bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of serum IGF‐I and IGFBP‐1 and ‐3 to cardiovascular risk indicators and early carotid atherosclerosis in healthy middle‐aged men
Authors: Boquist S. , Ruotolo G. , Skoglund‐Andersson C. , Tang R. , Björkegren J. , Bond M. G. , De Faire U. , Brismar K. , Hamsten A. 
Published: September 2007

SummaryObjectives  IGF‐I, IGFBP‐1 and IGFBP‐3 are putative mediators in cardiovascular disease. The present study examined (i) the correlations of circulating IGF‐I, IGFBP‐1 and IGFBP‐3 to established cardiovascular risk factors and signs of early atherosclerosis as reflected by ultrasound measurement of common carotid intima–media thickness (IMT), and (ii) whether serum concentrations of these analytes are modulated during alimentary lipaemia.Design  Cross‐sectional clinical study.Patients  A biobank and clinical database based on 96 healthy Caucasian men, aged 50 years, with an apolipoprotein (apo) E3/E3 genotype, who had originally undergone investigations of postprandial lipoprotein metabolism was used for the study.Measurements  Total IGF‐I, IGFBP‐1 and IGFBP‐3 were determined in serum by radioimmunoassay (RIA). Free IGF‐I was measured by a commercial two‐site immunoradiometric assay (IRMA).Results  In multivariate analyses, fasting serum free IGF‐I correlated inversely with IMT and accounted for 5% of the variation in multiple R2. When fasting serum IGFBP‐1 was entered in the models instead of IGF‐I, IGFBP‐1 correlated positively with IMT and accounted for 6% of the variation in IMT. IGFBP‐3 and total IGF‐I were unrelated to IMT. There were no associations between free IGF‐I and cardiovascular risk factors, whereas IGFBP‐1 behaved like a component of the insulin resistance syndrome. Serum free IGF‐I increased and IGFBP‐1 decreased postprandially.Conclusion  The data indicate that serum free IGF‐I and IGFBP‐1 are implicated in early atherosclerosis.
Modified‐release hydrocortisone for circadian therapy: a proof‐of‐principle study in dexamethasone‐suppressed normal volunteers
Authors: Newell‐Price J. , Whiteman M. , Rostami‐Hodjegan A. , Darzy K. , Shalet S. , Tucker G. T. , Ross R. J. M. 
Published: September 2007

SummaryBackground  All existing long‐term glucocorticoid replacement therapy is suboptimal as the normal nocturnal rise and waking morning peak of serum cortisol is not reproduced.Aim  To test whether it is possible to reproduce the normal overnight rise and morning peak in serum cortisol using an oral delayed and sustained release preparation of hydrocortisone (Cortisolds).Subjects and methods  Six healthy normal male volunteers attended on two occasions, in a single‐dose, open‐label, nonrandomized study. Endogenous cortisol secretion was suppressed by administration of dexamethasone. Cortisolds (formulation A or B) was administered at 2200 h on day 1. Blood samples for measurement of cortisol were taken from 2200 h every 30 min until 0700 h, then hourly until 2200 h on day 2. Fifteen body mass index (BMI)‐matched control subjects had serum cortisol levels measured at 20‐min intervals for 24 h. Serum cortisol profiles and pharmacokinetics after Cortisolds were compared with those in controls.Results  Formulations A and B were associated with delayed drug release (by 2 h and 4 h, respectively), with median peak cortisol concentrations at 4·5 h (0245 h) and 10 h (0800 h), respectively, thereby reproducing the normal early morning rise in serum cortisol. Total cortisol exposure was not different from controls.Conclusions  For the first time we have shown that it is possible to mimic the normal circadian rhythm of circulating cortisol with an oral modified‐release formulation of hydrocortisone, providing the basis for development of physiological circadian replacement therapy in patients with adrenal insufficiency.
Effects of serum TSH and FT4 levels and the TSHR‐Asp727Glu polymorphism on bone: the Rotterdam Study
Authors: Van Der Deure Wendy M. , Uitterlinden André G. , Hofman Albert , Rivadeneira Fernando , Pols Huibert A. P. , Peeters Robin P. , Visser Theo J. 
Published: September 2007

