A missense mutation in the FZD7 gene is associated with dilution of the red areas of the coat in Montbéliarde cattle.

Recently, a new genetically autosomal recessive color phenotype emerged in the red pied bovine Montbéliarde breed. It is characterized by a dilution of the red areas of the coat and was denominated 'milca'. A genome-wide homozygosity scan of 106 cases followed by haplotype analysis revealed a candidate region within BTA2 between positions 89.95 and 91.63 Mb. Analysis of whole-genome sequence data generated from milca animals identified a strong candidate variant within the coding region of the Frizzled-7 gene (FZD7). This gene encodes for a G-protein coupled receptor for Wnt signaling proteins. The variant induces a glycine to alanine substitution in the second extracellular loop, p.(Gly414Ala). Cross-species amino acid alignments revealed that this glycine is conserved among orthologs and most paralogs, suggesting that it plays an important role in FZD function. In addition, genotyping data revealed that the mutant allele is restricted to the Montbéliarde breed, at a 3.7% frequency. All homozygous cows for the mutant allele exhibited the milca phenotype whereas all heterozygotes had no coat color defects. In conclusion, this study strongly suggests that, in cattle, a mutation of FZD7 alone is sufficient to cause a coat color phenotype without any strong other adverse effect.

Switching behavior of droplets crossing nodes on a fiber network.

Lately, curious structures have been erected in arid regions: they are large nets able to catch water from fog. Tiny droplets condense on the mesh and are collected on the bottom of it. This innovative technology is crucial to obtain drinkable water in these inhospitable areas. Many studies aim to understand the behavior of droplets trapped on this entanglement of fibers. However, the motion of a droplet sliding on a network of inclined fibers and encountering several crossings when going down remains an open question. Here, we look at the path chosen by such a drop and, especially, we analyze its behavior at the different nodes of the array. We show that droplets may change from one fiber to another one depending on the slope and the diameter of these fibers. We prove that we can force a droplet to follow a specific path simply by carefully designing the fiber mesh. These findings are expected to provide a very convenient way to manipulate small droplets in applications from microfluidics to fog harvesting.

Childhood body mass index at 5.5 years mediates the effect of prenatal maternal stress on daughters' age at menarche: Project Ice Storm.

Early pubertal timing is known to put women at greater risk for adverse physiological and psychological health outcomes. Of the factors that influence girls' pubertal timing, stress experienced during childhood has been found to advance age at menarche (AAM). However, it is not known if stress experienced by mothers during or in the months before conception can be similarly associated with earlier pubertal timing. Prenatal maternal stress (PNMS) is associated with metabolic changes, such as increased childhood adiposity and risk of obesity, that have been associated with earlier menarchal age. Using a prospective longitudinal design, the present study tested whether PNMS induced by a natural disaster is either directly associated with earlier AAM, or whether there is an indirect association mediated through increased girls' body mass index (BMI) during childhood. A total of 31 girls, whose mothers were exposed to the Quebec's January 1998 ice storm during pregnancy were followed from 6 months to 15.5 years of age. Mother's stress was measured within 6 months of the storm. BMI was measured at 5.5 years, and AAM was assessed through teen's self-report at 13.5 and 15.5 years of age. Results revealed that greater BMI at 5.5 years mediated the effect of PNMS on decreasing AAM [B=-0.059, 95% confidence intervals (-0.18, -0.0035)]. The present study is the first to demonstrate that maternal experience of stressful conditions during pregnancy reduces AAM in the offspring through its effects on childhood BMI. Future research should consider the impact of AAM on other measures of reproductive ability.

Locally induced laminar convection in liquid nitrogen and silicone oils.

