bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of modelling, local stimulus enhancement, and affordance demonstration on the production of object‐directed actions in 6‐month‐old infants
Authors: Horne Pauline J. , Erjavec Mihela , Lovett Victoria E.
Published: April 2008

The present study investigated whether local stimulus enhancement and the demonstration of objects' affordances – both of which are inherent in modelling of object‐directed target actions – are themselves sufficient to evoke the target behaviour on imitation test trials. Six‐month‐old infants were presented with a puppet wearing a removable mitten and observed either a demonstration of mitten removal (modelling group), the experimenter pointing at the mitten (stimulus enhancement group), the mitten falling off apparently by itself (affordance demonstration group), or no specific action directed at the mitten (control group). For all infants, the puppet was next presented without any accompanying demonstrations and infants' mitten removal behaviours in the response period were recorded. The results showed that local stimulus enhancement and affordance demonstration were as effective as full modelling in evoking the target action. This finding shows that the performances of 6‐month‐old infants on imitation tests can be multiply determined and evoked by variables other than modelling of target behaviour.
The structure of the causal attribution belief network of patients with obesity
Authors: Brogan A. , Hevey D.
Published: April 2008

Objectives. Causal attributions form a significant part of how people understand and represent illness. The present study explored the structure of causal attributions in obesity using network analysis and examined the specific properties of this network in terms of extent, patterning, and direction.

Design. Cross‐sectional study.

Methods. Seventy‐two obese individuals (22 male, 50 female) completed a questionnaire, which asked them to rate the strength of all causal relationships between nine possible causes of obesity. Inductive eliminative analysis (IEA) was used to produce the networks and multidimensional scaling (MDS) determined the spatial structure of the network.

Results. A high percentage (70.4%) of participants endorsed the resultant network. Analysis revealed a two‐dimensional solution, with the MDS statistics of low level of stress (.05) and a dispersion accounted for (DAF) of .95 indicating a good fit between the data and the solution. The results indicated traumatic events, family problems, and addictive personality were perceived as distal causes of over‐eating and comfort eating, while more passive behaviours, less physical activity, over‐eating, and comfort eating were perceived as proximal causes of obesity. Family history did not contribute to the network.

Conclusions. Obese individuals appeared to hold a highly consensual and complex representation of their illness. From a multidisciplinary treatment perspective, this understanding would seem valuable in relation to achieving behaviour change.
Hasty decision‐making in a variety of tasks: Does it contribute to the development of delusions?
Authors: Ziegler Michael. , Rief Winfried. , Werner Sarah‐M. , Mehl Stephanie. , Lincoln Tania M.
Published: April 2008

Objectives. The finding that persons with delusions tend to jump‐to‐conclusions (JTC) in the beads task has often been replicated. This study investigates whether hasty decision‐making in the beads task is associated with hasty decisions in tasks with more relevance for everyday decision‐making. Furthermore, it is hypothesized that hasty decisions in these tasks will be associated with subclinical delusional beliefs.

Design. A correlational study.

Methods. A sample of students (N=85) completed the beads task and three additional non‐probabilistic decision‐tasks. Subclinical delusional beliefs were assessed using the Peters et al. delusions inventory (PDI; Peters, Joseph, & Garety, 1999).

Results. In support of the hypothesis, participants with hasty decisions in the beads task also made hasty decisions in two of the other tasks. Hasty decisions were only associated with higher subclinical delusional beliefs in one of the tasks (a letter recognition task).

Conclusions. Decision‐making in the beads task can be generalized to decisions in other contexts. Other decision‐making tasks may be more closely related to delusions than the beads task.
Body mass index and ovarian function are associated with endocrine and metabolic abnormalities in women with hyperandrogenic syndrome
Authors: Cupisti S , Kajaia N , Dittrich R , Duezenli H , W Beckmann M , Mueller A
Published: April 2008

Background

The aim of this study was to evaluate associations of clinical features, such as hirsutism, polycystic ovaries (PCOs), ovulatory dysfunction, and body mass index (BMI) ≥25 kg/m2, with metabolic abnormalities in hyperandrogenic women.

Methods

Hirsutism was based on the modified Ferriman–Gallwey score. Ovulatory function was classified as eumenorrhea, oligomenorrhea and amenorrhea, and PCOs were assessed using the ultrasound criteria recommended in the Rotterdam definition. An oral glucose tolerance test was performed. Different insulin resistance (IR) indices were calculated.

