387 research outputs found
Interactions between renal vascular resistance and endothelium-derived hyperpolarization in hypertensive rats in vivo:Renal endothelial hyperpolarization in hypertension
Innovative Education in Agroecology: Experiential Learning for a Sustainable Agriculture
The transdisciplinary field of agroecology provides a platform for experiential learning based on an expanded vision of research on sustainable farming and food systems and the application of results in creating effective learning landscapes for students. With increased recognition of limitations of fossil fuels, fresh water, and available farmland, educators are changing focus from strategies to reach maximum yields to those that feature resource use efficiency and resilience of production systems in a less benign climate. To help students deal with complexity and uncertainty and a wide range of biological and social dimensions of the food challenge, a whole-systems approach that involves life-cycle analysis and consideration of long-term impacts of systems is essential. Seven educational case studies in the Nordic Region and the U.S. Midwest demonstrate how educators can incorporate theory of the ecology of food systems with the action learning component needed to develop student potentials to create responsible change in society. New roles of agroecology instructors and students are described as they pursue a co-learning strategy to develop and apply technology to assure the productivity and security of future food system
Accumulation of Self-Reactive Naive and Memory B Cell Reveals Sequential Defects in B Cell Tolerance Checkpoints in Sjogren's Syndrome
This work was funded by grants number 18237 and 20089 from Arthritis Research UK (http://www.arthritisresearchuk.org) to MB and the William Harvey Research Foundation. EC was recipient of short-term travel fellowships from EMBO (ASTF 318-2010) and EFIS-IL
Eliminating viral hepatitis C in Belgium: the micro-elimination approach
Background: Hepatitis C virus is one of the leading causes of chronic liver disease and liver-related deaths worldwide. The estimated prevalence of chronic hepatitis C viral infection among the general Belgian population was 0.57% (n = 64,000) in 2015. Although Belgium has had a ‘Hepatitis C Plan’ since 2014, elimination efforts are unclear. This study employs the best available data and modelling estimates to define the burden of hepatitis C viral infection among key subgroups in Belgium, identify information gaps and propose potential approaches to screening, linkage to care and treatment, and cure.
Methods: We examined the peer-reviewed and grey literature since 2012 for data on the prevalence of hepatitis C viral infection in Belgium in key subgroups identified by national experts and in the literature. Ultimately, this research is primarily based on data provided by the key stakeholders themselves due to a lack of reliable data in the literature. Based on this, we modelled the treatment rates required to reach elimination of hepatitis C in several subgroups.
Results: Eleven potential subgroups were identified. There were no data available for two subgroups: generational cohorts and men who have sex with men. In six subgroups, fewer than 3000 people were reported or estimated to have hepatitis C infection. Migrants and people who inject drugs were the most affected subgroups, and children were the least affected subgroup. Only two subgroups are on target to achieve elimination by 2030: patients living with haemophilia and transplant recipients.
Conclusions: Removing Belgian treatment reimbursement restrictions in January 2019 was a big step towards eliminating HCV. In addition, increasing surveillance, including with a national registry, treatment prescription by other health-care providers and availability of treatment in local pharmacies are central to improving the current situation and getting on track to reach the 2030 WHO hepatitis C elimination targets in Belgium
Galectin-1-Binding Glycoforms of Haptoglobin with Altered Intracellular Trafficking, and Increase in Metastatic Breast Cancer Patients
Sera from 25 metastatic breast cancer patients and 25 healthy controls were subjected to affinity chromatography using immobilized galectin-1. Serum from the healthy subjects contained on average 1.2 mg per ml (range 0.7–2.2) galectin-1 binding glycoproteins, whereas serum from the breast cancer patients contained on average 2.2 mg/ml (range 0.8–3.9), with a higher average for large primary tumours. The major bound glycoproteins were α-2-macroglobulin, IgM and haptoglobin. Both the IgM and haptoglobin concentrations were similar in cancer compared to control sera, but the percentage bound to galectin-1 was lower for IgM and higher for haptoglobin: about 50% (range 20–80) in cancer sera and about 30% (range 25–50) in healthy sera. Galectin-1 binding and non-binding fractions were separated by affinity chromatography from pooled haptoglobin from healthy sera. The N-glycans of each fraction were analyzed by mass spectrometry, and the structural differences and galectin-1 mutants were used to identify possible galectin-1 binding sites. Galectin-1 binding and non-binding fractions were also analyzed regarding their haptoglobin function. Both were similar in forming complex with haemoglobin and mediate its uptake into alternatively activated macrophages. However, after uptake there was a dramatic difference in intracellular targeting, with the galectin-1 non-binding fraction going to a LAMP-2 positive compartment (lysosomes), while the galectin-1 binding fraction went to larger galectin-1 positive granules. In conclusion, galectin-1 detects a new type of functional biomarker for cancer: a specific type of glycoform of haptoglobin, and possibly other serum glycoproteins, with a different function after uptake into tissue cells
