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Normal Variation (normal + variation)
Selected AbstractsContribution of the LRP5 Gene to Normal Variation in Peak BMD in Women,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2005Daniel L Koller Abstract The role of the LRP5 gene in rare BMD-related traits has recently been shown. We tested whether variation in this gene might play a role in normal variation in peak BMD. Association between SNPs in LRP5 and hip and spine BMD was measured in 1301 premenopausal women. Only a small proportion of the BMD variation was attributable to LRP5 in our sample. Introduction: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene have been implicated as the cause of multiple distinct BMD-related rare Mendelian phenotypes. We sought to examine whether the LRP5 gene contributes to the observed variation in peak BMD in the normal population. Materials and Methods: We genotyped 12 single nucleotide polymorphisms (SNPs) in LRP5 using allele-specific PCR and mass spectrometry methods. Linkage disequilibrium between the genotyped LRP5 SNPs was measured. We tested for association between these SNPs and both hip and spine BMD (adjusted for age and body weight) in 1301 healthy premenopausal women who took part in a sibling pair study aimed at identifying the genes underlying peak bone mass. Our study used both population-based (ANOVA) and family-based (quantitative transmission disequilibrium test) association methodology. Results and Conclusions: The linkage disequilibrium pattern and haplotype block structure within the LRP5 gene were consistent with that observed in other studies. Although significant evidence of association was found between LRP5 SNPs and both hip and spine BMD, only a small proportion of the total variation in these phenotypes was accounted for. The genotyped SNPs accounted for ,0.8% of the variation in femoral neck BMD and 1.1% of the variation in spine BMD. Results from our sample suggest that natural variation in and around LRP5 is not a major contributor to the observed variability in peak BMD at either the femoral neck or lumbar spine in white women. [source] Genome Screen for Quantitative Trait Loci Underlying Normal Variation in Femoral StructureJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2001Daniel L. Koller Abstract Femoral structure contributes to bone strength at the proximal femur and predicts hip fracture risk independently of bone mass. Quantitative components of femoral structure are highly heritable traits. To identify genetic loci underlying variation in these structural phenotypes, we conducted an autosomal genome screen in 309 white sister pairs. Seven structural variables were measured from femoral radiographs and used in multipoint sib-pair linkage analyses. Three chromosomal regions were identified with significant evidence of linkage (log10 of the odds ratio [LOD] > 3.6) to at least one femoral structure phenotype. The maximum LOD score of 4.3 was obtained for femur neck axis length on chromosome 5q. Evidence of linkage to chromosome 4q was found with both femur neck axis length (LOD = 3.9) and midfemur width (LOD = 3.5). Significant evidence of linkage also was found to chromosome 17q, with a LOD score of 3.6 for femur head width. Two additional chromosomal regions 3q and 19p gave suggestive (LOD > 2.2) evidence of linkage with at least two of the structure phenotypes. Chromosome 3 showed evidence of linkage with pelvic axis length (LOD = 3.1), midfemur width (LOD = 2.8), and femur head width (LOD = 2.3), spanning a broad (60 cm) region of chromosome 3q. Linkage to chromosome 19 was supported by two phenotypes, femur neck axis length (LOD = 2.8) and femur head width (LOD = 2.8). This study is the first genome screen for loci underlying variation in femoral structure and represents an important step toward identifying genes contributing to the risk of osteoporotic hip fracture in the general population. [source] The occurrence of dominant spinocerebellar ataxias among 251 Finnish ataxia patients and the role of predisposing large normal alleles in a genetically isolated populationACTA NEUROLOGICA SCANDINAVICA, Issue 3 2005V. Juvonen Objectives,,, Frequency and distribution of dominant ataxias caused by dynamic mutations may vary in different populations, which has been explained on the basis of relative frequency of predisposing normal alleles. The aim of the study was to evaluate the occurrence of spinocerebellar ataxias (SCAs) and dentatorubral-pallidoluysian atrophy (DRPLA) in Finland, and to investigate the role of predisposing normal alleles in a genetically homogenous population. Material and methods,,, Mutation analyses for SCA1, 2, 3, 6, 7, 8, 10, 12, 17, and DRPLA and frataxin genes were performed for 251 unrelated Finnish patients who presented with progressive ataxia disorder. Results,,, Expansions of