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Perceptions of non-Western immigrant women on having breast cancer and their experiences with treatment-related changes in body weight and lifestyle : A qualitative study
Kruif, Anja J.Th.C.M. de; Chrifou, Rabab ; Langeslag, Ghislaine L. ; Sondaal, Annemijn E.C. ; Franssen, Margret M.M. ; Kampman, Ellen ; Winkels, Renate M. ; Boer, Michiel R. de; Visser, Marjolein ; Westerman, Marjan J. - \ 2020
PLoS ONE 15 (2020)7. - ISSN 1932-6203 - p. e0235662 - e0235662.
BACKGROUND: The number of non-Western immigrants with breast cancer in the Netherlands has increased over the past decades and is expected to triple by 2030. Due to insufficient representation in clinical studies, it is unclear what the specific experiences and needs of these women are. Understanding how culture and religion affect these women's experience of breast cancer and how they deal with chemotherapy and treatment-related changes in body weight and lifestyle is crucial for health care professionals to be able to provide effective support. METHODS: A qualitative study was conducted using semi-structured interviews with 28 immigrant women with a history of breast cancer treated with chemotherapy. RESULTS: Women often associated breast cancer with taboo, death or bad luck. Religion offered these women guidance, strength and meaning to the disease, but also limited the women to openly talk about their disease. Women perceived lifestyle factors to have little influence on the development and treatment of cancer. After treatment, however, their thinking changed and these lifestyle factors became of paramount importance to them. They realised that they missed out on information about managing their own diet, exercise and body weight and were eager to share their experiences with other women in their culture with newly diagnosed breast cancer. CONCLUSION: Women became aware during and after breast cancer treatment that it was difficult for them to actively deal with their illness under the influence of their culture and religion. Based on their own experiences and acquired knowledge, they would like to give advice to newly diagnosed women on how to deal with breast cancer within their own culture and religion. Their recommendations could be used by mosques, churches, support groups and health care professionals, to ensure interventions during breast cancer treatment meet their religious and cultural needs and thus improve their quality of life.
Laser Ablation Electrospray Ionization Hydrogen/Deuterium Exchange Ambient Mass Spectrometry Imaging
Geenen, Fred A.M.G. van; Claassen, Frank W. ; Franssen, Maurice C.R. ; Zuilhof, Han ; Nielen, Michel W.F. - \ 2020
Journal of the American Society for Mass Spectrometry 31 (2020)2. - ISSN 1044-0305 - p. 249 - 256.
ambient mass spectrometry - hydrogen deuterium exchange - laser ablation electrospray ionization - mass spectrometry imaging - structure elucidation
Identification and confirmation of known as well as unknown (bio)chemical entities in ambient mass spectrometry (MS) and MS imaging (MSI) mostly involve accurate mass determination, often in combination with MS/MS or MSn work flows. To further improve structural assignment, additional molecular information is required. Here we present an ambient hydrogen/deuterium exchange (HDX) laser ablation electrospray ionization (LAESI) MS method in which, apart from the accurate mass and MS/MS data, the number of exchangeable protons in (un)known molecules is obtained. While eventually presenting ambient HDX-LAESI-MSI, samples were not preincubated with deuterated solvents, but instead HDX occurred following fusion of ablated sample material with microdroplets generated by ESI of deuterated solvents. Therefore, the degree of HDX was first studied following ablation of nondeuterated sample solutions of melamine and monosaccharides. From these experiments, it was concluded that the set-up used could provide meaningful HDX data in support of molecular structure elucidation by significantly reducing the number of structure options from a measured elemental composition. This reduction was demonstrated with an unknown accurate m/z value obtained in the analysis of an orange slice, reducing the possible number of molecular structures having the same elemental composition by 87% due to the number of H/D exchanges observed. Next, deuterated and nondeuterated MS/MS experiments showed the number of exchangeable protons in the substructures from deuterated neutral losses in the product ion spectra, confirming the compound to be arginine. Finally, the potential of ambient HDX-LAESI-MSI was demonstrated by the imaging of (secondary) plant metabolites in a Phalaenopsis petal.
Flavoenzyme-mediated regioselective aromatic hydroxylation with coenzyme biomimetics
Guarneri, Alice ; Westphal, Adrie ; Leertouwer, J. ; Lunsonga, J. ; Franssen, M.C.R. ; Opperman, D.J. ; Hollmann, F. ; Berkel, W.J.H. van; Paul, C.E. - \ 2020
ChemCatChem 12 (2020)5. - ISSN 1867-3880 - p. 1368 - 1375.
Regioselective aromatic hydroxylation is desirable for the production of valuable compounds. External flavin‐containing monooxygenases activate and selectively incorporate an oxygen atom in phenolic compounds through flavin reduction by the nicotinamide adenine dinucleotide coenzyme and subsequent reaction with molecular oxygen. This study provides the proof of principle of flavoenzyme‐catalyzed selective aromatic hydroxylation with coenzyme biomimetics. The carbamoylmethyl‐substituted biomimetic in particular affords full conversion in less than two hours for the selective hydroxylation of 5 mM 3‐ and 4‐hydroxybenzoates, displaying similar rates as with NADH, achieving a 10 mM/h enzymatic conversion of the medicinal product gentisate. This biomimetic appears to generate less uncoupling of hydroxylation that typically leads to undesired hydrogen peroxide. Therefore, we show these flavoenzymes have the potential to be applied in combination with biomimetics.
