Biomedical subjects

Per Jensen

Publications and source records attributed to Per Jensen.

At least 19 recordsLinked to original sources

PubMed2007

Plumage color and feather pecking--behavioral differences associated with PMEL17 genotypes in chicken (Gallus gallus).

An F (5) generation of an advanced inter-cross between red junglefowl (wild-type) and White Leghorn (domesticated) was used to investigate earlier findings suggesting that a mutation in the plumage color gene PMEL17 protects against victimization to feather pecking (FP). F (4) parents were selected according to genotype to produce PMEL17 homozygous offspring (i/i and I/I respectively). Birds were raised and their behavior recorded in groups of either two wild-type i/i (dark colored) and one white I/I, or two I/I and one i/i. In addition each bird was tested for feather preference, reaction to novelty, open-field activity, fear for humans, and tonic-immobility. In the home-pens, i/i birds were more feather pecked and had poorer feather condition than I/I birds. No pecking preference for immobile dark colored feathers was observed. In the open-field test i/i birds vocalized more and earlier than I/I birds, and in the fear-for-human test I/I birds had higher activity at 21 weeks of age. No other behavior differences were observed, but clearly, genotypes of PMEL17 affected some aspects of behavior. Such behavioral differences might be important aspects of the mechanism which predispose i/i individuals for being victims of FP.

Aggression↗

PubMed2007

Quantitative trait loci for BMD and bone strength in an intercross between domestic and wildtype chickens.

UNLABELLED: With chicken used as a model species, we used QTL analysis to examine the genetic contribution to bone traits. We report the identification of four QTLs for femoral traits: one for bone strength, one for endosteal circumference, and two affecting mineral density of noncortical bone. INTRODUCTION: BMD is a highly heritable phenotype, governed by elements at numerous loci. In studies examining the genetic contribution to bone traits, many loci have been identified in humans and in other species. The goal of this study was to identify quantitative trait loci (QTLs) controlling BMD and bone strength in an intercross between wildtype and domestic chickens. MATERIALS AND METHODS: A set of 164 markers, covering 30 chromosomes (chr.), were used to genotype 337 F2-individuals from an intercross of domesticated white Leghorn and wildtype red junglefowl chicken. DXA and pQCT were used to measure BMD and bone structure. Three-point bending tests and torsional strength tests were performed to determine the biomechanical strength of the bone. QTLs were mapped using forward selection for loci with significant marginal effects. RESULTS: Four QTLs for femoral bone traits were identified in QTL analysis with body weight included as a covariate. A QTL on chr. 1 affected female noncortical BMD (LOD 4.6) and is syntenic to human 12q21-12q23. Also located on chr. 1, a locus with synteny to human 12q13-14 affected endosteal circumference (LOD 4.6). On chr. 2, a QTL corresponding to human 5p13-p15, 7p12, 18q12, 18q21, and 9q22-9q31 affected BMD in females; noncortical (LOD 4.0) and metaphyseal (LOD 7.0) BMD by pQCT and BMD by DXA (LOD 5.9). A QTL located on chr. 20 (LOD 5.2) affected bone biomechanical strength and had sex-dependent effects. In addition to the significant QTLs, 10 further loci with suggestive linkage to bone traits were identified. CONCLUSIONS: Four QTLs were identified: two for noncortical BMD, one for endosteal circumference, and one affecting bone biomechanical strength. The future identification of genes responsible for these QTLs will increase the understanding of vertebrate skeletal biology.

Animals↗

PubMed2006

Mutations in SLC45A2 cause plumage color variation in chicken and Japanese quail.