Enrichment of antioxidant capacity and vitamin E in pita made from barley
This study aimed to enhance total antioxidant and vitamin E content of pita bread, by replacing 50% of the standard baker's flour with flours milled from covered (WI2585 and Harrington) or hulless (Finniss) barley genotypes, previously shown to have high antioxidant and vitamin E levels at harvest. Pita breads were made from either 100% baker's flour (control) or 50% malt flour, whole-grain flour, or flour from barley grains pearled at 10%, 15%, and 20% grain weight. Antioxidant capacity and vitamin E content of flours and pitas were determined by their ability to scavenge 2,2-diphenyl-1-picrylhydrazyl radicals and high performance liquid chromatography, respectively. The physical and sensory properties of the pitas were also assessed. All pitas made from either whole grain or pearled barley flour had a higher antioxidant capacity and most also had higher vitamin E content than standard pita. The antioxidant and vitamin E levels were reduced in pearled compared to whole grains, however the extent of that reduction varied among genotypes. The greatest antioxidant and vitamin E levels were found in pita made from malt flour or Finniss whole grain flour. Furthermore, sensory analysis suggested these pitas were acceptable to consumers and retained similar physical and sensory properties to those in the control pita.Thi Thu Dung Do, Beverly Muhlhausler, Amanda Box and Amanda J. Abl
C9orf72 ALS/FTD dipeptide repeat protein levels are reduced by small molecules that inhibit PKA or enhance protein degradation
Intronic GGGGCC (G4C2) hexanucleotide repeat expansion within the human C9orf72 gene represents the most common cause of familial forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9ALS/FTD). Repeat-associated non-AUG (RAN) translation of repeat-containing C9orf72 RNA results in the production of neurotoxic dipeptide-repeat proteins (DPRs). Here, we developed a high-throughput drug screen for the identification of positive and negative modulators of DPR levels. We found that HSP90 inhibitor geldanamycin and aldosterone antagonist spironolactone reduced DPR levels by promoting protein degradation via the proteasome and autophagy pathways respectively. Surprisingly, cAMP-elevating compounds boosting protein kinase A (PKA) activity increased DPR levels. Inhibition of PKA activity, by both pharmacological and genetic approaches, reduced DPR levels in cells and rescued pathological phenotypes in a Drosophila model of C9ALS/FTD. Moreover, knockdown of PKA-catalytic subunits correlated with reduced translation efficiency of DPRs, while the PKA inhibitor H89 reduced endogenous DPR levels in C9ALS/FTD patient-derived iPSC motor neurons. Together, our results suggest new and druggable pathways modulating DPR levels in C9ALS/FTD
The benefits of collaboration:The Nordic Arthroplasty Register Association
â–¡ The Nordic Arthroplasty Register Association (NARA) was established in 2007 by arthroplasty register representatives from Sweden, Norway and Denmark with the overall aim to improve the quality of research and thereby enhance the possibility for quality improvement with arthroplasty surgery. Finland joined the NARA collaboration in 2010. â–¡ NARA minimal hip, knee and shoulder datasets were created with variables that all countries can deliver. They are dynamic datasets, currently with 25 variables for hip arthroplasty, 20 for knee arthroplasty and 20 for shoulder arthroplasty. â–¡ NARA has published statistical guidelines for the analysis of arthroplasty register data. The association is continuously working on the improvement of statistical methods and the application of new ones. â–¡ There are 31 published peer-reviewed papers based on the NARA databases and 20 ongoing projects in different phases. Several NARA publications have significantly affected clinical practice. For example, metal-on-metal total hip arthroplasty and resurfacing arthroplasty have been abandoned due to increased revision risk based on i.a. NARA reports. Further, the use of uncemented total hip arthroplasty in elderly patients has decreased significantly, especially in Finland, based on the NARA data. â–¡ The NARA collaboration has been successful because the countries were able to agree on a common dataset and variable definitions. The collaboration was also successful because the group was able to initiate a number of research projects and provide answers to clinically relevant questions. A number of specific goals, set up in 2007, have been achieved and new one has emerged in the process
The Nordic Arthroplasty Register Association: A unique collaboration between 3 national hip arthroplasty registries with 280,201 THRs
Background and purpose The possibility of comparing results and of pooling the data has been limited for the Nordic arthroplasty registries, because of different registration systems and questionnaires. We have established a common Nordic database, in order to compare demographics and the results of total hip replacement surgery between countries. In addition, we plan to study results in patient groups in which the numbers are too small to be studied in the individual countries
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