Peter Boer - Academia.edu (original) (raw)

Papers by Peter Boer

Research paper thumbnail of Studies of Laboulbeniales (Fungi, Ascomycota) on Myrmica ants: Rickia wasmannii in the Netherlands

Journal of Hymenoptera Research, 2015

An important group of fungal insect parasites is the Laboulbeniales (Ascomycota). These are micro... more An important group of fungal insect parasites is the Laboulbeniales (Ascomycota). These are microscopic in size and live attached to the cuticle of their arthropod hosts. Rickia wasmannii is a common European species limited to the ant genus Myrmica (Hymenoptera, Formicidae). We present new records of R. wasmannii in the Netherlands on three host species: Myrmica ruginodis, M. sabuleti, and M. scabrinodis. Our data show a mass infection of M. sabuleti by R. wasmannii. The average parasite prevalence is 38% (n = 3,876). The prevalence was much lower on the other Myrmica species. So far, R. wasmannii infections have been found only on Myrmica species in the rubra-group and the scabrinodis-group. We provide possible explanations for this observation. To date, Rickia wasmannii is known on nine Myrmica species in sixteen European countries; an overview is included in tabulated form.

Research paper thumbnail of Histone Variants during Gametogenesis and Early Development

Epigenetics and Human Health, 2010

... in mouse, present in human spermatozoa Chrom atin remod eling Ishiba shi et al. (2010 ), Ch a... more ... in mouse, present in human spermatozoa Chrom atin remod eling Ishiba shi et al. (2010 ), Ch adwick and Willa rd (2001 ) TH2B 17p11 ... meiosis, likely beyond Chrom atin remod eling Meistrich et al. 1985 ; van Ro ijen et al, 1998 ; Zalensky et al. 2002 ; Unni et al. 1995 H2BFWT ...

Research paper thumbnail of Ketamine effects on brain function — Simultaneous fMRI/EEG during a visual oddball task

Neuroimage, 2011

BackgroundBehavioral and electrophysiological human ketamine models of schizophrenia are used for... more BackgroundBehavioral and electrophysiological human ketamine models of schizophrenia are used for testing compounds that target the glutamatergic system. However, corresponding functional neuroimaging models are difficult to reconcile with functional imaging and electrophysiological findings in schizophrenia. Resolving the discrepancies between different observational levels is critical to understand the complex pharmacological ketamine action and its usefulness for modeling schizophrenia pathophysiology.

Research paper thumbnail of Parp1-XRCC1 and the repair of DNA double strand breaks in mouse round spermatids

Mutation research, Jan 5, 2010

The repair of DNA double strand breaks (DSBs) in male germ cells is slower and differently regula... more The repair of DNA double strand breaks (DSBs) in male germ cells is slower and differently regulated compared to that in somatic cells. Round spermatids show DSB repair and are radioresistant to apoptosis induction. Mutation induction studies using ionizing irradiation, indicated a high frequency of chromosome aberrations (CA) in the next generation. Since they are in a G1 comparable stage of the cell cycle, haploid spermatids are expected to repair DSBs by the non-homologous end-joining pathway (NHEJ). However, immunohistochemical evidence indicates that not all components of the classical NHEJ pathway are available since the presence of DNA-PKcs cannot be shown. Here, we demonstrate that round spermatids, as well as most other types of male germ cells express both Parp1 and XRCC1. Therefore, we have determined whether the alternative Parp1/XRCC1 dependent NHEJ pathway is active in these nuclei and also have tested for classical NHEJ activity by a genetic method. To evaluate DSB re...

Research paper thumbnail of Genetic probing of homologous recombination and non-homologous end joining during meiotic prophase in irradiated mouse spermatocytes

Mutation research, 2010

This study was designed to obtain a better insight into the relative contribution of homologous r... more This study was designed to obtain a better insight into the relative contribution of homologous recombination (HR) and non-homologous end joining (NHEJ) to the repair of radiation-induced DNA double-strand breaks (DSBs) at first meiotic prophase. Early and late pachytene and early diplotene spermatocytes that had completed crossing over were sampled. We studied the kinetics of gamma-H2AX chromatin foci removal after irradiation of mice deficient for HR and mice deficient for NHEJ. Analyzing gamma-H2AX signals in unirradiated RAD54/RAD54B deficient spermatocytes indicated incomplete meiotic recombination repair due to the pronounced increase of gamma-H2AX foci in late prophase primary spermatocytes. In these mice, 8h after irradiation, early pachytene spermatocytes showed a reduction of the numbers of gamma-H2AX foci by 52% compared to 82% in the wild type, the difference being significant. However, after crossing over (in late pachytene and early diplotene), no effect of RAD54/RAD54...