S*S (Silver), S*N (wild type/gold), and S*AL (sex-linked imperfect albinism) form a series of alleles at the S (Silver) locus on chicken (Gallus gallus) chromosome Z. Similarly, sex-linked imperfect albinism (AL*A) is the bottom recessive allele at the orthologous AL locus in Japanese quail (Coturnix japonica). The solute carrier family 45, member 2, protein (SLC45A2), previously denoted membrane-associated transporter protein (MATP), has an important role in vesicle sorting in the melanocytes. Here we report five SLC45A2 mutations. The 106delT mutation in the chicken S*AL allele results in a frameshift and a premature stop codon and the corresponding mRNA appears to be degraded by nonsense-mediated mRNA decay. A splice-site mutation in the Japanese quail AL*A allele causes in-frame skipping of exon 4. Two independent missense mutations (Tyr277Cys and Leu347Met) were associated with the Silver allele in chicken. The functional significance of the former mutation, associated only with Silver in White Leghorn, is unclear. Ala72Asp was associated with the cinnamon allele (AL*C) in the Japanese quail. The most interesting feature concerning the SLC45A2 variants documented in this study is the specific inhibition of expression of red pheomelanin in Silver chickens. This phenotypic effect cannot be explained on the basis of the current, incomplete, understanding of SLC45A2 function. It is an enigma why recessive null mutations at this locus cause an almost complete absence of both eumelanin and pheomelanin whereas some missense mutations are dominant and cause a specific inhibition of pheomelanin production.

Amino Acid Sequence↗

PubMed2006

Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial.

OBJECTIVES: To evaluate the long term effects of perioperative beta blockade on mortality and cardiac morbidity in patients with diabetes undergoing major non-cardiac surgery. DESIGN: Randomised placebo controlled and blinded multicentre trial. Analyses were by intention to treat. SETTING: University anaesthesia and surgical centres and one coordinating centre. PARTICIPANTS: 921 patients aged > 39 scheduled for major non-cardiac surgery. INTERVENTIONS: 100 mg metoprolol controlled and extended release or placebo administered from the day before surgery to a maximum of eight perioperative days. MAIN OUTCOME MEASURES: The composite primary outcome measure was time to all cause mortality, acute myocardial infarction, unstable angina, or congestive heart failure. Secondary outcome measures were time to all cause mortality, cardiac mortality, and non-fatal cardiac morbidity. RESULTS: Mean duration of intervention was 4.6 days in the metoprolol group and 4.9 days in the placebo group. Metoprolol significantly reduced the mean heart rate by 11% (95% confidence interval 9% to 13%) and mean blood pressure by 3% (1% to 5%). The primary outcome occurred in 99 of 462 patients in the metoprolol group (21%) and 93 of 459 patients in the placebo group (20%) (hazard ratio 1.06, 0.80 to 1.41) during a median follow-up of 18 months (range 6-30). All cause mortality was 16% (74/462) in the metoprolol group and 16% (72/459) in the placebo group (1.03, 0.74 to 1.42). The difference in risk for the proportion of patients with serious adverse events was 2.4% (- 0.8% to 5.6%). CONCLUSIONS: Perioperative metoprolol did not significantly affect mortality and cardiac morbidity in these patients with diabetes. Confidence intervals, however, were wide, and the issue needs reassessment. TRIAL REGISTRATION: Current Controlled Trials ISRCTN58485613.

Adrenergic beta-Antagonists↗

PubMed2006

A dispersed fluorescence and ab initio investigation of the X2B1 and A2A1 electronic states of the PH2 molecule.

In this work, the X2B1 and A2A1 electronic states of the phosphino (PH2) free radical have been studied by dispersed fluorescence and ab initio methods. PH2 molecules were produced in a molecular free-jet apparatus by laser vaporizing a silicon rod in the presence of phosphine (PH3) gas diluted in helium. The laser-induced fluorescence, from the excited A2A1 electronic state down to the ground electronic state, was dispersed and analyzed. Ten (upsilon1upsilon2upsilon3) vibrationally excited levels of the ground electronic state, with upsilon1 < or = 2, upsilon2 < or = 6, and upsilon3 = 0, have been observed. Ab initio potential-energy surfaces for the X2B1 and A2A1 electronic states have been calculated at 210 points. These two states correlate with a 2Pi(u) state at linearity and they interact by the Renner-Teller coupling and spin-orbit coupling. Using the ab initio potential-energy surfaces with our RENNER computer program system, the vibronic structure and relative intensities of the A2A1 --> X2B1 emission band system have been calculated in order to corroborate the experimental assignments.

Journal Article↗

PubMed2006

Cancer in persons working in dry cleaning in the Nordic countries.