SummaryBackground  TSH and thyroid hormone may have independent effects on bone. In this study we investigated the association of TSH and free T4 (FT4) with different bone parameters in human subjects. TSH and FT4 are known to be associated with body mass index (BMI) and a higher BMI gives a higher bone mineral density (BMD). Thus, we aimed to determine whether the effects of TSH and FT4 on bone are mediated by BMI. As TSH exerts its biological effect through the TSH receptor (TSHR), the TSHR gene might be a candidate gene affecting bone mass. The TSHR‐Asp727Glu polymorphism is associated with lower TSH levels. We therefore examined the association of this polymorphism with bone parameters.Method  Genotypes were determined by Taqman assay in 4934 elderly Caucasian men and women of the Rotterdam Study, of whom BMD and bone geometry data were available. Serum thyroid parameters were available in a random set of 1327 subjects,.Results  Femoral neck BMD as well as narrow neck BMD and cortical thickness increased with serum TSH. However, FT4 was more strongly and negatively associated with bone parameters. Regression models showed BMI‐dependent and ‐independent effects of both TSH and FT4 on bone. Carriers of the TSHR‐Glu727 allele had a 2·3% higher femoral neck BMD.Conclusion  In line with the effect of TSH on bone in mice, serum TSH shows a positive trend with BMD in human subjects, a finding that is strengthened by the association between the TSHR‐Asp727Glu polymorphism and femoral neck BMD. However, serum FT4 has a much greater influence on bone than TSH.
The degree of external genitalia virilization in girls with 21‐hydroxylase deficiency appears to be influenced by the CAG repeats in the androgen receptor gene
Authors: Rocha Rosana O. , Billerbeck Ana Elisa C. , Pinto Emília M. , Melo Karla F. S. , Lin Chin J. , Longui Carlos A. , Mendonca Berenice B. , Bachega Tânia A. S. S. 
Published: September 2007

SummaryBackground  Women with 21‐hydroxylase deficiency present much variability in external genitalia virilization, even among those with similar impairments of 21‐hydroxylase (21OH) activity.Objective  To evaluate if the number of CAG (nCAG) repeats of the androgen receptor gene influences the degree of external genitalia virilization in women with CYP21A2 mutations, grouped according to impairment of 21OH activity.Patients  The nCAG was determined in 106 congenital adrenal hyperplasia (CAH) patients and in 302 controls. The patients were divided, according to their CYP21A2 genotypes, into Groups A and B, which confer total and severe impairment of 21OH activity, respectively.Methods  The inactivation pattern of the X‐chromosome was studied through genomic DNA digestion with Hpa II. The CAG repeat region was amplified by polymerase chain reaction (PCR) and analysed by GeneScan.Results  The nCAG and the frequency of severe skewed X‐inactivation did not differ between normal women and patients. The nCAG median in genotype A was 20·7 (IQR 2·3) for Prader I + II, 22·5 (3·6) for Prader III and 21 (2·9) for Prader IV + V (P < 0·05 for Prader III and Prader IV + V). The nCAG median in genotype B was 21·3 (1·1) for Prader I + II, 20·5 (2·9) for Prader III and 22 (2·8) for Prader IV + V (P > 0·05). A significant difference was found regarding the nCAG median in patients presenting Prader III from genotypes A and B.Conclusions  We observed great variability in the degree of external genitalia virilization in both CYP21A2 genotypes, and we showed that the CAG repeats of the androgen receptor gene influences this phenotypic variability.
Cognitive impairment is prevalent in pseudohypoparathyroidism type Ia, but not in pseudopseudohypoparathyroidism: possible cerebral imprinting of Gsα
Authors: Mouallem M. , Shaharabany M. , Weintrob N. , Shalitin S. , Nagelberg N. , Shapira H. , Zadik Z. , Farfel Z. 
Published: September 2007

