41 results on '"Hartman Y"'
Search Results
2. Correction: Protocol of the Healthy Brain Study: An Accessible Resource for Understanding the Human Brain and How It Dynamically and Individually Operates in Its Bio-Social Context
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Healthy Brain Study consortium, Aarts, E, Akkerman, A, Altgassen, M, Bartels, R, Beckers, D, Bevelander, K, Bijleveld, E, Davidson, EB, Boleij, A, Bralten, J, Cillessen, T, Claassen, J, Cools, R, Cornelissen, I, Dresler, M, Eijsvogels, T, Faber, M, Fernández, G, Figner, B, Fritsche, M, Füllbrunn, S, Gayet, S, van Gelder, MMHJ, van Gerven, M, Geurts, S, Greven, CU, Groefsema, M, Haak, K, Hagoort, P, Hartman, Y, van der Heijden, B, Hermans, E, Heuvelmans, V, Hintz, F, den Hollander, J, Hulsman, AM, Idesis, S, Jaeger, M, Janse, E, Janzing, J, Kessels, RPC, Karremans, JC, de Kleijn, W, Klein, M, Klumpers, F, Kohn, N, Korzilius, H, Krahmer, B, de Lange, F, van Leeuwen, J, Liu, H, Luijten, M, Manders, P, Manevska, K, Marques, JP, Matthews, J, McQueen, JM, Medendorp, P, Melis, R, Meyer, A, Oosterman, J, Overbeek, L, Peelen, M, Popma, J, Postma, G, Roelofs, K, van Rossenberg, YGT, Schaap, G, Scheepers, P, Selen, L, Starren, M, Swinkels, DW, Tendolkar, I, Thijssen, DHJ, Timmerman, H, Tutunji, R, Tuladhar, A, Veling, H, Verhagen, M, Verkroost, J, Vink, J, Vriezekolk, V, Vrijsen, J, Vyrastekova, J, van der Wal, S, Willems, R, Willemsen, A, and Language, Communication and Cognition
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Questionnaires ,Male ,Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1] ,COVID-19/diagnosis ,230 Affective Neuroscience ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Social Sciences ,Social Environment ,330 000 Food & Cognition ,Social Development ,Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] ,Analytical Chemistry ,RC1200 ,Experimental Psychopathology and Treatment ,Study Protocol ,Cognition ,Surveys and Questionnaires ,130 000 Cognitive Neurology & Memory ,Affect/physiology ,Medicine and Health Sciences ,Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] ,Psychology ,Public and Occupational Health ,Cognition/physiology ,Work, Health and Performance ,Intelligence Tests ,Grammar ,Psycholinguistics ,Multidisciplinary ,Non-nativeness in Communication ,Brain ,220 Statistical Imaging Neuroscience ,180 000 Predictive Brain ,Cognitive artificial intelligence ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,Semantics ,Research Design ,Medicine ,Female ,Behavioral and Social Aspects of Health ,Institute for Management Research ,Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5] ,Personality Tests ,Adult ,110 000 Neurocognition of Language ,Psychometrics ,Science ,Decision Making ,Sensation ,BF ,Neuroimaging ,Research and Analysis Methods ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,Language and Speech, Learning and Therapy ,QH301 ,All institutes and research themes of the Radboud University Medical Center ,Humans ,Speech Production and Comprehension ,Sensation/physiology ,320 000 MR Structural Quantitative Imaging ,Behavior ,Survey Research ,Behaviour Change and Well-being ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,Neuro- en revalidatiepsychologie ,Action, intention, and motor control ,Neuropsychology and rehabilitation psychology ,Other Research Radboud Institute for Health Sciences [Radboudumc 0] ,Cognitive Psychology ,Biology and Life Sciences ,COVID-19 ,Linguistics ,Brain/diagnostic imaging ,QP ,Language & Communication ,Communication and Media ,Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10] ,Affect ,Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] ,Narrative, Cognition & Communication ,RC0321 ,Cognitive Science ,Digital Security ,170 000 Motivational & Cognitive Control ,Developmental Psychopathology ,Neuroscience - Abstract
The endeavor to understand the human brain has seen more progress in the last few decades than in the previous two millennia. Still, our understanding of how the human brain relates to behavior in the real world and how this link is modulated by biological, social, and environmental factors is limited. To address this, we designed the Healthy Brain Study (HBS), an interdisciplinary, longitudinal, cohort study based on multidimensional, dynamic assessments in both the laboratory and the real world. Here, we describe the rationale and design of the currently ongoing HBS. The HBS is examining a population-based sample of 1,000 healthy participants (age 30–39) who are thoroughly studied across an entire year. Data are collected through cognitive, affective, behavioral, and physiological testing, neuroimaging, bio-sampling, questionnaires, ecological momentary assessment, and real-world assessments using wearable devices. These data will become an accessible resource for the scientific community enabling the next step in understanding the human brain and how it dynamically and individually operates in its bio-social context. An access procedure to the collected data and bio-samples is in place and published on https://www.healthybrainstudy.nl/en/data-and-methods/access. Trail registration: https://www.trialregister.nl/trial/7955.
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- 2022
3. Experiences, adherence and satisfaction with a combined exercise and dietary intervention for patients with ovarian cancer undergoing chemotherapy: A mixed-methods study
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Stelten, S, van Lonkhuijzen, L R C W, Hartman, Y A W, van Driel, W J, Winkels, R M, Kenter, G G, Buffart, L M, Hoedjes, M, Stelten, S, van Lonkhuijzen, L R C W, Hartman, Y A W, van Driel, W J, Winkels, R M, Kenter, G G, Buffart, L M, and Hoedjes, M
- Abstract
Objective: This study examined experiences, adherence and satisfaction with a combined exercise and dietary intervention in patients with ovarian cancer and their healthcare professionals (HCPs) as part of the randomized PADOVA trial.Methods: A mixed-methods approach was used in 24 patients with ovarian cancer receiving first-line chemotherapy who were randomly allocated to a combined exercise and dietary intervention or usual care with counseling sessions post-treatment. Qualitative data on intervention experiences, adherence and satisfaction was collected using semi-structured interviews with patients and their HCPs (n = 18 physical therapists; n = 5 dietitians). Quantitative data on adherence and satisfaction was collected to provide context to qualitative data.Results: Exercise relative dose intensity ranged from 36 to 100% (median 72%) and patients attended 33-133% (median 100%) of the prescribed dietary counseling sessions. Patients appreciated guidance on exercise and nutrition and perceived benefits including improved physical fitness, quality of life, peer support and recovery after surgery and/or chemotherapy cycles. Both patients and HCPs were satisfied with the intervention and perceived that participation exceeded prior expectations. Median patient satisfaction score with the intervention was 8.5 out of 10. Suggestions for improving the intervention included further personalization of the number, content and scheduling of the sessions to preferences of patients and HCPs. Patients in the usual care group reported counseling sessions post-chemotherapy to be too little too late.Conclusions: Patients with ovarian cancer adhered well to the intervention. Numerous perceived benefits of the intervention were reported by patients and HCPs. Good adherence and positive experiences support successful implementation in clinical practice.
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- 2022
4. Phase-contrast hard X-ray microtomography by Bragg-Fresnel optics
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Hartman, Y., Kohn, V., Kuznetsov, S., Snigirev, A., and Snigireva, I.
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- 1997
- Full Text
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5. Improvements in fitness are not obligatory for exercise training-induced improvements in CV risk factors
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Hartman, Y., Hopman, M., Schreuder, T., Verheggen, R., Scholten, R., Oudegeest-Sander, M., Poelkens, F., Maiorana, Andrew, Naylor, L., Willems, P., Tack, C., Thijssen, D., Green, D., Hartman, Y., Hopman, M., Schreuder, T., Verheggen, R., Scholten, R., Oudegeest-Sander, M., Poelkens, F., Maiorana, Andrew, Naylor, L., Willems, P., Tack, C., Thijssen, D., and Green, D.