The Medicago truncatula nodule identity gene MtNOOT1 is required for coordinated apical-basal development of the root
Shen, Defeng ; Kulikova, Olga ; Guhl, Kerstin ; Franssen, Henk ; Kohlen, Wouter ; Bisseling, Ton ; Geurts, René - \ 2019
BMC Plant Biology 19 (2019)1. - ISSN 1471-2229
Medicago truncatula - NBCL - NIN - NOOT-BOP-COCHLEATA-LIKE - NOOT1 - Rhizobium susceptible zone - Xylem cell differentiation
Background: Legumes can utilize atmospheric nitrogen by hosting nitrogen-fixing bacteria in special lateral root organs, called nodules. Legume nodules have a unique ontology, despite similarities in the gene networks controlling nodule and lateral root development. It has been shown that Medicago truncatula NODULE ROOT1 (MtNOOT1) is required for the maintenance of nodule identity, preventing the conversion to lateral root development. MtNOOT1 and its orthologs in other plant species -collectively called the NOOT-BOP-COCH-LIKE (NBCL) family- specify boundary formation in various aerial organs. However, MtNOOT1 is not only expressed in nodules and aerial organs, but also in developing roots, where its function remains elusive. Results: We show that Mtnoot1 mutant seedlings display accelerated root elongation due to an enlarged root apical meristem. Also, Mtnoot1 mutant roots are thinner than wild-type and are delayed in xylem cell differentiation. We provide molecular evidence that the affected spatial development of Mtnoot1 mutant roots correlates with delayed induction of genes involved in xylem cell differentiation. This coincides with a basipetal shift of the root zone that is susceptible to rhizobium-secreted symbiotic signal molecules. Conclusions: Our data show that MtNOOT1 regulates the size of the root apical meristem and vascular differentiation. Our data demonstrate that MtNOOT1 not only functions as a homeotic gene in nodule development but also coordinates the spatial development of the root.
Tryptophan intake and tryptophan losses in hemodialysis patients : A balance study
Post, Adrian ; Huberts, Marleen ; Poppe, Enya ; Faassen, Martijn van; Kema, Ido P. ; Vogels, Steffie ; Geleijnse, Johanna M. ; Westerhuis, Ralf ; Ipema, Karin J.R. ; Bakker, Stephan J.L. ; Franssen, Casper F.M. - \ 2019
Nutrients 11 (2019)12. - ISSN 2072-6643
Dialysis - Dietary diaries - Excretion - Hydroxyindoleacetic acid - Kynurenine - Tryptophan
Tryptophan depletion is common in hemodialysis patients. The cause of this depletion remains largely unknown, but reduced nutritional tryptophan intake, losses during dialysis or an increased catabolism due to an inflammatory state are likely contributors. Currently, little is known about tryptophan homeostasis in hemodialysis patients. We assessed dietary tryptophan intake, measured plasma tryptophan during dialysis, and measured the combined urinary and dialysate excretion of tryptophan in 40 hemodialysis patients (66 ± 15 years and 68% male). Patients had low tryptophan concentrations (27 ± 9 µmol/L) before dialysis. Mean dietary tryptophan intake was 4454 ± 1149 µmol/24 h. Mean urinary tryptophan excretion was 15.0 ± 12.3 µmol/24 h, dialysate excretion was 209 ± 67 µmol/24 h and combined excretion was 219 ± 66 µmol/24 h, indicating only 5% of dietary tryptophan intake was excreted. No associations were found between plasma tryptophan concentration and tryptophan intake, plasma kynurenine/tryptophan ratio or inflammatory markers. During dialysis, mean plasma tryptophan concentration increased 16% to 31 ± 8 µmol/L. Intradialytic increase in plasma tryptophan was associated with a lower risk of mortality, independent of age, sex and dialysis vintage (HR: 0.87 [0.76–0.99]; P = 0.04). Tryptophan intake was well above the dietary recommendations and, although tryptophan was removed during dialysis, mean plasma tryptophan increased during dialysis. The cause of this phenomenon is unknown, but it appears to be protective.
Parasite load and site-specific parasite pressure as determinants of immune indices in two sympatric rodent species
Hofmeester, Tim R. ; Bügel, Esther J. ; Hendrikx, Bob ; Maas, Miriam ; Franssen, Frits F.J. ; Sprong, Hein ; Matson, Kevin D. - \ 2019
Animals 9 (2019)12. - ISSN 2076-2615
Ecological immunology - Haptoglobin - Immune strategy - Natural antibodies - Neutrophil to lymphocyte ratio - Parasitology - Rodents - Vector-borne pathogens - Zoonosis
Wildlife is exposed to parasites from the environment. This parasite pressure, which differs among areas, likely shapes the immunological strategies of animals. Individuals differ in the number of parasites they encounter and host, and this parasite load also influences the immune system. The relative impact of parasite pressure vs. parasite load on different host species, particularly those implicated as important reservoirs of zoonotic pathogens, is poorly understood. We captured bank voles (Myodes glareolus) and wood mice (Apodemus sylvaticus) at four sites in the Netherlands. We sampled sub-adult males to quantify their immune function, infestation load for ecto-and gastrointestinal parasites, and infection status for vector-borne microparasites. We then used regression trees to test if variation in immune indices could be explained by among-site differences (parasite pressure), among-individual differences in infestation intensity and infection status (parasite load), or other intrinsic factors. Regression trees revealed splits among sites for haptoglobin, hemagglutination, and body-mass corrected spleen size. We also found splits based on infection/infestation for haptoglobin, hemolysis, and neutrophil to lymphocyte ratio. Furthermore, we found a split between species for hemolysis and splits based on body mass for haptoglobin, hemagglutination, hematocrit, and body-mass corrected spleen size. Our results suggest that both parasite pressure and parasite load influence the immune system of wild rodents. Additional studies linking disease ecology and ecological immunology are needed to understand better the complexities of host–parasite interactions and how these interactions shape zoonotic disease risk.
