Colour-sidedness in Gloucester cattle is associated with a complex structural variant impacting regulatory elements downstream of KIT.

Colour-sidedness is a striking coat colour pattern found in a number of cattle breeds, typically characterised by a white stripe that extends along the back, head and belly of the animal. This dominant phenotype is caused by two related translocations (Cs6 and Cs29 ) that alter a region downstream of the KIT gene. Gloucester cattle are native to the UK and are known for an unusual colour-sided pattern that does not extend to the head. We carried out whole-genome sequencing of two Gloucester bulls as well as colour-sided Irish Moiled, British White and Pustertaler Sprinzen for comparison. We found that the Gloucester cattle also have a complex structural variant downstream of KIT, which overlaps the regions involved in Cs6 and Cs29 . All three alleles potentially disrupt a number of putative regulatory elements downstream of KIT. These results complement and expand on the recently published work focused on the Pinzgauer breed from Austria, a carrier of the same colour-sided pattern as seen in Gloucester cattle.

Body composition assessment in nutrition research: value of BIA technology.

BACKGROUND/OBJECTIVES: There is wide variability in the shape and size of an individual and their body composition. This partly reflects inherent genetic differences, but to a large extent is determined by the extent to which their intake of energy and nutrients has adequately matched their needs over extended periods of time. SUBJECTS/METHODS: During childhood, the effective partitioning of nutrients to tissues reflects the hierarchy of demand for growth and maturation during critical periods of development. At all ages, the structural relationships at the molecular, cellular, tissue and whole-body levels are indicative of functional capability and the capacity to cope with internal and external stresses. RESULTS: Reliable measurements of body composition and their interpretation can mark health, be indicative of the risk of ill-health and be a direct cause of pathology and disease. The bioelectrical impedance of the body has been used as an indirect measure for body composition, because it is a reflection of both its structural and functional characteristics, but the specifics of the relationships between these considerations still need to be determined. CONCLUSIONS: The measurement of bioelectrical impedance is simple to carry out and is non-invasive. It could be further refined and developed to fully explore and exploit its potential utility in practice.

Detection of copy number variants in the horse genome and examination of their association with recurrent laryngeal neuropathy.

We used the data from a recently performed genome-wide association study using the Illumina Equine SNP50 beadchip for the detection of copy number variants (CNVs) and examined their association with recurrent laryngeal neuropathy (RLN), an important equine upper airway disease compromising performance. A total of 2797 CNVs were detected for 477 horses, covering 229 kb and seven SNPs on average. Overlapping CNVs were merged to define 478 CNV regions (CNVRs). CNVRs, particularly deletions, were shown to be significantly depleted in genes. Fifty-two of the 67 common CNVRs (frequency ≥ 1%) were validated by association mapping, Mendelian inheritance, and/or Mendelian inconsistencies. None of the 67 common CNVRs were significantly associated with RLN when accounting for multiple testing. However, a duplication on chromosome 10 was detected in 10 cases (representing three breeds) and two unphenotyped parents but in none of the controls. The duplication was embedded in an 8-Mb haplotype shared across breeds.

Molecular heterogeneity of XY sex reversal in horses.

Male-to-female 64,XY sex reversal is a frequently reported chromosome abnormality in horses. Despite this, the molecular causes of the condition are as yet poorly understood. This is partially because only limited molecular information is available for the horse Y chromosome (ECAY). Here, we used the recently developed ECAY map and carried out the first comprehensive study of the Y chromosome in XY mares (n=18). The integrity of the ECAY in XY females was studied by FISH and PCR using markers evenly distributed along the euchromatic region. The results showed that the XY sex reversal condition in horses has two molecularly distinct forms: (i) a Y-linked form that is characterized by Y chromosome deletions and (ii) a non-Y-linked form where the Y chromosome of affected females is molecularly the same as in normal males. Further analysis of the Y-linked form (13 cases) showed that the condition is molecularly heterogeneous: the smallest deletions spanned about 21 kb, while the largest involved the entire euchromatic region. Regardless of the size, all deletions included the SRY gene. We show that the deletions were likely caused by inter-chromatid recombination events between repeated sequences in ECAY. Further, we hypothesize that the occurrence of SRY-negative XY females in some species (horse, human) but not in others (pig, dog) is because of differences in the organization of the Y chromosome. Finally, in contrast to the Y-linked SRY-negative form of equine XY sex reversal, the molecular causes of SRY-positive XY mares (5 cases) remain as yet undefined.