- Abstract
Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society The purpose of this study was to assess whether changes in physical fitness relate to changes in cardiovascular risk factors following standardized, center-based and supervised exercise training programs in subjects with increased cardiovascular risk. We pooled data from exercise training studies of subjects with increased cardiovascular risk (n = 166) who underwent 8–52 weeks endurance training. We determined fitness (i.e., peak oxygen uptake) and traditional cardiovascular risk factors (body mass index, blood pressure, total cholesterol, high-density lipoprotein cholesterol), before and after training. We divided subjects into quartiles based on improvement in fitness, and examined whether these groups differed in terms of risk factors. Associations between changes in fitness and in cardiovascular risk factors were further tested using Pearson correlations. Significant heterogeneity was apparent in the improvement of fitness and individual risk factors, with nonresponder rates of 17% for fitness, 44% for body mass index, 33% for mean arterial pressure, 49% for total cholesterol, and 49% for high-density lipoprotein cholesterol. Neither the number, nor the magnitude, of change in cardiovascular risk factors differed significantly between quartiles of fitness change. Changes in fitness were not correlated with changes in cardiovascular risk factors (all P >  0.05). Our data suggest that significant heterogeneity exists in changes in peak oxygen uptake after training, while improvement in fitness did not relate to improvement in cardiovascular risk factors. In subjects with increased cardiovascular risk, improvements in fitness are not obligatory for training-induced improvements in cardiovascular risk factors.
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- 2018
6. Genomic regions under selection in crop-wild hybrids of lettuce: implications for crop breeding and environmental risk assessment
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Hartman, Y., van Tienderen, Peter, Hooftman, D.A.P., and Experimental Plant Systematics (IBED, FNWI)
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fungi ,food and beverages - Abstract
The results of this thesis show that the probability of introgression of a putative transgene to wild relatives indeed depends strongly on the insertion location of the transgene. The study of genomic selection patterns can identify crop genomic regions under negative selection in multiple environments and in several cultivar-wild crosses, which could be applicable to TM strategies. For lettuce, a fitness QTL region was identified on LG7 where the crop allele conferred a selective disadvantage through delayed flowering, lower survival, and a lower fitness and possibly through a lower competitive ability. This crop genomic background is likely deleterious in the wild habitat, especially in environments with high density competition and a seasonal flowering period. However, QTL results were also (partly) cultivar specific, so that implementation in ERA will still need to be on a case-by-case basis, which decreases its general applicability. In addition, our results show that it is more informative to identify specific genomic regions under selection than to estimate average hybrid fitness. Fitness distributions indicated there is a high likelihood in lettuce for novel crop-wild hybrids to arise that have a higher fitness than the wild parent even though the average fitness of the hybrid offspring was lower. This provides an avenue for introgression of crop alleles into the wild population. A mitigation strategy based solely on placing a transgene close to a major negatively selected crop gene could have a huge quantitative effect by reducing the chances of introgression, but it would be difficult to design a strategy that would prevent it with certainty. It is commendable to evaluate the remaining risk in the perspective of the potential consequences an escape would have for the recipient environment, as well as the foreseen benefits of the GM crop.
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- 2012
7. Genomic regions in crop-wild hybrids of lettuce are affected differently in different environments: implications for crop breeding
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Hartman, Y., Hooftman, D.A.P., Uwimana, B., van de Wiel, C.C.M., Smulders, M.J.M., Visser, R.G.F., van Tienderen, P.H., and Experimental Plant Systematics (IBED, FNWI)
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domestication traits ,natural environments ,avena-barbata ,food and beverages ,arabidopsis-thaliana ,Plant Breeding ,genetically-modified crops ,Laboratorium voor Plantenveredeling ,population-genetics ,quantitative trait loci ,tandem constructs ,EPS ,field conditions ,lactuca-serriola asteraceae - Abstract
Many crops contain domestication genes that are generally considered to lower fitness of crop–wild hybrids in the wild environment. Transgenes placed in close linkage with such genes would be less likely to spread into a wild population. Therefore, for environmental risk assessment of GM crops, it is important to know whether genomic regions with such genes exist, and how they affect fitness. We performed quantitative trait loci (QTL) analyses on fitness(-related) traits in two different field environments employing recombinant inbred lines from a cross between cultivated Lactuca sativa and its wild relative Lactuca serriola. We identified a region on linkage group 5 where the crop allele consistently conferred a selective advantage (increasing fitness to 212% and 214%), whereas on linkage group 7, a region conferred a selective disadvantage (reducing fitness to 26% and 5%), mainly through delaying flowering. The probability for a putative transgene spreading would therefore depend strongly on the insertion location. Comparison of these field results with greenhouse data from a previous study using the same lines showed considerable differences in QTL patterns. This indicates that care should be taken when extrapolating experiments from the greenhouse, and that the impact of domestication genes has to be assessed under field conditions.
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- 2012
8. Recognition of Streptococcus pneumoniae and muramyl dipeptide by NOD2 results in potent induction of MMP-9, which can be controlled by lipopolysaccharide stimulation
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Vissers, M., Hartman, Y., Groh, L., Jong, D.J. de, Jonge, M.I. de, Ferwerda, G., Vissers, M., Hartman, Y., Groh, L., Jong, D.J. de, Jonge, M.I. de, and Ferwerda, G.
- Abstract
Item does not contain fulltext, Matrix metallopeptidase 9 (MMP-9) is a protease involved in the degradation of extracellular matrix collagen. Evidence suggests that MMP-9 is involved in pathogenesis during Streptococcus pneumoniae infection. However, not much is known about the induction of MMP-9 and the regulatory processes involved. We show here that the Gram-positive bacteria used in this study induced large amounts of MMP-9, in contrast to the Gram-negative bacteria that were used. An important pathogen-associated molecular pattern (PAMP) for Gram-positive bacteria is muramyl dipeptide (MDP). MDP is a very potent inducer of MMP-9 and showed a dose-dependent MMP-9 induction. Experiments using peripheral blood mononuclear cells (PBMCs) from Crohn's disease patients with nonfunctional NOD2 showed that MMP-9 induction by Streptococcus pneumoniae and MDP is NOD2 dependent. Increasing amounts of lipopolysaccharide (LPS), an important PAMP for Gram-negative bacteria, resulted in decreasing amounts of MMP-9. Moreover, the induction of MMP-9 by MDP could be counteracted by simultaneously adding LPS. The inhibition of MMP-9 expression by LPS was found to be regulated posttranscriptionally, independently of tissue inhibitor of metalloproteinase 1 (TIMP-1), an endogenous inhibitor of MMP-9. Collectively, these data show that Streptococcus pneumoniae is able to induce large amounts of MMP-9. These high MMP-9 levels are potentially involved in Streptococcus pneumoniae pathogenesis.
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- 2014
9. Abiotic stress QTLs in lettuce crop–wild hybrids: comparing greenhouse and field experiments
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Hartman, Y., Hooftman, D.A.P., Uwimana, B., Schranz, M.E., van de Wiel, C.C.M., Smulders, M.J.M., Visser, R.G.F., Michelmore, R.W., van Tienderen, P.H., Hartman, Y., Hooftman, D.A.P., Uwimana, B., Schranz, M.E., van de Wiel, C.C.M., Smulders, M.J.M., Visser, R.G.F., Michelmore, R.W., and van Tienderen, P.H.
- Abstract
The development of stress-tolerant crops is an increasingly important goal of current crop breeding. A higher abiotic stress tolerance could increase the probability of introgression of genes from crops to wild relatives. This is particularly relevant to the discussion on the risks of new GM crops that may be engineered to increase abiotic stress resistance. We investigated abiotic stress QTL in greenhouse and field experiments in which we subjected recombinant inbred lines from a cross between cultivated Lactuca sativa cv. Salinas and its wild relative L. serriola to drought, low nutrients, salt stress, and aboveground competition. Aboveground biomass at the end of the rosette stage was used as a proxy for the performance of plants under a particular stress. We detected a mosaic of abiotic stress QTL over the entire genome with little overlap between QTL from different stresses. The two QTL clusters that were identified reflected general growth rather than specific stress responses and colocated with clusters found in earlier studies for leaf shape and flowering time. Genetic correlations across treatments were often higher among different stress treatments within the same experiment (greenhouse or field), than among the same type of stress applied in different experiments. Moreover, the effects of the field stress treatments were more correlated with those of the greenhouse competition treatments than to those of the other greenhouse stress experiments, suggesting that competition rather than abiotic stress is a major factor in the field. In conclusion, the introgression risk of stress tolerance (trans-)genes under field conditions cannot easily be predicted based on genomic background selection patterns from controlled QTL experiments in greenhouses, especially field data will be needed to assess potential (negative) ecological effects of introgression of these transgenes into wild relatives.