U.S. studies have reported an increased risk of esophageal and some other cancers in dry cleaners exposed to tetrachloroethylene. We investigated whether the U.S. findings could be reproduced in the Nordic countries using a series of case-control studies nested in cohorts of laundry and dry-cleaning workers identified from the 1970 censuses in Denmark, Norway, Sweden, and Finland. Dry-cleaning work in the Nordic countries during the period when tetrachloroethylene was the dominant solvent was not associated with an increased risk of esophageal cancer [rate ratio (RR) = 0.76; 95% confidence interval (CI), 0.34-1.69], but our study was hampered by some unclassifiable cases. The risks of cancer of the gastric cardia, liver, pancreas, and kidney and non-Hodgkin lymphoma were not significantly increased. Assistants in dry-cleaning shops had a borderline significant excess risk of cervical cancer not found in women directly involved in dry cleaning. We found an excess risk of bladder cancer (RR = 1.44; 95% CI, 1.07-1.93) not associated with length of employment. The finding of no excess risk of esophageal cancer in Nordic dry cleaners differs from U.S. findings. Chance, differences in level of exposure to tetrachloroethylene, and confounding may explain the findings. The overall evidence on bladder cancer in dry cleaners is equivocal.

Case-Control Studies↗

PubMed2005

A calculation of the rovibronic energies and spectrum of the B1A1 electronic state of SiH2.

The B1A1 electronic state of silylene (SiH2) is the second excited singlet state of the molecule and, like the analogous c state of methylene (CH2), it is quasilinear with symmetry 1sigmag+ at linearity. This state dissociates to Si(1D) + H2(1sigmag+). At equilibrium, the B state of SiH2 has an energy that we calculate to be 0.71 eV above that of the dissociation products. However, there is a barrier to dissociation that allows quasibound rovibrational levels to occur, and some have been observed recently [Y. Muramoto et al., J. Chem. Phys. 122, 154302 (2005)]. Starting with our analytical ab initio potential-energy surface, we adjusted it in a fitting to the experimental term values in order to determine the optimum potential-energy function in the bound region. This potential has a C2v equilibrium structure with a SiH bond length of 1.459 angstroms and a bond angle of 165.4 degrees; the barrier to linearity is only 129 cm(-1). Using the optimized potential-energy surface we calculate B-state term values, and using our calculated y and z dipole moment surfaces, we simulate the rotation-vibration spectrum of the state in order to assist in the detection of the matrix isolation spectrum.

Journal Article↗

PubMed2005

Potential-energy surface for the electronic ground state of NH3 up to 20,000 cm-1 above equilibrium.

Ab initio coupled cluster calculations with single and double substitutions and a perturbative treatment of connected triple excitations [CCSD(T)] with the augmented correlation-consistent polarized valence triple-zeta aug-cc-pVTZ basis at 51 816 geometries provide a six-dimensional potential-energy surface for the electronic ground state of NH3. At 3814 selected geometries, CBS+ energies are obtained by extrapolating the CCSD(T) results for the aug-cc-pVXZ(X=T,Q,5) basis sets to the complete basis set (CBS) limit and adding corrections for core-valence correlation and relativistic effects. CBS** ab initio energies are generated at 51,816 geometries by an empirical extrapolation of the CCSD(T)/aug-cc-pVTZ results to the CBS+ limit. They cover the energy region up to 20,000 cm-1 above equilibrium. Parametrized analytical functions are fitted through the ab initio points. For these analytical surfaces, vibrational term values and transition moments are calculated by means of a variational program employing a kinetic-energy operator expressed in the Eckart-Sayvetz frame. Comparisons against experiment are used to assess the quality of the generated potential-energy surfaces. A "spectroscopic" potential-energy surface of NH3 is determined by a slight empirical adjustment of the ab initio potential to the experimental vibrational term values. Variational calculations on this refined surface yield rms deviations from experiment of 0.8 cm-1 for 24 inversion splittings and 0.4 (3.0) cm-1 for 34 (51) vibrational term values up to 6100 (10,300) cm-1.

Journal Article↗

PubMed2005

Dipole moment and rovibrational intensities in the electronic ground state of NH3: bridging the gap between ab initio theory and spectroscopic experiment.

