Visceral adipose tissue activated macrophage content and inflammatory adipokine secretion is higher in pre-eclampsia than in healthy pregnancy

Obesity increases preeclampsia risk. Adipose tissue inflammation may contribute to the clinical syndrome of pre-eclampsia. We compared adipose tissue macrophage infiltration and release of pro-inflammatory adipokines in pre-eclampsia and healthy pregnancy. Subcutaneous and visceral adipose tissue biopsies were collected from healthy (n=13) and preeclampsia (n=13) mothers. Basal and lipopolysaccharide stimulated adipocyte TNFα, IL-6, CCL-2 and CRP release was measured. Adipose tissue cell densities of activated (cfms(+)) and total (CD68(+)) macrophages were determined. In pre-eclampsia only, visceral adipose tissue TNFα release was increased after lipopolysaccharide stimulation (57 [76] vs 81 [97] pg/mL/ug DNA, p=0.030). Basal TNFα release was negatively correlated insulin sensitivity of visceral adipocytes (r=-0.61, p=0.030) in pre-eclampsia. Visceral adipocyte IL-6 release was increased after lipopolysaccharide stimulation in pre-eclampsia only (566 [696] vs 852 [914] pg/mL/ugDNA, p=0.019). Visceral adipocyte CCL-2 basal (67 [61] vs 187 [219] pg/mL/ugDNA, p=0.049) and stimulated (46 [46] vs 224 [271] pg/mL/ugDNA, p=0.003) release was greater than in subcutaneous adipocytes in pre-eclampsia only. In pre-eclampsia, median TNF mRNA expression in visceral adipose tissue was higher than controls (1.94 [1.13-4.14] vs 0.8 [0.00-1.27] TNF / PPIA ratio, p=0.006). In visceral adipose tissue, CSF1R (a marker of activated macrophages) mRNA expression (24.8[11.0] vs 51.0[29.9] CSF1R/PPIA ratio, p=0.011) and activated (cfms+) macrophage count (6.7[2.6] vs 15.2[8.8] % cfms+/adipocyte, p=0.031) were higher in pre-eclampsia than in controls. In conclusion, our study demonstrates dysregulation of inflammatory pathways predominantly in visceral adipose tissue in pre-eclampsia. Inflammation of visceral adipose tissue may mediate many of the adverse metabolic effects associated with pre-eclampsia

Effectiveness of long-term (twelve months) nonsurgical weight loss interventions for obese women with polycystic ovary syndrome: a systematic review

Polycystic ovary syndrome (PCOS) affects 2%–26% of women of reproductive age and is often accompanied by obesity. Modest weight loss reduces health risks and ameliorates effects of the syndrome. Weight loss interventions are mainly of short duration and have limited success. A systematic review of the literature was carried out to assess the efficacy of long-term (12 months), nonsurgical weight loss interventions for women with PCOS. Fifteen databases were searched, resulting in eight papers that met the search criteria. Comparison of results and meta-analysis was difficult due to heterogeneity of studies. Behavioral components of interventions were poorly described, and compliance was difficult to ascertain. The results suggested that the inclusion of a lifestyle component improves outcomes, but protocols must be clearly described to maintain study validity and to identify successful behavioral strategies

The Adaptive Subject Pedagogy Model: Empowering Student Teachers of Design & Technology Education to Create their own Pedagogy

Technology Education subjects encompass a diverse range of concepts, ideas and subject content. In our experience, however, student teachers find it challenging to develop the types of evidence-informed pedagogies these necessitate. To be effective in the long term, teacher education must enable students to critically synthesise theory, practice and different forms of knowledge in ways that allow effective subject pedagogy to emerge. Yet this is ambitious. As teacher educators, it requires us to move beyond ideas of simply bridging the theory-practice gap, and away from pedagogical thinking which is led by overly instrumental approaches to lesson planning that can mitigate creativity and omit reasoning. It forces us to think through how we might help students to develop better pedagogical expertise in richer and more considered ways. Here, we present a new andragogical model for teacher education, created as part of the Design & Technology Teacher Education programme at the University of Glasgow, Scotland. The Adaptive Subject Pedagogy Model, or ASPM, is developed from the work of Lee Shulman and draws upon theoretical and empirical understanding from content and pedagogical knowledge for teaching, reflective practice, learning progression and transformation. Rather than viewing pedagogy as generic, the ASPM purposefully promotes curriculum driven pedagogy and does not privilege published evidence over expertise. Specifically, the ASPM asks students to: • Identify an area or topic for learning in the Technologies curriculum and the pupils who would be learning. • Explicitly represent and explain the subject matter in that topic. • Reflect upon their own experience of both teaching and learning the subject matter. • Critically investigate the evidence-base. • Synthesise the understanding gained from these elements to form a pedagogical approach for the topic which students could then draw upon when planning different lessons. The model is being co-developed by staff and students using an iterative and participatory methodology. Empirical data is gathered at key points in the process using focus groups, student evaluations, and the written submissions of students form their use of the ASPM in their own learning. The data reported on here were analysed using thematic networks analysis (Attride-Stirling, 2001: https://doi.org/10.1177/146879410100100307). Findings show that the ASPM has potential in helping students to organise and connect their thinking and, for some students, revealed a deeper level of pedagogical reasoning than was previously seen. For some students, the model enabled them to create pedagogical approaches that were both evidence-informed and unique to them. Overall, students found the model helpful, but intellectually challenging. They appreciated the research element, but some students found it to be more effective if they had the chance to reflect beforehand, and this led to the model being altered. By reflecting first, it meant that some of their personal theories could be challenged or more fully understood. The ASPM required a slower pace of learning to allow for deeper engagement by the students. Those who found it most helpful viewed it as something to inform lesson creation, whilst those who were more doubtful viewed as something for planning lessons