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- 2014
10. Kan de Groenknolorchis overleven in Nederland?
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Hartman, Y., Oostermeijer, J.G.B., and Experimental Plant Systematics (IBED, FNWI)
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- 2006
11. Sedentary Behavior and Cardiovascular Disease Risk: Mediating Mechanisms.
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Carter, Sophie, Hartman, Yvonne, Holder, Sophie, Thijssen, Dick H., Hopkins, Nicola D., Carter, S, Hartman, Y, Holder, S, Thijssen, D H, and Hopkins, N D
- Abstract
Sedentary behavior has a strong association with cardiovascular disease (CVD) risk, which may be independent of physical activity. To date, the mechanism(s) that mediate this relationship are poorly understood. We hypothesize that sedentary behavior modifies key hemodynamic, inflammatory, and metabolic processes resulting in impaired arterial health. Subsequently, these vascular impairments directly and indirectly contribute to the development of CVD. [ABSTRACT FROM AUTHOR]
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- 2017
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12. Inferring population and metapopulation dynamics of Liparis loeselii from single-census and inventory data
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Oostermeijer, J.G.B., primary and Hartman, Y., additional
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- 2014
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13. Genomic and environmental selection patterns in two distinct lettuce crop-wild hybrid crosses
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Hartman, Y., Uwimana, B., Hooftman, D.A.P., Schranz, M.E., van de Wiel, C.C.M., Smulders, M.J.M., Visser, R.G.F., van Tienderen, P.H., Hartman, Y., Uwimana, B., Hooftman, D.A.P., Schranz, M.E., van de Wiel, C.C.M., Smulders, M.J.M., Visser, R.G.F., and van Tienderen, P.H.
- Abstract
Genomic selection patterns and hybrid performance influence the chance that crop (trans)genes can spread to wild relatives. We measured fitness(-related) traits in two different field environments employing two different crop–wild crosses of lettuce. We performed quantitative trait loci (QTL) analyses and estimated the fitness distribution of early- and late-generation hybrids. We detected consistent results across field sites and crosses for a fitness QTL at linkage group 7, where a selective advantage was conferred by the wild allele. Two fitness QTL were detected on linkage group 5 and 6, which were unique to one of the crop–wild crosses. Average hybrid fitness was lower than the fitness of the wild parent, but several hybrid lineages outperformed the wild parent, especially in a novel habitat for the wild type. In early-generation hybrids, this may partly be due to heterosis effects, whereas in late-generation hybrids transgressive segregation played a major role. The study of genomic selection patterns can identify crop genomic regions under negative selection across multiple environments and cultivar–wild crosses that might be applicable in transgene mitigation strategies. At the same time, results were cultivar-specific, so that a case-by-case environmental risk assessment is still necessary, decreasing its general applicability.
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- 2013
14. QTL analysis reveals the genetic architecture of domestication traits in Crisphead lettuce
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Hartman, Y., Hooftman, D.A.P., Schranz, M.E., van Tienderen, P.H., Hartman, Y., Hooftman, D.A.P., Schranz, M.E., and van Tienderen, P.H.
- Abstract
The genetic architecture of crop domestication is generally characterized by three trends: relatively few genomic regions with major QTL effects are involved, QTL are often clustered, and alleles derived from the crop do not always contribute to the crop phenotype. We have investigated the genetic architecture of lettuce using a recombinant inbred line population from a cross between a crop Lactuca sativa (‘Salinas’) and its wild relative L. serriola. Few genomic regions with major QTL, plus various intermediate QTL, largely control the transition from wild to cultivated Crisphead lettuce. Allelic effects of all major QTL were in the expected direction, but there were intermediate QTL where the crop contributed to the wild phenotype and vice versa. We found two main regions with clusters of QTL, one on linkage group 3, where the crop allele induced lower seed output, another on linkage group 7, where the crop allele caused a delay in flowering time. Potentially, knowledge of genetic changes due to the domestication could be relevant for the chance that a transgene inserted in a crop genome will spread to wild relatives due to hitchhiking effects. If a transgene would be inserted in one of these regions, background selection on the crop alleles may lead to a reduced fitness of hybrids with the transgene. QTL research on the effects of domestication genes can thus indicate regions in the crop genome that are less likely to introgress, although these still need to be verified under field conditions.
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- 2013
15. vermengen van populaties: steuntje in de rug of duwtje de afgrond in?
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Oostermeijer, G., Hartman, Y., Luijten, S., Nijs, H. den, Oostermeijer, G., Hartman, Y., Luijten, S., and Nijs, H. den
- Abstract
Onlangs verscheen een inzichtelijke, goed onderbouwde beslisboom, om het risico in te schatten van uitteeltdepressie. Dat is de vermindering van prestaties die op kan treden na vermenging van populaties. Wij willen deze beslisboom graag met enige toelichting voorleggen aan de Nederlandse natuurbeheerders en beleidsmakers.
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- 2013
16. Hybridization between crops and wild relatives: the contribution of cultivated lettuce to the vigour of crop-wild hybrids under drought, salinity and nutrient deficiency conditions
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Uwimana, B., Smulders, M.J.M., Hooftman, D.A.P., Hartman, Y., van Tienderen, P.H., Jansen, J., McHale, L.K., Michelmore, R.W., van de Wiel, C.C.M., Visser, R.G.F., Uwimana, B., Smulders, M.J.M., Hooftman, D.A.P., Hartman, Y., van Tienderen, P.H., Jansen, J., McHale, L.K., Michelmore, R.W., van de Wiel, C.C.M., and Visser, R.G.F.
- Abstract
With the development of transgenic crop varieties, crop–wild hybridization has received considerable consideration with regard to the potential of transgenes to be transferred to wild species. Although many studies have shown that crops can hybridize with their wild relatives and that the resulting hybrids may show improved fitness over the wild parents, little is still known on the genetic contribution of the crop parent to the performance of the hybrids. In this study, we investigated the vigour of lettuce hybrids using 98 F2:3 families from a cross between cultivated lettuce and its wild relative Lactuca serriola under non-stress conditions and under drought, salinity and nutrient deficiency. Using single nucleotide polymorphism markers, we mapped quantitative trait loci associated with plant vigour in the F2:3 families and determined the allelic contribution of the two parents. Seventeen QTLs (quantitative trait loci) associated with vigour and six QTLs associated with the accumulation of ions (Na+, Cl- and K+) were mapped on the nine linkage groups of lettuce. Seven of the vigour QTLs had a positive effect from the crop allele and six had a positive effect from the wild allele across treatments, and four QTLs had a positive effect from the crop allele in one treatment and from the wild allele in another treatment. Based on the allelic effect of the QTLs and their location on the genetic map, we could suggest genomic locations where transgene integration should be avoided when aiming at the mitigation of its persistence once crop–wild hybridization takes place
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- 2012
17. Crop to wild introgression in lettuce: following the fate of crop genome segments in backcross populations
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Uwimana, B., Smulders, M.J.M., Hooftman, D.A.P., Hartman, Y., van Tienderen, P.H., Jansen, J., McHale, L.K., Michelmore, R., Visser, R.G.F., van de Wiel, C.C.M., Uwimana, B., Smulders, M.J.M., Hooftman, D.A.P., Hartman, Y., van Tienderen, P.H., Jansen, J., McHale, L.K., Michelmore, R., Visser, R.G.F., and van de Wiel, C.C.M.
- Abstract
After crop-wild hybridization, some of the crop genomic segments may become established in wild populations through selfing of the hybrids or through backcrosses to the wild parent. This constitutes a possible route through which crop (trans)genes could become established in natural populations. The likelihood of introgression of transgenes will not only be determined by fitness effects from the transgene itself but also by the crop genes linked to it. Although lettuce is generally regarded as self-pollinating, outbreeding does occur at a low frequency. Backcrossing to wild lettuce is a likely pathway to introgression along with selfing, due to the high frequency of wild individuals relative to the rarely occurring crop-wild hybrids. To test the effect of backcrossing on the vigour of inter-specific hybrids, Lactuca serriola, the closest wild relative of cultivated lettuce, was crossed with L. sativa and the F1 hybrid was backcrossed to L. serriola to generate BC1 and BC2 populations. Experiments were conducted on progeny from selfed plants of the backcrossing families (BC1S1 and BC2S1). Plant vigour of these two backcrossing populations was determined in the greenhouse under non-stress and abiotic stress conditions (salinity, drought, and nutrient deficiency). Results Despite the decreasing contribution of crop genomic blocks in the backcross populations, the BC1S1 and BC2S1 hybrids were characterized by a substantial genetic variation under both non-stress and stress conditions. Hybrids were identified that performed equally or better than the wild genotypes, indicating that two backcrossing events did not eliminate the effect of the crop genomic segments that contributed to the vigour of the BC1 and BC2 hybrids. QTLs for plant vigour under non-stress and the various stress conditions were detected in the two populations with positive as well as negative effects from the crop. Conclusion As it was shown that the crop contributed QTLs with either a positive or a ne
- Published
- 2012
18. INTESTINAL EXTRACELLULAR MATRIX DOWN-REGULATION OF PROINFLAMMATORY BLOOD MONOCYTES IS DEVELOPMENTALLY REGULATED.
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Maheshwari, A., primary, Smythies, L. E., additional, Rowe, M. J., additional, Hartman, Y., additional, Smith, P. D., additional, and Ohls, R. K., additional
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- 2007
- Full Text
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19. Effects of the Microstructuring Process on Diffraction Properties of Bragg–Fresnel Lenses
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Hartman, Y, primary
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- 1996
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20. Causes of cracking of vacuum deposited thick amorphous silicon film
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Avrutin, V. S., Izumskaya, N. F., Hartman, Y. M., Andreeva, A. V., Vyatkin, A. F., and Mehlik, N. N.