We report theoretical values for the transition moments of an extensive set of vibrational bands in the electronic ground state of (14)NH(3). For selected bands, we have further made detailed simulations of the rotational structure. The calculations are carried out by means of recently developed computational procedures for describing the nuclear motion and are based on a high-level ab initio potential energy surface, and high-level dipole moment surfaces, for the electronic ground state of NH(3). The reported theoretical intensity values are compared to, and found to agree very well with, corresponding experimental results. It is believed that the computational method, in conjunction with high-quality ab initio potential energy and dipole moment surfaces, can simulate rotation-vibration spectra of XY(3) pyramidal molecules prior to observation with sufficient accuracy to facilitate the observation of these spectra. By degrading the accuracy of selected elements of the calculations, we have also investigated the influence of customary approximations on the computed intensity values.

Journal Article↗

PubMed2005

Developmental differences in childhood motor coordination predict adult alcohol dependence: proposed role for the cerebellum in alcoholism.

BACKGROUND: The Danish Longitudinal Study of Alcoholism has identified a number of early biological indicators that predicted alcohol dependence 30 years later. In light of recent evidence linking deficits of the cerebellum to certain neuropsychiatric disorders often comorbid with alcoholism, we hypothesized that developmental deficits in the cerebellar vermis may also play a role in the initiation of adult alcohol dependence. The present study evaluated whether measures of motor development in the first year of life predict alcohol dependence three decades later. METHODS: A total of 241 subjects of the original 330 infants who were entered into this study completed the 30-year follow-up (12 had died). The subjects were men who were drawn from a large birth cohort born in Copenhagen, Denmark, from 1959 to 1961. A comprehensive series of measures were obtained on each subject before, during, and shortly after birth as well as at 1 year of age. Muscle tone at birth and day 5 as well as 1-year measures of motor coordination--age to sitting, standing, and walking--were examined. A DSM-III-R diagnosis of alcohol dependence and a measure of lifetime problem drinking served as the 30-year outcome variables. RESULTS: Several measures of childhood motor development significantly predicted alcohol dependence at 30 years of age. These included deficits in muscle tone 5 days after birth, delays in the age to sitting, and delays in the age to walking. CONCLUSIONS: Relationships found between adult alcoholism and early delays in motor development offer support for the theory that cerebellar deficits may play a causal role in the addiction process.

Adult↗

PubMed2005

Neonatal vitamin K might reduce vulnerability to alcohol dependence in Danish men.

OBJECTIVE: Levels of oxidative defenses and blood-clotting factors are normally reduced in newborns, increasing the risk of injury to developing brain structures around the time of birth. This early neonatal vulnerability corresponds to a timeframe in which the development of reward-related limbic structures is particularly active. Taking advantage of a serendipitous event in the history of treating newborns, we tested the hypothesis that vitamin K supplementation, administered to facilitate the synthesis of blood-clotting proteins within this critical timeframe, might also reduce the development of alcohol dependence later in life. METHOD: Subjects were approximately full-term male infants, selected from a large Danish birth cohort. Two thirds of the original 330 subjects in this study were high-risk sons of alcoholic fathers; 241 of the total completed the 30-year follow-up. Of subjects reported on for this article (N = 238), 44 received vitamin K supplementation at birth; 161 were considered high risk, and 66 were categorized as having lower birth weight (<6 lbs). A comprehensive series of measures was obtained on each subject before, during and shortly after birth as well as at 1 year of age. The Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, diagnosis of alcohol dependence and a measure of lifetime problem drinking served as the 30-year outcome variables. RESULTS: Vitamin K treatment, inherited risk and low birth weight each independently predicted alcohol dependence and problem drinking at age 30. Vitamin K treatment was associated with significantly lower rates of alcohol dependence and fewer symptoms of problem drinking. CONCLUSIONS: Vitamin K treatment at birth might protect against the development of alcoholism in adults by reducing early postnatal hemorrhage and oxidative brain damage.

Adolescent↗

PubMed2005

Genomics meets ethology: a new route to understanding domestication, behavior, and sustainability in animal breeding.