Results

Hirsute women had significantly higher BMI, DHEA sulfate (DHEAS) and free androgen index (FAI), and significantly lower values for sex hormone-binding globulin (SHBG). Women with amenorrhea were younger in comparison to women with eumenorrhea and had significantly higher values for fasting insulin (FI) and 1- and 2-h insulin levels; lower values for glucose to insulin ratio (GIR), quantitative insulin sensitivity check index (QUICKI), and SHBG. Women with PCO had significantly higher levels of LH and low-density lipoprotein (LDL), whereas high-density lipoprotein (HDL) levels were significantly lower. Women with a BMI ≥25 kg/m2 had significantly higher values for age, fasting plasma glucose, FI, and 1- and 2-h glucose and insulin levels, homeostatic model for assessment of IR (HOMA-IR), homeostatic model for assessment of B-cell function (HOMA-B), and FAI, whereas their GIR, insulin sensitivity index, QUICKI, SHBG, and HDL were significantly lower.

Conclusions

In women with hyperandrogenic syndrome, BMI≥25 kg/m2 and amenorrhea appear to be associated with severe endocrine and metabolic abnormalities.
Association between gynecomastia and aromatase (CYP19) polymorphisms
Authors: Czajka-Oraniec Izabella , Zgliczynski Wojciech , Kurylowicz Alina , Mikula Michal , Ostrowski Jerzy
Published: April 2008

Objective

Aromatase cytochrome P45019 (CYP19) is a key enzyme in estrogen biosynthesis, and polymorphisms within its gene are associated with an increased risk of estrogen-dependent diseases. Enhanced estrogen stimulation of breast tissue in men may lead to gynecomastia. We assessed whether intron 4 (TTTA)n repeat and TCT deletion/insertion polymorphisms and an exon 10 (3′-UTR) C/T single nucleotide polymorphism of CYP19 are associated with gynecomastia.

Design/methods

We performed a genetic association study of 100 patients referred to the endocrinological outpatient clinic with breast glandular tissue enlargement confirmed by clinical and ultrasound examinations and 99 healthy volunteers without gynecomastia. Microsatellite (TTTA)n and insertion/deletion polymorphisms were studied using capillary electrophoresis, and the C/T polymorphism in the 3′-UTR was analyzed using the TaqMan assay.

Results

Significantly increased risk of gynecomastia was found in subjects carrying a CYP19 exon 10 T allele that was previously related to the high aromatase activity. Frequency of the TT genotype was significantly higher in patients when compared with controls (40.6 vs 26.3%; TT versus CT and CC genotypes; Pc<0.05). We found strong linkage disequilibrium between the alleles of studied polymorphic loci. T allele in the 3′-UTR was in linkage disequilibrium with the long alleles of the intron 4 polymorphism, mainly (TTTA)11. However, our findings did not show significant correlation of alleles having more than nine TTTA repeats with gynecomastia.

Conclusions

The CYP19 polymorphisms might contribute to the incidence of gynecomastia, but further studies in larger groups are needed to confirm these results.
Natural course of small adrenal lesions in multiple endocrine neoplasia type 1: an endoscopic ultrasound imaging study
Authors: Schaefer S , Shipotko M , Meyer S , Ivan D , Klose K J , Waldmann J , Langer P , Kann P H
Published: April 2008

Objective

Adrenal lesion is one of the features of multiple endocrine neoplasia type 1 (MEN1). This study aimed to assess prevalence, natural course and clinical relevance of small adrenal lesions without clinical symptoms, endocrine activity, or mechanical problems and thus without clear indication for surgical therapy by endoscopic ultrasound (EUS).

Design and methods

Forty-nine patients with familial MEN1 were studied. Twenty-seven of these with adrenal lesions were detected by EUS and at least two performed EUS examinations were included into a subgroup where changes in adrenal morphology were studied by measuring changes in the largest diameter of the dominant adrenal tumour.

Results

EUS detected adrenal lesions in 36 (73%) patients: 6 (12%) plump adrenals, 17 (35%) nodular hyperplasia, 12 (24%) adenomas and 1 (2%) cyst. Bilateral adrenal lesions were detected in 17 patients and unilateral in 19 patients. A change in the largest tumour diameter was found to be for nodular hyperplasia −0.02±1.41% per month (range −2.56 to 4.58%) and for adenomas −0.61±1.95% per month (range −6.25 to 1.15%). One patient had an adrenal cyst with significant growth. There was no evidence of carcinoma or metastatic disease during the study.

