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Combining CRISPR–Cas12a with terminal deoxynucleotidyl transferase dependent reporter elongation for pathogen detection using lateral flow test strips

Berghuis, N.F. (author), Mars-Groenendijk, R.H. (author), Busker, R.W. (author), Paauw, A. (author), van Leeuwen, H.C. (author)

CRISPR–Cas (CC)-based detection technologies have some exceptional features, which hold the promise of developing into the nextgeneration diagnostic platforms. One of these features is the ability to trigger non-specific single-stranded DNA/RNA cleavage activity after specific target recognition and Cas enzyme activation. This cleavage activity...

article 2022

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The mechanistic overview of SARS-CoV-2 using angiotensin-converting enzyme 2 to enter the cell for replication Possible treatment options related to the renin-angiotensin system

Offringa, A. (author), Montijn, R. (author), Singh, S. (author), Paul, M. (author), Pinto, Y.M. (author), Pinto-Sietsma, S.J. (author)

The SARS-CoV-2 pandemic is a healthcare crisis caused by insufficient knowledge applicable to effectively combat the virus. Therefore, different scientific discovery strategies need to be connected, to generate a rational treatment which can be made available as rapidly as possible. This relies on a solid theoretical understanding of the...

article 2020

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Genome annotation and antimicrobial properties of Bacillus toyonensis VU-DES13, isolated from the Folsomia candida gut

Agamennone, V. (author), van Straalen, J. (author), Brouwer, A. (author), de Boer, T.E. (author), Hensbergen, P.J. (author), Zaagman, N. (author), Braster, M. (author), van Straalen, N.M. (author), Roelofs, D. (author), Janssens, T.K.S. (author)

Antibiotic resistance necessitates the search for new bioactive compounds with novel mechanisms of action. Natural products derived from bacteria and fungi are widely used in the field of medicine and new environments can be explored as sources of antimicrobials. Bacteria associated with springtails have shown high inhibitory activity against...

article 2019

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Search for natural solutions for controlling pathogenic clostridia

Abeln, E. (author)

TNO is searching for partners for a consortium research project aiming at the identification of novel solutions for controlling pathogenic Clostridia such as Clostridium difficile and C. perfringens. These are a serious threat for human and animal health and a major reason for using antibiotics. Novel solutions preventing disease development...

other 2017

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In vitro phenotypic differentiation towards commensal and pathogenic oral biofilms

Janus, M.M. (author), Keijser, B.J.F. (author), Bikker, F.J. (author), Exterkate, R.A.M. (author), Crielaard, W. (author), Krom, B.P. (author)

Commensal oral biofilms, defined by the absence of pathology-related phenotypes, are ubiquitously present. In contrast to pathological biofilms commensal biofilms are rarely studied. Here, the effect of the initial inoculum and subsequent growth conditions on in vitro oral biofilms was studied. Biofilms were inoculated with saliva and grown...

article 2015

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Differential modulation by Akkermansia muciniphila and faecalibacterium prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse gut organoids

Lukovac, S. (author), Belzer, C. (author), Pellis, L. (author), Keijser, B.J. (author), de Vos, W.M. (author), Montijn, R.C. (author), Roeselers, G. (author)

The gut microbiota is essential for numerous aspects of human health. However, the underlying mechanisms of many host-microbiota interactions remain unclear. The aim of this study was to characterize effects of the microbiota on host epithelium using a novel ex vivo model based on mouse ileal organoids. We have explored the transcriptional...

article 2014

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Arachidonic acid/docosahexaenoic acid-supplemented diet in early life reduces body weight gain, plasma lipids, and adiposity in later life in ApoE*3 Leiden mice

Wielinga, P.Y., (author), Harthoorn, L.F., (author), Verschuren, L., (author), Schoemaker, M.H., (author), Jouni, Z.E., (author), van, Tol, E.A.F. (author), Kleemann, R., (author), Kooistra, T. (author)

Scope: This study addresses whether early life arachidonic acid (ARA)/docosahexaenoic acid (DHA) supplementation or eicosapentaenoic acid (EPA)/DHA (Omacor) supplementation affects body weight gain, lipid metabolism, and adipose tissue quantity and quality in later life in ApoE*3Leiden-transgenic mice, a humanized model for hyperlipidemia and...

article 2012

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A comparison of molecular technologies and genomotyping for tracing and strain characterization of Campylobacter isolates

van der Vossen, J. (author), Keijser, B. (author), Schuren, F. (author), Nocker, A. (author), Montijn, R. (author)