We present an experimental study of a laminar convective phenomenon induced by a centimetric heater totally immersed in a liquid pool (Rayleigh number ranging from 10(4) to 10(7)). This local heating is observed to induce a laminar convection that differs from the classical Rayleigh-Bénard cells created by heating the whole bottom of the fluid: the convection pattern is no more periodic. In order to obtain a complete map of the velocity field, we use Particle Image Velocimetry technique. The vertical velocity between the counter-rotating convective cells is used as the relevant physical parameter to describe the phenomenon. The potential cooling applications of this problem lead us to choose liquid nitrogen as an experimental fluid. We thus compare the results obtained for various temperature gradients in liquid nitrogen with experiments performed at room temperature with silicone oils of various viscosities. The theoretical law for the maximal vertical velocity from classical Rayleigh-Bénard experiments is adapted to the specific geometry investigated by using a new definition for the characteristic wavelength. This length is studied and appears to be dependent on the liquid properties. We finally obtain a remarkable agreement between theory and experimental data.

Effects of panel sex composition on the physiological stress responses to psychosocial stress in healthy young men and women.

Men and women differ in regard to psychosocial stress responses. Biological and contextual factors are known to mediate these differences; however, few studies investigated their interaction. In the present study, we examined contributions of both contextual and biological factors to the stress response of young healthy adults. Men and women were exposed to a modified version of Trier Social Stress Test. The participants gave a speech in front of a panel of judges, composed of either male or female panelists. Both men, and women presented a cortisol increase only when exposed to opposite sex panelists. Interestingly, this effect was only observed in women in their follicular phase. This finding showed that the induction of a psychosocial stress response does not strictly rely on direct social evaluation, but also depends on the sex composition of the panel. Implications for future studies are discussed.

Sporadic Legionnaires' disease: the role of domestic electric hot-water tanks.

Sporadic community-acquired legionellosis (SCAL) can be acquired through contaminated aerosols from residential potable water. Electricity-dependent hot-water tanks are widely used in the province of Quebec (Canada) and have been shown to be frequently contaminated with Legionella spp. We prospectively investigated the homes of culture-proven SCAL patients from Quebec in order to establish the proportion of patients whose domestic potable hot-water system was contaminated with the same Legionella isolate that caused their pneumonia. Water samples were collected in each patient's home. Environmental and clinical isolates were compared using pulsed-field gel electrophoresis. Thirty-six patients were enrolled into the study. Legionella was recovered in 12/36 (33%) homes. The residential and clinical isolates were found to be microbiologically related in 5/36 (14%) patients. Contaminated electricity-heated domestic hot-water systems contribute to the acquisition of SCAL. The proportion is similar to previous reports, but may be underestimated.

Effects of unilateral amygdala dopamine depletion on behaviour in the elevated plus maze: role of sex, hemisphere and retesting.

A growing body of literature suggests that sex differences exist in both rodents and humans in terms of the central processing of stress and emotion, and an important factor in this regard may involve differential hemispheric specialization. The amygdala has been shown to be functionally asymmetrical in both rats and humans and its involvement in stress and emotion processing is well documented. Given that amygdala function is importantly modulated by dopamine (DA), the present study examined the effects of left vs. right unilateral DAergic depletion targeting the basolateral amygdala in male and female rats. We examined behaviour in the elevated plus maze over two consecutive days, and plasma adrenocorticotropic hormone (ACTH) levels in response to a separate 30min restraint stress. Overall, females showed significantly more exploration of open arms of the plus maze than males, while not differing in general activity reflected in closed arm entries. Significant SexxHemisphere interactions were observed for all measures related to open arm exploration, as right amygdala DA depletion produced an anxiolytic effect in males, increasing open arm exploration, but reduced this behaviour in females. Moreover, open arm exploration was greatly reduced on the second maze exposure in males, but unchanged in females. A SexxHemisphere interaction was also found for plasma ACTH levels. It is suggested that the role of amygdala DA on stress-related behaviour and physiology reflects inherent differences in amygdala function dependent on both sex and hemisphere.

Measuring indices of lifelong estrogen exposure: self-report reliability.