SCA1, SCA2, SCA6, SCA7, SCA8, and SCA17 genes were detected in 2, 1, 1, 7, 22, and 1 patients, respectively. Altogether, 39 and 7% of dominant and sporadic SCA patients, respectively, harboured expansions at some of the investigated loci. Normal variation, collected from 477 to 502 chromosomes at each disease loci, revealed that Finns were different from the Japanese but largely similar to other Caucasians. Conclusions,,, Lack of SCA3 and excess of SCA8 are characteristic to the Finnish population. Homozygosity for the SCA8 expansion increases penetrance. Frequencies of large normal alleles at the SCA loci predict poorly prevalence of the respective diseases in Finland. Prioritization in DNA testing, based on ethnic origin and geographical location, is recommendable in Finland, and analogous approach may be applied to other countries as well. [source] Balancing needs and means: the dilemma of the ,-cell in the modern worldDIABETES OBESITY & METABOLISM, Issue 2009G. Leibowitz The insulin resistance of type 2 diabetes mellitus (T2DM), although important for its pathophysiology, is not sufficient to establish the disease unless major deficiency of ,-cell function coexists. This is demonstrated by the fact that near-physiological administration of insulin (CSII) achieved excellent blood glucose control with doses similar to those used in insulin-deficient type 1 diabetics. The normal ,-cell adapts well to the demands of insulin resistance. Also in hyperglycaemic states some degree of adaptation does exist and helps limit the severity of disease. We demonstrate here that the mammalian target of rapamycin (mTOR) system might play an important role in this adaptation, because blocking mTORC1 (complex 1) by rapamycin in the nutritional diabetes model Psammomys obesus caused severe impairment of ,-cell function, increased ,-cell apoptosis and progression of diabetes. On the other hand, under exposure to high glucose and FFA (gluco-lipotoxicity), blocking mTORC1 in vitro reduced endoplasmic reticulum (ER) stress and ,-cell death. Thus, according to the conditions of stress, mTOR may have beneficial or deleterious effects on the ,-cell. ,-Cell function in man can be reduced without T2DM/impaired glucose tolerance (IGT). Prospective studies have shown subjects with reduced insulin response to present, several decades later, an increased incidence of IGT/T2DM. From these and other studies we conclude that T2DM develops on the grounds of ,-cells whose adaptation capacity to increased nutrient intake and/or insulin resistance is in the lower end of the normal variation. Inborn and acquired factors that limit ,-cell function are diabetogenic only in a nutritional/metabolic environment that requires high functional capabilities from the ,-cell. [source] Differentiating normal, abnormal, and disordered personalityEUROPEAN JOURNAL OF PERSONALITY, Issue 4 2005W. John Livesley Interest in the interface between normality and psychopathology was renewed with the publication of DSM-III more than 20 years ago. The use of a separate axis to classify disorders of personality brought increased attention to these conditions. At the same time, the definition of personality disorder as inflexible and maladaptive traits stimulated interest in the relationship between normal and disordered personality structure and functioning. The evidence suggests that the traits delineating personality disorder are continuous with normal variation and that the structural relationships among these traits resemble the structures described by normative trait theories. Recognition that personality disorder represents the extremes of trait dimensions emphasizes the importance of differentiating normal, abnormal, and disordered personality. It is argued that while abnormal personality may be considered extreme variation, personality disorder is more than statistical variation. A definition of personality disorder is suggested based on accounts of the adaptive functions of personality. Copyright © 2005 John Wiley & Sons, Ltd. [source] Comparison of the firing patterns of human postganglionic sympathetic neurones and spinal , motoneurones during brief burstsEXPERIMENTAL PHYSIOLOGY, Issue 1 2004Vaughan G. Macefield Focal recordings from individual postganglionic sympathetic neurones in awake human subjects have revealed common firing properties. One of the most striking features is that they tend to fire only once per sympathetic burst. Why this should be so is not known, but we propose that the short duration of the burst may limit the number of times a sympathetic neurone can fire. Indeed, while the normal variation in cardiac interval and burst duration is too narrow to reveal a correlation between burst duration and the number of spikes generated, we know that spike generation is doubled when burst duration is doubled following ectopic heart beats. To test the hypothesis that the burst