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- 1996
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21. Two-dimensional X-ray microfocusing using a curved crystal Bragg-Fresnel lens
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Hartman, Y., Freund, A. K., Snigireva, I., Souvorov, A., and Snigirev, A.
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- 1997
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22. Crop to wild introgression in lettuce: following the fate of crop genome segments in backcross populations
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Uwimana Brigitte, Smulders Marinus JM, Hooftman Danny AP, Hartman Yorike, van Tienderen Peter H, Jansen Johannes, McHale Leah K, Michelmore Richard W, Visser Richard GF, and van de Wiel Clemens CM
- Subjects
Botany ,QK1-989 - Abstract
Abstract Background After crop-wild hybridization, some of the crop genomic segments may become established in wild populations through selfing of the hybrids or through backcrosses to the wild parent. This constitutes a possible route through which crop (trans)genes could become established in natural populations. The likelihood of introgression of transgenes will not only be determined by fitness effects from the transgene itself but also by the crop genes linked to it. Although lettuce is generally regarded as self-pollinating, outbreeding does occur at a low frequency. Backcrossing to wild lettuce is a likely pathway to introgression along with selfing, due to the high frequency of wild individuals relative to the rarely occurring crop-wild hybrids. To test the effect of backcrossing on the vigour of inter-specific hybrids, Lactuca serriola, the closest wild relative of cultivated lettuce, was crossed with L. sativa and the F1 hybrid was backcrossed to L. serriola to generate BC1 and BC2 populations. Experiments were conducted on progeny from selfed plants of the backcrossing families (BC1S1 and BC2S1). Plant vigour of these two backcrossing populations was determined in the greenhouse under non-stress and abiotic stress conditions (salinity, drought, and nutrient deficiency). Results Despite the decreasing contribution of crop genomic blocks in the backcross populations, the BC1S1 and BC2S1 hybrids were characterized by a substantial genetic variation under both non-stress and stress conditions. Hybrids were identified that performed equally or better than the wild genotypes, indicating that two backcrossing events did not eliminate the effect of the crop genomic segments that contributed to the vigour of the BC1 and BC2 hybrids. QTLs for plant vigour under non-stress and the various stress conditions were detected in the two populations with positive as well as negative effects from the crop. Conclusion As it was shown that the crop contributed QTLs with either a positive or a negative effect on plant vigour, we hypothesize that genomic regions exist where transgenes could preferentially be located in order to mitigate their persistence in natural populations through genetic hitchhiking.
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- 2012
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- View/download PDF
23. Utility of Targeted Positron Emission Tomography Imaging to Predict Schwannoma Growth in a Murine Tumor Model.
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Morgan J, Manickavel S, Sorace A, Hartman Y, Eli A, Massicano A, Gonzalez ML, Warram JM, and Walsh E
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- Animals, Mice, Mice, Nude, Vascular Endothelial Growth Factor A, Positron-Emission Tomography methods, Immunoglobulin G, Positron Emission Tomography Computed Tomography, Neurilemmoma diagnostic imaging
- Abstract
Objective: To identify if targeted positron emission tomography (PET) imaging with radiolabeled antibodies can predict tumor growth rate and ultimate tumor size in a murine flank schwannoma model., Study Design: Animal research study., Methods: Rat schwannoma cells were cultured and implanted into 40 athymic nude mice. Once tumors reached 5 mm in diameter, 30 mice were injected with zirconium-89 labeled antibodies (HER2/Neu, vascular endothelial growth factor receptor 2 (VEGFR2), or IgG isotype). PET/CT was performed, and standardized uptake values (SUV) were recorded. Tumors were serially measured until mice were sacrificed per IACUC protocol. Statistical analysis was performed to measure correlations between SUV values, tumor size, and growth., Results: Mean tumor sizes in mm
3 on Day 0 were 144 ± 162 for anti-HER2/Neu, 212 ± 247 for anti-VEGFR2, and 172 ± 204 for IgG isotype groups respectively. Mean growth rates in mm3 /day were 531 ± 250 for HER2, 584 ± 188 for VEGFR2, and 416 ± 163 for the IgG isotype group. For both initial tumor size and growth rates, there was no significant difference between groups. There were significant correlations between maximum tumor volume and both the SUV max in the HER2 group (p = 0.0218, R2 = 0.5020), and we observed significant correlations between growth rate, and SUV values (p = 0.0156, R2 = 0.5394). Respectively, in the anti-VEGFR2 group, there were no significant correlations., Conclusion: In a murine schwannoma model, immunotargeted PET imaging with anti-HER2/Neu antibodies predicted tumor growth rate and final tumor size. Laryngoscope, 134:1372-1380, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)- Published
- 2024
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24. The Ultrasound Window Into Vascular Ageing: A Technology Review by the VascAgeNet COST Action.
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Bianchini E, Guala A, Golemati S, Alastruey J, Climie RE, Dalakleidi K, Francesconi M, Fuchs D, Hartman Y, Malik AEF, Makūnaitė M, Nikita KS, Park C, Pugh CJA, Šatrauskienė A, Terentes-Printizios D, Teynor A, Thijssen D, Schmidt-Trucksäss A, Zupkauskienė J, Boutouyrie P, Bruno RM, and Reesink KD
- Subjects
- Humans, Ultrasonography methods, Algorithms, Technology, Arteries diagnostic imaging, Ultrasonography, Doppler
- Abstract
Non-invasive ultrasound (US) imaging enables the assessment of the properties of superficial blood vessels. Various modes can be used for vascular characteristics analysis, ranging from radiofrequency (RF) data, Doppler- and standard B/M-mode imaging, to more recent ultra-high frequency and ultrafast techniques. The aim of the present work was to provide an overview of the current state-of-the-art non-invasive US technologies and corresponding vascular ageing characteristics from a technological perspective. Following an introduction about the basic concepts of the US technique, the characteristics considered in this review are clustered into: 1) vessel wall structure; 2) dynamic elastic properties, and 3) reactive vessel properties. The overview shows that ultrasound is a versatile, non-invasive, and safe imaging technique that can be adopted for obtaining information about function, structure, and reactivity in superficial arteries. The most suitable setting for a specific application must be selected according to spatial and temporal resolution requirements. The usefulness of standardization in the validation process and performance metric adoption emerges. Computer-based techniques should always be preferred to manual measures, as long as the algorithms and learning procedures are transparent and well described, and the performance leads to better results. Identification of a minimal clinically important difference is a crucial point for drawing conclusions regarding robustness of the techniques and for the translation into practice of any biomarker., (© 2023 The Authors. Journal of Ultrasound in Medicine published by Wiley Periodicals LLC on behalf of American Institute of Ultrasound in Medicine.)
- Published
- 2023
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25. Metformin Reduces Tumor Growth in a Murine Flank Schwannoma Model.