Research paper thumbnail of Role of H2AX in DNA damage response and human cancers

Mutation Research/Reviews in Mutation Research, 2009

H2AX, the evolutionarily conserved variant of histone H2A, has been identified as one of the key ... more H2AX, the evolutionarily conserved variant of histone H2A, has been identified as one of the key histones to undergo various post-translational modifications in response to DNA double-strand breaks (DSBs). By virtue of these modifications, that include acetylation, phosphorylation and ubiquitination, H2AX marks the damaged DNA double helix, facilitating local recruitment and retention of DNA repair and chromatin remodeling factors to restore genomic integrity. These modifications are essential for effective DSB repair, so is their removal for cell, to recover from checkpoint arrest. Because of these vital roles during DSB signaling and also its activation during early cancer stages, H2AX is emerging as an intriguing gene in tumor biology, supported further by frequent deletion of the region harboring this gene. This review focuses on the insights gained from recent studies on dynamic regulation of H2AX in DSB repair. Also, posing future challenges in the area of chromatin reorganization and retention of epigenetic signature post-DSB-repair with implication of its haploinsufficiency in human cancers.

Research paper thumbnail of CONVERSION TO MYCOPHENOLATE MOFETIL IN CONJUNCTION WITH STEPWISE WITHDRAWAL OF CYCLOSPORINE IN STABLE RENAL TRANSPLANT RECIPIENTS1

Transplantation, 2000

Mycophenolate mofetil (MMF) is now part of standard immunosuppression in the first phase after re... more Mycophenolate mofetil (MMF) is now part of standard immunosuppression in the first phase after renal transplantation. A relevant question is if it can replace drugs such as cyclosporine (CsA) in the maintenance treatment, improving cardiovascular risk profile. In 17 patients with a stable renal function (at least 6 months) posttransplantation, we studied the effect of CsA replacement by MMF. After starting MMF (1 g b.i.d.), CsA dosage was reduced from regular to low (median trough level 130 microg/L, respectively, 45 microg/L), followed by complete withdrawal, while prednisone (7.5 mg daily) was continued. We measured ambulatory blood pressure, glomerular filtration rate, renal plasma flow, renal vascular resistance, and metabolic factors at start and after 8 weeks on regular, low-dose CsA, respectively, no CsA with MMF and prednisone. Two patients dropped out after the switch to low-dose CsA/MMF, due to diarrhea in one and a steroid responsive rejection in the other. The complete switch from CsA to MMF was successful in all 15 patients and accompanied by a decrease in 24 hr systolic blood pressure (from 152+/-13 to 145+/-13 mmHg; P<0.01), diastolic blood pressure (93+/-9 to 89+/-12 mmHg; P<0.05), RVR (0.29+/-0.06 to 0.25+/-0.09 mmHg.ml/min; P<0.05), and an increase in glomerular filtration rate (46.6+/-8.8 to 58.0+/-10.5 ml/min; P<0.01) and renal plasma flow. Intermediate low density lipoprotein-cholesterol decreased (0.79+/-0.37 to 0.41+/-0.16 mmol/L; P<0.01). High density lipoprotein-cholesterol decreased, but remained in the safe range. After 1 year two patients stopped the MMF; one because of Kaposi's sarcoma and one because of recurrent infections The stepwise switch from CsA to MMF was safe and mostly successful, and had beneficial effects on blood pressure, glomerular hemodynamics, and lipid profile. Beneficial trends were already present after partial withdrawal of CsA.

Research paper thumbnail of Memoirs of an insult: sperm as a possible source of transgenerational epimutations and genetic instability