Abridged international perspectives of technology education and its connection to STEM education

STEM (Science, Technology, Engineering, and Mathematics) areas are integral content disciplines in all economies. Although most countries have and continue to ensure quality science (S) and Mathematics (M) education for primary (elementary) and secondary school students, the technology (T) and engineering (E) content areas tend not to be regarded as core to national curricula in the same way that science and mathematics are regarded as essential. This article discusses efforts in various countries to better promote and integrate Technology and Engineering Education (TEE) in schools. This paper highlights common themes and argues that we can learn from each other’s efforts in TEE. We argue that dialogue across nations can help us to build international STEM education collaboration networks, better understand the nature of STEM and how to better engage pupils and students in STEM subjects, and work towards gaining inputs to national TEE policy that can leverage positive change

Trafficking and processing of bacterial proteins by mammalian cells: Insights from chondroitinase ABC.

BACKGROUND: There is very little reported in the literature about the relationship between modifications of bacterial proteins and their secretion by mammalian cells that synthesize them. We previously reported that the secretion of the bacterial enzyme Chondroitinase ABC by mammalian cells requires the strategic removal of at least three N-glycosylation sites. The aim of this study was to determine if it is possible to enhance the efficacy of the enzyme as a treatment for spinal cord injury by increasing the quantity of enzyme secreted or by altering its cellular location. METHODOLOGY/PRINCIPAL FINDINGS: To determine if the efficiency of enzyme secretion could be further increased, cells were transfected with constructs encoding the gene for chondroitinase ABC modified for expression by mammalian cells; these contained additional modifications of strategic N-glycosylation sites or alternative signal sequences to direct secretion of the enzyme from the cells. We show that while removal of certain specific N-glycosylation sites enhances enzyme secretion, N-glycosylation of at least two other sites, N-856 and N-773, is essential for both production and secretion of active enzyme. Furthermore, we find that the signal sequence directing secretion also influences the quantity of enzyme secreted, and that this varies widely amongst the cell types tested. Last, we find that replacing the 3'UTR on the cDNA encoding Chondroitinase ABC with that of β-actin is sufficient to target the enzyme to the neuronal growth cone when transfected into neurons. This also enhances neurite outgrowth on an inhibitory substrate. CONCLUSION/SIGNIFICANCE: Some intracellular trafficking pathways are adversely affected by cryptic signals present in the bacterial gene sequence, whilst unexpectedly others are required for efficient secretion of the enzyme. Furthermore, targeting chondroitinase to the neuronal growth cone promotes its ability to increase neurite outgrowth on an inhibitory substrate. These findings are timely in view of the renewed prospects for gene therapy, and of direct relevance to strategies aimed at expressing foreign proteins in mammalian cells, in particular bacterial proteins

The dual endothelin converting enzyme/neutral endopeptidase inhibitor SLV-306 (daglutril), inhibits systemic conversion of big endothelin-1 in humans

Aims - Inhibition of neutral endopeptidases (NEP) results in a beneficial increase in plasma concentrations of natriuretic peptides such as ANP. However NEP inhibitors were ineffective anti-hypertensives, probably because NEP also degrades vasoconstrictor peptides, including endothelin-1 (ET-1). Dual NEP and endothelin converting enzyme (ECE) inhibition may be more useful. The aim of the study was to determine whether SLV-306 (daglutril), a combined ECE/NEP inhibitor, reduced the systemic conversion of big ET-1 to the mature peptide. Secondly, to determine whether plasma ANP levels were increased. Main methods - Following oral administration of three increasing doses of SLV-306 (to reach an average target concentration of 75, 300, 1200 ng ml− 1 of the active metabolite KC-12615), in a randomised, double blinded regime, big ET-1 was infused into thirteen healthy male volunteers. Big ET-1 was administered at a rate of 8 and 12 pmol kg− 1 min− 1 (20 min each). Plasma samples were collected pre, during and post big ET-1 infusion. ET-1, C-terminal fragment (CTF), big ET-1, and atrial natriuretic peptide (ANP) were measured. Key findings - At the two highest concentrations tested, SLV-306 dose dependently attenuated the rise in blood pressure after big ET-1 infusion. There was a significant increase in circulating big ET-1 levels, compared with placebo, indicating that SLV-306 was inhibiting an increasing proportion of endogenous ECE activity. Plasma ANP concentrations also significantly increased, consistent with systemic NEP inhibition. Significance - SLV-306 leads to inhibition of both NEP and ECE in humans. Simultaneous augmentation of ANP and inhibition of ET-1 production is of potential therapeutic benefit in cardiovascular disease