Ambient laser ablation electrospray ionization mass spectrometry imaging
Geenen, Freddie A.M.G. van - \ 2019
Wageningen University. Promotor(en): M.W.F. Nielen; H. Zuilhof, co-promotor(en): M.C.R. Franssen. - Wageningen : Wageningen University - ISBN 9789463439220 - 164
Several molecular imaging techniques are available to study and understand biological objects, like positron-emission tomography, fluorescence, and magnetic resonance imaging. These techniques often require chemical probes and image in a targeted approach. As many biological questions can only be answered in a systems approach, molecular imaging methods that can simultaneously measure many molecules are desired. Mass spectrometry imaging (MSI) is capable of measuring many molecules simultaneously without the use of chemical probes. MSI experiments often require sample stage vacuum conditions and extensive sample pretreatment such as matrix application. Vacuum conditions can disrupt or damage biological samples, and sample pretreatment prevents real-time analyses and can cause analyte losses, analyte delocalization and denaturation of proteins. Ambient ionization was introduced to measure samples under ambient conditions without any sample pretreatment, and ambient MSI followed rapidly after that. A next generation of ambient MSI techniques is desired to improve its sensitivity, molecular mass range, and spatial resolution. This work aims to improve the capabilities and broaden the scope of laser ablation electrospray ionization (LAESI) MSI.
In order to broaden the scope and increase the understanding of ambient LAESI-MS(I), polymer materials and synthetic fibers were investigated. The direct analysis of synthetic fibers under ambient conditions is highly desired to identify the polymer, the finishes applied and irregularities that may compromise its performance and value. In Chapter 2 LAESI ion mobility MS was used for the analysis of synthetic polymers and fibers. The key to this analysis was the absorption of laser light by aliphatic and aromatic nitrogen functionalities in the polymers. Analysis of polyamide (PA) 6, 46, 66, and 12 pellets and PA 6, 66, polyaramid and M5 fibers yielded characteristic fragment ions, enabling their unambiguous identification. Synthetic fibers are, in addition, commonly covered with a surface layer for improved adhesion and processing. The same setup, but operated in a transient infrared matrix-assisted laser desorption electrospray ionization mode, allowed the detailed characterization of the fiber finish layer and the underlying polymer. Differences in finish layer distribution may cause variations in local properties of synthetic fibers. In Chapter 2, also the feasibility of mass spectrometry imaging (MSI) of the distribution of a finish layer on the synthetic fiber and the successful detection of local surface defects was shown.
Reactions in confined compartments like charged microdroplets are of increasing interest, notably because of their substantially increased reaction rates. When combined with ambient MS, reactions in charged microdroplets can be used to improve the detection of analytes or to study the molecular details of the reactions in real time. In Chapter 3, we introduce a reactive LAESI time-resolved MS method to perform and study reactions in charged microdroplets. This approach was demonstrated with so-called click chemistry reactions between substituted tetrazines and a strained alkyne or alkene. Click reactions are high-yielding reactions with a high atom efficiency. Although click reactions are typically at least moderately fast, in a reactive LAESI approach a substantial increase of reaction time is Summary 149 required for these reactions to occur. This increase was achieved using microdroplet chemistry and followed by MS using the insertion of a reaction tube between the LAESI source and the MS inlet, leading to near complete conversions due to significantly extended microdroplet lifetime. This novel approach allowed for the collection of kinetic data for a model click reaction and showed in addition excellent instrument stability, improved sensitivity, and applicability to other click reactions. In Chapter 3, reactive LAESI was also demonstrated in a mass spectrometry imaging setting to show its feasibility in future imaging experiments.
In drug discovery it is important to identify phase I metabolic modifications as early as possible to screen for inactivation of drugs and/or activation of prodrugs. As the major class of reactions in phase I metabolism are oxidation reactions, oxidation of drugs with TiO2 photocatalysis can be used as a simple non-biological method to initially eliminate (pro)drug candidates with an undesired phase I oxidation metabolism. Analysis of reaction products is commonly achieved with mass spectrometry coupled to chromatography. However, sample throughput can be substantially increased by eliminating pretreatment steps and exploiting the potential of ambient MS. Furthermore, online monitoring of reactions in a time-resolved way would identify sequential modification steps. In Chapter 4 we introduce a novel (time-resolved) TiO2-photocatalysis LAESI-MS method for the analysis of drug candidates. This method was proven to be compatible with both TiO2-coated glass slides as well as solutions containing suspended TiO2 nanoparticles, and the results were in excellent agreement with studies on biological oxidation of several drugs. Additionally, a time-resolved LAESI-MS setup was developed and results for verapamil showed excellent analytical stability for online photocatalyzed oxidation reactions within the set-up up to at least one hour.