A 4,103 marker integrated physical and comparative map of the horse genome.

A comprehensive second-generation whole genome radiation hybrid (RH II), cytogenetic and comparative map of the horse genome (2n = 64) has been developed using the 5000rad horse x hamster radiation hybrid panel and fluorescence in situ hybridization (FISH). The map contains 4,103 markers (3,816 RH; 1,144 FISH) assigned to all 31 pairs of autosomes and the X chromosome. The RH maps of individual chromosomes are anchored and oriented using 857 cytogenetic markers. The overall resolution of the map is one marker per 775 kilobase pairs (kb), which represents a more than five-fold improvement over the first-generation map. The RH II incorporates 920 markers shared jointly with the two recently reported meiotic maps. Consequently the two maps were aligned with the RH II maps of individual autosomes and the X chromosome. Additionally, a comparative map of the horse genome was generated by connecting 1,904 loci on the horse map with genome sequences available for eight diverse vertebrates to highlight regions of evolutionarily conserved syntenies, linkages, and chromosomal breakpoints. The integrated map thus obtained presents the most comprehensive information on the physical and comparative organization of the equine genome and will assist future assemblies of whole genome BAC fingerprint maps and the genome sequence. It will also serve as a tool to identify genes governing health, disease and performance traits in horses and assist us in understanding the evolution of the equine genome in relation to other species.

Construction of a medium-density horse gene map.

A medium-density map of the horse genome (Equus caballus) was constructed using genes evenly distributed over the human genome. Three hundred and twenty-three exonic primer pairs were used to screen the INRA and the CHORI-241 equine BAC libraries by polymerase chain reaction and by filter hybridization respectively. Two hundred and thirty-seven BACs containing equine gene orthologues, confirmed by sequencing, were isolated. The BACs were localized to horse chromosomes by fluorescent in situ hybridization (FISH). Overall, 165 genes were assigned to the equine genomic map by radiation hybrid (RH) (using an equine RH(5000) panel) and/or by FISH mapping. A comparison of localizations of 713 genes mapped on the horse genome and on the human genome revealed 59 homologous segments and 131 conserved segments. Two of these homologies (ECA27/HSA8 and ECA12p/HSA11p) had not been previously identified. An enhanced resolution of conserved and rearranged chromosomal segments presented in this study provides clarification of chromosome evolution history.

A critical review of the validity of ego development theory and its measurement.

Loevinger's (1976) theory of ego development represents an important and original approach to understanding personality development. More than 20 years have elapsed since the last substantial critical review of the validity of the theory and its measurement (Loevinger, 1979). Our article provides an updated critical review of the theory by reviewing the considerable body of research that has accumulated over the past 20 years. This review addresses the construct, predictive, and discriminant validity of ego development theory and the Washington University Sentence Completion Test (WUSCT; Loevinger & Wessler, 1970; Loevinger, Wessler, & Redmore, 1970) as its measurement. We conclude that there is substantial empirical support for the conceptual soundness of ego development theory and the WUSCT.

Novel adenosine A1 receptor antagonists. Synthesis and structure-activity relationships of a novel series of 3-(2-cyclohexenyl-3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazolo[1,5 -a]pyridines.