SummaryObjective  Pseudohypoparathyroidism type Ia (PHP‐Ia) is a hereditary disorder characterized by resistance to multiple hormones that work via cAMP such as PTH and TSH, accompanied by typical skeletal features including short stature and brachydactyly, termed Albright hereditary osteodystrophy (AHO). In affected kindreds, some members may have AHO but not hormone resistance; they are termed as pseudopseudohypoparathyroidism (PPHP). The molecular basis for the disorder is heterozygous inactivating mutation of the Gsα gene. In affected families, subjects with both PHP‐Ia and PPHP have the same Gsα mutations. The skeletal features common to PPHP and PHP‐Ia are presumably caused by tissue‐specific Gsα haploinsufficiency. Other features that distinguish between PPHP and PHP‐Ia, such as the multihormone resistance, are presumably caused by tissue‐specific paternal imprinting of Gsα. This suggests that major differences in phenotype between PHP‐Ia and PPHP point to specific tissues with Gsα imprinting. One such major difference may be cognitive function in PHP‐Ia and PPHP.Design  Description of a large family with PHP‐Ia and PPHP.Patients  Eleven affected subjects with PHP‐Ia or PPHP in one family.Measurements  Cognitive impairment (CI) was defined by a history of developmental delay, learning disability and the Wechsler intelligence scale.Results  CI occurred only in the five PHP‐Ia but not in the six PPHP subjects. Hypothyroidism which occurred in all PHP‐Ia subjects was apparently not the cause of CI as it was mild, and was treated promptly. Analysis of additional Israeli cases, and the published cases from the literature, all with documented Gsα mutations, revealed that CI is prevalent in PHP‐Ia [60 of 77 subjects (79%)] but not in PPHP [3 of 30 subjects (10%)] (P < 1 × 10−6).Conclusion  We suggest that Gsα is imprinted in the brain.
Depth migration anisotropy analysis in the time domain
Authors: Kumar Chandan , Sen Mrinal K. , Ferguson Robert J. 
Published: September 2007

ABSTRACTIn areas of complex geology such as the Canadian Foothills, the effects of anisotropy are apparent in seismic data and estimation of anisotropic parameters for use in seismic imaging is not a trivial task. Here we explore the applicability of common‐focus point (CFP)‐based velocity analysis to estimate anisotropic parameters for the variably tilted shale thrust sheet in the Canadian Foothills model. To avoid the inherent velocity‐depth ambiguity, we assume that the elastic properties of thrust‐sheet with respect to transverse isotropy symmetry axis are homogeneous, the reflector below the thrust‐sheet is flat, and that the anisotropy is weak. In our CFP approach to velocity analysis, for a poorly imaged reflection point, a traveltime residual is obtained as the time difference between the focusing operator for an assumed subsurface velocity model and the corresponding CFP response obtained from the reflection data. We assume that this residual is due to unknown values for anisotropy, and we perform an iterative linear inversion to obtain new model parameters that minimize the residuals. Migration of the data using parameters obtained from our inversion results in a correctly positioned and better focused reflector below the thrust sheet. For traveltime computation we use a brute force mapping scheme that takes into account weakly tilted transverse isotropy media. For inversion, the problem is set up as a generalized Newton's equation where traveltime error (differential time shift) is linearly dependent on the parameter updates. The iterative updates of parameters are obtained by a least‐squares solution of Newton's equations. The significance of this work lies in its applicability to areas where transverse isotropy layers are heterogeneous laterally, and where transverse isotropy layers are overlain by complex structures that preclude a moveout curve fitting.
Female red squirrels fit Williams’ hypothesis of increasing reproductive effort with increasing age
Authors: DESCAMPS SÉBASTIEN , BOUTIN STAN , BERTEAUX DOMINIQUE , GAILLARD JEAN‐MICHEL 
Published: September 2007

Summary

Williams predicted that reproductive effort should increase as individuals age and their reproductive value declines. This simple prediction has proven difficult to test because conventional measures of energy expenditure on reproduction may not be a true reflection of reproductive effort.
We investigated age‐specific variation in female reproductive effort in a stable population of North American red squirrels where energy expenditure on reproduction is likely to reflect actual reproductive effort. We used seven measures of reproductive effort spanning conception to offspring weaning.
We found that females completed growth by age 3 and that reproductive value decreased after this age likely because of reproductive and survival senescence. We therefore, predicted that reproductive effort would increase from age 3 onwards.
The probability of breeding, litter mass at weaning, and likelihood of territory bequeathal were all lower for 1‐ and 2‐year‐old females than for females older than 3 years, the age at which growth is completed. That growing females are faced with additional energetic requirements might account for their lower allocation to reproduction as compared with older females.
The probability of attempting a second reproduction within the same breeding season and the propensity to bequeath the territory to juveniles increased from 3 years of age onwards, indicating an increase in reproductive effort with age. We think this increase in reproductive effort is an adaptive response of females to declining reproductive values when ageing, thereby supporting Williams’ prediction.
Portion size selection of fruits and vegetables by 9‐ to 10‐year‐old children in Liverpool
Authors: Mullarkey D. , Johnson B. , Hackett A. 
Published: September 2007