Identification and confirmation of (bio)chemical entities in ambient MS mostly involves accurate mass determination, often in combination with MS/MS work flows. However, an accurate mass only provides the elemental composition of the (bio)molecule, still resulting in numerous possible structures. MS/MS procedures are often insufficient in differentiating between the hundreds possible candidate substances in database searches. Obtaining additional information and thereby improving structural assignment as well as reducing the vast number of possible candidates is thus of high importance in any ambient MS(I) study. In Chapter 5 we present an ambient hydrogen/deuterium exchange (HDX) LAESI-MS method for structure elucidation and confirmation of (bio)molecules. The concept was demonstrated with small molecules, peptides, and proteins. Moreover, the same approach could be applied to MSI as shown by the ambient MSI of arginine and oligosaccharides on an orange slice. Eventually, this approach will allow spatially resolved MSI of different protein conformers and may have a major impact in the life sciences.
The main achievements that are described in this thesis offer insights on sample compatibility, hardware improvements to enable online time-resolved reactions and structure elucidation approaches. The outcome of the research chapters shows that LAESI-MS(I) is a highly versatile technique applicable to many research areas. Although the technique is highly 150 dependent on endogenous water in samples for analysis of intact molecules, LAESI can also be exploited for the analysis and identification of (water free) polymer materials. Unfortunately, LAESI sensitivity relative to electrospray ionization is weak, and therefore the technique can currently not live up to the status of the next generation of ambient MSI. Analytes that are present in high abundance are feasible for imaging by LAESI-MS. For low abundance analytes, however, several hardware improvements are required to substantially increase the sensitivity of the results. When the hardware improvements are developed and implemented, the road is open for many end users in, e.g., microbiology, pathology, and botany, to make significant breakthroughs in their fields.
TiO2 Photocatalyzed Oxidation of Drugs Studied by Laser Ablation Electrospray Ionization Mass Spectrometry
Geenen, Fred A.M.G. Van; Franssen, Maurice C.R. ; Miikkulainen, Ville ; Ritala, Mikko ; Zuilhof, Han ; Kostiainen, Risto ; Nielen, Michel W.F. - \ 2019
Journal of the American Society for Mass Spectrometry 30 (2019)4. - ISSN 1044-0305 - p. 639 - 646.
In drug discovery, it is important to identify phase I metabolic modifications as early as possible to screen for inactivation of drugs and/or activation of prodrugs. As the major class of reactions in phase I metabolism is oxidation reactions, oxidation of drugs with TiO2 photocatalysis can be used as a simple non-biological method to initially eliminate (pro)drug candidates with an undesired phase I oxidation metabolism. Analysis of reaction products is commonly achieved with mass spectrometry coupled to chromatography. However, sample throughput can be substantially increased by eliminating pretreatment steps and exploiting the potential of ambient ionization mass spectrometry (MS). Furthermore, online monitoring of reactions in a time-resolved way would identify sequential modification steps. Here, we introduce a novel (time-resolved) TiO2-photocatalysis laser ablation electrospray ionization (LAESI) MS method for the analysis of drug candidates. This method was proven to be compatible with both TiO2-coated glass slides as well as solutions containing suspended TiO2 nanoparticles, and the results were in excellent agreement with studies on biological oxidation of verapamil, buspirone, testosterone, andarine, and ostarine. Finally, a time-resolved LAESI MS setup was developed and initial results for verapamil showed excellent analytical stability for online photocatalyzed oxidation reactions within the set-up up to at least 1 h.
Seasonal streamflow forecasts for Europe - Part 2 : Sources of skill
Greuell, Wouter ; Franssen, Wietse H.P. ; Hutjes, Ronald W.A. - \ 2019
Hydrology and Earth System Sciences 23 (2019)1. - ISSN 1027-5606 - p. 371 - 391.
This paper uses hindcasts (1981-2010) to investigate the sources of skill in seasonal hydrological forecasts for Europe. The hindcasts were produced with WUSHP (Wageningen University Seamless Hydrological Prediction system). Skill was identified in a companion paper. In WUSHP, hydrological processes are simulated by running the Variable Infiltration Capacity (VIC) hydrological model forced with an ensemble of bias-corrected output from the seasonal forecast system 4 (S4) of the European Centre for Medium-Range Weather Forecasts (ECMWF). We first analysed the meteorological forcing. The precipitation forecasts contain considerable skill for the first lead month but hardly any significant skill at longer lead times. Seasonal forecasts of temperature have more skill. Skill in summer temperature is related to climate change and is more or less independent of lead time. Skill in February and March is unrelated to climate change. Different sources of skill in hydro-meteorological variables were isolated with a suite of specific hydrological hindcasts akin to ensemble streamflow prediction (ESP). These hindcasts show that in Europe, initial conditions of soil moisture (SM) form the dominant source of skill in run-off. From April to July, initial conditions of snow contribute significantly to the skill. Some remarkable skill features are due to indirect effects, i.e. skill due to forcing or initial conditions of snow and soil moisture at an earlier stage is stored in the hydrological state (snow and/or soil moisture) of a later stage, which then contributes to persistence of skill. Skill in evapotranspiration (ET) originates mostly in the meteorological forcing. For run-off we also compared the full hindcasts (with S4 forcing) with two types of ESP (or ESP-like) hindcasts (with identical forcing for all years). Beyond the second lead month, the full hindcasts are less skilful than the ESP (or ESP-like) hindcasts, because inter-annual variations in the S4 forcing consist mainly of noise which enhances degradation of the skill.