Animal behavior is a central part of animal welfare, a keystone in sustainable animal breeding. During domestication, animals have adapted with respect to behavior and an array of other traits. We compared the behavior of junglefowl and White Leghorn layers, selected for egg production (and indirectly for growth). Jungle-fowl had a more active behavior in social, exploratory, anti-predatory, and feeding tests. A genome scan for Quantitative Trait Loci (QTLs) in a junglefowl x White Leghorn intercross revealed several significant or suggestive QTLs for different traits. Some production QTLs coincided with QTLs for behavior, suggesting that pleiotropic effects may be important for the development of domestication phenotypes. One gene has been located, which has a strong effect on the risk of being a victim of feather pecking, a detrimental behavior disorder. Modern genomics paired with analysis of behavior may help in designing more sustainable and robust breeding in the future.

Animals↗

PubMed2004

Chicken genomics: feather-pecking and victim pigmentation.

Feather-pecking in domestic birds is associated with cannibalism and severe welfare problems. It is a dramatic example of a spiteful behaviour in which the victim's fitness is reduced for no immediate direct benefit to the perpetrator and its evolution is unexplained. Here we show that the plumage pigmentation of a chicken may predispose it to become a victim: birds suffer more drastic feather-pecking when the colour of their plumage is due to the expression of a wild recessive allele at PMEL17, a gene that controls plumage melanization, and when these birds are relatively common in a flock. These findings, obtained using an intercross between a domestic fowl and its wild ancestor, have implications for the welfare of domestic species and offer insight into the genetic changes associated with the evolution of feather-pecking during the early stages of domestication.

Aggression↗

PubMed2004

Fertility pattern does not explain social gradient in breast cancer in denmark.

The present study was undertaken to assess the impact of reproductive behavior on the social class gradient in breast cancer occurrence in Denmark. Objectives were to study whether the gradient across socioeconomic groups could be explained by fertility differences, whether the gradient across educational groups could be explained by fertility differences and whether the effect of socioeconomic group on breast cancer incidence and mortality could be explained by education and vice versa. We studied 674,084 women aged 20-39 at the census on 9 November 1970 for whom we had complete data on fertility history. The cohort was followed up for breast cancer incidence and mortality until 8 November 1998. Fertility history varied considerably across socioeconomic group, where 38% of the academics were childless at the age of 30, in contrast to only 8% of women in agriculture. The academics had the highest risk of breast cancer and women in agriculture had the lowest risk. For incidence, the gradient in the relative risks was 1.74, which changed to 1.49 when fertility history was incorporated and to 1.29 when school education was also taken into account. For school education, women with > or = 12 years of schooling had the highest risk and women with < or = 7 years of schooling had the lowest risk. For incidence, the gradient in the relative risk was 1.38, which changed to 1.26 when fertility history was incorporated and to 1.22 when socioeconomic group was also taken into account.

Adult↗

PubMed2004

A novel test of the phenotype-linked fertility hypothesis reveals independent components of fertility.

The phenotype-linked fertility hypothesis predicts that male sexual ornaments signal fertilizing efficiency and that the coevolution of male ornaments and female preference for such ornaments is driven by female pursuit of fertility benefits. In addition, directional testicular asymmetry frequently observed in birds has been suggested to reflect fertilizing efficiency and to covary with ornament expression. However, the idea of a phenotypic relationship between male ornaments and fertilizing efficiency is often tested in populations where environmental effects mask the underlying genetic associations between ornaments and fertilizing efficiency implied by this idea. Here, we adopt a novel design, which increases genetic diversity through the crossing of two divergent populations while controlling for environmental effects, to test: (i) the phenotypic relationship between male ornaments and both, gonadal (testicular mass) and gametic (sperm quality) components of fertilizing efficiency; and (ii) the extent to which these components are phenotypically integrated in the fowl, Gallus gallus. We show that consistent with theory, the testosterone-dependent expression of a male ornament, the comb, predicted testicular mass. However, despite their functional inter-dependence, testicular mass and sperm quality were not phenotypically integrated. Consistent with this result, males of one parental population invested more in testicular and comb mass, whereas males of the other parental population had higher sperm quality. We found no evidence that directional testicular asymmetry covaried with ornament expression. These results shed new light on the evolutionary relationship between male fertilizing efficiency and ornaments. Although testosterone-dependent ornaments may covary with testicular mass and thus reflect sperm production rate, the lack of phenotypic integration between gonadal and gametic traits reveals that the expression of an ornament is unlikely to reflect the overall fertilizing efficiency of a male.