Conclusions

The prevalence of adrenal lesions in MEN1 is higher than that reported earlier. Except one cystic lesion, no significant change in the tumour size was observed over a mean observation period of more than 2 years. In a typical situation, small adrenal lesions in MEN1 seem to be constant in their morphology.
Association between tumoral GH-releasing peptide receptor type 1a mRNA expression and in vivo response to GH-releasing peptide-6 in ACTH-dependent Cushing's syndrome patients
Authors: Machado Marcio Carlos , Valeria de Sa Sandra , Correa-Giannella Maria Lucia , Giorgi Ricardo Rodrigues , Pereira Maria Adelaide Albergaria , Cescato Valter Angelo S , Giannella-Neto Daniel , Salgado Luiz Roberto
Published: April 2008

Objective

GH secretagogues (GHS) produce exaggerated ACTH and cortisol responses in Cushing's disease (CD) patients, attributable to their direct action on GH-releasing peptide receptor type 1a (GHSR-1a). However, there are no studies correlating the in vivo response to GHS and GHSR-1a mRNA expression in ACTH-dependent Cushing's syndrome (CS) patients. The aim of this study is to correlate the patterns of ACTH and cortisol response to GH-releasing peptide-6 (GHRP-6) to GHSR-1a expression in ACTH-dependent CS patients.

Design

Prospective study in a tertiary referral hospital center. Fifteen CD patients and two ectopic ACTH syndrome (EAS) patients were studied.

Methods

Tumor fragments were submitted to RNA extraction, and GHSR-1a expression was studied through real-time qPCR and compared with normal tissue samples. The patients were also submitted to desmopressin test and vasopressin receptor type 1B (AVPR1B) mRNA analysis by qPCR.

Results

GHSR-1a expression was similar in normal pituitary samples and in corticotrophic tumor samples. GHSR-1a expression was higher in patients (CD and EAS) presenting in vivo response to GHRP-6. Higher expression of AVPR1B was observed in the EAS patients responsive to desmopressin, as well as in corticotrophic tumors, as compared with normal pituitary samples, but no correlation between AVPR1B expression and response to desmopressin was observed in the CD patients.

Conclusions

Our results revealed a higher expression of GHSR-1a in the ACTH-dependent CS patients responsive to GHRP-6, suggesting an association between receptor gene expression and in vivo response to the secretagogue in both the CD and the EAS patients.
Endothelial nitric oxide synthase intron 4a/b polymorphism and early atherosclerotic changes in hypopituitary GH-deficient adult patients
Authors: Sen Fatma , Demirturk Mustafa , Abaci Neslihan , Golcuk Ebru , Oflaz Huseyin , Elitok Ali , Kutluturk Faruk , Issever Halim , Unaltuna Nihan Erginel , Ozbey Nese Colak
Published: April 2008

Objective

Endothelial nitric oxide synthase (eNOS) intron 4a/b polymorphism is associated with plasma NO concentrations and coronary artery disease/hypertension in various populations. GH deficiency in adulthood predisposes to reduced NO concentrations and premature atherosclerosis. Our aim was to determine whether intron 4a/b polymorphism of eNOS gene influences endothelial function and early atherosclerotic changes in GH-deficient hypopituitary patients.

Design

Thirty-three hypopituitary GH-deficient patients on conventional replacement therapy other than GH and 43 age-, sex-, and body mass index (BMI)-matched controls were studied in this cross-sectional case–control study.

Methods

Early atherosclerotic changes were determined by flow-mediated dilation (FMD) of brachial artery and carotid artery intima-media thickness (IMT). eNOS4a/b polymorphism was detected by PCR.

Results

Hypopituitary patients had significantly higher total/low-density lipoprotein cholesterol and fat mass and lower IGF-I concentrations compared with controls. IMT was significantly higher in patients (0.777±0.23 vs 0.639±0.17 mm, P<0.01). No significant difference was observed with respect to FMD measurements. eNOS4a/b genotype frequencies were similar between patients and controls. Patients carrying ‘a’ allele (a/a and a/b) had significantly higher IMT compared with controls carrying ‘a’ allele and bb genotype (P<0.05). However, logistic regression analysis revealed that presence of hypopituitarism, age≥45 years, and BMI≥27.9 kg/m2 were significant independent predictors of IMT≥0.65 mm.