Protrudin functions from the endoplasmic reticulum to support axon regeneration in the adult CNS

Funder: Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation); doi: https://doi.org/10.13039/100000865Funder: Christopher and Dana Reeve Foundation (Christopher & Dana Reeve Foundation); doi: https://doi.org/10.13039/100001305Funder: International Foundation for Research in Paraplegia (Internationale Stiftung für Forschung in Paraplegie); doi: https://doi.org/10.13039/501100001708Funder: Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.); doi: https://doi.org/10.13039/100000009Funder: Christopher and Dana Reeve Foundation (Christopher & Dana Reeve Foundation)Abstract: Adult mammalian central nervous system axons have intrinsically poor regenerative capacity, so axonal injury has permanent consequences. One approach to enhancing regeneration is to increase the axonal supply of growth molecules and organelles. We achieved this by expressing the adaptor molecule Protrudin which is normally found at low levels in non-regenerative neurons. Elevated Protrudin expression enabled robust central nervous system regeneration both in vitro in primary cortical neurons and in vivo in the injured adult optic nerve. Protrudin overexpression facilitated the accumulation of endoplasmic reticulum, integrins and Rab11 endosomes in the distal axon, whilst removing Protrudin’s endoplasmic reticulum localization, kinesin-binding or phosphoinositide-binding properties abrogated the regenerative effects. These results demonstrate that Protrudin promotes regeneration by functioning as a scaffold to link axonal organelles, motors and membranes, establishing important roles for these cellular components in mediating regeneration in the adult central nervous system

Preserving the Royalty-Free Standards Ecosystem

It has long been recognized in Europe and elsewhere that standards-development organizations (SDOs) may adopt policies that require their participants to license patents essential to the SDO’s standards (standards-essential patents or SEPs) to manufacturers of standardized products (“implementers”) on a royalty-free (RF) basis.1 This requirement contrasts with SDO policies that permit SEP holders to charge implementers monetary patent royalties, sometimes on terms that are specified as “fair, reasonable and nondiscriminatory” (FRAND). As demonstrated by two decades of intensive litigation around the world, FRAND royalties have given rise to intractable disputes regarding the manner in which such royalties should be calculated and adjudicated. In contrast, standards distributed on an RF basis are comparatively free from litigation and the attendant transaction costs.2 Accordingly, numerous SDOs around the world have adopted RF licensing policies and many widely adopted standards, including Bluetooth, USB, IPv6, HTTP, HTML and XML, are distributed on an RF basis. This note briefly discusses the commercial considerations surrounding RF standards, the relationship between RF standards and open source software (OSS) and the SDO policy mechanisms – including “universal reciprocity” -- that enable RF licensing to succeed in the marketplace

Camau i'r Dyfodol: Curriculum for Wales: evolving understandings of progression in learning

This project is a collaboration between the University of Wales Trinity Saint David (UWTSD) and the University of Glasgow (UofG), funded by the Welsh Government, and working with education professionals in Wales to further support curriculum reform. The Phase 1 report explores understandings of progression and co-construction in the system and reviews published evidence to develop future phases of the project. Various research methods involving education professionals in Wales were used, providing key findings and insights about where education professionals are in the change process, and the challenges and opportunities associated with realisation of the new Curriculum for Wales. The report develops the project’s approach to co-construction and reviews evidence about the relationships between curriculum, assessment, pedagogy, and progression. The key findings of the Phase 1 report include a desire among educational partners for a shared understanding of progression in learning, challenges to co-construction activities, and questions about how to change towards a learner-focused assessment culture. Additionally, the report suggests that progression in Curriculum for Wales is a broader concept than the learning progressions found in most of the research literature, and that it is unclear whether there is consistency in understandings of the new curriculum across the system. The report’s findings, including understandings developed from the literature and the challenges, approaches, and implications identified, were integral to establishing co-construction activity in Phase 2 of the project. Key findings and considerations were also made for the wider system. As the Camau i’r Dyfodol project moves forward, it is committed to ongoing co-construction with educational partners to support the development of practical understanding of progression in learning as part of Wales’ ambitious curricular reform. This collaborative approach will help to ensure that the curriculum is continuously evolving and improving, in response to the changing needs and demands of learners