A novel series of 3-(2-cyclohexenyl-3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazol o[1,5-a]pyridines was synthesized and evaluated for in vitro adenosine A1 and A2A receptor binding activities. Most of the cyclohexenyl derivatives (7a-e, 8a-s) were found to be potent adenosine A1 receptor antagonists. In a series of analogues of FR166124 (3a), alcohol 7c, nitrile 7e and amide derivatives (7d, 8c, 8r) were found to be more potent A1 antagonists with higher A2A/A1 selectivity than FR166124. Amongst them, 8r showed considerable water solubility (33.3 mg/mL), but lower than that of the sodium salt of FR166124 (> 200 mg/mL). Additionally, FR166124 had strong diuretic activity by both p.o. and iv administration in rats (minimum effective dose=0.1 and 0.032 mg/kg, respectively).

Discovery of FR166124, a novel water-soluble pyrazolo-[1,5-a]pyridine adenosine A1 receptor antagonist.

Novel 3-(2-cycloalkyl and cycloalkenyl-3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazo lo [1,5-a]-pyridines were synthesized and evaluated for their adenosine A1 receptor binding activities. In this series, FR166124 (3) was found to be the most potent and selective adenosine A1 receptor antagonist, and the double bond of the cyclohexenyl acetic acid group was essential for selectivity of A1 receptor binding. Furthermore, the solubility in water of the sodium salt of FR 166124 was high.

Adolescent reputation enhancement: differentiating delinquent, nondelinquent, and at-risk youths.

This research reports the findings of two studies conducted to measure and then investigate differences between delinquent, nondelinquent, and at-risk youths' orientations towards reputation enhancement. In the first study, concerning item selection and scale development, the factor structure and content validity of a potential Reputation Enhancement Scale were tested by examining the item responses of the scale completed by 230 high-school students. In the second study, the scale was validated by comparing the item responses of 80 delinquent, 90 at-risk, and 90 nondelinquent adolescents with the responses of the original students. The instrument was found to be reliable (alphas from .64 to .92), indicating that the factors are dependable across different samples, and the coefficients of congruence were sufficiently high to investigate meaningful group differences. Three second-order factors (Conforming Reputation, Nonconforming Reputation, Self-presentation) were derived from the 15 first-order factors. Although multivariate analyses revealed significant differences between the reputational orientations of delinquent, at-risk, and nondelinquent participants, the self-presentation second-order factor did not differentiate the three groups.

Belief term development in children with autism, Asperger syndrome, specific language impairment, and normal development: links to theory of mind development.

This study examined the relationship between the development of theory of mind and the development of the belief terms think, know, and guess. Children with autism and Asperger syndrome, matched to children with specific language impairment and normal development, completed false belief, belief term comprehension, and belief term expression tasks. The autistic group's performance on the false belief, belief term comprehension, and belief term expression tasks was significantly poorer than that of the Asperger, language impaired, and normal groups. Across groups an association was found between false belief and belief term performance. Results support a growing body of literature demonstrating links between the development of theory of mind and communicative competence.

Health care costs for volunteers and non-volunteers in an intervention for people with osteoarthritis.

OBJECTIVE: To determine whether older people who volunteered for a health intervention study used the health care system differently from a randomly selected group of eligible non-volunteers. METHODS: Three hundred sixty-three volunteers and 92 non-volunteers were compared; both groups were members of a large health maintenance organization (HMO). RESULTS: Volunteers were more educated and had been members of the HMO longer. Volunteers used the health care system significantly more at all time periods, but their cost per contact was significantly lower than that for non-volunteers. Non-volunteers were more likely to have a comorbid condition and had fewer arthritis-related health care contacts. CONCLUSIONS: There will always be problems in generalizing results of studies with volunteers, but volunteers are, nevertheless, the most appropriate controls if the experimental participants are also volunteers. Designs should ideally include both volunteer and non-volunteer controls.

Amateur tattooing practices and beliefs among high school adolescents.

PURPOSE: The objective of this research was to investigate the reasons, experiences, methods, and perceived health consequences of obtaining tattoos among a sample of Western Australian high school adolescents. METHODS: Information pertaining to levels of health awareness and school social behavior were obtained. Data were gathered in two phases using a questionnaire and follow-up interviews. RESULTS: Findings revealed that over 13% of participants had acquired tattoos and that the majority had been self-administered with crude implements. Some participants identified possible methods of removal, with a small number having attempted removal, again using crude implements. CONCLUSIONS: Statistical analyses revealed a number of significant main effects for gender, age, and tattoo status on the dependent variables for health awareness and school social behavior.