Molecular Human Reproduction, 2010

Male transgenerational epigenetic effects have been discovered in the discipline of mouse radiati... more Male transgenerational epigenetic effects have been discovered in the discipline of mouse radiation genetics, using genetic and non-genetic readouts. The mechanism to explain the origin of the transmission of epigenetic and genetic instability is still unknown. In a search for a hypothesis that could satisfy the data, we propose that regulation of chromosome structure in the germline, by the occupancy of matrix/scaffold associated regions, contains molecular memory function. The male germline is strikingly dynamic as to chromatin organization. This could explain why experience of irradiation stress leaves a persistent mark in the male germline only. To be installed, such memory requires both S-phase and chromatin reorganization during spermatogenesis and in the zygote, that likely also involves reorganization of loop domains. By this reorganization, another layer of information is added, needed to accommodate early embryonic development. Observations point at the involvement of DNA repair as inducer of transgenerational epigenetic modulation. Nuclear structure, chromatin composition and loop domain organization are aspects of human sperm variability that in many cases of assisted reproduction is increased due to inclusion of more incompletely differentiated/maturated sperm nuclei. Adjustment of loop domains in early embryo development can be anticipated and zygotic and cleavage stage S-phase repair activity will have to deal with potential paternal DNA lesions. Therefore, by changing male nucleus structure due to reproduction from impaired spermatogenesis, the transgenerational information content could be changed as well. We discuss aspects of male reproductive performance in the context of this hypothesis.

Research paper thumbnail of Losartan-sensitive renal damage caused by chronic NOS inhibition does not involve increased renal angiotensin II concentrations

Kidney International, 1999

tion. This important role of Ang II does not seem to Ang II was not significantly different from ... more tion. This important role of Ang II does not seem to Ang II was not significantly different from the control. Blood relate to circulating renin levels, which have been re-Ang II was not significantly different from the control on days ported to be increased [5, 7], decreased [3, 8, 9], un-4, 7, and 14 but was significantly increased after 21 days of changed [4, 6], or variable [10] after chronic NOS inhibil-NNA treatment (215 Ϯ 35 vs. 78 Ϯ 13 fmol/ml in control, tion. P Ͻ 0.05). Ang II type-1 (AT 1 ) receptor blockade prevented the severe renal injury and hypertension induced by chronic This apparent contradiction might be explained by NOS inhibition.

Research paper thumbnail of Blood volume, colloid osmotic pressure and F-cell ratio in children with the nephrotic syndrome

Kidney International, 1996

The pathogenesis of edema in the nephrotic syndrome (NS) is classically explained by a decrease i... more The pathogenesis of edema in the nephrotic syndrome (NS) is classically explained by a decrease in blood volume secondary to low plasma colloid osmotic pressure () , resulting in stimulation of renal sodium reabsorption via neural [2] and endocrine pathways. However, we have previously measured blood volume in a large group of adult nephrotic subjects and found values predominantly within the normal range . Compensatory mechanisms such as a decrease in interstitial appear to play a major role in the defense of circulating blood volume in the NS [5].

Research paper thumbnail of The neutral comet assay detects double strand DNA damage in selected and unselected human spermatozoa of normospermic donors

International Journal of Andrology, 2004

The occurrence of DNA breaks in human sperm is of concern to genetic safety in artificial reprodu... more The occurrence of DNA breaks in human sperm is of concern to genetic safety in artificial reproduction techniques. Here, we have explored the neutral comet assay (NCA) for evaluating the frequency of spermatozoa with double strand (ds) DNA breaks in normospermic donors. The NCA results into DNA tail formation by fibre extension and by the separation of DNA fragments. Gamma-irradiated native, lysed and lysed plus RNA and protein degraded human sperm nuclei have been used to assess sensitivity and specificity of fragment formation as an indication for ds DNA breaks. At 5 and 10 Gy gamma irradiation, the sensitivity increases in the order: native, lysed, lysed plus RNA and protein degraded. At 10 Gy, a uniform response between donors was obtained. For technical and biological reasons, the NCA underestimates the true incidence of ds DNA breaks by an unknown factor. Semen samples of six healthy normospermic donors were differentiated by swim up and by Percoll density centrifugation, followed by the NCA. In native semen, percentages of sperm nuclei with ds DNA breaks ranged from 15 to 25%. Swim up and selection for high-density sperm nuclei (high Percoll fraction) reduced the frequency of sperm with ds DNA breaks by about one third, whereas an increased frequency was found in the low Percoll fraction. In conclusion, the response to gamma irradiation of DNA fragment formation indicates the NCA to demonstrate ds DNA breaks which is in keeping with theory and experimental results from somatic cells. Ds DNA breaks are a characteristic of the sperm population of normal donors. Current sperm selection procedures reduce the fractions of sperm with ds DNA breaks, yet are not effective in eliminating these cells.

