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J Bakker

Publications and source records attributed to J Bakker.

At least 19 recordsLinked to original sources
PubMed2006

Mapping phenotypic plasticity and genotype-environment interactions affecting life-history traits in Caenorhabditis elegans.

Phenotypic plasticity and genotype-environment interactions (GEI) play an important role in the evolution of life histories. Knowledge of the molecular genetic basis of plasticity and GEI provides insight into the underlying mechanisms of life-history changes in different environments. We used a genomewide single-nucleotide polymorphism map in a recombinant N2 x CB4856 inbred panel of the nematode Caenorhabditis elegans to study the genetic control of phenotypic plasticity to temperature in four fitness-related traits, that is, age at maturity, fertility, egg size and growth rate. We mapped quantitative trait loci (QTL) for the respective traits at 12 and 24 degrees C, as well as their plasticities. We found genetic variation and GEI for age at maturity, fertility, egg size and growth rate. GEI in fertility and egg size was attributed to changes in rank order of reaction norms. In case of age at maturity and growth rate, GEI was caused mainly by differences in the among-line variance. In total, 11 QTLs were detected, five QTL at 12 degrees C and six QTL at 24 degrees C, which were associated with life-history traits. Five QTL associated with age at maturity, fertility and growth rate showed QTL x environment interaction. These colocalized with plasticity QTL for the respective traits suggesting allelic sensitivity to temperature. Further fine mapping, complementation analyses and gene silencing are planned to identify candidate genes underlying phenotypic plasticity for age at maturity, fertility and growth.

Animals↗
PubMed2005

Male aromatase-knockout mice exhibit normal levels of activity, anxiety and "depressive-like" symptomatology.

It is well known that estradiol derived from neural aromatization of testosterone plays a crucial role in the development of the male brain and the display of sexual behaviors in adulthood. It was recently found that male aromatase knockout mice (ArKO) deficient in estradiol due to a mutation in the aromatase gene have general deficits in coital behavior and are sexually less motivated. We wondered whether these behavioral deficits of ArKO males could be related to changes in activity, exploration, anxiety and "depressive-like" symptomatology. ArKO and wild type (WT) males were subjected to open field (OF), elevated plus maze (EPM), and forced swim tests (FST), after being exposed or not to chronic mild stress (CMS). CMS was used to evaluate the impact of chronic stressful procedures and to unveil possible differences between genotypes. There was no effect of genotype on OF, EPM and FST behavioral parameters. WT and ArKO mice exposed to CMS or not exhibited the same behavioral profile during these three types of tests. However, all CMS-exposed mice (ArKO and WT) spent less time in the center of the EPM. Additionally, floating duration measured in the FST increased between two tests in both WT and ArKO mice, though that increase was less prominent in mice previously subjected to CMS than in controls. Therefore, both ArKO and WT males displayed the same behavior and had the same response to CMS however CMS exposure slightly modified the behavior displayed by mice of both genotypes in the FST and EPM paradigms. These results show that ArKO males display normal levels of activity, exploration, anxiety and "depressive-like" symptomatology and thus their deficits in sexual behavior are specific in nature and do not result indirectly from other behavioral changes.

Analysis of Variance↗
PubMed2004

[Sepsis, a complicated syndrome with major medical and social consequences].

Severe sepsis is a life-threatening complication of infection. Due to associated organ-failure treatment in an Intensive Care Unit is usually indicated. Since sepsis is defined by the combination and progression of clinical events, correct definitions are essential to enable good comparison between study results and determination of suitable treatment. Severe sepsis is associated with a mortality of 20-60% and decreases the health-related quality of life in survivors. It is estimated that annually in the Netherlands 9000 patients are admitted to an Intensive Care Unit with severe sepsis. Direct medical costs of severe sepsis are estimated at [symbol: see text] 19,500 per patient. Costs correlate strongly with the length of stay. Annually Euro dollar 168,6 million is spent on severe sepsis, which represents 0.5% of all health-care costs and 1.7% of the annual hospital budget in the Netherlands.

Costs and Cost Analysis↗
PubMed2004

Prevalence of exposure and infection of Lawsonia intracellularis among slaughter-age pigs.