Antineoplastic agents 337. Synthesis of dolastatin 10 structural modifications.

New structural modifications of the marine shell-less mollusk peptide constituent dolastatin 10 (1) have been synthesized, and evaluated against a variety of cancer cell lines and for their ability to inhibit tubulin polymerization. A number of useful structure-activity relationships were uncovered. The most important observation was that the dolaphenine unit of dolastatin 10 could be satisfactorily replaced with a phenethylamine. Peptide 11C, designated auristatin PE, was found to exhibit inhibition of cancer cell growth and tubulin assembly comparable to that of dolastatin 10.

Public health aspects of tattooing among Australian adults.

Medical, criminological and psychiatric literatures have pointed to risks associated with tattooing, but most of this work has been conducted with samples which have other known risk factors or disturbances. This paper investigates the reasons, experiences, methods, and perceived consequences of obtaining tattoos among a sample of Australian adults. The findings complement, extend and in some respects contrast with earlier research. Like other researchers, we found that most people acquire tattoos when they are relatively young. Unlike earlier research, we did not find widespread dissatisfaction and regret. Sex differences emerged in location and design of tattoos. A majority of tattooed people report awareness of others' negative stereotypes of them.

Children's and adolescents' awareness of the physical and mental health risks associated with tattooing: a focus group study.

This article explores children's and adolescents' awareness of the physical and mental health risks associated with the increasing practice of tattooing. Twelve focus group discussions on attitudes toward tattoos and beliefs about normative behavior, health beliefs, awareness of the long-term consequences of tattooing, and stigmatization were conducted with 80 volunteers, six to 17 years of age. The videotaped discussions revealed that participants' were knowledgeable about tattoos and the process, and were aware that viral transmission and physical disfigurement were possible results. Generally, attitudes toward tattoos were negative, with almost all participants associating them with illicit type activities. However, a more favorable attitude toward small tattoos was discernible among females during early adolescence. Participants suggested that because of the location of tattoos, they might be embarrassing in some instances, and that because of their permanency, young people might regret having them later in life. Some participants revealed they had removed tattoos using crude implements. These data suggest an urgent need for research on prevention of unsafe use of tattooing and piercing implements.

Polysemy and the subjective lexicon: semantic relatedness and the salience of intraword senses.

Subjective perceptions of the senses of polysemous English words are collected in questionnaire studies and the effects of variability in semantic distances among these senses are examined in an experiment. In the first of two questionnaire studies, native speakers produce meanings for 175 polysemous words; from their responses, the most frequently produced meaning for each word is identified as its dominant sense. In a second questionnaire, independent subjects rate the semantic relatedness between the dominant meaning and the other senses generated for each word in the first study. Relatedness measures vary, raising the possibility that polysemous words vary in terms of the salience of their different senses in different contexts. This is confirmed in an experiment showing that salience ratings are influenced by the interacting factors of sentential context, extent of relatedness of the senses, and the dominance status of the senses.

Television and sex-role acquisition. 1: Content.

Television has earned considerable public and academic criticism in recent years for the alleged bias in its sex-role content. A fundamental concern of many critics is with the representation of male and female roles that confronts children. This paper reviews the evidence accumulating from numerous content analyses of both adult and children's television. Overall, the evidence confirms that there are marked differences in the ways the medium presents the sexes. These differences are both quantitative and qualitative but the general pattern at either level is to present males as dominant and females as nurturant and complementary. Some qualifications, exceptions and gaps in the literature are discussed. The paper is the first of a three-part review series of television and sex-role acquisition: the subsequent papers will review respectively the effects of sex-stereotyped TV content upon children and the prospects for counter-stereotyped programmes aiming to modify young viewers' beliefs and attitudes.