Conclusion

No compelling data are evident to suggest that eNOS4a/b polymorphism modifies the atherosclerotic process in GH-deficient situations. A large case–control study is needed to confirm our findings.
Significance of low levels of thyroglobulin in fine needle aspirates from cervical lymph nodes of patients with a history of differentiated thyroid cancer
Authors: Borel Anne-Laure , Boizel Robert , Faure Patrice , Barbe Geneviève , Boutonnat Jean , Sturm Nathalie , Seigneurin Daniel , Bricault Ivan , Caravel Jean-Pierre , Chaffanjon Philippe , Chabre Olivier
Published: April 2008

Objective

Measurement of thyroglobulin in the washout of lymph node (LN) fine needle aspirates is recommended in the follow-up of patients with differentiated thyroid cancer (DTC). The significance of low fine needle aspirates thyroglobin (FNATg) levels remains a question, which we addressed.

Method

Prospective study comparing FNATg with FNA cytology. Exploration of 34 DTC patients (53 cervical LNs), 26 non-thyroidectomized patients with a thyroid-unrelated cervical mass (negative controls) and 13 with 21 thyroid nodules (positive controls). The 12 DTC patients (19 LNs) with a malignant FNA cytology and/or high FNATg level received LN surgery (11 patients) or I131-iodine treatment (1 patient) and the outcome measure was pathological or scintigraphic evidence of DTC LN metastasis.

Results

All 26 negative controls showed FNATg <1 ng/FNA and all 21 positive controls showed high levels of FNATg (127–210 000 ng/FNA, median 38 000). Among DTC patients in 25 LNs with a benign FNA cytology, FNATg was undetectable in 24 and low in 1 (6 ng/FNA); in 19 LNs with a malignant FNA cytology, FNATg was high in 17 (80–140 000 ng/FNA, median 7174 ng/FNA) and low in 2 (6.6 and 7.1 ng/FNA), which proved to be low Tg immunostaining oncocytic DTC metastasis; in 9 LNs with a non-informative cytology, FNATg was undetectable in 8 but 11 825 ng/FNA in 1, which proved a DTC metastasis. Measurement of FNA albumin demonstrated that contamination of FNA by serum proteins was negligible.

Conclusion

Low FNATg levels can indicate a DTC metastasis. It cannot be related to clinically relevant levels of serum Tg.
Variation in the bone morphogenetic protein-2 gene: effects on fat and lean body mass in young and elderly women
Authors: McGuigan Fiona , Larzenius Emma , Callreus Mattias , Gerdhem Paul , Luthman Holger , Åkesson Kristina
Published: April 2008

Objective

Bone morphogenetic protein-2 (BMP2) plays a critical role in osteoblastogenesis and adipogenesis from osteoprogenitor cells. The balance between osteogenic and adipogenic effects is influenced by BMP2 concentration, transcription factors and age. BMP2 single nucleotide polymorphisms (SNPs) may contribute to osteoporosis risk, but the relationship between adiposity and body composition has not been explored. We investigated the relationship between BMP2 polymorphisms and body composition in young and elderly women.

Design

Population-based association study.

Methods

Four BMP2 SNPs studied. Total body fat and lean mass measured by DEXA in two cohorts: ‘PEAK-25’ women aged 25 (±0.00) (n=993) and osteoporosis prospective risk assessment (OPRA) women aged 75 (±0.00) years (n=1001).

Results

We found no association between BMP2 SNPs and fat or lean mass, however, we observed consistent although non-significant trends. Polymorphisms, rs235767 and Ser37Ala, exerted opposing effects on most parameters of soft tissue and bone mass in both cohorts. This relationship appeared to be age specific with large differences between alleles observed (fat mass; Ser37Ala: 14.3% (PEAK-25), −3.5% (OPRA)). These initial results appear to suggest that alleles exerting a beneficial effect in young women may subsequently contribute to phenotypes associated with osteoporosis risk in elderly women.