The extent of clinical or subclinical infection associated with Lawsonia intracellularis within Dutch pig herds was uncertain. A case-control study of slaughter age pigs was used to study natural infection within Dutch herds and to compare diagnostic methods. From six case herds where clinical disease had been identified recently, and six disease-free herds, 40 pigs of slaughter-age were examined postmortem. The diagnostic methods used were: serology, gross examination, Haematoxylin and Eosin stain (HE), Warthin-Starry silver stain, Lawsonia-specific indirect immunoperoxidase of the ileum, and PCR of ileum mucosa and colon contents. There were 59% seropositive pigs in case herds and 26% seropositive pigs in control herds. Using immunohistochemistry, 57% of case herds and 46% of control herds were bacteria positive in the ileum mucosa. It was concluded that a majority of Dutch herds contain L. intracellularis infected finisher pigs. In some herds this is associated with clinical outbreaks of acute haemorrhagic enteropathy but in other herds no clinical disease is apparent. Many seropositive pigs in herds without clinical disease had evidence of Lawsonia antigen in sites other than the apical cytoplasm of proliferating epithelial cells, particularly the supranuclear region. It was uncertain whether to classify these pigs as having "recovered" from an infection or whether they have a sub-clinical or chronic form of the disease. We concluded that PCR examination of faeces and serology probably provide more specific results than gross examinations at slaughter, and that a monoclonal antibody-based examination of ileum mucosa should be the accepted screening method for this infection.

Animals↗
PubMed2004

Restoration of male sexual behavior by adult exogenous estrogens in male aromatase knockout mice.

We previously found that male aromatase knockout (ArKO) mice that carry a targeted mutation in exons 1 and 2 of the CYP19 gene and as a result cannot aromatize androgen to estrogen show impaired sexual behavior in adulthood. To determine whether this impairment was due to a lack of activation of sexual behavior by estradiol, we studied here male coital behavior as well as olfactory investigation of sexually relevant odors in male ArKO mice following adult treatment with estradiol benzoate (EB) or dihydrotestosterone propionate (DHTP). Again, we found that gonadally intact ArKO males show pronounced behavioral deficits affecting their male coital behavior as well as their olfactory investigation of volatile body odors but not that of soiled bedding. Deficits in male coital behavior were largely corrected following adult treatment with EB and the androgen DHTP, suggesting that estradiol has prominent activational effects on this behavior. By contrast, adult treatment with EB to either castrated or gonadally intact ArKO males did not stimulate olfactory investigation of volatile body odors, suggesting that this impairment may result from a lack of proper organization of this behavior during ontogeny due to the chronic lack of estrogens. In conclusion, the present studies suggest that the behavioral deficits in sexual behavior in male ArKO mice result predominantly from a lack of activation of the behavior by estrogens. This is in contrast with earlier pharmacological studies performed on rats and ferrets that have suggested strong organizational effects of estradiol on male sexual behavior.

Analysis of Variance↗
PubMed2004

Relationships between aromatase activity in the brain and gonads and behavioural deficits in homozygous and heterozygous aromatase knockout mice.

The present study was carried out to determine whether aromatase knockout (ArKO) mice are completely devoid of aromatase activity in their brain and gonads and to compare aromatase activity in wild-type and ArKO mice, as well as in heterozygous (HET) mice of both sexes that were previously shown to display a variety of reproductive behaviours at levels intermediate between wild-type and ArKO mice. Aromatase activity was extremely low, and undetectable by the tritiated water assay, in homogenates of the preoptic area-hypothalamus of adult wild-type mice, but was induced following a 12-day treatment with testosterone. The induction of aromatase activity by testosterone was significantly larger in males than in females. Even after 12 days exposure to testosterone, no aromatase activity was detected in the brain of ArKO mice of either sex whereas HET mice showed intermediate levels of activity between ArKO and wild-type. Aromatase activity was also undetectable in the ovary of adult ArKO females but was very high in the wild-type ovary and intermediate in the HET ovary. In wild-type mice, a high level of aromatase activity was detected on the day of birth even without pretreatment with testosterone. This neonatal activity was higher in males than in females, but females nevertheless appear to display a substantial level of oestrogen production in their brain. Aromatase activity was undetectable in the brain of newborn ArKO males and females and was intermediate between wild-type and ArKO in HET mice. In conclusion, the present study confirms that ArKO mice are unable to synthesize any oestrogens, thereby validating the ArKO mouse as a valuable tool in the study of the physiological roles of oestradiol. In addition, it demonstrates that the intermediate behaviour of HET mice presumably reflects the effect of gene dosage on aromatase expression and activity, that aromatase activity is sexually differentiated in mice during the neonatal period as well as in adulthood and, finally, that the neonatal female brain produces substantial amounts of oestrogens that could play a significant role in the sexual differentiation of the female brain early in life.