AbstractBackground  It is important to promote the intake of fruit and vegetables but it is not clear how children interpret the term ‘portion’. The aim of this study was to describe portion sizes of various fruits and vegetables selected by primary school children.Methods  A cross‐sectional study collected data on children’s self‐selected portions of fruits and vegetables. Forty‐three boys and 52 girls aged 9–10 years attending after school food clubs in Liverpool took part. Children placed a ‘portion’ of each fruit and vegetable into an empty bowl which was weighed using digital scales accurate to 1 g.Results  Mean portion sizes ranged from 126 g for satsumas to 61 g for peas but there were no significant differences between boys and girls. Portions of fruits were larger than portions of vegetables and although there were statistically significant correlations between the portion sizes selected by individual children they were not particularly strong.Conclusions  These children had all taken part in activities promoting ‘5‐a‐day’ but their perception of ‘a portion’ varied enormously. It is recommended that children receive targeted activities to help them improve their understanding of what constitutes a ‘portion’.
Cryo‐fluorescence microscopy facilitates correlations between light and cryo‐electron microscopy and reduces the rate of photobleaching
Authors: SCHWARTZ CINDI L. , SARBASH VASILY I. , ATAULLAKHANOV FAZOIL I. , MCINTOSH J. RICHARD , NICASTRO DANIELA 
Published: September 2007

SummaryFluorescence light microscopy (LM) has many advantages for the study of cell organization. Specimen preparation is easy and relatively inexpensive, and the use of appropriate tags gives scientists the ability to visualize specific proteins of interest. LM is, however, limited in resolution, so when one is interested in ultrastructure, one must turn to electron microscopy (EM), even though this method presents problems of its own. The biggest difficulty with cellular EM is its limited utility in localizing macromolecules of interest while retaining good structural preservation. We have built a cryo‐light microscope stage that allows us to generate LM images of vitreous samples prepared for cryo‐EM. Correlative LM and EM allows one to find areas of particular interest by using fluorescent proteins or vital dyes as markers within vitrified samples. Once located, the sample can be placed in the EM for further study at higher resolution. An additional benefit of the cryo‐LM stage is that photobleaching is slower at cryogenic temperatures (−140°C) than at room temperature.
A handheld support system to facilitate stereological measurements and mapping of branching structures
Authors: GARDI J.E. , WULFSOHN D. , NYENGAARD J.R. 
Published: September 2007

SummaryBranchSampler is a system for computer‐assisted manual stereology written for handheld devices running Windows CE. The system has been designed specifically to streamline data collection and optimize sampling of tree‐like branching structures, with particular aims of reducing user errors, saving time, and saving data in formats suited for further analysis in other software, for example, a spreadsheet. The system can be applied in a wide range of applications, from biomedical science to agriculture and horticulture. It can be applied for sampling nested generations of lung bronchioles and renal arterioles or for collection and optimizing sampling of crops for precision agriculture. Although the system has been designed specifically for sampling branching structures, it is sufficiently flexible to be used for other applications involving nested stereological designs. We describe the system specifications, software and Graphical User Interface development, functionality and application of the handheld system using four examples: (a) sampling monkey lung bronchioles for estimation of diameter and wall thickness (b) sampling rat kidney for estimating number of arteries and arterioles in a specific generation (c) mapping fruit (apple) tree yield in an orchard and (d) estimating the total leaf surface area of chrysanthemum plants in a greenhouse.
Landscape genetics of the self‐compatible forest herbGeum urbanum: effects of habitat age, fragmentation and local environment
Authors: VANDEPITTE K. , JACQUEMYN H. , ROLDÁN‐RUIZ I. , HONNAY O. 
Published: September 2007