Analysis of Variance↗

PubMed2004

Major growth QTLs in fowl are related to fearful behavior: possible genetic links between fear responses and production traits in a red junglefowl x white leghorn intercross.

The aim of this work was to study fear responses and their relation to production traits in red junglefowl ( Gallus gallus spp.), White Leghorn ( Gallus domesticus ), and their F2-progeny. Quantitative trait locus (QTL) analyses were performed for behavioral traits to gain information about possible genetic links between fear-related behaviors and production. Four behavioral tests were performed that induce different levels of acute fear (open field [OF], exposure to a novel object, tonic immobility, and restraint). Production traits, that is, egg production, sexual maturity (in females), food intake, and growth, were measured individually. A genome scan using 105 microsatellite markers was carried out to identify QTLs controlling the traits studied. In the OF and novel object tests (NO), Leghorns showed less fear behavior than junglefowl, whereas junglefowl behaved less fearfully in the tonic immobility test (TI) and were more active in the restraint test. In the F2 progeny, only weak phenotypic associations were found between production traits and fear behavior. A significant QTL for TI duration was found on chromosome 1 that coincided with a QTL for egg weight and growth in the same animals. Another QTL for NO in males coincided with another major growth QTL. These two known growth QTLs affected a wide range of reactions in different tests. Several other significant and suggestive QTLs for behavioral traits related to fear were found. These QTLs did not coincide with QTLs for production traits, indicating that these fear variables may not be genetically linked to the production traits we measured here. The results show that loci affecting important production traits are located in the same chromosomal region as loci affecting different fear-related behaviors.

Animals↗

PubMed2004

The Dominant white, Dun and Smoky color variants in chicken are associated with insertion/deletion polymorphisms in the PMEL17 gene.

Dominant white, Dun, and Smoky are alleles at the Dominant white locus, which is one of the major loci affecting plumage color in the domestic chicken. Both Dominant white and Dun inhibit the expression of black eumelanin. Smoky arose in a White Leghorn homozygous for Dominant white and partially restores pigmentation. PMEL17 encodes a melanocyte-specific protein and was identified as a positional candidate gene due to its role in the development of eumelanosomes. Linkage analysis of PMEL17 and Dominant white using a red jungle fowl/White Leghorn intercross revealed no recombination between these loci. Sequence analysis showed that the Dominant white allele was exclusively associated with a 9-bp insertion in exon 10, leading to an insertion of three amino acids in the PMEL17 transmembrane region. Similarly, a deletion of five amino acids in the transmembrane region occurs in the protein encoded by Dun. The Smoky allele shared the 9-bp insertion in exon 10 with Dominant white, as expected from its origin, but also had a deletion of 12 nucleotides in exon 6, eliminating four amino acids from the mature protein. These mutations are, together with the recessive silver mutation in the mouse, the only PMEL17 mutations with phenotypic effects that have been described so far in any species.

Amino Acid Sequence↗

PubMed2003

A global search reveals epistatic interaction between QTL for early growth in the chicken.

We have identified quantitative trait loci (QTL) explaining a large proportion of the variation in body weights at different ages and growth between chronological ages in an F(2) intercross between red junglefowl and White Leghorn chickens. QTL were mapped using forward selection for loci with significant marginal genetic effects and with a simultaneous search for epistatic QTL pairs. We found 22 significant loci contributing to these traits, nine of these were only found by the simultaneous two-dimensional search, which demonstrates the power of this approach for detecting loci affecting complex traits. We have also estimated the relative contribution of additive, dominance, and epistasis effects to growth and the contribution of epistasis was more pronounced prior to 46 days of age, whereas additive genetic effects explained the major portion of the genetic variance later in life. Several of the detected loci affected either early or late growth but not both. Very few loci affected the entire growth process, which points out that early and late growth, at least to some extent, have different genetic regulation.

Aging↗