Research paper thumbnail of How ants find each other; temporal and spatial patterns in nuptial flights

Insectes Sociaux, 2008

Reproduction is a key factor in understanding population ecology and therefore species occurrence... more Reproduction is a key factor in understanding population ecology and therefore species occurrence. However, patterns in reproductive behaviour for distinct ant species remain insufficiently known. In this paper strategies in mate finding are studied for six ant species (Lasius niger, Lasius umbratus, Temnothorax nylanderi, Myrmica rubra, Myrmica ruginodis, Stenamma debile) in a forest -forest edge -agricultural field gradient. Using window traps, we studied whether these species had a restricted nuptial flight season, displayed swarming behaviour, and whether the alates aggregated at the forest edge. The flight season was limited to one month or less for L. niger, T. nylanderi, M. rubra, M. ruginodis and S. debile. Swarming behaviour occurred in all but one (L. umbratus) species. Although none of the six species seemed to have highest nest density at the forest edge, three of them, M. rubra, M. ruginodis and S. debile, showed male aggregations there, indicating this to be the main reproduction site. This last finding could be due to a more suitable micro-climate, but most likely, edges are conspicuous land marks which are used by ants to meet mates. The behavioural patterns of ant sexuals at the forest edge can influence dispersal possibilities in fragmented landscapes, reproductive success and nest densities.

Research paper thumbnail of Effects of vegetation management by mowing on ground-dwelling arthropods

Ecological Engineering, 2010

... The diversity analysis was run with the four groups pooled; while for the analysis on the art... more ... The diversity analysis was run with the four groups pooled; while for the analysis on the arthropod abundances, we omitted the ant abundances, since these numbers mainly reflect distances to nests and not abundance in the plots. 2.3. Vegetation characterisation. ...

Research paper thumbnail of Differences in DNA double strand breaks repair in male germ cell types: Lessons learned from a differential expression of Mdc1 and 53BP1

DNA Repair, 2007

Meiosis Spermatogenesis DNA repair a b s t r a c t In male germ cells the repair of DNA double st... more Meiosis Spermatogenesis DNA repair a b s t r a c t In male germ cells the repair of DNA double strand breaks (DSBs) differs from that described for somatic cell lines. Irradiation induced immunofluorescent foci (IRIF's) signifying a double strand DNA breaks, were followed in spermatogenic cells up to 16 h after the insult. Foci were characterised for Mdc1, 53BP1 and Rad51 that always were expressed in conjecture with ␥-H2AX. Subsequent spermatogenic cell types were found to have different repair proteins.

Research paper thumbnail of Increased frequency of asynapsis and associated meiotic silencing of heterologous chromatin in the presence of irradiation-induced extra DNA double strand breaks

Developmental Biology, 2008

In meiotic prophase of male placental mammals, the heterologous X and Y chromosomes remain largel... more In meiotic prophase of male placental mammals, the heterologous X and Y chromosomes remain largely unsynapsed, which activates meiotic sex chromosome inactivation (MSCI), leading to formation of the transcriptionally silenced XY body. MSCI is most likely related to meiotic silencing of unsynapsed chromatin (MSUC), a mechanism that can silence autosomal unsynapsed chromatin. However, heterologous synapsis and escape from silencing also occur. In mammalian species, formation of DNA double strand breaks (DSBs) during leptotene precedes meiotic chromosome pairing. These DSBs are essential to achieve full synapsis of homologous chromosomes. We generated 25% extra meiotic DSBs by whole body irradiation of mice. This leads to a significant increase in meiotic recombination frequency. In mice carrying translocation chromosomes with synaptic problems, we observed an approximately 35% increase in asynapsis and MSUC of the nonhomologous region in the smallest chromosome pair following irradiation. However, the same nonhomologous region in the largest chromosome pair, shows complete synapsis and escape from MSUC in almost 100% of the nuclei, irrespective of exposure to irradiation. We propose that prevention of synapsis and associated activation of MSUC is linked to the presence of unrepaired meiotic DSBs in the nonhomologous region. Also, spreading of synaptonemal complex formation from regions of homology may act as an opposing force, and drive heterologous synapsis.

Research paper thumbnail of Sperm-derived histones contribute to zygotic chromatin in humans

BMC Developmental Biology, 2008

Background: about 15% to 30% of the DNA in human sperm is packed in nucleosomes and transmission ... more Background: about 15% to 30% of the DNA in human sperm is packed in nucleosomes and transmission of this fraction to the embryo potentially serves as a mechanism to facilitate paternal epigenetic programs during embryonic development. However, hitherto it has not been established whether these nucleosomes are removed like the protamines or indeed contribute to paternal zygotic chromatin, thereby potentially contributing to the epigenome of the embryo.

