The regulation of matrix metalloproteinases and their inhibitors

The matrix metalloproteinases (MMP) are a family of 23 enzymes in man. These enzymes were originally described as cleaving extracellular matrix (ECM) substrates with a predominant role in ECM homeostasis, but it is now clear that they have much wider functionality. Control over MMP and/or tissue inhibitor of metalloproteinases (TIMP) activity in vivo occurs at different levels and involves factors such as regulation of gene expression, activation of zymogens and inhibition of active enzymes by specific inhibitors. Whilst these enzymes and inhibitors have clear roles in physiological tissue turnover and homeostasis, if control of their expression or activity is lost, they contribute to a number of pathologies including e.g. cancer, arthritis and cardiovascular disease. The expression of many MMPs and TIMPs is regulated at the level of transcription by a variety of growth factors, cytokines and chemokines, though post-transcriptional pathways may contribute to this regulation in specific cases. The contribution of epigenetic modifications has also been uncovered in recent years. The promoter regions of many of these genes have been, at least partly, characterised including the role of identified single nucleotide polymorphisms. This article aims to review current knowledge across these gene families and use a bioinformatic approach to fill the gaps where no functional data are available

Child and young person development: biological, environmental and interpersonal influences

Chapter from book 'Contemporary issues in childhood: a bio-ecological approach', Eds. Stephen Ward and Zeta Brown

The placement journey: Do year one placement modules support Childhood Studies students��� professional development?

This study investigated changes made to the Childhood Studies placement journey of one post-1992 University in England. The Childhood Studies degree includes ���practitioner options��� that requires students to complete 200���h placement experience, including 50 h in year one. In 2014, the participant university responded to this expectation by developing a year one placement module. The study sought to investigate whether the placement module supported the development of student���s professional identities in the first year of their studies. The study primarily used questionnaires, with a small amount of interviews and focus groups during 2014���2015. It found three key themes that students associated with their year one placement and their professional development. These were the importance of placement, links made from theory to practice and links from practice to theory. Students did however state disparities in their experiences of placement, especially in the range of responsibilities they were given. Students commented generally on the benefits (to their professional development) of relating theory to their year one practice, but noted frustration that there were minimal opportunities to reflect on practice in module assessments. The study contributes to existing literature by questioning how theory to practice and practice to theory links can be made more explicit in year one programmes

AP-1 Proteins Regulate Autophagy in Skeletal Muscle Progenitor Cells

Autophagy has been observed to be a key regulator in myogenesis, maintenance of quiescence in satellite cells (SC) and regenerative capacity of skeletal muscle. Activator protein-1 (AP-1) transcription factors have been proteins of interest in autophagy regulation in various cancers due to the established roles of AP-1 in cellular proliferation, death and survival. However, AP-1 involvement in the regulation autophagy in skeletal muscle progenitor cells has not been extensively assessed. AP-1 protein c-Jun is expressed in paired box gene 7 (Pax7) positive satellite cells. AP-1 proteins c-Jun and JunB regulate autophagy. Changes to c-Jun expression lead to changed autophagosome content in C2C12 cells in both growth conditions and induced autophagy conditions. Additionally, c-Jun knockdown altered autophagosome content in cultures containing Pax7+ and Pax7- cells. AP-1 protein c-Jun appeared to be regulated by mTor. AP-1 proteins act as autophagy regulators dependent on cell type and autophagy induction method

Dissociable Neural Mechanisms Underlying the Modulation of Pain and Anxiety? An fMRI Pilot Study