Verification of Seasonal Climate Forecast Towards Hydro-Climatic Information Needs of Rice Farmers in Northern Ghana
Nyadzi, Emmanuel ; Werners, S.E. ; Biesbroek, Robbert ; Phi Long, Hoang ; Franssen, W.H.P. ; Ludwig, F. - \ 2019
Weather, climate and society 11 (2019)1. - ISSN 1948-8327 - p. 127 - 142.
Farmers in sub-Saharan Africa face many difficulties when making farming decisions due to unexpected changes in weather and climate. Access to hydroclimatic information can potentially assist farmers to adapt. This study explores the extent to which seasonal climate forecasts can meet hydroclimatic information needs of rice farmers in northern Ghana. First, 62 rice farmers across 12 communities were interviewed about their information needs. Results showed that importance of hydroclimatic information depends on the frequency of use and farming type (rain-fed, irrigated, or both). Generally, farmers perceived rainfall distribution, dam water level, and temperature as very important information, followed by total rainfall amount and onset ranked as important. These findings informed our skills assessment of rainfall (Prcp), minimum temperature (Tmin), and maximum temperature (Tmax) from the European Centre for Medium-Range Weather Forecasts (ECMWF-S4) and at lead times of 0 to 2 months. Forecast bias, correlation, and skills for all variables vary with season and location but are generally unsystematic and relatively constant with forecast lead time. Making it possible to meet farmers’ needs at their most preferred lead time of 1 month before the farming season. ECMWF-S4 exhibited skill in Prcp, Tmin, and Tmax in northern Ghana except for a few grid cells in MAM for Prcp and SON for Tmin and Tmax. Tmin and Tmax forecasts were more skillful than Prcp. We conclude that the participatory coproduction approach used in this study provides better insight for understanding demand-driven climate information services and that the ECMWF-S4 seasonal forecast system has the potential to provide actionable hydroclimatic information that may support farmers’ decisions.
Global multi-pollutant modelling of water quality: scientific challenges and future directions
Strokal, M. ; Spanier, Emiel ; Kroeze, C. ; Koelmans, A.A. ; Florke, Martina ; Franssen, W.H.P. ; Hofstra, N. ; Langan, Simon ; Ting, Tang ; Vliet, M.T.H. van; Wada, Yoshihide ; Wang, M. ; Wijnen, Jikke van; Williams, R. - \ 2019
Current Opinion in Environmental Sustainability 36 (2019). - ISSN 1877-3435 - p. 116 - 125.
Assessing global water quality issues requires a multi-pollutant modelling approach. We discuss scientific challenges and future directions for such modeling. Multi-pollutant river models need to integrate information on sources of pollutants such as plastic debris, nutrients, chemicals, pathogens, their effects and possible solutions. In this paper, we first explain what we consider multi-pollutant modelling. Second, we discuss scientific challenges in multi-pollutant modelling relating to consistent model inputs, modelling approaches and model evaluation. Next, we illustrate the potential of global multi-pollutant modelling for hotspot analyses. We show hotspots of river pollution with microplastics, nutrients, triclosan and Cryptosporidium in many sub-basins of Europe, North America and South Asia. Finally, we reflect on future directions for multi-pollutant modelling, and for linking model results to policy-making.
Renal sulfate reabsorption in healthy individuals and renal transplant recipients
Post, Adrian ; Minović, Isidor ; Berg, Else van den; Eggersdorfer, Manfred L. ; Navis, Gerjan J. ; Geleijnse, Johanna M. ; Gans, Reinold O.B. ; Goor, Harry van; Struck, Joachim ; Franssen, Casper F.M. ; Kema, Ido P. ; Bakker, Stephan J.L. - \ 2018
Physiological Reports 6 (2018)8. - ISSN 2051-817X
Kidney donation - renal sulfate handling - renal transplant recipients - sulfate reabsorption
Inorganic sulfate is essential for normal cellular function and its homeostasis is primarily regulated in the kidneys. However, little is known about renal sulfate handling in humans and particularly in populations with impaired kidney function such as renal transplant recipients (RTR). Hence, we aimed to assess sulfate reabsorption in kidney donors and RTR. Plasma and urinary sulfate were determined in 671 RTR and in 251 kidney donors. Tubular sulfate reabsorption (TSR) was defined as filtered load minus sulfate excretion and fractional sulfate reabsorption (FSR) was defined as 1-fractional excretion. Linear regression analyses were employed to explore associations of FSR with baseline parameters and to identify the determinants of FSR in RTR. Compared to kidney donors, RTR had significantly lower TSR (15.2 [11.2–19.5] vs. 20.3 [16.7–26.3] μmol/min), and lower FSR (0.56 [0.48–0.64] vs. 0.64 [0.57–0.69]) (all P < 0.001). Kidney donation reduced both TSR and FSR by circa 50% and 25% respectively (both P < 0.001). In RTR and donors, both TSR and FSR associated positively with renal function. In RTR, FSR was independently associated with urinary thiosulfate (β = −0.18; P = 0.002), growth hormone (β = 0.12; P = 0.007), the intakes of alcohol (β = −0.14; P = 0.002), methionine (β = −0.34; P < 0.001), cysteine (β = −0.41; P < 0.001), and vitamin D (β = −0.14; P = 0.009). In conclusion, TSR and FSR are lower in RTR compared to kidney donors and both associated with renal function. Additionally, FSR is determined by various dietary and metabolic factors. Future research should determine the mechanisms behind sulfate handling in humans and the prognostic value of renal sulfate reabsorption in RTR.