Research paper thumbnail of Studies of Laboulbeniales (Fungi, Ascomycota) on Myrmica ants: Rickia wasmannii in the Netherlands

Journal of Hymenoptera Research, 2015

An important group of fungal insect parasites is the Laboulbeniales (Ascomycota). These are micro... more An important group of fungal insect parasites is the Laboulbeniales (Ascomycota). These are microscopic in size and live attached to the cuticle of their arthropod hosts. Rickia wasmannii is a common European species limited to the ant genus Myrmica (Hymenoptera, Formicidae). We present new records of R. wasmannii in the Netherlands on three host species: Myrmica ruginodis, M. sabuleti, and M. scabrinodis. Our data show a mass infection of M. sabuleti by R. wasmannii. The average parasite prevalence is 38% (n = 3,876). The prevalence was much lower on the other Myrmica species. So far, R. wasmannii infections have been found only on Myrmica species in the rubra-group and the scabrinodis-group. We provide possible explanations for this observation. To date, Rickia wasmannii is known on nine Myrmica species in sixteen European countries; an overview is included in tabulated form.

Research paper thumbnail of Histone Variants during Gametogenesis and Early Development

Epigenetics and Human Health, 2010

... in mouse, present in human spermatozoa Chrom atin remod eling Ishiba shi et al. (2010 ), Ch a... more ... in mouse, present in human spermatozoa Chrom atin remod eling Ishiba shi et al. (2010 ), Ch adwick and Willa rd (2001 ) TH2B 17p11 ... meiosis, likely beyond Chrom atin remod eling Meistrich et al. 1985 ; van Ro ijen et al, 1998 ; Zalensky et al. 2002 ; Unni et al. 1995 H2BFWT ...

Research paper thumbnail of Ketamine effects on brain function — Simultaneous fMRI/EEG during a visual oddball task

Neuroimage, 2011

BackgroundBehavioral and electrophysiological human ketamine models of schizophrenia are used for... more BackgroundBehavioral and electrophysiological human ketamine models of schizophrenia are used for testing compounds that target the glutamatergic system. However, corresponding functional neuroimaging models are difficult to reconcile with functional imaging and electrophysiological findings in schizophrenia. Resolving the discrepancies between different observational levels is critical to understand the complex pharmacological ketamine action and its usefulness for modeling schizophrenia pathophysiology.

Research paper thumbnail of Parp1-XRCC1 and the repair of DNA double strand breaks in mouse round spermatids

Mutation research, Jan 5, 2010

The repair of DNA double strand breaks (DSBs) in male germ cells is slower and differently regula... more The repair of DNA double strand breaks (DSBs) in male germ cells is slower and differently regulated compared to that in somatic cells. Round spermatids show DSB repair and are radioresistant to apoptosis induction. Mutation induction studies using ionizing irradiation, indicated a high frequency of chromosome aberrations (CA) in the next generation. Since they are in a G1 comparable stage of the cell cycle, haploid spermatids are expected to repair DSBs by the non-homologous end-joining pathway (NHEJ). However, immunohistochemical evidence indicates that not all components of the classical NHEJ pathway are available since the presence of DNA-PKcs cannot be shown. Here, we demonstrate that round spermatids, as well as most other types of male germ cells express both Parp1 and XRCC1. Therefore, we have determined whether the alternative Parp1/XRCC1 dependent NHEJ pathway is active in these nuclei and also have tested for classical NHEJ activity by a genetic method. To evaluate DSB re...

Research paper thumbnail of Genetic probing of homologous recombination and non-homologous end joining during meiotic prophase in irradiated mouse spermatocytes

Mutation research, 2010

This study was designed to obtain a better insight into the relative contribution of homologous r... more This study was designed to obtain a better insight into the relative contribution of homologous recombination (HR) and non-homologous end joining (NHEJ) to the repair of radiation-induced DNA double-strand breaks (DSBs) at first meiotic prophase. Early and late pachytene and early diplotene spermatocytes that had completed crossing over were sampled. We studied the kinetics of gamma-H2AX chromatin foci removal after irradiation of mice deficient for HR and mice deficient for NHEJ. Analyzing gamma-H2AX signals in unirradiated RAD54/RAD54B deficient spermatocytes indicated incomplete meiotic recombination repair due to the pronounced increase of gamma-H2AX foci in late prophase primary spermatocytes. In these mice, 8h after irradiation, early pachytene spermatocytes showed a reduction of the numbers of gamma-H2AX foci by 52% compared to 82% in the wild type, the difference being significant. However, after crossing over (in late pachytene and early diplotene), no effect of RAD54/RAD54...