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Manickavel S, Hartman Y, Burns A, Lora Gonzalez MA, Warram J, Walsh E, Hunter JB, and Killeen DE
- Subjects
- Rats, Animals, Mice, Mice, Nude, Aspirin therapeutic use, Neurilemmoma drug therapy, Neuroma, Acoustic, Metformin pharmacology, Metformin therapeutic use
- Abstract
Hypothesis: Metformin and aspirin reduce vestibular schwannoma (VS) growth., Background: There have been reported associations between patients with VS prescribed metformin and decreased tumor volumetric growth. Aspirin has also been associated with decreased VS growth in animal studies., Methods: Rat schwannoma cell lines were grown and implanted into 50 athymic nude mice. Tumors were grown to 5 mm, and then mice were injected with either low- or high-dose metformin, aspirin, or saline daily. Tumors were measured until 14 days elapsed or mice demonstrated symptoms such as ulceration, inability to walk, or passed away., Results: There were no significant differences in day 0 tumor sizes between the control and the treatment groups ( p = 0.73). In the low-dose, but not high-dose groups, day 7 volumes were significantly different for both metformin ( p = 0.04) and aspirin ( p = 0.02) compared with placebo. Mean tumor growth rates were 126.6 ± 65.6 mm 3 /day for saline compared with 73.7 ± 29.5 mm 3 /day for low-dose metformin ( p = 0.03) and 68.7 ± 34.8 mm 3 /day for low-dose aspirin ( p = 0.016). There were no significant differences in tumor sizes ( p = 0.59) or growth rates ( p = 0.75) between low-dose metformin and aspirin groups. Low-dose groups had treatment stopped at 14 days, with continued monitoring demonstrating significant increases in tumor growth off treatment for both aspirin ( p = 0.006) and metformin ( p = 0.048)., Conclusions: Metformin treatment significantly reduced VS growth to a similar level as aspirin. Furthermore, when removing both metformin and aspirin treatment, tumor growth significantly increased., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)
- Published
- 2023
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26. War damages compensation: a case study on Ukraine.
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Izarova I, Hartman Y, and Nate S
- Subjects
- Ukraine, Commerce, International Cooperation
- Abstract
Russia's illegal, brazen and cynical full-scale invasion of Ukraine began on February 24th, 2022, and is still ongoing at the time of this research (July 2023). The damages incurred by Ukraine and its citizens during the years of occupation of the territories and the war are calculated in millions, although it is difficult to definitively determine both the methodology and specific numbers. To restore justice, it seems much more important to define a fair, transparent, and understandable procedure for compensating the losses suffered by citizens and businesses as a result of these events. This is especially important in the context of the need to implement the goals of sustainable development, in particular, ensuring equal access to justice for all. The article is devoted to these and related issues. To determine the procedure for compensating losses and damages caused by the war, we first determined what exactly can be compensated and who can apply for compensation. These and other factors determine the peculiarities of the procedure for the restoration of rights and compensation for damage caused by the war in Ukraine. In searching for an answer to the researched question, we analyzed the current legislation of Ukraine and draft laws proposed to regulate relations related to compensation for damages. We also conducted a comprehensive analysis of concepts such as losses, damages, compensation, reparations, and reimbursement as defined in national legislation and international treaties. The generalization of the case law of national courts (more than 200 analyzed decisions of the courts of the first and appeal and cassation instances for the period from February 20, 2014 to March 1, 2023, examples of which are presented in the study) indicates the presence of various approaches of compensation for damage, in understanding how to restore the violated rights of citizens., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Izarova I et al.)
- Published
- 2023
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27. Experiences, adherence and satisfaction with a combined exercise and dietary intervention for patients with ovarian cancer undergoing chemotherapy: A mixed-methods study.
- Author
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Stelten S, van Lonkhuijzen LRCW, Hartman YAW, van Driel WJ, Winkels RM, Kenter GG, Buffart LM, and Hoedjes M
- Subjects
- Carcinoma, Ovarian Epithelial drug therapy, Female, Humans, Patient Satisfaction, Personal Satisfaction, Ovarian Neoplasms drug therapy, Quality of Life
- Abstract
Objective: This study examined experiences, adherence and satisfaction with a combined exercise and dietary intervention in patients with ovarian cancer and their healthcare professionals (HCPs) as part of the randomized PADOVA trial., Methods: A mixed-methods approach was used in 24 patients with ovarian cancer receiving first-line chemotherapy who were randomly allocated to a combined exercise and dietary intervention or usual care with counseling sessions post-treatment. Qualitative data on intervention experiences, adherence and satisfaction was collected using semi-structured interviews with patients and their HCPs (n = 18 physical therapists; n = 5 dietitians). Quantitative data on adherence and satisfaction was collected to provide context to qualitative data., Results: Exercise relative dose intensity ranged from 36 to 100% (median 72%) and patients attended 33-133% (median 100%) of the prescribed dietary counseling sessions. Patients appreciated guidance on exercise and nutrition and perceived benefits including improved physical fitness, quality of life, peer support and recovery after surgery and/or chemotherapy cycles. Both patients and HCPs were satisfied with the intervention and perceived that participation exceeded prior expectations. Median patient satisfaction score with the intervention was 8.5 out of 10. Suggestions for improving the intervention included further personalization of the number, content and scheduling of the sessions to preferences of patients and HCPs. Patients in the usual care group reported counseling sessions post-chemotherapy to be too little too late., Conclusions: Patients with ovarian cancer adhered well to the intervention. Numerous perceived benefits of the intervention were reported by patients and HCPs. Good adherence and positive experiences support successful implementation in clinical practice., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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28. Correction: Protocol of the Healthy Brain Study: An accessible resource for understanding the human brain and how it dynamically and individually operates in its bio-social context.
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Aarts E, Akkerman A, Altgassen M, Bartels R, Beckers D, Bevelander K, Bijleveld E, Davidson EB, Boleij A, Bralten J, Cillessen T, Claassen J, Cools R, Cornelissen I, Dresler M, Eijsvogels T, Faber M, Fernández G, Figner B, Fritsche M, Füllbrunn S, Gayet S, van Gelder MMHJ, Gerven MV, Geurts S, Greven CU, Groefsema M, Haak K, Hagoort P, Hartman Y, van der Heijden B, Hermans E, Heuvelmans V, Hintz F, Hollander JD, Hulsman AM, Idesis S, Jaeger M, Janse E, Janzing J, Kessels RPC, Karremans JC, Kleijn W, Klein M, Klumpers F, Kohn N, Korzilius H, Krahmer B, Lange F, Leeuwen JV, Liu H, Luijten M, Manders P, Manevska K, Marques JP, Matthews J, McQueen JM, Medendorp P, Melis R, Meyer A, Oosterman J, Overbeek L, Peelen M, Popma J, Postma G, Roelofs K, van Rossenberg YGT, Schaap G, Scheepers P, Selen L, Starren M, Swinkels DW, Tendolkar I, Thijssen D, Timmerman H, Tutunji R, Tuladhar A, Veling H, Verhagen M, Verkroost J, Vink J, Vriezekolk V, Vrijsen J, Vyrastekova J, Wal SV, Willems R, and Willemsen A
- Abstract
[This corrects the article DOI: 10.1371/journal.pone.0260952.].
- Published
- 2022
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29. Protocol of the Healthy Brain Study: An accessible resource for understanding the human brain and how it dynamically and individually operates in its bio-social context.
- Author
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Aarts E, Akkerman A, Altgassen M, Bartels R, Beckers B, Bevelander K, Bijleveld E, Davidson EB, Boleij A, Bralten J, Cillessen T, Claassen J, Cools R, Cornelissen I, Dresler M, Eijsvogels T, Faber M, Fernández G, Figner B, Fritsche M, Füllbrunn S, Gayet S, van Gelder MMHJ, van Gerven M, Geurts S, Greven CU, Groefsema M, Haak K, Hagoort P, Hartman Y, van der Heijden B, Hermans E, Heuvelmans V, Hintz F, den Hollander J, Hulsman AM, Idesis S, Jaeger M, Janse E, Janzing J, Kessels RPC, Karremans JC, de Kleijn W, Klein M, Klumpers F, Kohn N, Korzilius H, Krahmer B, de Lange F, van Leeuwen J, Liu H, Luijten M, Manders P, Manevska K, Marques JP, Matthews J, M. McQueen J, Medendorp P, Melis R, Meyer A, Oosterman J, Overbeek L, Peelen M, Popma J, Postma G, Roelofs K, van Rossenberg YGT, Schaap G, Scheepers P, Selen L, Starren M, Swinkels DW, Tendolkar I, Thijssen D, Timmerman H, Tutunji R, Tuladhar A, Veling H, Verhagen M, Verkroost J, Vink J, Vriezekolk V, Vrijsen J, Vyrastekova J, van der Wal S, Willems R, and Willemsen A
- Subjects
- Adult, Affect physiology, Behavior, Brain diagnostic imaging, COVID-19 diagnosis, Cognition physiology, Female, Humans, Male, Neuroimaging, Sensation physiology, Surveys and Questionnaires, Brain physiology, Social Environment
- Abstract
The endeavor to understand the human brain has seen more progress in the last few decades than in the previous two millennia. Still, our understanding of how the human brain relates to behavior in the real world and how this link is modulated by biological, social, and environmental factors is limited. To address this, we designed the Healthy Brain Study (HBS), an interdisciplinary, longitudinal, cohort study based on multidimensional, dynamic assessments in both the laboratory and the real world. Here, we describe the rationale and design of the currently ongoing HBS. The HBS is examining a population-based sample of 1,000 healthy participants (age 30-39) who are thoroughly studied across an entire year. Data are collected through cognitive, affective, behavioral, and physiological testing, neuroimaging, bio-sampling, questionnaires, ecological momentary assessment, and real-world assessments using wearable devices. These data will become an accessible resource for the scientific community enabling the next step in understanding the human brain and how it dynamically and individually operates in its bio-social context. An access procedure to the collected data and bio-samples is in place and published on https://www.healthybrainstudy.nl/en/data-and-methods/access. Trail registration: https://www.trialregister.nl/trial/7955., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
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30. Correlation of carotid artery reactivity with cardiovascular risk factors and coronary artery vasodilator responses in asymptomatic, healthy volunteers.