One-Step Generation of Reactive Superhydrophobic Surfaces via SiHCl3-Based Silicone Nanofilaments
Slagman, Sjoerd ; Pujari, Sidharam P. ; Franssen, Maurice C.R. ; Zuilhof, Han - \ 2018
Langmuir 34 (2018)45. - ISSN 0743-7463 - p. 13505 - 13513.
Superhydrophobic surfaces gain ever-growing attention because of their applicability in many (consumer) products/materials as they often display, among others, antifouling, anti-icing, and/or self-cleaning properties. A simple way to achieve superhydrophobicity is through the growth of silicone nanofilaments. These nanofilaments, however, are very often nonreactive and thus difficult to utilize in subsequent chemistries. In response, we have developed a single-step procedure to grow (SiHCl3-based) silicone nanofilaments with selective reactivity that are intrinsically superhydrophobic. The silicone nanofilaments could be further functionalized via Pt-catalyzed hydrosilylation of exposed Si-H moieties. These surfaces are easily obtained using mild conditions and are stable under hydrolytic conditions (neutral water, 24 h at 80 °C) while remaining highly transparent, which makes them well suited for optical and photochemical experiments.
Kauniolide synthase is a P450 with unusual hydroxylation and cyclization-elimination activity
Liu, Qing ; Beyraghdar Kashkooli, Arman ; Manzano, David ; Pateraki, Irini ; Richard, Lea ; Kolkman, Pim ; Lucas, Maria Fátima ; Guallar, Victor ; Vos, Ric C.H. de; Franssen, Maurice C.R. ; Krol, Alexander van der; Bouwmeester, Harro - \ 2018
Nature Communications 9 (2018)1. - ISSN 2041-1723
Guaianolides are an important class of sesquiterpene lactones with unique biological and pharmaceutical properties. They have been postulated to be derived from germacranolides, but for years no progress has been made in the elucidation of their biosynthesis that requires an unknown cyclization mechanism. Here we demonstrate the isolation and characterization of a cytochrome P450 from feverfew (Tanacetum parthenium), kauniolide synthase. Kauniolide synthase catalyses the formation of the guaianolide kauniolide from the germacranolide substrate costunolide. Unlike most cytochrome P450s, kauniolide synthase combines stereoselective hydroxylation of costunolide at the C3 position, with water elimination, cyclization and regioselective deprotonation. This unique mechanism of action is supported by in silico modelling and docking experiments. The full kauniolide biosynthesis pathway is reconstructed in the heterologous hosts Nicotiana benthamiana and yeast, paving the way for biotechnological production of guaianolide-type sesquiterpene lactones.
Mild oxidation and functionalisation of synthetic polymer surfaces
Slagman, Sjoerd - \ 2018
Wageningen University. Promotor(en): J.T. Zuilhof, co-promotor(en): M.C.R. Franssen. - Wageningen : Wageningen University - ISBN 9789463435116 - 163
How to extend the lifetime of plastics? This might sound as a somewhat odd question in the age of bio-degradable plastics, but plastics that can withstand extreme conditions can be (re)used more often and thereby thus contribute to an eco-friendly economy. In order to improve these plastics, we need to adjust them and that is not easy! Traditional plastic modification technologies often require a lot of energy or dangerous chemicals. To by-pass these traditional measures, we explored, and pushed, the boundaries of novel eco-friendly technologies. We studied how enzymes, nature’s architects, modified plastic drinking water filtration membranes, which proved to occur in in a completely unprecedented manner. Additionally, a novel eco-friendly chemical tool for modifying plastics opened up a whole new route towards water-repellent materials. We hope that, through our research, we get yet a little closer to a sustainable future.
Chapter 1 provides the required background knowledge for any chemically oriented scholar to comprehend the interdisciplinary work presented herein. Crucial topics, such as polymer surface modification and analysis, wetting behaviour and adhesion prevention were introduced. Current methodologies for modifying polymer surfaces typically require harsh chemicals and conditions. The research described herein has therefore been focussed on acquiring a better understanding and increasing the scope of novel tools for mildly modifying polymers.
One of these novel tools is the laccase-mediated surface functionalisation of poly(ethersulfone) membranes using 4-hydroxybenzoic acid (4-HBA). The resulting overlayer minimised membrane fouling by several biofoulants. In order to comprehend the underlying functionalisation mechanism, the solution-phase oligomerisation of 4-HBA had to be studied first, which is described in Chapter 2. Initial conversion of 4-HBA proved to occur only slowly and resulted in two main products: a C3-C3’-bound and a C3-O-bound dimer. A plurality of other products were found after 24 h of incubation, which included a C1-C3’-bound and possibly a C1-O-bound dimer. Furthermore, laccase-mediated conversion of these dimers proved to be far more rapid than conversion of 4-HBA itself, and correlated strongly with the abundance of the individual dimers. The influence of dimer reactivity on their abundance was confirmed by quantum chemical calculations. These findings provided us with handles for designing phenols with enhanced reactivity and controlled binding profiles.