Research paper thumbnail of Role of H2AX in DNA damage response and human cancers

Mutation Research/Reviews in Mutation Research, 2009

H2AX, the evolutionarily conserved variant of histone H2A, has been identified as one of the key ... more H2AX, the evolutionarily conserved variant of histone H2A, has been identified as one of the key histones to undergo various post-translational modifications in response to DNA double-strand breaks (DSBs). By virtue of these modifications, that include acetylation, phosphorylation and ubiquitination, H2AX marks the damaged DNA double helix, facilitating local recruitment and retention of DNA repair and chromatin remodeling factors to restore genomic integrity. These modifications are essential for effective DSB repair, so is their removal for cell, to recover from checkpoint arrest. Because of these vital roles during DSB signaling and also its activation during early cancer stages, H2AX is emerging as an intriguing gene in tumor biology, supported further by frequent deletion of the region harboring this gene. This review focuses on the insights gained from recent studies on dynamic regulation of H2AX in DSB repair. Also, posing future challenges in the area of chromatin reorganization and retention of epigenetic signature post-DSB-repair with implication of its haploinsufficiency in human cancers.

Research paper thumbnail of CONVERSION TO MYCOPHENOLATE MOFETIL IN CONJUNCTION WITH STEPWISE WITHDRAWAL OF CYCLOSPORINE IN STABLE RENAL TRANSPLANT RECIPIENTS1

Transplantation, 2000

Mycophenolate mofetil (MMF) is now part of standard immunosuppression in the first phase after re... more Mycophenolate mofetil (MMF) is now part of standard immunosuppression in the first phase after renal transplantation. A relevant question is if it can replace drugs such as cyclosporine (CsA) in the maintenance treatment, improving cardiovascular risk profile. In 17 patients with a stable renal function (at least 6 months) posttransplantation, we studied the effect of CsA replacement by MMF. After starting MMF (1 g b.i.d.), CsA dosage was reduced from regular to low (median trough level 130 microg/L, respectively, 45 microg/L), followed by complete withdrawal, while prednisone (7.5 mg daily) was continued. We measured ambulatory blood pressure, glomerular filtration rate, renal plasma flow, renal vascular resistance, and metabolic factors at start and after 8 weeks on regular, low-dose CsA, respectively, no CsA with MMF and prednisone. Two patients dropped out after the switch to low-dose CsA/MMF, due to diarrhea in one and a steroid responsive rejection in the other. The complete switch from CsA to MMF was successful in all 15 patients and accompanied by a decrease in 24 hr systolic blood pressure (from 152+/-13 to 145+/-13 mmHg; P<0.01), diastolic blood pressure (93+/-9 to 89+/-12 mmHg; P<0.05), RVR (0.29+/-0.06 to 0.25+/-0.09 mmHg.ml/min; P<0.05), and an increase in glomerular filtration rate (46.6+/-8.8 to 58.0+/-10.5 ml/min; P<0.01) and renal plasma flow. Intermediate low density lipoprotein-cholesterol decreased (0.79+/-0.37 to 0.41+/-0.16 mmol/L; P<0.01). High density lipoprotein-cholesterol decreased, but remained in the safe range. After 1 year two patients stopped the MMF; one because of Kaposi's sarcoma and one because of recurrent infections The stepwise switch from CsA to MMF was safe and mostly successful, and had beneficial effects on blood pressure, glomerular hemodynamics, and lipid profile. Beneficial trends were already present after partial withdrawal of CsA.

Research paper thumbnail of Memoirs of an insult: sperm as a possible source of transgenerational epimutations and genetic instability