- Author
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van Mil AC, Hartman Y, van Oorschot F, Heemels A, Bax N, Dawson EA, Hopkins N, Hopman MT, Green DJ, Oxborough DL, and Thijssen DH
- Subjects
- Adult, Age Factors, Aged, Aged, 80 and over, Blood Flow Velocity, Cardiovascular Diseases physiopathology, Carotid Arteries diagnostic imaging, Carotid Intima-Media Thickness, Cold Temperature, Female, Healthy Volunteers, Humans, Male, Middle Aged, Risk Factors, Young Adult, Carotid Arteries physiology, Coronary Vessels physiology, Vasodilation
- Abstract
Objectives: Carotid artery reactivity (CAR%), involving carotid artery diameter responses to a cold pressor test (CPT), is a noninvasive measure of conduit artery function in humans. This study examined the impact of age and cardiovascular risk factors on the CAR% and the relationship between CAR% and coronary artery vasodilator responses to the CPT., Methods: Ultrasound was used to measure resting and peak carotid artery diameters during the CPT, with CAR% being calculated as the relative change from baseline (%). We compared CAR% between young (n = 50, 24 ± 3 years) and older participants (n = 44, 61 ± 8 years), and subsequently assessed relationships between CAR% and traditional cardiovascular risk factors in 50 participants (44 ± 21 years). Subsequently, we compared left anterior descending (LAD) artery velocity (using transthoracic Doppler) with carotid artery diameter (i.e. CAR%) during the CPT (n = 33, 37 ± 17 years)., Results: A significantly larger CAR% was found in young versus older healthy participants (4.1 ± 3.7 versus 1.8 ± 2.6, P < 0.001). Participants without cardiovascular risk factors demonstrated a higher CAR% than those with at least two risk factors (2.9 ± 2.9 versus 0.5 ± 2.9, P = 0.019). Carotid artery diameter and LAD velocity increased during CPT (P < 0.001). Carotid diameter and change in velocity correlated with LAD velocity (r = 0.486 and 0.402, P < 0.004 and 0.02, respectively)., Conclusion: Older age and cardiovascular risk factors are related to lower CAR%, while CAR% shows good correlation with coronary artery responses to the CPT. Therefore, CAR% may represent a valuable technique to assess cardiovascular risk, while CAR% seems to reflect coronary artery vasodilator function.
- Published
- 2017
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31. Epidermal growth factor receptor inhibition by anti-CD147 therapy in cutaneous squamous cell carcinoma.
- Author
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Frederick JW, Sweeny L, Hartman Y, Zhou T, and Rosenthal EL
- Subjects
- Animals, Carcinoma, Squamous Cell pathology, Cell Line, Tumor, Cell Movement drug effects, Cell Proliferation drug effects, Down-Regulation, Humans, Mice, Nude, RNA, Small Interfering metabolism, Skin Neoplasms pathology, Xenograft Model Antitumor Assays, Antibodies, Monoclonal pharmacology, Basigin immunology, Carcinoma, Squamous Cell drug therapy, ErbB Receptors antagonists & inhibitors, Skin Neoplasms drug therapy
- Abstract
Background: Advanced cutaneous squamous cell carcinoma (SCC) is an uncommon and aggressive malignancy. As a result, there is limited understanding of its biology and pathogenesis. CD147 and epidermal growth factor receptor (EGFR) have been identified as oncologically important targets, but their relationship remains undefined in cutaneous SCC., Methods: Multiple cutaneous SCC cell lines (Colo-16, SRB-1, and SRB-12), were treated in vitro with a range of chimeric anti-CD147 monoclonal antibody (mAb) (0, 50, 100, and 200 µg/mL) or transfected with a small interfering RNA against CD147 (SiCD147). Cell proliferation, migration (scratch wound healing assay), and protein expression was then assessed. In vivo, Colo-16 flank xenografts were treated anti-CD147 mAb (150 µg i.p. triweekly)., Results: After treatment with anti-CD147 (200 µg/mL), there was a significant decrease in proliferation for all cell lines relative to controls (p < .005). In addition, treatment with anti-CD147 (200 µg/mL) resulted in decreased cell migration for all cell lines, with an average of 43% reduction in closure compared to controls (p < .001). Colo-16 SiCD147 expression demonstrated similar reduction in proliferation and wound closure. Anti-CD147 antibody therapy and siRNA mediated reduction in CD147 expression were both found to decrease protein expression of EGFR, which correlated with a reduction in downstream total and phosphorylated protein kinase B (pAKT). Tumor growth in vivo was reduced for both the anti-CD147 treatment group and the SiCD147 group relative to controls., Conclusion: Inhibition and downregulation of CD147 in cutaneous SCC resulted in suppression of the malignant phenotype in vitro and in vivo, which may be mediated in part by an alteration in EGFR expression. As a result, CD147 may serve as a potential therapeutic target for advanced cutaneous SCC., (© 2014 Wiley Periodicals, Inc.)
- Published
- 2016
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32. Fluorescence-guided resection of experimental malignant glioma using cetuximab-IRDye 800CW.
- Author
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Warram JM, de Boer E, Korb M, Hartman Y, Kovar J, Markert JM, Gillespie GY, and Rosenthal EL
- Subjects
- Animals, Brain Neoplasms pathology, Cell Line, Tumor, ErbB Receptors, Female, Glioblastoma pathology, Image Processing, Computer-Assisted, Immunohistochemistry, Infrared Rays, Mice, Mice, Nude, Neoplasm Transplantation, Benzenesulfonates, Brain Neoplasms surgery, Cetuximab, Fluorescent Dyes, Glioblastoma surgery, Indoles, Neurosurgical Procedures methods, Surgery, Computer-Assisted methods
- Abstract
The standard treatment for glioblastoma multiforme (GBM) remains maximal safe surgical resection. Here, we evaluated the ability of a systemically administered antibody-dye probe conjugate (cetuximab-IRDye 800CW) to provide sufficient fluorescent contrast for surgical resection of disease in both subcutaneous and orthotopic animal models of GBM. Multiple luciferase-positive GBM cell lines (D-54MG, U-87MG, and U-251MG; n = 5) were implanted in mouse flank and tumors were fluorescently imaged daily using a closed-field near-infrared (NIR) system after cetuximab-IRDye 800CW systemic administration. Orthotopic models were also generated (n = 5), and tumor resection was performed under white light and fluorescence guidance using an FDA-approved wide-field NIR imaging system. Residual tumor was monitored using luciferase imaging. Immunohistochemistry was performed to characterize tumor fluorescence, epidermal growth factor receptor (EGFR) expression, and vessel density. Daily imaging of tumors revealed an average tumor-to-background (TBR) of 4.5 for U-87MG, 4.1 for D-54MG, and 3.7 for U-251MG. Fluorescence intensity within the tumors peaked on day-1 after cetuximab-IRDye 800CW administration, however the TBR increased over time in two of the three cell lines. For the orthotopic model, TBR on surgery day ranged from 19 to 23 during wide-field, intraoperative imaging. Surgical resection under white light on day 3 after cetuximab-IRDye 800CW resulted in an average 41% reduction in luciferase signal while fluorescence-guided resection using wide-field NIR imaging resulted in a significantly (P = 0.001) greater reduction in luciferase signal (87%). Reduction of luciferase signal was found to correlate (R (2) = 0.99) with reduction in fluorescence intensity. Fluorescence intensity was found to correlate (P < 0.05) with EGFR expression in D-54MG and U-251MG tumor types but not U-87MG. However, tumor fluorescence was found to correlate with vessel density for the U-87MG tumors. Here we show systemic administration of cetuximab-IRDye 800CW in combination with wide-field NIR imaging provided robust and specific fluorescence contrast for successful localization of disease in subcutaneous and orthotopic animal models of GBM.