OBJECTIVE: The utility of clinical markers of lifelong estrogen exposure is established in the understanding of breast cancer, osteoporosis and dementia, among others. However, a good number of studies rely on self-reports to ascertain the involvement of certain estrogen exposure indices. The goal of this study is to assess the reliability of self-reported lifelong estrogen exposure indices by measuring correlation between two repeats. METHODS: A questionnaire assessing lifelong indices of estrogen exposure was developed (revised version included) and completed by 36 healthy postmenopausal women twice within a 4-year interval (age range from 50 to 79 years). Reliability was tested using Pearson's correlation coefficient. RESULTS: Strong significant correlations were observed for most estrogen exposure indices and an effect of age was revealed. Age at menopause and age at initiation of hormone therapy were the two variables leading to weaker correlations across time of measurements; no relation was found between Time 1 and Time 2 when looking at the group of older women (over 65 years of age). CONCLUSIONS: Overall, these results support the use of self-reported measures for most of the lifelong estrogen exposure indices, but they also warn us about the pitfalls of the climacteric period. However, the design of the current study did not allow us to test accuracy; thus, the validity of these self-reported variables needs to be addressed in the future.

A Generalized Caprine-like Hypoplasia Syndrome is localized within a 6-cM interval on bovine chromosome 13 in the Montbéliarde breed.

Caprine-like Generalized Hypoplasia Syndrome (or SHGC) is a new hereditary disorder described in the Montbéliarde breed. We report here the characterization of this new disease, based on the visual examination of animals affected by SHGC, and on physiological and biochemical studies undertaken on samples of both SHGC and normal animals. Biological samples for more than 150 affected calves and their parents have been collected over the past 4 years within the framework of the Bovine Genetic Disease Observatory. First, pedigree analyses showed that the mode of inheritance is most probably autosomal recessive. Then, a genome scan with 113 animals and 140 microsatellite markers revealed a single locus within a 35-cM region on bovine chromosome 13. Genotypes of 261 animals for 18 new microsatellite markers from the region confirmed the localization of the disorder to a 6-cM interval. Finally, based on the analysis of haplotypes in 463 Montbéliarde sires, we estimated the frequency of the SHGC mutated allele in the population and could propose a strategy for the systematic eradication of this disorder in the near future.

Influence of maternal lipid profile on placental protein expression of LDLr and SR-BI.

Maternal hyperlipidemia is a characteristic feature during pregnancy, it has been reported that modification of the maternal lipid profile can induce disturbance during pregnancy. In this study, we evaluated the impact of maternal lipid profile on the placental protein expression of two major receptors in cholesterol metabolism, the low density lipoprotein receptor (LDLr) and the scavenger receptor type B1 (SR-B1). We demonstrate an increase in the level of maternal total circulating cholesterol leads to a significant decrease in the level of the LDLr protein expression, while the level of the SR-BI expression remains unchanged. A similar change, for LDLr, is observed in association with the maternal pre-pregnancy body mass index and weight gain. Our data suggest that the LDLr plays a role in regulating cholesterol delivered to the baby from the placenta.

Identification of a doublet missense substitution in the bovine LRP4 gene as a candidate causal mutation for syndactyly in Holstein cattle.

Syndactyly in Holstein cattle is an autosomal recessive abnormality characterized by the fusion of the functional digits. This disorder has been previously mapped to the telomeric part of bovine chromosome 15. Here, we describe the fine-mapping of syndactyly in Holstein cattle to a 3.5-Mb critical interval using a comparative mapping approach and an extended pedigree generated by embryo transfer. We report genetic evidence for the exclusion of two genes previously suggested as candidates (EXT2 and ALX4) and describe the identification of a doublet mutation in complete linkage disequilibrium with syndactyly in one gene of the critical interval: LRP4. Finally, based on recent discoveries concerning the mouse mutants dan and mdig and a mouse knockout for Lrp4, we present solid evidence that the subsequent substitution in LRP4 exon 33 is a strong candidate causal mutation for syndactyly in Holstein cattle.