Conclusions

While further analyses in other comparative populations are necessary, in this study of almost 2000 women we observed interesting, although non-significant trends, regarding the effects of variation in the BMP2 gene on parameters of body mass. Although the exact nature of the relationship remains uncertain, we suggest that the mechanisms are influenced by age and environmental factors.
Evaluation of health-related quality of life in patients with Cushing's syndrome with a new questionnaire
Authors: Webb S M , Badia X , Barahona M J , Colao A , Strasburger C J , Tabarin A , van Aken M O , Pivonello R , Stalla G , Lamberts S W J , Glusman J E
Published: April 2008

Chronic exposure to hypercortisolism has significant impact on patient's health and health-related quality of life (HRQoL), as demonstrated with generic questionnaires. We have developed a disease-generated questionnaire to evaluate HRQoL in patients with Cushing's syndrome (CS; CushingQoL).

Objective

Validate the CushingQoL questionnaire in patients with CS in clinical practice conditions.

Design

Observational, international, cross-sectional study.

Methods

A total of 125 patients were recruited by 14 investigators from Spain, France, Germany, The Netherlands, and Italy over a 2-month period. Clinical and hormonal data were collected and correlated with results of the generic short form 36 (SF-36) questionnaire, a question on self-perceived general health status and the CushingQoL score.

Results

A total of 107 patients were pituitary-dependent and 18 adrenal-dependent CS; 104 (83%) were females, mean age 45 years (range 20–73 years); 39 (31%) were currently hypercortisolemic; and 47 (38%) adrenal insufficient. In clinical practice, CushingQoL was feasible (117; 94% of patients fully responded to the questionnaire in a mean time of 4 min), reliable (Crohnbach's α=0.87), and valid (factorial analysis demonstrated unidimensionality and Rasch analysis lead to a final version with 12 items). A significant (P<0.001) correlation was observed between CushingQoL score and patients self-perceived general health status and dimensions of SF-36 (Pearson's correlation coefficient ≥0.597). Patients with current hypercortisolism scored worse (lower) than those without (44±22 vs 56±21, P=0.004). Linear regression analysis identified female gender and hypercortisolism as significant predictors for worse QoL.

Conclusion

CushingQoL is useful to evaluate HRQoL in patients with CS and correlates with clinical parameters.
Variations in the uncoupling protein-3 gene are associated with specific obesity phenotypes
Authors: van Abeelen Annet F M , de Krom Mariken , Hendriks Judith , Grobbee Diederick E , Adan Roger A H , van der Schouw Yvonne T
Published: April 2008

Objective

Uncoupling protein 3 (UCP-3) uncouples oxidative metabolism from ATP synthesis, resulting in the production of heat instead of energy storage. Single nucleotide polymorphisms (SNPs) in UCP-3 might result in a reduced function or expression of UCP-3 and therefore lead to an increased capacity to store energy as fat.

Design

We conducted a population-based, cross-sectional single-center study among 400 Dutch men between 40 and 80 years.

Methods

Seven SNPs in the UCP-3 gene were genotyped by means of an allele-specific real-time TaqMan PCR. Linear regression analyses were performed to examine the independent effects of these SNPs on obesity phenotypes.

Results

We found a significant association between homozygosity for the minor allele of rs647126, rs1685356, and rs2075577 and an increase in body mass index (BMI; P=0.033, P=0.016, and P=0.019 respectively). Heterozygosity for rs1685354 was associated with a significant decrease in visceral fat mass (P=0.030).

Conclusions

Our results suggest that genetic variations in the UCP-3 gene are associated with an increase in BMI. A plausible mechanism by which these SNPs lead to an increase in BMI is that due to these SNPs, the UCP-3 activity might be decreased. As a result, uncoupling activity may also decrease, which will lead to an increase in body weight and BMI.
Autoimmune polyendocrine syndrome type I in Slovakia: relevance of screening patients with autoimmune Addison's disease
Authors: F. Magitta Ng'weina , Pura Mikuláš , S Bøe Wolff Anette , Vanuga Peter , Meager Anthony , M Knappskog Per , Husebye Eystein S
Published: April 2008

Background

Autoimmune polyendocrine syndrome type I (APS I) is a monogenic disease affecting endocrine glands and other organs due to mutations of the autoimmune regulator (AIRE) gene. There is a wide variability in clinical phenotypes in patients with APS I, which makes the diagnosis a challenge.

Objective

To screen for APS I among Slovakian patients with sporadic Addison's disease and clinical features that raised the suspicion of APS I.

Methods

All 14 exons and exon–intron boundaries of the AIRE gene were sequenced. In addition, autoantibodies specific for Addison's disease and polyendocrine syndromes were assayed.