- Published
- 2015
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33. Time-dependent pretreatment with bevacuzimab increases tumor specific uptake of cetuximab in preclinical oral cavity cancer studies.
- Author
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Chung TK, Warram J, Day KE, Hartman Y, and Rosenthal EL
- Subjects
- Animals, Bevacizumab administration & dosage, Cell Line, Tumor, Cetuximab administration & dosage, Disease Models, Animal, Humans, Mice, Mice, Nude, Mouth Neoplasms pathology, Bevacizumab therapeutic use, Cetuximab therapeutic use, Mouth Neoplasms drug therapy
- Abstract
Inadequate delivery of therapeutics into tumors has been suggested as a reason for poor response. We hypothesize that bevacizumab, an antibody to vascular endothelial growth factor (VEGF), can improve cetuximab uptake in squamous cell carcinoma tumors. Athymic nude mice were implanted with OSC19 and SCC1 human cancer lines in a subcutaneous flank model. Mice were imaged daily for 14 days after intravenous tail vein injections of the following groups: IgG-IRDye800 (Control), cetuximab-IRDye800 (CTX800 Only), bevacizumab-IRDye800 (BVZ800 Only), cetuximab-IRDye800 + bevacuzimuab-IRDye800 (Simultaneous), and unlabeled bevacizumab followed by cetuximab-IRDye800 3 days later (Neoadjuvant). Within single-agent groups, the CTX800 Only tumor-specific uptake (TSU) was significantly higher than BVZ800 Only at Day 13 (TSU 8.6 vs 2.8, P < 0.001). The Simultaneous treatment with BVZ800 and CTX800 demonstrated no increase in antibody delivery. However, administration of unlabeled bevacizumab 3 days prior to CTX800 (Neoadjuvant group) resulted in significantly higher tumor specific delivery than administration of both antibodies at the same time (11.8 vs Simultaneous 5.0, P < 0.001). This difference can be attributed to a slower decline in tumor fluorescence intensity (-6.8% vs. Simultaneous -11.5% per day, respectively). Structural changes in pericyte coverage and functional vessel changes demonstrating decreased proliferation and tumor growth corroborate these fluorescence results. Although simultaneous administration of bevacizumab with cetuximab failed to increase antibody delivery to the tumor, pretreatment with bevacizumab improved TSU reflecting an increase in tumor-specific uptake of cetuximab as a result of vessel normalization.
- Published
- 2015
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34. Recognition of Streptococcus pneumoniae and muramyl dipeptide by NOD2 results in potent induction of MMP-9, which can be controlled by lipopolysaccharide stimulation.
- Author
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Vissers M, Hartman Y, Groh L, de Jong DJ, de Jonge MI, and Ferwerda G
- Subjects
- Cells, Cultured, Crohn Disease immunology, Humans, Leukocytes, Mononuclear immunology, Acetylmuramyl-Alanyl-Isoglutamine metabolism, Host-Pathogen Interactions, Lipopolysaccharides metabolism, Matrix Metalloproteinase 9 biosynthesis, Nod2 Signaling Adaptor Protein metabolism, Streptococcus pneumoniae physiology
- Abstract
Matrix metallopeptidase 9 (MMP-9) is a protease involved in the degradation of extracellular matrix collagen. Evidence suggests that MMP-9 is involved in pathogenesis during Streptococcus pneumoniae infection. However, not much is known about the induction of MMP-9 and the regulatory processes involved. We show here that the Gram-positive bacteria used in this study induced large amounts of MMP-9, in contrast to the Gram-negative bacteria that were used. An important pathogen-associated molecular pattern (PAMP) for Gram-positive bacteria is muramyl dipeptide (MDP). MDP is a very potent inducer of MMP-9 and showed a dose-dependent MMP-9 induction. Experiments using peripheral blood mononuclear cells (PBMCs) from Crohn's disease patients with nonfunctional NOD2 showed that MMP-9 induction by Streptococcus pneumoniae and MDP is NOD2 dependent. Increasing amounts of lipopolysaccharide (LPS), an important PAMP for Gram-negative bacteria, resulted in decreasing amounts of MMP-9. Moreover, the induction of MMP-9 by MDP could be counteracted by simultaneously adding LPS. The inhibition of MMP-9 expression by LPS was found to be regulated posttranscriptionally, independently of tissue inhibitor of metalloproteinase 1 (TIMP-1), an endogenous inhibitor of MMP-9. Collectively, these data show that Streptococcus pneumoniae is able to induce large amounts of MMP-9. These high MMP-9 levels are potentially involved in Streptococcus pneumoniae pathogenesis., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
- Published
- 2014
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35. Abiotic stress QTL in lettuce crop-wild hybrids: comparing greenhouse and field experiments.
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Hartman Y, Hooftman DA, Uwimana B, Schranz ME, van de Wiel CC, Smulders MJ, Visser RG, Michelmore RW, and van Tienderen PH
- Abstract
The development of stress-tolerant crops is an increasingly important goal of current crop breeding. A higher abiotic stress tolerance could increase the probability of introgression of genes from crops to wild relatives. This is particularly relevant to the discussion on the risks of new GM crops that may be engineered to increase abiotic stress resistance. We investigated abiotic stress QTL in greenhouse and field experiments in which we subjected recombinant inbred lines from a cross between cultivated Lactuca sativa cv. Salinas and its wild relative L. serriola to drought, low nutrients, salt stress, and aboveground competition. Aboveground biomass at the end of the rosette stage was used as a proxy for the performance of plants under a particular stress. We detected a mosaic of abiotic stress QTL over the entire genome with little overlap between QTL from different stresses. The two QTL clusters that were identified reflected general growth rather than specific stress responses and colocated with clusters found in earlier studies for leaf shape and flowering time. Genetic correlations across treatments were often higher among different stress treatments within the same experiment (greenhouse or field), than among the same type of stress applied in different experiments. Moreover, the effects of the field stress treatments were more correlated with those of the greenhouse competition treatments than to those of the other greenhouse stress experiments, suggesting that competition rather than abiotic stress is a major factor in the field. In conclusion, the introgression risk of stress tolerance (trans-)genes under field conditions cannot easily be predicted based on genomic background selection patterns from controlled QTL experiments in greenhouses, especially field data will be needed to assess potential (negative) ecological effects of introgression of these transgenes into wild relatives.
- Published
- 2014
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36. Genomic and environmental selection patterns in two distinct lettuce crop-wild hybrid crosses.
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Hartman Y, Uwimana B, Hooftman DA, Schranz ME, van de Wiel CC, Smulders MJ, Visser RG, and van Tienderen PH
- Abstract
Genomic selection patterns and hybrid performance influence the chance that crop (trans)genes can spread to wild relatives. We measured fitness(-related) traits in two different field environments employing two different crop-wild crosses of lettuce. We performed quantitative trait loci (QTL) analyses and estimated the fitness distribution of early- and late-generation hybrids. We detected consistent results across field sites and crosses for a fitness QTL at linkage group 7, where a selective advantage was conferred by the wild allele. Two fitness QTL were detected on linkage group 5 and 6, which were unique to one of the crop-wild crosses. Average hybrid fitness was lower than the fitness of the wild parent, but several hybrid lineages outperformed the wild parent, especially in a novel habitat for the wild type. In early-generation hybrids, this may partly be due to heterosis effects, whereas in late-generation hybrids transgressive segregation played a major role. The study of genomic selection patterns can identify crop genomic regions under negative selection across multiple environments and cultivar-wild crosses that might be applicable in transgene mitigation strategies. At the same time, results were cultivar-specific, so that a case-by-case environmental risk assessment is still necessary, decreasing its general applicability.
- Published
- 2013
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37. Hybridization between crops and wild relatives: the contribution of cultivated lettuce to the vigour of crop-wild hybrids under drought, salinity and nutrient deficiency conditions.