duration constrains the firing of individual sympathetic neurones to one per burst, we used the human skeletomotor system as a model for the sympathetic nervous system, which allowed us to vary burst duration and amplitude experimentally. Intramuscular recordings were made from 27 single motor units (, motoneurones) in the tibialis anterior or soleus muscles of seven subjects; multiunit EMG activity was recorded via surface electrodes and blood pressure was recorded continuously. Subjects were instructed to generate EMG bursts of varying amplitude in the intervals between heart beats. By constraining the firing of , motoneurones to brief (,400 ms) bursts we could emulate real sympathetic bursts. Individual motoneurones generated 0,7 spikes during the emulated sympathetic bursts, with firing patterns similar to those exhibited by real sympathetic neurones. Eleven motor units showed significant positive linear correlations between the number of spikes they generated within a burst and its amplitude, whereas for 17 motor units there were significant positive correlations between the number of spikes and burst duration. This indicates that burst duration is a major determinant of the number of times an , motoneurone will fire during a brief burst, and we suggest that the same principle may explain the firing pattern typical of human sympathetic neurones. [source] Contribution of the LRP5 Gene to Normal Variation in Peak BMD in Women,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2005Daniel L Koller Abstract The role of the LRP5 gene in rare BMD-related traits has recently been shown. We tested whether variation in this gene might play a role in normal variation in peak BMD. Association between SNPs in LRP5 and hip and spine BMD was measured in 1301 premenopausal women. Only a small proportion of the BMD variation was attributable to LRP5 in our sample. Introduction: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene have been implicated as the cause of multiple distinct BMD-related rare Mendelian phenotypes. We sought to examine whether the LRP5 gene contributes to the observed variation in peak BMD in the normal population. Materials and Methods: We genotyped 12 single nucleotide polymorphisms (SNPs) in LRP5 using allele-specific PCR and mass spectrometry methods. Linkage disequilibrium between the genotyped LRP5 SNPs was measured. We tested for association between these SNPs and both hip and spine BMD (adjusted for age and body weight) in 1301 healthy premenopausal women who took part in a sibling pair study aimed at identifying the genes underlying peak bone mass. Our study used both population-based (ANOVA) and family-based (quantitative transmission disequilibrium test) association methodology. Results and Conclusions: The linkage disequilibrium pattern and haplotype block structure within the LRP5 gene were consistent with that observed in other studies. Although significant evidence of association was found between LRP5 SNPs and both hip and spine BMD, only a small proportion of the total variation in these phenotypes was accounted for. The genotyped SNPs accounted for ,0.8% of the variation in femoral neck BMD and 1.1% of the variation in spine BMD. Results from our sample suggest that natural variation in and around LRP5 is not a major contributor to the observed variability in peak BMD at either the femoral neck or lumbar spine in white women. [source] Scanning Electron Microscopy Study of Dental Enamel Surface Exposed to 35% Hydrogen Peroxide: Alone, With Saliva, and With 10% Carbamide PeroxideJOURNAL OF ESTHETIC AND RESTORATIVE DENTISTRY, Issue 3 2003MARIANNE SPALDING MS ABSTRACT Several vital bleaching systems have been introduced in response to the demand in esthetic dentistry. The active agents are commonly hydrogen peroxide or carbamide peroxide used in at-home or in-office techniques. Although generally positive results have been reported concerning the whitening ability of these agents, concerns still remain as to their effects on dental tissues. The purpose of this investigation was to evaluate the effect of these bleaching agents on the enamel surface morphology. Twelve extracted teeth were used according to three experimental protocols. In experimental protocol 1, specimens were treated with 35% hydrogen peroxide. In experimental protocol 2, after treatment with 35% hydrogen peroxide the specimens were immersed in natural saliva for 1 week. In experimental protocol 3, 35% hydrogen peroxide was applied once and 10% carbamide peroxide was applied for 1 week (12 h of 10% carbamide peroxide alternating with 12 h saliva). Scanning electron microscopy evaluation revealed that regional variation in tooth morphology surface sometimes exceeded the effects of the peroxide used according to experimental protocols. Thirty-five percent hydrogen peroxide had a tendency to promote an increase in density