Molecular Human Reproduction, 2010

Male transgenerational epigenetic effects have been discovered in the discipline of mouse radiati... more Male transgenerational epigenetic effects have been discovered in the discipline of mouse radiation genetics, using genetic and non-genetic readouts. The mechanism to explain the origin of the transmission of epigenetic and genetic instability is still unknown. In a search for a hypothesis that could satisfy the data, we propose that regulation of chromosome structure in the germline, by the occupancy of matrix/scaffold associated regions, contains molecular memory function. The male germline is strikingly dynamic as to chromatin organization. This could explain why experience of irradiation stress leaves a persistent mark in the male germline only. To be installed, such memory requires both S-phase and chromatin reorganization during spermatogenesis and in the zygote, that likely also involves reorganization of loop domains. By this reorganization, another layer of information is added, needed to accommodate early embryonic development. Observations point at the involvement of DNA repair as inducer of transgenerational epigenetic modulation. Nuclear structure, chromatin composition and loop domain organization are aspects of human sperm variability that in many cases of assisted reproduction is increased due to inclusion of more incompletely differentiated/maturated sperm nuclei. Adjustment of loop domains in early embryo development can be anticipated and zygotic and cleavage stage S-phase repair activity will have to deal with potential paternal DNA lesions. Therefore, by changing male nucleus structure due to reproduction from impaired spermatogenesis, the transgenerational information content could be changed as well. We discuss aspects of male reproductive performance in the context of this hypothesis.

Research paper thumbnail of Losartan-sensitive renal damage caused by chronic NOS inhibition does not involve increased renal angiotensin II concentrations

Kidney International, 1999

tion. This important role of Ang II does not seem to Ang II was not significantly different from ... more tion. This important role of Ang II does not seem to Ang II was not significantly different from the control. Blood relate to circulating renin levels, which have been re-Ang II was not significantly different from the control on days ported to be increased [5, 7], decreased [3, 8, 9], un-4, 7, and 14 but was significantly increased after 21 days of changed [4, 6], or variable [10] after chronic NOS inhibil-NNA treatment (215 Ϯ 35 vs. 78 Ϯ 13 fmol/ml in control, tion. P Ͻ 0.05). Ang II type-1 (AT 1 ) receptor blockade prevented the severe renal injury and hypertension induced by chronic This apparent contradiction might be explained by NOS inhibition.

Research paper thumbnail of Blood volume, colloid osmotic pressure and F-cell ratio in children with the nephrotic syndrome

Kidney International, 1996

The pathogenesis of edema in the nephrotic syndrome (NS) is classically explained by a decrease i... more The pathogenesis of edema in the nephrotic syndrome (NS) is classically explained by a decrease in blood volume secondary to low plasma colloid osmotic pressure () , resulting in stimulation of renal sodium reabsorption via neural [2] and endocrine pathways. However, we have previously measured blood volume in a large group of adult nephrotic subjects and found values predominantly within the normal range . Compensatory mechanisms such as a decrease in interstitial appear to play a major role in the defense of circulating blood volume in the NS [5].

Research paper thumbnail of The neutral comet assay detects double strand DNA damage in selected and unselected human spermatozoa of normospermic donors

International Journal of Andrology, 2004

The occurrence of DNA breaks in human sperm is of concern to genetic safety in artificial reprodu... more The occurrence of DNA breaks in human sperm is of concern to genetic safety in artificial reproduction techniques. Here, we have explored the neutral comet assay (NCA) for evaluating the frequency of spermatozoa with double strand (ds) DNA breaks in normospermic donors. The NCA results into DNA tail formation by fibre extension and by the separation of DNA fragments. Gamma-irradiated native, lysed and lysed plus RNA and protein degraded human sperm nuclei have been used to assess sensitivity and specificity of fragment formation as an indication for ds DNA breaks. At 5 and 10 Gy gamma irradiation, the sensitivity increases in the order: native, lysed, lysed plus RNA and protein degraded. At 10 Gy, a uniform response between donors was obtained. For technical and biological reasons, the NCA underestimates the true incidence of ds DNA breaks by an unknown factor. Semen samples of six healthy normospermic donors were differentiated by swim up and by Percoll density centrifugation, followed by the NCA. In native semen, percentages of sperm nuclei with ds DNA breaks ranged from 15 to 25%. Swim up and selection for high-density sperm nuclei (high Percoll fraction) reduced the frequency of sperm with ds DNA breaks by about one third, whereas an increased frequency was found in the low Percoll fraction. In conclusion, the response to gamma irradiation of DNA fragment formation indicates the NCA to demonstrate ds DNA breaks which is in keeping with theory and experimental results from somatic cells. Ds DNA breaks are a characteristic of the sperm population of normal donors. Current sperm selection procedures reduce the fractions of sperm with ds DNA breaks, yet are not effective in eliminating these cells.