We used the gained knowledge to synthesise novel positively charged phenolic monomers that were anticipated to, upon laccase-mediated surface functionalisation, introduce anti-bacterial properties to the membrane while allowing it to be used as support membrane for layer-by-layer deposition. As is described in Chapter 3, however, in-situ laccase-mediated conversion of these phenolics did not lead to significant surface functionalisation. In order to understand why functionalisation was achieved for other monomers (i.e. 4-HBA), 4-HBA, laccase and any of several PES model compounds were incubated together and the resultant mixture was studied using LC-MS. However, no covalent bond formation between (oligomeric) 4-HBA and either of the soluble, insoluble or resin-bound PES model compounds could be observed. The use of phenols bearing negatively charged substituents did also not lead to membrane surface modification. Finally, membranes having an overlayer of oligomeric 4-HBA proved to be extensively decolourised upon washing with a detergent solution. Considering all of the above, it was concluded that laccase-mediated surface modification resulted from strong physisorption, rather than from covalent grafting of oligomeric 4-HBA.
As it was challenging to reveal the mechanisms underlying our functionalisation strategy, we anticipated that other researchers might also have encountered similar challenges. It is therefore that in Chapter 4 recently published laccase-mediated surface modification strategies are discussed and assessed on whether grafting is likely to have occurred. This assessment was based on five factors: mechanistic rationale, pre-treatment, control experiments, washing/cleaning and the used analytical tools. Generally speaking, laccase-mediated grafting on lignocelluloses proved to be likely. Quite commonly, however, grafting coincided with physical adsorption due to insufficient washing. We concluded that a lack of proper surface analyses and studies towards the mechanisms underlying grafting on polysaccharides, proteins and synthetic polymers regularly hampered achieving covalent grafting on these materials.
Apart from enzymatic surface modification, additional chemical strategies for achieving mild polymer functionalisation were assessed too. PMMA activation was accordingly achieved through peroxidative copper catalysis, followed by sodium borohydride reduction to result in surface hydroxylation. As was described in Chapter 5, this offered a platform for the robust growth of SiHCl3-based silicone nanofilaments, while maintaining polymer transparency. Due to their intricate nanostructure, these silicone nanofilaments granted superhydrophobicity (SWCA > 150°, sliding angles < 1°) to the material. The presence of Si-H moieties on the surface allowed for further functionalisation through hydrosilylation. As a proof of principle, we employed platinum-catalysed hydrosilylation to decorate the surface with extensively fluorinated alkenes and alkanes. This fluorinated exterior provided the material with protection towards hydrolytic degradation. We have thereby developed the first intrinsically superhydrophobic reactive silicone nanofilament-coated transparent polymer surface.
Finally, Chapter 6 summarises the highlights of previous chapters, while offering an in-depth discussion on possible improvements and future work.
Reactive Laser Ablation Electrospray Ionization Time-Resolved Mass Spectrometry of Click Reactions
Geenen, Fred A.M.G. van; Franssen, Maurice C.R. ; Zuilhof, Han ; Nielen, Michel W.F. - \ 2018
Analytical Chemistry 90 (2018)17. - ISSN 0003-2700 - p. 10409 - 10416.
Reactions in confined compartments like charged microdroplets are of increasing interest, notably because of their substantially increased reaction rates. When combined with ambient ionization mass spectrometry (MS), reactions in charged microdroplets can be used to improve the detection of analytes or to study the molecular details of the reactions in real time. Here, we introduce a reactive laser ablation electrospray ionization (reactive LAESI) time-resolved mass spectrometry (TRMS) method to perform and study reactions in charged microdroplets. We demonstrate this approach with a class of reactions new to reactive ambient ionization MS: so-called click chemistry reactions. Click reactions are high-yielding reactions with a high atom efficiency, and are currently drawing significant attention from fields ranging from bioconjugation to polymer modification. Although click reactions are typically at least moderately fast (time scale of minutes to a few hours), in a reactive LAESI approach a substantial increase of reaction time is required for these reactions to occur. This increase was achieved using microdroplet chemistry and followed by MS using the insertion of a reaction tube - up to 1 m in length - between the LAESI source and the MS inlet, leading to near complete conversions due to significantly extended microdroplet lifetime. This novel approach allowed for the collection of kinetic data for a model (strain-promoted) click reaction between a substituted tetrazine and a strained alkyne and showed in addition excellent instrument stability, improved sensitivity, and applicability to other click reactions. Finally, the methodology was also demonstrated in a mass spectrometry imaging setting to show its feasibility in future imaging experiments.
Elucidating the mechanism behind the laccase-mediated modification of poly(ethersulfone)
Slagman, Sjoerd ; Jonkers, Wendy A. ; Zuilhof, Han ; Franssen, Maurice C.R. - \ 2018
RSC Advances : An international journal to further the chemical sciences 8 (2018)48. - ISSN 2046-2069 - p. 27101 - 27110.