Thermophilic Campylobacter species are the most common cause of gastroenteritis in developed countries. Campylobacter spp. are ubiquitous in nature and widespread in livestock. Infections occur sporadically, and are believed to occur through consumption of contaminated meat products and from environmental sources. DNA-based techniques are...

conference paper 2011

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DMBT1 functions as pattern-recognition molecule for poly-sulfated and poly-phosphorylated ligands

End, C. (author), Bikker, F.J. (author), Renner, M. (author), Bergmann, G. (author), Lyer, S. (author), Blaich, S. (author), Hudler, M. (author), Helmke, B. (author), Gassler, N. (author), Autschbach, F. (author), Ligtenberg, A.J.M. (author), Benner, A. (author), Holmskov, U. (author), Schirmacher, P. (author), Nieuw Amerongen, A.V. (author), Rosenstiel, P. (author), Sina, C. (author), Franke, A. (author), Hafner, M. (author), Kioschis, P. (author), Schreiber, S. (author), Poustka, A. (author), Mollenhauer, J. (author)

Deleted in malignant brain tumors 1 (DMBT1) is a secreted glycoprotein displaying a broad bacterial-binding spectrum. Recent functional and genetic studies linked DMBT1 to the suppression of LPS-induced TLR4-mediated NF-kappaB activation and to the pathogenesis of Crohn's disease. Here, we aimed at unraveling the molecular basis of its function...

article 2009

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Activation of toll-like receptors and dendritic cells by a broad range of bacterial molecules

Boele, L.C.L. (author), Bajramovic, J.J. (author), de Vries, A.M.M.B.C. (author), Voskamp-Visser, I.A.I. (author), Kaman, W.E. (author), van der Kleij, D. (author), TNO Defensie en Veiligheid (author)

Activation of pattern recognition receptors such as Toll-like receptors (TLRs) by pathogens leads to activation and maturation of dendritic cells (DC), which orchestrate the development of the adaptive immune response. To create an overview of the effects of a broad range of pathogenic bacteria, their capacity to activate TLRs and to affect DC...

article 2009

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Safety evaluation of an IPP tripeptide-containing milk protein hydrolysate

Ponstein-Simarro Doorten, A.Y. (author), van de Wiel, J.A.G. (author), Jonker, D. (author), TNO Kwaliteit van Leven (author)

Tensguard™ is a milk protein hydrolysate containing the lactotripeptide IPP. It is derived from cow's milk, which is present in the human diet and has a safe history of consumption. The final Tensguard™ product, a supplement or a functional food ingredient, is intended for use by people who want to follow a healthy diet and lifestyle in order to...

article 2009

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Identification of resistance and virulence factors in an epidemic Enterobacter hormaechei outbreak strain

Paauw, A. (author), Caspers, M.P.M. (author), Leverstein-van Hall, M.A. (author), Schuren, F.H.J. (author), Montijn, R.C. (author), Verhoef, J. (author), Fluit, A.C. (author), TNO Kwaliteit van Leven (author)

Bacterial strains differ in their ability to cause hospital outbreaks. Using comparative genomic hybridization, Enterobacter cloacae complex isolates were studied to identify genetic markers specific for Enterobacter cloacae complex outbreak strains. No outbreak-specific genes were found that were common in all investigated outbreak strains....

article 2009

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Induction of EAE by T cells specific for alpha B-crystallin depends on prior viral infection in the CNS

Verbeek, R. (author), van Dongen, H. (author), Wawrousek, E.F. (author), Amor, S. (author), van Noort, J.M. (author), TNO Kwaliteit van Leven TNO Defensie en Veiligheid (author)

While myelin-reactive T cells are widely believed to play a pathogenic role in multiple sclerosis (MS), no substantial differences appear to exist in T-cell responses to myelin antigens between MS patients and healthy subjects. As an example, indistinguishable peripheral T-cell responses and serum antibody levels have been found in MS patients...

article 2007

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2D and 3D assessment of neuropathology in rat brain after prenatal exposure to methylazoxymethanol, a model for developmental neurotoxicty

de Groot, D.M.G. (author), Hartgring, S. (author), van de Horst, L. (author), Moerkens, M. (author), Otto, M. (author), Bos-Kuijpers, M.H.M. (author), Kaufmann, W.S.H. (author), Lammers, J.H.C.M. (author), O'Callaghan, J.P. (author), Waalkens-Berendsen, I.D.H. (author), Pakkenberg, B. (author), Gundersen, H.G. (author), TNO Kwaliteit van Leven (author)