Animals↗
PubMed2004

Oestrogen-deficient female aromatase knockout (ArKO) mice exhibit depressive-like symptomatology.

We recently found that female aromatase knockout (ArKO) mice that are deficient in oestradiol due to a targeted mutation in the aromatase gene show deficits in sexual behaviour that cannot be corrected by adult treatment with oestrogens. We determined here whether these impairments are associated with changes in general levels of activity, anxiety or 'depressive-like' symptomatology due to chronic oestrogen deficiency. We also compared the neurochemical profile of ArKO and wild-type (WT) females, as oestrogens have been shown to modulate dopaminergic, serotonergic and noradrenergic brain activities. ArKO females did not differ from WT in spontaneous motor activity, exploration or anxiety. These findings are in line with the absence of major neurochemical alterations in hypothalamus, prefrontal cortex or striatum, which are involved in the expression of these behaviours. By contrast, ArKO females displayed decreased active behaviours, such as struggling and swimming, and increased passive behaviours, such as floating, in repeated sessions of the forced swim test, indicating that these females exhibit 'depressive-like' symptoms. Adult treatment with oestradiol did not reverse the behavioural deficits observed in the forced swim test, suggesting that they may be due to the absence of oestradiol during development. Accordingly, an increased serotonergic activity was observed in the hippocampus of ArKO females compared with WT, which was also not reversed by adult oestradiol treatment. The possible organizational role of oestradiol on the hippocampal serotonergic system and the 'depressive-like' profile of ArKO females provide new insights into the pathophysiology of depression and the increased vulnerability of women to depression.

Animals↗
PubMed2004

Differences between low and high trait impulsivity are not associated with differences in inhibitory motor control.

OBJECTIVE: The present study investigates whether there is an association between trait impulsivity in the normal population and inhibitory motor control as assessed by the stop task. METHOD: Low- and high-impulsive participants (as assessed by the I7 questionnaire; both groups n = 31) performed the stop task. Differences in performance were analyzed by an independent samples t-test. Furthermore, a short meta-analysis was performed on this study and three previous studies with a similar aim. RESULTS: The low- and high-impulsive groups did not differ on the speed to stop the response (SSRT). However, the meta-analysis revealed that high-impulsives are marginally slower in stopping than low-impulsives (effect size = -0.26, p= 0.06). CONCLUSIONS: There is only minor evidence that impulsivity inthe common population is associated with poor inhibitory motor control.

Adolescent↗
PubMed2003

Genetic and physical mapping of homologues of the virus resistance gene Rx1 and the cyst nematode resistance gene Gpa2 in potato.

Nine resistance gene homologues (RGHs) were identified in two diploid potato clones (SH and RH), with a specific primer pair based on conserved motifs in the LRR domain of the potato cyst nematode resistance gene Gpa2 and the potato virus X resistance gene Rx1. A modified AFLP method was used to facilitate the genetic mapping of the RGHs in the four haplotypes under investigation. All nine RGHs appeared to be located in the Gpa2/ Rx1 cluster on chromosome XII. Construction of a physical map using bacterial artificial chromosome (BAC) clones for both the Solanum tuberosum ssp. tuberosum and the S. tuberosum ssp. andigena haplotype of SH showed that the RGHs are located within a stretch of less than 200 kb. Sequence analysis of the RGHs revealed that they are highly similar (93 to 95%) to Gpa2 and Rx1. The sequence identities among all RGHs range from 85 to 100%. Two pairs of RGHs are identical, or nearly so (100 and 99.9%), with each member located in a different genotype. Southern-blot analysis on genomic DNA revealed no evidence for additional homologues outside the Gpa2/ Rx1 cluster on chromosome XII.

Base Sequence↗
PubMed2003

[Admission and discharge criteria for intensive care departments].