Radiation hybrid mapping of genes and newly identified microsatellites in candidate regions for bovine arthrogryposis-palatoschisis and progressive ataxia based on comparative data from man, mouse and rat.

A comparative pathology and mapping strategy was used to initiate a study on two bovine genetic diseases: arthrogryposis-palatoschisis and progressive ataxia, which affect mainly Charolais cattle. Bibliographic studies provided information on the pathology of these diseases, which helped to define similar diseases in other species. Animals affected by bovine arthrogryposis-palatoschisis display similar symptoms to those of muscular dysgenesis, mouse mutants and animals with progressive ataxia to those of Long Evans Shaker rat mutants. Candidate regions are respectively human chromosome 1q32 (BTA16) containing the gene CACNA1S and human chromosome 18q23 (BTA24) containing the gene myelin basic protein (MBP). Primer pairs were designed for 15 loci around each candidate gene, in a region of about 20 megabases and were used to screen a bovine Bacterial Artificial Chromosome (BAC) library. Eighteen microsatellites were found in the identified BAC clones, 11 on BTA24 and seven on BTA16. The genes and microsatellites were mapped by radiation hybrid (RH) analysis and a RH map was obtained for each region with 18 new localizations on BTA16 and 23 on BTA24. Comparative human-bovine analysis of the MBP region shows a good conservation of gene order while that of the CACNA1S region shows several breakpoints.

Fracture properties of the human mandible.

A total of seven human mandibles were struck to breaking point under standardised conditions using a pendulum. The cortical deformation for two impact directions was measured with strain gauge strips located at eight defined sites. Fronto-median impacts led to mostly bilateral and always multiple fractures in the posterior area of the bone, especially in the collum and the condyle. The fracture threshold was between 2.5 and 3.1 kN. Lateral impact caused fractures near the impact area as direct fractures of the ipsilateral corpus. Mainly single and double fractures were observed. For lateral impact the fracture threshold was between 0.6 and 0.8 kN.

Deformation characteristics of the human mandible in low impact experiments.

A total of 11 human mandibles were subjected to physical impacts under standardised conditions. Two impact sites and directions were tested and the impact load was varied in four steps. Two occlusional strengths were applied and the influence of simulated soft tissue covering was recorded. The deformation of the bones was measured using strain gauge strips located at eight defined sites. In a series of frontal to occipital impacts the frontal areas and the collum showed the largest length changes. Increasing impact intensities led to a proportional increase of the length changes. An increase of the occlusional strength was either protective (at the collum) or it increased the deformation (frontal area). The soft tissue covering was only partly protective. Lateral impact was characterised by a compression on the side of the impact and stretching on the other side only. The intensity and speed of deformation increased with increasing distance from the site of impact. A fixed occlusion caused an increase of compression at the site of impact and an increasing stretching in the frontal part of the bone and at the opposite collum.

Paget disease of bone: mapping of two loci at 5q35-qter and 5q31.

Paget disease of bone is characterized by focal increases of the bone-remodeling process. It is the second most common metabolic bone disease after osteoporosis. Genetic factors play a major role in the etiology of Paget disease of bone, and two loci have been mapped for the disorder: PDB1 and PDB2. The gene(s) causing the typical form of the disorder remains to be characterized. To decipher the molecular basis of Paget disease of bone, we performed genetic linkage analysis in 24 large French Canadian families (479 individuals) in which the disorder was segregating as an autosomal dominant trait. After exclusion of PDB2, a genomewide scan was performed on the three most informative family nuclei. LOD scores >1.0 were observed at seven locations. The 24 families were then used to detect strong evidence for linkage to chromosome 5q35-qter. Under heterogeneity, a maximum LOD score of 8.58 was obtained at D5S2073, at straight theta= .1. The same characteristic haplotype was carried by all patients in eight families, suggesting a founder effect. A recombination event in a key family confined the disease region within a 6-cM interval between D5S469 and the telomere. The 16 other families, with very low conditional probability of linkage to 5q35-qter, were further used, to map a second locus at 5q31. Under heterogeneity, a maximum LOD score of 3.70 was detected at D5S500 with straight theta=.00. Recombination events refined the 5q31 region within 12.2 cM, between D5S642 and D5S1972. These observations demonstrate the mapping of two novel loci for Paget disease of bone and provide further evidence for genetic heterogeneity of this highly prevalent disorder. It is proposed that the 5q35-qter and 5q31 loci be named "PDB3" and "PDB4," respectively.