The down-regulation of pain through beliefs is commonly discussed as a form of emotion regulation. In line with this interpretation, the analgesic effect has been shown to co-occur with reduced anxiety and increased activity in the ventrolateral prefrontal cortex (VLPFC), which is a key region of emotion regulation. This link between pain and anxiety modulation raises the question whether the two effects are rooted in the same neural mechanism. In this pilot fMRI study, we compared the neural basis of the analgesic and anxiolytic effect of two types of threat modulation: a “behavioral control” paradigm, which involves the ability to terminate a noxious stimulus, and a “safety signaling” paradigm, which involves visual cues that signal the threat (or absence of threat) that a subsequent noxious stimulus might be of unusually high intensity. Analgesia was paralleled by VLPFC activity during behavioral control. Safety signaling engaged elements of the descending pain control system, including the rostral anterior cingulate cortex that showed increased functional connectivity with the periaqueductal gray and VLPFC. Anxiety reduction, in contrast, scaled with dorsolateral prefrontal cortex activation during behavioral control but had no distinct neural signature during safety signaling. Our pilot data therefore suggest that analgesic and anxiolytic effects are instantiated in distinguishable neural mechanisms and differ between distinct stress- and pain-modulatory approaches, supporting the recent notion of multiple pathways subserving top-down modulation of the pain experience. Additional studies in larger cohorts are needed to follow up on these preliminary findings

Nutritional status, growth and disease management in children with single and dual diagnosis of type 1 diabetes mellitus and coeliac disease

Background: The consequences of subclinical coeliac disease (CD) in Type 1 diabetes mellitus (T1DM) remain unclear. We looked at growth, anthropometry and disease management in children with dual diagnosis (T1DM + CD) before and after CD diagnosis.<p></p> Methods: Anthropometry, glycated haemoglobin (HbA1c) and IgA tissue transglutaminase (tTg) were collected prior to, and following CD diagnosis in 23 children with T1DM + CD. This group was matched for demographics, T1DM duration, age at CD diagnosis and at T1DM onset with 23 CD and 44 T1DM controls.<p></p> Results: No differences in growth or anthropometry were found between children with T1DM + CD and controls at any time point. Children with T1DM + CD, had higher BMI z-score two years prior to, than at CD diagnosis (p <0.001). BMI z-score change one year prior to CD diagnosis was lower in the T1DM + CD than the T1DM group (p = 0.009). At two years, height velocity and change in BMI z-scores were similar in all groups. No differences were observed in HbA1c between the T1DM + CD and T1DM groups before or after CD diagnosis. More children with T1DM + CD had raised tTg levels one year after CD diagnosis than CD controls (CDx to CDx + 1 yr; T1DM + CD: 100% to 71%, p = 0.180 and CD: 100% to 45%, p < 0.001); by two years there was no difference.<p></p> Conclusions: No major nutrition or growth deficits were observed in children with T1DM + CD. CD diagnosis does not impact on T1DM glycaemic control. CD specific serology was comparable to children with single CD, but those with dual diagnosis may need more time to adjust to gluten free diet

Modelling for the proposed roll-out of the ‘111’ service in Wales: a case study

NHS Direct Wales provides a single point of access where members of the public can telephone and seek medical support and/or advice. The service is provided for all the Health Boards in Wales by a single virtual call centre run from a main location in Swansea with 2 satellite locations. Patients in Wales can also access a local General Practitioner service during the evenings and at weekends, by phoning their Out of Hours service. The introduction of a ‘111’ service is intended to combine these two operations on a pan-Wales basis using the existing NHS Direct Wales call centre and staff, with the existing Health Board Out of Hours ‘hubs’. The merger of the two services is intended to improve the overall performance of both services. This paper focuses on the planned introduction of ‘111’ in Cwm Taf and Hywel Dda University Health Boards. The purpose of the case study was to support the merger of the two telephony systems from both an organisational and service delivery perspective, by developing a Discrete Event Simulation to model the impact on service levels and staffing. In particular, to examine the percentage increase / decrease in the staffing requirements needed under partial or full integration of the two services. The results from the scenario analysis highlight that extra staffing resources would be required in certain groups (nurses and call handlers) whilst savings could be achieved in others, provided that there wasn’t an increase in call volume after implementation of the new service

Men in Childcare: Does it matter to children, what do they say? (Stage 2)