Admission and discharge criteria for intensive care departments have been drawn up in order to optimise the use of scarce and costly intensive care facilities. Every patient who could benefit from admission must be assessed by the intensive care specialist beforehand. Admission is indicated for patients with disrupted vital functions in whom recovery of dysfunctioning or failing organ systems is expected, patients who will act as organ donors and patients who undergo diagnostic investigations associated with a high risk of vital complications. Frequent assessment (several times per day) of the 'indication to stay' is indicated in the case of many patients in order to maximise the admission capacity. Discharge from the intensive care department is indicated if the vital functions are stable without life support and no longer require monitoring or treatment, if nursing the patient in the ward is possible, if continuation of the medical treatment is no longer worthwhile, if the patient no longer consents to the treatment and if the benefit of a treatment no longer outweights its negative effects.

Cost-Benefit Analysis↗
PubMed2003

New mutations in two Dutch patients with early infantile galactosialidosis.

Galactosialidosis is an autosomal recessive lysosomal storage disease caused by a combined deficiency of lysosomal beta-galactosidase and neuraminidase as a result of a primary defect in the protective protein/cathepsin A (PPCA). We report the first 2 Dutch cases of early infantile galactosialidosis, both presenting with neonatal ascites. The defect was identified in urine, leukocytes, and fibroblasts. Residual activity was determined with a modified assay for cathepsin A and was <5% in leukocytes and <1% in fibroblasts. Histological examination of the placenta in case 1 showed extensive vacuolization in all cell types. Northern blot analysis of RNA isolated from the patients' cultured fibroblasts showed substantially decreased levels of the PPCA transcript, which nevertheless had the correct size of 2 kb. Mutation analysis of both mRNA and genomic DNA from the patients identified two novel mutations in the PPCA locus. Case 1 was a compound heterozygote, with a single missense mutation in one allele, which resulted in Gly57Ser amino acid substitution, and a single C insertion at nucleotide position 899 in the second allele, which gave rise to a frame shift and premature termination codon. Case 2 was homozygous for the same C899 insertion found in case 1.

Base Sequence↗
PubMed2003

Sexual differentiation of the neuroendocrine mechanisms regulating mate recognition in mammals.

When in breeding condition, male and female mammals seek out and mate with opposite-sex conspecifics. The neural mechanisms controlling mate recognition and heterosexual partner preference are sexually differentiated by the perinatal actions of sex steroid hormones. Many mammalian species use odours to identify potential mates. Thus, sex differences in partner preference may actually reflect sex differences in how male and female mammals perceive socially relevant odours. Two olfactory systems have evolved in vertebrates that differ considerably in their anatomy and function. It is generally believed that the main olfactory system is used to detect a wide variety of volatile odours derived from food prey among many sources, whereas the accessory olfactory system has evolved to detect and process primarily nonvolatile odours shown to influence reproductive behaviours and neuroendocrine functions. Some recent results obtained in oestradiol-deficient aromatase knockout (ArKO) mice that provide evidence for a developmental role of oestradiol in olfactory investigation of volatile body odours are discussed, suggesting that: (i) oestrogens contribute to the development of the main olfactory system and (ii) mate recognition is mediated by the main as opposed to the accessory olfactory system. Thus, sex differences in mate recognition and sexual partner preference may reflect sex differences in the perception of odours by the main olfactory system.

Animals↗
PubMed2003

The aromatase knockout (ArKO) mouse provides new evidence that estrogens are required for the development of the female brain.

The classic view of sexual differentiation is that the male brain develops under the influence of testicular secretions, whereas the female brain develops in the absence of any hormonal stimulation. However, several studies have suggested a possible role of estradiol in female neural development, although they did not provide unequivocal evidence that estradiol is indispensable for the development of the female brain and behavior. As a result, the hypothesis subsequently languished because of the lack of a suitable animal model to test estrogen's possible contribution to female differentiation. The recent introduction of the aromatase knockout (ArKO) mouse, which is deficient in aromatase activity because of a targeted mutation in the CYP19 gene and therefore cannot aromatize androgen to estrogen, has provided a new opportunity to reopen the debate of whether estradiol contributes to the development of the female brain. Female ArKO mice showed reduced levels of lordosis behavior after adult treatment with estradiol and progesterone, suggesting that estradiol is required for the development of the neural mechanisms controlling this behavior in female mice. The neural systems affected may include the olfactory systems in that ArKO females also showed impairments in olfactory investigation of odors from conspecifics. Thus, the classic view of sexual differentiation, that is, the female brain develops in the absence of any hormonal secretion, needs to be re-examined.

Animals↗