To evaluate the ability of a tiered quantitative morphological approach to reveal developmental neurotoxicity, morphometric parameters were measured in the offspring of rats treated with methylazoxymethanol (MAM) during days 13-15 of pregnancy. Treatment was aimed at inhibiting the proliferation phase of hippocampal neurons while leaving...

article 2005

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Novel approaches in food microbiology

Montijn, R. (author), Schuren, F. (author), van Spek, H.D. (author), Keijser, B. (author), Brul, S. (author), TNO Voeding (author)

The development of genomics technologies for guiding the predictive modeling of microorganism behavior to make food preservation treatments effective, are discussed. A fully genomewide description of cellular response to environmental conditions lies in the combination of a transcriptome and proteome/metabolome analysis. The predictive models...

article 2004

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Role of bacterial virulence proteins in Agrobacterium-mediated transformation of Aspergillus awamori

Michielse, C.B. (author), Ram, A.F.J. (author), Hooykaas, P.J.J. (author), van den Hondel, C.A.M.J.J. (author), TNO Voeding (author)

The Agrobacterium-mediated transformation of Aspergillus awamori was optimized using defined co-cultivation conditions, which resulted in a reproducible and efficient transformation system. Optimal co-cultivation conditions were used to study the role of Agrobacterium tumefaciens virulence proteins in T-DNA transfer. This study revealed that...

article 2004

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Asthma-like symptoms following intratracheal exposure of guinea pigs to sulfur mustard aerosol: Therapeutic efficacy of exogenous lung surfactant Curosurf and Salbutamol

van Helden, H.P.M. (author), Kuijpers, W.C. (author), Diemel, R.V. (author)

The purpose of the present study was to investigate: (1) the acute effects of sulfur mustard on airway, lung, and surface tension of bronchoalveolar lavage fluid (BALfluid) in guinea pigs following intratracheal (i.t.) exposure to 1LD50 of an aerosolized solution of sulfur mustard in saline, and (2) the therapeutic efficacy of i.t....

article 2004

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Protection of rats against perfluoroisobutene (PFIB)-induced pulmonary edema by Curosurf and N-acetylcysteine

van Helden, H.P.M. (author), van de Meent, D. (author), Oostdijk, J.P. (author), Joosen, M.J.A. (author), van Esch, J.H.M. (author), Hammer, A.H. (author), Diemel, R.V. (author)

Airborne exposure to lung-toxic agents may damage the lung surfactant system and epithelial and endothelial cells, resulting in a life-threatening pulmonary edema that is known to be refractory to treatment. The aim of this study was to investigate in rats (1) the respiratory injury caused by nose-only exposure to perfluoroisobutene (PFIB), and ...

article 2004

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A human flora-associated rat model of the breast-fed infant gut

TNO BIBRA (author), Edwards, C.A. (author), Rumney, C. (author), Davies, M. (author), Parrett, A.M. (author), Dore, J. (author), Martin, F. (author), Schmitt, J. (author), Stahl, B. (author), Norin, E. (author), Midtvedt, T. (author), Rowland, I.R. (author), Heavey, P. (author), Köhler, H. (author), Stocks, B. (author), Schroten, H. (author)

Objectives: Bacterial colonization of the infant gut may have important influences on the development of gastrointestinal, respiratory, and allergic disease. Early diet is a major determinant of the gut microflora. It is very difficult to carry out studies in human infants that can investigate the interaction of diet, flora, and mucosa. In this...

article 2003

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Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with L-lysine

Peschel, A. (author), Jack, R.W. (author), Otto, M. (author), Collins, L.V. (author), Staubitz, P. (author), Nicholson, G. (author), Kalbacher, H. (author), Nieuwenhuizen, W.F. (author), Jung, G. (author), Tarkowski, A. (author), van Kessel, K.P.M. (author), van Strijp, J.A.G. (author)

Defensins, antimicrobial peptides of the innate immune system, protect human mucosal epithelia and skin against microbial infections and are produced in large amounts by neutrophils. The bacterial pathogen Staphylococcus aureus is insensitive to defensins by virtue of an unknown resistance mechanism. We describe a novel staphylococcal gene, mprF...

article 2001