AbstractTo investigate the role of habitat fragmentation, fragment age and local environment in shaping the genetics of plant populations, we examined the genetic structure of the self‐compatible forest herbGeum urbanumusing microsatellite markers. A historical land‐use reconstruction assigned the studied populations to two age classes: populations in primary forest fragments, and populations in secondary fragments. Local environmental conditions were quantified on the basis of the herb‐layer community composition. A stepwise general linear model revealed that levels of within‐population genetic diversity were best explained by population size, landscape connectivity and the interaction between both. Connectivity was positively correlated with the genetic diversity of small populations, but did not significantly affect the diversity of large populations. Contrary to what we expected, secondary‐forest populations showed lower divergence relative to populations located in primary patches. Small populations were genetically more diverged compared to large populations. Mantel tests showed no significant isolation by distance and no significant correlation between habitat similarity and genetic differentiation. We conclude that gene flow has probably prevented founder events from being reflected in the present genetic structure ofG. urbanum. Gene flow towards low‐connectivity populations, however, seemed to be insufficient to counteract the effects of drift in small populations.
Mycoplasma genitalium: an efficient strategy to generate genetic variation from a minimal genome
Authors: Ma Liang , Jensen Jørgen S. , Myers Leann , Burnett Judy , Welch Mary , Jia Qiuyao , Martin David H. 
Published: September 2007

Summary Mycoplasma genitalium, a human pathogen associated with sexually transmitted diseases, is unique in that it has smallest genome of any known free‐living organism. The goal of this study was to investigate if and how M. genitalium uses a minimal genome to generate genetic variations. We analysed the sequence variability of the third gene (MG192 or mgpC) of the M. genitalium MgPa adhesion operon, demonstrated that the MG192 gene is highly variable among and within M. genitalium strains in vitro and in vivo, and identified MG192 sequence shifts in the course of in vitro passage of the G37 type strain and in sequential specimens from an M. genitalium‐infected patient. In order to establish the origin of the MG192 variants, we examined nine genomic loci containing partial copies of the MgPa operon, known as MgPar sequences. Our analysis suggests that the MG192 sequence variation is achieved by recombination between the MG192 expression site and MgPar sequences via gene cross‐over and, possibly, also by gene conversion. It appears plausible that M. genitalium has the ability to generate unlimited variants from its minimized genome, which presumably allows the organism to adapt to diverse environments and/or to evade host defences by antigenic variation.
Expression of the Fis protein is sustained in late‐exponential‐ and stationary‐phase cultures of Salmonella enterica serovar Typhimurium grown in the absence of aeration
Authors: Cróinín Tadhg Ó , Dorman Charles J. 
Published: September 2007

SummaryThe classic expression pattern of the Fis global regulatory protein during batch culture consists of a high peak in the early logarithmic phase of growth, followed by a sharp decrease through mid‐exponential growth phase until Fis is almost undetectable at the end of the exponential phase. We discovered that this pattern is contingent on the growth regime. In Salmonella enterica serovar Typhimurium cultures grown in non‐aerated SPI1‐inducing conditions, Fis can be detected readily in stationary phase. On the other hand, cultures grown with standard aeration showed the classic Fis expression pattern. Sustained Fis expression in non‐aerated cultures was also detected in some Escherichia coli strains, but not in others. This novel pattern of Fis expression was independent of sequence differences in the fis promoter regions of Salmonella and E. coli. Instead, a clear negative correlation between the expression of the Fis protein and of the stress‐and‐stationary‐phase sigma factor RpoS was observed in a variety of strains. An rpoS mutant displayed elevated levels of Fis and had a higher frequency of epithelial cell invasion under these growth conditions. We discuss a model whereby Fis and RpoS levels vary in response to environmental signals allowing the expression and repression of SPI1 invasion genes.
Borrelia burgdorferi adhesins identified using in vivo phage display
Authors: Antonara Styliani , Chafel Rebecca M. , LaFrance Michelle , Coburn Jenifer 
Published: September 2007

Summary Borrelia burgdorferi, the agent of Lyme disease, disseminates from the site of deposition by Ixodes ticks to cause systemic infection. Dissemination occurs through the circulation and through tissue matrices, but the B. burgdorferi molecules that mediate interactions with the endothelium in vivo have not yet been identified. In vivo selection of filamentous phage expressing B. burgdorferi protein fragments on the phage surface identified several new candidate adhesins, and verified the activity of one adhesin that had been previously characterized in vitro. P66, a B. burgdorferi ligand for β3‐chain integrins, OspC, a protein that is essential for the establishment of infection in mammals, and Vls, a protein that undergoes antigenic variation in the mammal, were all selected for binding to the murine endothelium in vivo. Additional B. burgdorferi proteins for which no functions have been identified, including all four members of the OspF family and BmpD, were identified as candidate adhesins. The use of in vivo phage display is one approach to the identification of adhesins in pathogenic bacteria that are not easily grown in the laboratory, or for which genetic manipulations are not straightforward.