Standard SARS-CoV-2 testing protocols using nasopharyngeal/throat (NP/T) swabs are invasive and require trained medical staff for reliable sampling. In addition, it has been shown that PCR is more sensitive as compared to antigen-based tests. Here we describe the analytical and clinical evaluation of our in-house RNA extraction-free saliva-based molecular assay for the detection of SARS-CoV-2. Analytical sensitivity of the test was equal to the sensitivity obtained in other Dutch diagnostic laboratories that process NP/T swabs. In this study, 955 individuals participated and provided NP/T swabs for routine molecular analysis (with RNA extraction) and saliva for comparison. Our RT-qPCR resulted in a sensitivity of 82,86% and a specificity of 98,94% compared to the gold standard. A false-negative ratio of 1,9% was found. The SARS-CoV-2 detection workflow described here enables easy, economical, and reliable saliva processing, useful for repeated testing of individuals.
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Summary: Xpaths is a collection of algorithms that allow for the prediction of compound-induced molecular mechanisms of action by integrating phenotypic endpoints of different species; and proposes follow-up tests for model organisms to validate these pathway predictions. The Xpaths algorithms are applied to predict developmental and reproductive toxicity (DART) and implemented into an in silico platform, called DARTpaths.
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Despite tremendous efforts, the exact structure of SARS-CoV-2 and related betacoronaviruses remains elusive. SARS-CoV-2 envelope is a key structural component of the virion that encapsulates viral RNA. It is composed of three structural proteins, spike, membrane (M), and envelope, which interact with each other and with the lipids acquired from the host membranes. Here, we developed and applied an integrative multi-scale computational approach to model the envelope structure of SARS-CoV-2 with near atomistic detail, focusing on studying the dynamic nature and molecular interactions of its most abundant, but largely understudied, M protein. The molecular dynamics simulations allowed us to test the envelope stability under different configurations and revealed that the M dimers agglomerated into large, filament-like, macromolecular assemblies with distinct molecular patterns. These results are in good agreement with current experimental data, demonstrating a generic and versatile approach to model the structure of a virus de novo.
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The specific fibrinolytic properties of both high molecular weight (55 kd) and low molecular weight (30 kd) pro-urokinase from a monkey kidney cell culture were evaluated in a plasma clot lysis system and compared with those of human urokinase. The system was composed of a radiolabelled plasma clot immersed in plasma containing the fibrinolytic agent. On unit base, 55 kd pro-urokinase was approximately 1.5 times more effective in lysing the clot than 30 kd pro-urokinase and equally effective as urokinase. In contrast to urokinase, both pro-urokinase forms induced clot lysis without degrading fibrinogen in the surrounding plasma. However, a considerable activation of the fibrinolytic system in the plasma occurred as a large amount of alpha 2-antiplasmin was consumed, indicating that pro-urokinase was not fully fibrin-specific. Quenching antibodies against tissue-type plasminogen activator (t-PA) added to the plasma clot lysis system retarded but did not prevent pro-urokinase-induced clot lysis. This indicated that not only was t-PA in plasma involved in the activation of pro-urokinase (probably via plasmin), but that an additional mechanism also existed.
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The agrifood sector is crucial for achieving global food security and environmental sustainability. In the Netherlands, innovations in food technology and adjacent areas are achieved in attractive projects at Universities of Applied Sciences (UASs) in close interaction with government, industry, other knowledge institutes and society. By providing students central positions in innovative joint efforts that answer to the demands of small and medium sized enterprises, the curricula stay up to date and appealing. Examples of such efforts are the Food Innovation Academy (FIA), the World Horti Centre (WHC) and the Food Innovation Community Amsterdam (FICA). Interdisciplinary projects in these settings help to encourage students to choose for a future in agrifood. Exposure is key to reach the target groups. For that reason, several paths on the roadmap of the human capital agenda have to be taken. We developed inspiring learning materials that appeal to students and teachers in secondary schools. A “Genomics Cookbook” to introduce biological knowledge behind nutrigenomics and a velcro-model called “DNAbAND” to explain principles behind the Polymerase Chain Reaction for food safety applications, are examples. These are ways to increase influx into green colleges and universities, and thereby efflux to the agrifood sector.
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How to encourage students to choose for a future in agrifood? Not like we always did. The labor market shows an increasing shortage. The agrifood sector plays a significant role in achieving global food security and environmental sustainability. Scholars hardly realize what they can contribute to these social, ecologic and economic issues. The sector needs to expand the range of career opportunities in the agriculture-food-nutrition-environment nexus. Most importantly, it means creating incentives that encourage young people to see agrifood as one of the best options for a career choice. We developed inspiring learning materials to achieve awareness in secondary schools in the Netherlands. A Genomics Cookbook with food metaphors to explain biological principles is highly appreciated by both teachers and students. It is a way to increase influx into green colleges and universities, and thereby efflux to the agrifood sector.