Results

Using clinical criteria we identified four patients with APS I in three families. Two patients had a novel missense mutation in exon 2 (c.274C>T, p.R92W) and either the Finnish major mutation (c.769C>T) or the common 13 bp deletion (c.967–979del13bp). APS I was diagnosed in a brother of the latter after his death due to an adrenal crisis. A fourth patient had primary adrenal failure and hypoparathyroidism without AIRE mutations or APS-I specific autoantibodies.

Conclusions

Four patients with APS I were found in a Slovakian cohort of Addison patients, although the lack of detectable AIRE mutations and APS I-specific autoantibodies raises uncertainty regarding the pathogenesis in one of the patients. This study demonstrates the merits of screening patients with phenotypic features or autoantibody findings that could indicate APS I, even in adult patients. It is necessary to identify APS I patients in order to provide appropriate treatment and follow-up of the various components of APS I.
Variable number of tandem repeats polymorphism in parathyroid hormone-related protein as predictor of peak bone mass in young healthy Finnish males
Authors: Gupta Ajay , Välimäki Ville-Valtteri , J Välimäki Matti , Löyttyniemi Eliisa , Richard Marilyn , L Bukka Prasanna , Goltzman David , C Karaplis Andrew
Published: April 2008

Objective

Mice with osteoblast-specific deletion of parathyroid hormone-related protein (PTHrP) exhibit impaired recruitment and increased apoptosis of osteogenic cells resulting in decreased bone formation and premature osteoporosis. The PTHrP levels within the bone microenvironment are therefore critical in influencing bone mass acquisition. Whether this is applicable in humans has not been established. Here, we studied the association of a variable number of tandem repeats (VNTR) polymorphism in PTHrP with peak bone mass.

Methods

Enrolled in the study were 234 young Finnish males, with median age of 19.6 years (range 18.3–20.6 years). Lifestyle factors, serum bone markers, osteodensitometric measurements (lumbar spine and hip) and calcaneal quantitative ultrasound readings were obtained. The PTHrP VNTR length was determined by the PCR amplification of genomic DNA extracted from peripheral blood and correlated to bone parameters by the multiple regression models.

Results

The presence of at least one 252 bp allele was associated with increased lumbar spine bone mineral density (BMD; P<0.0034), broadband ultrasound attenuation (BUA; P<0.0012) and speed-of-sound (SOS; P<0.0023) measurements. The correlation with increased lumbar spine BMD (P=0.0008), BUA (P=0.005) and SOS (P=0.001) was further strengthened by the pairing of the 252 bp allele with a 460 bp allele in comparison with those without any 252 bp allele. Electrophoretic mobility shift assays were used to illustrate the potential transcriptional functionality of the VNTR sequence.

Conclusion

The results indicate that the PTHrP VNTR sequence likely modulates local PTHrP expression within the skeletal microenvironment and could serve as a diagnostic predictor of peak bone mass acquisition.
The role of F-18-fluorodeoxyglucose positron emission tomography in the postoperative evaluation of differentiated thyroid cancer
Authors: Al-Zahrani Ali S , Abouzied Mohei-Eldin M , Salam Suzan Abdel , Mohamed Gamal , Rifai Ayman , Al Sugair Abdulaziz , Amin Tarik
Published: April 2008

Objectives

The objective of the study was to compare F-18-fluorodeoxyglucose position emission tomography (FDG-PET) with diagnostic whole body scanning (DxWBS) and post-ablation radioiodine whole body scanning (TxWBS) and to assess its prognostic value in newly diagnosed differentiated thyroid cancer (DTC) patients, hypothesizing that FDG-PET is more likely to disclose locoregional and distant metastases.

Patients and methods

DxWBS and FDG-PET scanning were performed in 26 newly diagnosed DTC patients who underwent thyroidectomy and TxWBS in 24 cases who had radioactive iodine ablation. The results of the FDG-PET scans were correlated with the stage of the disease and the long-term outcome of DTC.

Results

Overall, 18 FDG-PET scans (69.2%) were positive showing a total of 40 foci while 8 scans (30.8%) were negative. The corresponding 26 DxWBS were all positive and showed a total of 47 foci. DxWBS and TxWBS showed similar foci in the 24 patients who had ablation therapy. In contrast to the FDG-PET scans that showed uptake of 26 foci (65%) outside the thyroid bed, 45 foci (95.7%) on DxWBS were in the thyroid bed while 2 foci (4.3%) were in cervical lymph nodes and no focus was seen outside the neck area (P=0.000). There was a clear correlation between the FDG-PET results, the stage of the disease and long-term outcome; seven of the eight negative FDG-PET scans were in stage 1, while all patients with disease higher than stage 1 (six patients) had positive scans. Over a median of 30 months (10–48), seven out of eight patients (87.5%) with negative FDG-PET scans were in remission compared with only eight patients (44.4%) with positive FDG-PET (P=0.04).