Research paper thumbnail of How ants find each other; temporal and spatial patterns in nuptial flights

Insectes Sociaux, 2008

Reproduction is a key factor in understanding population ecology and therefore species occurrence... more Reproduction is a key factor in understanding population ecology and therefore species occurrence. However, patterns in reproductive behaviour for distinct ant species remain insufficiently known. In this paper strategies in mate finding are studied for six ant species (Lasius niger, Lasius umbratus, Temnothorax nylanderi, Myrmica rubra, Myrmica ruginodis, Stenamma debile) in a forest -forest edge -agricultural field gradient. Using window traps, we studied whether these species had a restricted nuptial flight season, displayed swarming behaviour, and whether the alates aggregated at the forest edge. The flight season was limited to one month or less for L. niger, T. nylanderi, M. rubra, M. ruginodis and S. debile. Swarming behaviour occurred in all but one (L. umbratus) species. Although none of the six species seemed to have highest nest density at the forest edge, three of them, M. rubra, M. ruginodis and S. debile, showed male aggregations there, indicating this to be the main reproduction site. This last finding could be due to a more suitable micro-climate, but most likely, edges are conspicuous land marks which are used by ants to meet mates. The behavioural patterns of ant sexuals at the forest edge can influence dispersal possibilities in fragmented landscapes, reproductive success and nest densities.

Research paper thumbnail of Effects of vegetation management by mowing on ground-dwelling arthropods

Ecological Engineering, 2010

... The diversity analysis was run with the four groups pooled; while for the analysis on the art... more ... The diversity analysis was run with the four groups pooled; while for the analysis on the arthropod abundances, we omitted the ant abundances, since these numbers mainly reflect distances to nests and not abundance in the plots. 2.3. Vegetation characterisation. ...

Research paper thumbnail of Differences in DNA double strand breaks repair in male germ cell types: Lessons learned from a differential expression of Mdc1 and 53BP1

DNA Repair, 2007

Meiosis Spermatogenesis DNA repair a b s t r a c t In male germ cells the repair of DNA double st... more Meiosis Spermatogenesis DNA repair a b s t r a c t In male germ cells the repair of DNA double strand breaks (DSBs) differs from that described for somatic cell lines. Irradiation induced immunofluorescent foci (IRIF's) signifying a double strand DNA breaks, were followed in spermatogenic cells up to 16 h after the insult. Foci were characterised for Mdc1, 53BP1 and Rad51 that always were expressed in conjecture with ␥-H2AX. Subsequent spermatogenic cell types were found to have different repair proteins.

Research paper thumbnail of Increased frequency of asynapsis and associated meiotic silencing of heterologous chromatin in the presence of irradiation-induced extra DNA double strand breaks

Developmental Biology, 2008

In meiotic prophase of male placental mammals, the heterologous X and Y chromosomes remain largel... more In meiotic prophase of male placental mammals, the heterologous X and Y chromosomes remain largely unsynapsed, which activates meiotic sex chromosome inactivation (MSCI), leading to formation of the transcriptionally silenced XY body. MSCI is most likely related to meiotic silencing of unsynapsed chromatin (MSUC), a mechanism that can silence autosomal unsynapsed chromatin. However, heterologous synapsis and escape from silencing also occur. In mammalian species, formation of DNA double strand breaks (DSBs) during leptotene precedes meiotic chromosome pairing. These DSBs are essential to achieve full synapsis of homologous chromosomes. We generated 25% extra meiotic DSBs by whole body irradiation of mice. This leads to a significant increase in meiotic recombination frequency. In mice carrying translocation chromosomes with synaptic problems, we observed an approximately 35% increase in asynapsis and MSUC of the nonhomologous region in the smallest chromosome pair following irradiation. However, the same nonhomologous region in the largest chromosome pair, shows complete synapsis and escape from MSUC in almost 100% of the nuclei, irrespective of exposure to irradiation. We propose that prevention of synapsis and associated activation of MSUC is linked to the presence of unrepaired meiotic DSBs in the nonhomologous region. Also, spreading of synaptonemal complex formation from regions of homology may act as an opposing force, and drive heterologous synapsis.

Research paper thumbnail of Sperm-derived histones contribute to zygotic chromatin in humans

BMC Developmental Biology, 2008

Background: about 15% to 30% of the DNA in human sperm is packed in nucleosomes and transmission ... more Background: about 15% to 30% of the DNA in human sperm is packed in nucleosomes and transmission of this fraction to the embryo potentially serves as a mechanism to facilitate paternal epigenetic programs during embryonic development. However, hitherto it has not been established whether these nucleosomes are removed like the protamines or indeed contribute to paternal zygotic chromatin, thereby potentially contributing to the epigenome of the embryo.