This is a joint research project between London Early Years Foundation and the University of Wolverhampton. We asked How do children perceive male practitioners? How do children characterise their relationship with the male practitioners ? Do children consistently choose staff they like for the activities they do well rather than the associate gender connection. ( For example choosing a woman to play football because she is really good rather than a man)? This research is mainly qualitative and based in a sociocultural perspective. The methods are participatory and are based on praxeological values by involving teachers as research partners. Key findings are: Children need high quality teachers, male and female, who are ‘good at’ activities. Children associate fun activities with the person not the gender (balance) Where males are visible in the setting, seen to be engaging in all activities and, not just as ‘a novelty event’ children did not associate the activity with the gender There can be a tendency in some areas to fall back on gender stereotypes when staff or children faced with activities that are not a favourite or are unpleasant

Review of best management practices for aquatic vegetation control in stormwater ponds, wetlands, and lakes

Auckland Council (AC) is responsible for the development and operation of a stormwater network across the region to avert risks to citizens and the environment. Within this stormwater network, aquatic vegetation (including plants, unicellular and filamentous algae) can have both a positive and negative role in stormwater management and water quality treatment. The situations where management is needed to control aquatic vegetation are not always clear, and an inability to identify effective, feasible and economical control options may constrain management initiatives. AC (Infrastructure and Technical Services, Stormwater) commissioned this technical report to provide information for decision- making on aquatic vegetation management with in stormwater systems that are likely to experience vegetation-related issues. Information was collated from a comprehensive literature review, augmented by knowledge held by the authors. This review identified a wide range of management practices that could be potentially employed. It also demonstrated complexities and uncertainties relating to these options that makes the identification of a best management practice difficult. Hence, the focus of this report was to enable users to screen for potential options, and use reference material provided on each option to confirm the best practice to employ for each situation. The report identifies factors to define whether there is an aquatic vegetation problem (Section 3.0), and emphasises the need for agreed management goals for control (e.g. reduction, mitigation, containment, eradication). Resources to screen which management option(s) to employ are provided (Section 4.0), relating to the target aquatic vegetation, likely applicability of options to the system being managed, indicative cost, and ease of implementation. Initial screening allows users to shortlist potential control options for further reference (Section 5.0). Thirty-five control options are described (Section 5.0) in sufficient detail to consider applicability to individual sites and species. These options are grouped under categories of biological, chemical or physical control. Biological control options involve the use of organisms to predate, infect or control vegetation growth (e.g. classical biological control) or manipulate conditions to control algal growth (e.g. pest fish removal, microbial products). Chemical control options involve the use of pesticides and chemicals (e.g. glyphosate, diquat), or the use of flocculants and nutrient inactivation products that are used to reduce nutrient loading, thereby decreasing algal growth. Physical control options involve removing vegetation or algal biomass (e.g. mechanical or manual harvesting), or setting up barriers to their growth (e.g. shading, bottom lining, sediment capping). Preventative management options are usually the most cost effective, and these are also briefly described (Section 6.0). For example, the use of hygiene or quarantine protocols can reduce weed introductions or spread. Catchment- based practices to reduce sediment and nutrient sources to stormwater are likely to assist in the avoidance of algal and possibly aquatic plant problems. Nutrient removal may be a co-benefit where harvesting of submerged weed biomass is undertaken in stormwater systems. It should also be considered that removal of substantial amounts of submerged vegetation may result in a sudden and difficult-to-reverse s witch to a turbid, phytoplankton dominated state. Another possible solution is the conversion of systems that experience aquatic vegetation issues, to systems that are less likely to experience issues. The focus of this report is on systems that receive significant stormwater inputs, i.e. constructed bodies, including ponds, amenity lakes, wetlands, and highly-modified receiving bodies. However, some information will have application to other natural water bodies

Development and Validation of Spatially Explicit Habitat Models for Cavity-nesting Birds in Fishlake National Forest, Utah

The ability of USDA Forest Service Forest Inventory and analysis (FIA) generated spatial products to increase the predictive accuracy of spatially explicit, macroscale habitat models was examined for nest-site selection by cavity-nesting birds in Fishlake National Forest, Utah. One FIA-derived variable (percent basal area of aspen trees) was significant in the habitat model; however, the incorporation of FIA stand structure information did not increase model accuracy. Cavity-nesting birds respond strongly to nest-tree attributes unable to be modeled spatially for this study. Future modeling efforts should focus on larger taxa (e.g., ungulates) and richness/diversity studies