of pits. Precipitates were observed on specimen surfaces immersed in natural saliva according to protocol 2. A smooth and shiny surface was observed in specimens treated according to protocol 3. The potential relationship between surface alterations and differences in enamel permeability is currently under investigation. CLINICAL SIGNIFICANCE The differences in various articles written on the subject cannot be reconciled because of the lack of standardization of baseline data regarding factors such as location on the tooth, type of tooth, eruption or noneruption, and age in the oral cavity. This article demonstrates that, despite changes observed in the enamel surface after bleaching, normal variation in tooth morphology may exceed the effects of 35% hydrogen peroxide and 10% carbamide peroxide on the teeth. Hence, considering the morphologic features of the tooth surface, bleaching, as described in this study, can be considered safe for enamel. [source] Heritabilities of somatotype components in a population from rural MozambiqueAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 6 2008Sílvio Pedro José Saranga There have been few genetic studies of normal variation in body size and composition conducted in Africa. In particular, the genetic determinants of somatotype remain to be established for an African population. (1) To estimate the heritabilities of aspects of somatotype and (2) to compare the quantitative genetic effects in an African population to those that have been assessed in European and American populations. The sample composed of 329 subjects (173 males and 156 females) aged 7,17 years, belonging to 132 families. The sibships in the sample ranged in size from two to seven individuals. All sampled individuals were residents of the Calanga region, an area located to the north of Maputo in Mozambique. Somatotype was assessed using the Heath-Carter technique. Herit abilities were estimated using SAGE software. Moderate heritabilities were determined for each trait. Between 30 and 40% of the variation in each somatotype measure was attributable to genetic factors. The heritability of ectomorphy was 31%. Mesomorphy was similarly moderately heritable, with ,30% of the variationattributable to genetic factors. The heritability of endomorph was higher in the Calanga population (h2 = 0.40). Quantitative genetic analyses of somatotype variation among siblings indicate that genetic factors significantly influence endomorphy, mesomorhpy, and ectomorphy. However, environmental factors also have significant effects on the variation in physique present in the population of Calanga. Lack of proper nutrition, housing, medical assistance, and primary health care, together with very demanding and sex-specific daily chores may contribute to the environmental effects on these traits. Am. J. Hum. Biol., 2008. © 2008 Wiley-Liss, Inc. [source] Atrial Anatomy and Imaging in Atrial Fibrillation AblationJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2006ANDREW D. McGAVIGAN M.B.Ch.B., M.D. Catheter ablation of atrial fibrillation (AF) can be a technically challenging procedure, requiring detailed knowledge of the anatomy of the atria and thoracic veins to achieve successful cure of AF with a low complication rate. In this article, we review the anatomy relevant to AF ablation: the intraatrial septum, the pulmonary veins and left atrial antral region, the left atrial vestibule, the right atrium and related veins, and the esophagus. We focus on normal variations of anatomy and the role of the available imaging modalities in facilitating safe and effective ablation of this common and complex arrhythmia. [source] Unsolved problems in observational astronomy.ASTRONOMISCHE NACHRICHTEN, Issue 6-8 2004Abstract The existence of rapidly slewing robotic telescopes and fast alert distribution via the Internet is revolutionizing our capability to study the physics of fast astrophysical transients. But the salient challenge that optical time domain surveys must conquer is mining the torrent of data to recognize important transients in a scene full of normal variations. Humans simply do not have the attention span, memory, or reaction time required to recognize fast transients and rapidly respond. Autonomous robotic instrumentation with the ability to extract pertinent information from the data stream in real time will therefore be essential for recognizing transients and commanding rapid follow-up observations while the ephemeral behavior is still present. Here we discuss how the development and integration of three technologies: (1) robotic telescope networks; (2) machine learning; and (3) advanced database technology, can enable the construction of smart robotic telescopes, which we loosely call "thinking" telescopes, capable of mining the sky in real time. (© 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] | |||||||||||||