- Author
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Uwimana B, Smulders MJ, Hooftman DA, Hartman Y, van Tienderen PH, Jansen J, McHale LK, Michelmore RW, van de Wiel CC, and Visser RG
- Subjects
- Alleles, Chromosome Mapping, Chromosomes, Plant, Crops, Agricultural growth & development, Crosses, Genetic, Genetic Linkage, Genotype, Lactuca growth & development, Phenotype, Plants, Genetically Modified genetics, Quantitative Trait Loci, Stress, Physiological, Transgenes, Crops, Agricultural genetics, Droughts, Hybridization, Genetic, Lactuca genetics, Salinity
- Abstract
With the development of transgenic crop varieties, crop-wild hybridization has received considerable consideration with regard to the potential of transgenes to be transferred to wild species. Although many studies have shown that crops can hybridize with their wild relatives and that the resulting hybrids may show improved fitness over the wild parents, little is still known on the genetic contribution of the crop parent to the performance of the hybrids. In this study, we investigated the vigour of lettuce hybrids using 98 F(2:3) families from a cross between cultivated lettuce and its wild relative Lactuca serriola under non-stress conditions and under drought, salinity and nutrient deficiency. Using single nucleotide polymorphism markers, we mapped quantitative trait loci associated with plant vigour in the F(2:3) families and determined the allelic contribution of the two parents. Seventeen QTLs (quantitative trait loci) associated with vigour and six QTLs associated with the accumulation of ions (Na(+), Cl(-) and K(+)) were mapped on the nine linkage groups of lettuce. Seven of the vigour QTLs had a positive effect from the crop allele and six had a positive effect from the wild allele across treatments, and four QTLs had a positive effect from the crop allele in one treatment and from the wild allele in another treatment. Based on the allelic effect of the QTLs and their location on the genetic map, we could suggest genomic locations where transgene integration should be avoided when aiming at the mitigation of its persistence once crop-wild hybridization takes place.
- Published
- 2012
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38. Genomic regions in crop-wild hybrids of lettuce are affected differently in different environments: implications for crop breeding.
- Author
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Hartman Y, Hooftman DA, Uwimana B, van de Wiel CC, Smulders MJ, Visser RG, and van Tienderen PH
- Abstract
Many crops contain domestication genes that are generally considered to lower fitness of crop-wild hybrids in the wild environment. Transgenes placed in close linkage with such genes would be less likely to spread into a wild population. Therefore, for environmental risk assessment of GM crops, it is important to know whether genomic regions with such genes exist, and how they affect fitness. We performed quantitative trait loci (QTL) analyses on fitness(-related) traits in two different field environments employing recombinant inbred lines from a cross between cultivated Lactuca sativa and its wild relative Lactuca serriola. We identified a region on linkage group 5 where the crop allele consistently conferred a selective advantage (increasing fitness to 212% and 214%), whereas on linkage group 7, a region conferred a selective disadvantage (reducing fitness to 26% and 5%), mainly through delaying flowering. The probability for a putative transgene spreading would therefore depend strongly on the insertion location. Comparison of these field results with greenhouse data from a previous study using the same lines showed considerable differences in QTL patterns. This indicates that care should be taken when extrapolating experiments from the greenhouse, and that the impact of domestication genes has to be assessed under field conditions.
- Published
- 2012
- Full Text
- View/download PDF
39. CD147 and AGR2 expression promote cellular proliferation and metastasis of head and neck squamous cell carcinoma.
- Author
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Sweeny L, Liu Z, Bush BD, Hartman Y, Zhou T, and Rosenthal EL
- Subjects
- Animals, Basigin metabolism, Carcinoma, Squamous Cell metabolism, Cell Movement, Cell Proliferation, Female, Head and Neck Neoplasms metabolism, Humans, Mice, Mice, Nude, Mucoproteins, Neoplasms, Experimental metabolism, Neoplasms, Experimental pathology, Neoplasms, Experimental secondary, Oncogene Proteins, Tumor Cells, Cultured, Basigin biosynthesis, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell secondary, Head and Neck Neoplasms pathology, Head and Neck Neoplasms secondary, Proteins metabolism
- Abstract
The signaling pathways facilitating metastasis of head and neck squamous cell carcinoma (HNSCC) cells are not fully understood. CD147 is a transmembrane glycoprotein known to induce cell migration and invasion. AGR2 is a secreted peptide also known to promote cell metastasis. Here we describe their importance in the migration and invasion of HNSCC cells (FADU and OSC-19) in vitro and in vivo. In vitro, knockdown of CD147 or AGR2 decreased cellular proliferation, migration and invasion. In vivo, knockdown of CD147 or AGR2 expression decreased primary tumor growth as well as regional and distant metastasis., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
40. Existence of vigorous lineages of crop-wild hybrids in Lettuce under field conditions.
- Author
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Hooftman DA, Hartman Y, Oostermeijer JG, and Den Nijs HJ
- Subjects
- Chimera genetics, Lactuca genetics, Chimera growth & development, Lactuca growth & development
- Abstract
Plant to plant gene flow is a route of environmental exposure for GM plants specifically since crosses with wild relatives could lead to the formation of more vigorous hybrids, which could increase the rate of introgression and the environmental impact. Here, we test the first step in the process of potential transgene introgression: whether hybrid vigor can be inherited to the next generation, which could lead to fixation of altered, i.e., elevated, quantitative traits. The potential for a permanent elevated fitness was tested using individual autogamous progeny lineages of hybrids between the crop Lactuca sativa (Lettuce) and the wild species Lactuca serriola (Prickly Lettuce). We compared progeny from motherplants grown under either greenhouse or field conditions. The survival of young plants depended strongly on maternal environment. Furthermore, we observed that offspring reproductive fitness components were correlated with maternal fitness. Our study demonstrates that post-zygotic genotypic sorting at the young plants stage reduces the number of genotypes non-randomly, leading to inheritance of high levels of reproductive traits in the surviving hybrid lineages, compared to the pure wild relatives. Consequently, directional selection could lead to displacement of the pure wild relative and fixation of more vigorous genome segments originating from crops, stabilizing plant traits at elevated levels. Such information can be used to indentify segments which are less likely to introgress into wild relative populations as a target for transgene insertion., (© ISBR, EDP Sciences, 2010.)
- Published
- 2009
- Full Text
- View/download PDF
41. Epithelial cells in fetal intestine produce chemerin to recruit macrophages.
- Author
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Maheshwari A, Kurundkar AR, Shaik SS, Kelly DR, Hartman Y, Zhang W, Dimmitt R, Saeed S, Randolph DA, Aprahamian C, Datta G, and Ohls RK
- Subjects
- Adult, Amino Acid Sequence, Caco-2 Cells, Chemokines genetics, Culture Media, Conditioned metabolism, Fetus immunology, Gene Expression Regulation, Developmental, Gestational Age, Humans, Ileum embryology, Immunohistochemistry, Infant, Newborn, Intercellular Signaling Peptides and Proteins, Jejunum embryology, Molecular Sequence Data, Promoter Regions, Genetic, RNA, Messenger metabolism, Receptors, Retinoic Acid metabolism, Reverse Transcriptase Polymerase Chain Reaction, Chemokines metabolism, Chemotaxis, Epithelial Cells immunology, Ileum immunology, Jejunum immunology, Macrophages immunology
- Abstract
Macrophages are first seen in the fetal intestine at 11-12 wk and rapidly increase in number during the 12- to 22-wk period of gestation. The development of macrophage populations in the fetal intestine precedes the appearance of lymphocytes and neutrophils and does not require the presence of dietary or microbial antigens. In this study, we investigated the role of chemerin, a recently discovered, relatively selective chemoattractant for macrophages, in the recruitment of macrophage precursors to the fetal intestine. Chemerin mRNA/protein expression was measured in jejunoileal tissue from 10- to 24-wk human fetuses, neonates operated for intestinal obstruction, and adults undergoing bariatric surgery. The expression of chemerin in intestinal epithelial cells (IECs) was confirmed by using cultured primary IECs and IEC-like cell lines in vitro. The regulatory mechanisms involved in chemerin expression were investigated by in silico and immunolocalization techniques. IECs in the fetal, but not mature, intestine express chemerin. Chemerin expression peaked in the fetal intestine at 20-24 wk and then decreased to original low levels by full term. During the 10- to 24-wk period, chemerin accounted for most of the macrophage chemotactic activity of cultured fetal IECs. The maturational changes in chemerin expression correlated with the expression of retinoic acid receptor-beta in the intestine. Chemerin is an important mediator of epithelial-macrophage cross talk in the fetal/premature, but not in the mature, intestine. Understanding the regulation of the gut macrophage pool is an important step in development of novel strategies to boost mucosal immunity in premature infants and other patient populations at risk of microbial translocation.
- Published
- 2009
- Full Text
- View/download PDF
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