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Understanding taste is key for optimizing the palatability of seaweeds and other non-animal-based foods rich in protein. The lingual papillae in the mouth hold taste buds with taste receptors for the five gustatory taste qualities. Each taste bud contains three distinct cell types, of which Type II cells carry various G protein-coupled receptors that can detect sweet, bitter, or umami tastants, while type III cells detect sour, and likely salty stimuli. Upon ligand binding, receptor-linked intracellular heterotrimeric G proteins initiate a cascade of downstream events which activate the afferent nerve fibers for taste perception in the brain. The taste of amino acids depends on the hydrophobicity, size, charge, isoelectric point, chirality of the alpha carbon, and the functional groups on their side chains. The principal umami ingredient monosodium l-glutamate, broadly known as MSG, loses umami taste upon acetylation, esterification, or methylation, but is able to form flat configurations that bind well to the umami taste receptor. Ribonucleotides such as guanosine monophosphate and inosine monophosphate strongly enhance umami taste when l-glutamate is present. Ribonucleotides bind to the outer section of the venus flytrap domain of the receptor dimer and stabilize the closed conformation. Concentrations of glutamate, aspartate, arginate, and other compounds in food products may enhance saltiness and overall flavor. Umami ingredients may help to reduce the consumption of salts and fats in the general population and increase food consumption in the elderly.
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Lichamelijke zwakte is een belangrijk onderdeel van kwetsbaarheid en komt veel voor bij oudere volwassenen. Terwijl vrouwen een hogere prevalentie en een eerder begin van kwetsbaarheid kennen zijn sekseverschillen in de ontwikkeling van lichamelijke zwakte nauwelijks bestudeerd. Daarom hebben we in spieren de veranderingen onderzocht die onderscheid maken tussen fitte en zwakke ouderen voor elk geslacht afzonderlijk. Mannen (n = 28) en vrouwen (n = 26) van 75 jaar en ouder werden gegroepeerd op basis van hun fysieke prestatiecriteria. Er werd gebruik gemaakt van spierbiopten genomen uit de vastus lateralis-spier voor genexpressie- en histologisch onderzoek. Er werden paarsgewijze vergelijkingen gemaakt tussen de sterkste en de zwakste groepen voor elk geslacht afzonderlijk, en potentiële geslachts-specifieke effecten werden beoordeeld. Zwakke vrouwen toonden een hogere expressie van ontstekingsroutes, infiltratie van NOX2-immuuncellen, samen met een hogere VCAM1-expressie. Zwakke mannen werden gekenmerkt door een kleinere diameter van type 2 (snelle) spiervezels en lagere expressie van PRKN. Zwakte-geassocieerde genexpressie-veranderingen in de spieren waren verschillend van veroudering-geassocieerde genexpressie-veranderingen, wat erop wijst dat de pathofysiologie van fysieke zwakte niet noodzakelijkerwijs afhankelijk is van veroudering. We concluderen dat zwakte-geassocieerde veranderingen in de spieren sekse-specifiek zijn. Aanbevolen wordt om bij onderzoek naar kwetsbaarheid rekening te houden met sekseverschillen, omdat deze verschillen een grote impact kunnen hebben over de ontwikkeling van (farmaceutische) interventies tegen kwetsbaarheid.
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Background: Glucocorticoids are potent anti-inflammatory agents used for the treatment of diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease and psoriasis. Unfortunately, usage is limited because of metabolic side-effects, e.g. insulin resistance, glucose intolerance and diabetes. To gain more insight into the mechanisms behind glucocorticoid induced insulin resistance, it is important to understand which genes play a role in the development of insulin resistance and which genes are affected by glucocorticoids. Medline abstracts contain many studies about insulin resistance and the molecular effects of glucocorticoids and thus are a good resource to study these effects. Results: We developed CoPubGene a method to automatically identify gene-disease associations in Medline abstracts. We used this method to create a literature network of genes related to insulin resistance and to evaluate the importance of the genes in this network for glucocorticoid induced metabolic side effects and anti-inflammatory processes. With this approach we found several genes that already are considered markers of GC induced IR, such as phosphoenolpyruvate carboxykinase (PCK) and glucose-6-phosphatase, catalytic subunit (G6PC). In addition, we found genes involved in steroid synthesis that have not yet been recognized as mediators of GC induced IR. Conclusions: With this approach we are able to construct a robust informative literature network of insulin resistance related genes that gave new insights to better understand the mechanisms behind GC induced IR. The method has been set up in a generic way so it can be applied to a wide variety of disease networks. © 2013 Fleuren et al.; licensee BioMed Central Ltd.
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