Endochondral ossification of costal cartilage is arrested after chondrocytes have reached hypertrophic stage of late differentiation.

Late cartilage differentiation during endochondral bone formation is a multistep process. Chondrocytes transit through a differentiation cascade under the direction of environmental signals that either stimulate or repress progression from one step to the next. In human costal cartilage, chondrocytes reach very advanced stages of late differentiation and express collagen X. However, remodeling of the tissue into bone is strongly repressed. The second hypertrophy marker, alkaline phosphatase, is not expressed before puberty. Upon sexual maturity, both alkaline phosphatase and collagen X activity levels are increased and slow ossification takes place. Thus, the expression of the two hypertrophy markers is widely separated in time in costal cartilage. Progression of endochondral ossification in this tissue beyond the stage of hypertrophic cartilage appears to be associated with the expression of alkaline phosphatase activity. Costal chondrocytes in culture are stimulated by parathyroid hormone in a PTH/PTHrP receptor-mediated manner to express the fully differentiated hypertrophic phenotype. In addition, the hormone stimulates hypertrophic development even more powerfully through its carboxyterminal domain, presumably by interaction with receptors distinct from PTH/PTHrP receptors. Therefore, PTH can support late cartilage differentiation at very advanced stages, whereas the same signal negatively controls the process at earlier stages.

DNA analysis of abortion material assisted by histology screening.

In cases of rape leading to fertilization, paternity testing can retrospectively identify the assailant. Abortion material commonly represents a mixture of maternal and fetal tissue and blood, which cannot be differentiated with the naked eye. Consequently, DNA typing of abortion material may be complicated, including band overlap if maternal tissue predominates. Therefore, histology screening of the abortion content for typical fetal tissue components, such as chorionic villi, followed by selected DNA typing of this sample is suggested. This combined approach is illustrated by a selected case demonstrating the reliability and concurrence of the histology and genetic results.

Relationship between impact velocity and injuries in fatal pedestrian-car collisions.

The most common type of fatal pedestrian-car collision, i.e. a passenger car with a wedge or pontoon shaped front striking an erect adult with this front, was investigated. A reliable calculation of the impact velocity range by a technical expert and a comprehensive autopsy suitable for traffic accidents were performed in every case. A total of 47 fatalities form the material of this study and the impact velocities varied between 18 and 142 km/h. Primary and secondary injuries did not show a relationship to impact velocity. The occurrence of four types of indirect injuries revealed a clear relationship to impact velocity, i.e. spinal fractures, ruptures of the thoracic aorta, inguinal skin ruptures and dismemberment of the body. Important parameters such as the type of car, impact velocity range and indirect injuries are listed for each individual case. Because of the limited number of cases, the impact velocity ranges (3-30 km/h) instead of mean values were considered. A cautious interpretation of the data can be summarised in the following conclusions: If there is no spinal fracture, the velocity was below 70 km/h and probably below 50 km/h. Aortic and inguinal skin ruptures are always present if the velocity was above 100 km/h but never occurred below 50-60 km/h. If dismemberment occurs, the velocity was above 90 km/h. Consequently, an estimation of the impact velocity from the presence or absence of indirect injuries is possible in pedestrian-car collisions of the type examined. However, the selection criteria applied in this study and additional parameters influencing the collision dynamics have to be considered carefully.