Laccase-mediated oligomerisation of 4-hydroxybenzoic acid (4-HBA) derivatives and simultaneous in situ surface modification has proven to be a cost-effective, easily applicable and eco-friendly strategy for preventing biofouling of poly(ethersulfone) (PES) water filtration membranes. Modification of the membrane surface has previously been hypothesised to occur through covalent bonding of enzymatically generated phenolic radicals to the polymeric membrane. The current study shows, however, that in situ formation of soluble phenolic oligomers does not result in covalent membrane modification. We studied in situ laccase-mediated oligomerisation of custom-synthesised positively charged and commercially available negatively charged monomeric phenols, and demonstrated that their mode of binding to PES is not covalent. In addition, soluble, non-soluble and on-resin PES model compounds were synthesised and used in the laccase-mediated oligomerisation of 4-HBA. Covalent bond formation between these model compounds and (oligomeric) 4-HBA could not be observed either. Furthermore, extensive washing of PES membranes modified through laccase-mediated oligomerisation of 4-HBA resulted in substantial discolouration of the membrane surface, showing that the layer of oligomerised phenolics could easily be removed. Altogether, it was concluded that laccase-assisted modification of PES membranes resulted from strong physical adsorption of phenolic oligomers and polymers rather than from covalent bonding of those.
Seasonal streamflow forecasts for Europe-Part I : Hindcast verification with pseudo- A nd real observations
Greuell, Wouter ; Franssen, Wietse H.P. ; Biemans, Hester ; Hutjes, Ronald W.A. - \ 2018
Hydrology and Earth System Sciences 22 (2018)6. - ISSN 1027-5606 - p. 3453 - 3472.
Seasonal predictions of river flow can be exploited among others to optimise hydropower energy generation, navigability of rivers and irrigation management to decrease crop yield losses. This paper is the first of two papers dealing with a physical model-based system built to produce probabilistic seasonal hydrological forecasts, applied here to Europe. This paper presents the development of the system and the evaluation of its skill. The variable infiltration capacity (VIC) hydrological model is forced with bias-corrected output of ECMWF's seasonal forecast system 4. For the assessment of skill, we analysed hindcasts (1981-2010) against a reference run, in which VIC was forced by gridded meteorological observations. The reference run was also used to generate initial hydrological conditions for the hindcasts. The skill in run-off and discharge hindcasts is analysed with monthly temporal resolution, up to 7 months of lead time, for the entire annual cycle. Using the reference run output as pseudo-observations and taking the correlation coefficient as metric, hot spots of significant theoretical skill in discharge and run-off were identified in Fennoscandia (from January to October), the southern part of the Mediterranean (from June to August), Poland, northern Germany, Romania and Bulgaria (mainly from November to January), western France (from December to May) and the eastern side of Great Britain (January to April). Generally, the skill decreases with increasing lead time, except in spring in regions with snow-rich winters. In some areas some skill persists even at the longest lead times (7 months). Theoretical skill was compared to actual skill as determined with real discharge observations from 747 stations. Actual skill is generally substantially less than theoretical skill. This effect is stronger for small basins than for large basins. Qualitatively, the use of different skill metrics (correlation coefficient; relative operating characteristics, ROC, area; and ranked probability skill score, RPSS) leads to broadly similar spatiooral patterns of skill, but the level of skill decreases, and the area of skill shrinks, in the following order: Correlation coefficient; ROC area below-normal (BN) tercile; ROC area above-normal (AN) tercile; ranked probability skill score; and, finally, ROC near-normal (NN) tercile.
Fast increases in river pollution from sewage: a global trend
Strokal, M. ; Kroeze, C. ; Franssen, W.H.P. ; Hofstra, N. ; Koelmans, A.A. ; Siegfried, Max ; Vliet, M.T.H. van; Wijnen, Jikke van; Vermeulen, L.C. - \ 2018
Geophysical Research Abstracts 20 (2018). - ISSN 1029-7006 - 1 p.
Laccase-Mediated Grafting on Biopolymers and Synthetic Polymers : A Critical Review
Slagman, Sjoerd ; Zuilhof, Han ; Franssen, Maurice C.R. - \ 2018
ChemBioChem 19 (2018)4. - ISSN 1439-4227 - p. 288 - 311.
biomass - enzyme catalysis - grafting - polymers - surface chemistry
Laccase-mediated grafting on lignocelluloses has gained considerable attention as an environmentally benign method to covalently modify wood, paper and cork. In recent decades this technique has also been employed to modify fibres with a polysaccharide backbone, such as cellulose or chitosan, to infer colouration, antimicrobial activity or antioxidant activity to the material. The scope of this approach has been further widened by researchers, who apply mediators or high redox potential laccases and those that modify synthetic polymers and proteins. In all cases, the methodology relies on one- or two-electron oxidation of the surface functional groups or of the graftable molecule in solution. However, similar results can very often be achieved through simple deposition, even after extensive washing. This unintended adsorption of the active substance could have an adverse effect on the durability of the applied coating. Differentiating between actual covalent binding and adsorption is therefore essential, but proves to be challenging. This review not only covers excellent research on the topic of laccase-mediated grafting over the last five to ten years, but also provides a critical comparison to highlight either the lack or presence of compelling evidence for covalent grafting.