkina Faso

BACKGROUND: Malaria transmission depends on the presence of gametocytes in the peripheral blood. In this study, the age-dependency of gametocytaemia was examined by microscopy and molecular tools. METHODS: A total of 5,383 blood samples from individuals of all ages were collected over six cross sectional surveys in Burkina Faso. One cross-sectional study used quantitative nucleic acid sequence based amplification (QT-NASBA) for parasite quantification (n = 412). The proportion of infections with concurrent gametocytaemia and median proportion of gametocytes among all parasites were calculated. RESULTS: Asexual parasite prevalence and gametocyte prevalence decreased with age. Gametocytes made up 1.8% of the total parasite population detected by microscopy in the youngest age group. This proportion gradually increased to 18.2% in adults (p < 0.001). Similarly, gametocytes made up 0.2% of the total parasite population detected by QT-NASBA in the youngest age group, increasing to 5.7% in adults (p < 0.001). This age pattern in gametocytaemia was also evident in the proportion of gametocyte positive slides without concomitant asexual parasites which increased from 13.4% (17/127) in children to 45.6% (52/114) in adults (OR 1.55, 95% CI 1.38-1.74, p < 0.001). CONCLUSIONS: The findings of this study suggest that although gametocytes are most commonly detected in children, the proportion of asexual parasites that is committed to develop into gametocytes may increase with age. These findings underscore the importance of adults for the human infectious reservoir for malaria

Social stress increases the susceptibility to infection in the ant Harpegnathos saltator

Aggressive interactions between members of a social group represent an important source of social stress with all its negative follow-ups. We used the ponerine ant Harpegnathos saltator to study the effects of frequent aggressive interactions on the resistance to different stressors. In these ants, removal or death of reproducing animals results in a period of social instability within the colony that is characterized by frequent ritualized aggressive interactions leading to the establishment of a new dominance structure. Animals are more susceptible to infections during this period, whereas their resistance against other stressors remained unchanged. This is associated with a shift from glutathione-S-transferase activities towards glutathione peroxidase activities, which increases the antioxidative capacity at the expense of their immune competence