Conclusions

In the postoperative evaluation of DTC, compared with DxWBS and TxWBS, FDG-PET scans are more likely to reveal uptake outside the thyroid bed and to correlate with the stage of the disease and long-term outcome.
The methylenetetrahydrofolate reductase C677T genotype and the risk of obesity in three large population-based cohorts.
Authors: Lewis Sarah J , Lawlor Debbie A , Nordestgaard Børge G , Tybjærg-Hansen Anne , Ebrahim Shah , Zacho Jeppe , Ness Andy , Leary Sam , Smith George Davey
Published: April 2008

Objective

Epidemiological studies have shown that low folate levels are associated with a high body mass index (BMI). These findings have potentially important health implications and warrant further investigation to determine whether a causal relationship exists and the direction of this relationship. The methylenetetrahydrofolate reductase (MTHFR)C677T TTgenotype is associated with reduced folate availability and may be a surrogate for measuring folate levels. We sought to determine whetherMTHFR C677Tgenotype was associated with obesity.

Design

We carried out our study on four populations from three longitudinal studies based in the UK and Denmark in which DNA for genotyping was obtained along with measures of obesity.

Methods

Our subjects were taken from the British Women's Heart and Health Study (BWHHS), the Avon Longitudinal Study of Parents and Children (two populations: mothers and children) and the Copenhagen City Heart Study. We performed analyses separately by population, and then carried out a meta-analysis, combining similar populations.

Results

Initial findings in the BWHHS suggested that theTTgenotype may be associated with an increased risk of obesity BMI≥30, however, no association was found with BMI or central adiposity in this cohort. This genotype was not associated with obesity in our other cohorts.

Conclusions

Our results suggest that the initial positive finding with obesity in the BWHHS was a chance finding. Our findings do not support a causal effect of low folate on obesity.
The Effects of Recombination Rate on the Distribution and Abundance of Transposable Elements
Authors: Dolgin Elie S , Charlesworth Brian
Published: April 2008

Transposable elements (TEs) often accumulate in regions of the genome with suppressed recombination. But it is unclear whether this pattern reflects a reduction in the efficacy of selection against deleterious insertions or a relaxation of ectopic recombination. Discriminating between these two hypotheses has been difficult, because no formal model has investigated the effects of recombination under the deleterious insertion model. Here we take a simulation-based approach to analyze this scenario and determine the conditions under which element accumulation is expected in low recombination regions. We show that TEs become fixed as a result of Hill–Robertson effects in the form of Muller's ratchet, but only in regions of extremely low recombination when excision is effectively absent and synergism between elements is weak. These results have important implications for differentiating between the leading models of how selection acts on TEs and should help to interpret emerging population genetic and genomic data.
An Improved Method for Quantitative Trait Loci Detection and Identification of Within-Line Segregation in F2 Intercross Designs
Authors: Rönnegård Lars , Besnier Francois , Carlborg Örjan
Published: April 2008

We present a new flexible, simple, and powerful genome-scan method (flexible intercross analysis, FIA) for detecting quantitative trait loci (QTL) in experimental line crosses. The method is based on a pure random-effects model that simultaneously models between- and within-line QTL variation for single as well as epistatic QTL. It utilizes the score statistic and thereby facilitates computationally efficient significance testing based on empirical significance thresholds obtained by means of permutations. The properties of the method are explored using simulations and analyses of experimental data. The simulations showed that the power of FIA was as good as, or better than, Haley–Knott regression and that FIA was rather insensitive to the level of allelic fixation in the founders, especially for pedigrees with few founders. A chromosome scan was conducted for a meat quality trait in an F2 intercross in pigs where a mutation in the halothane (Ryanodine receptor, RYR1) gene with a large effect on meat quality was known to segregate in one founder line. FIA obtained significant support for the halothane-associated QTL and identified the base generation allele with the mutated allele. A genome scan was also performed in a previously analyzed chicken F2 intercross. In the chicken intercross analysis, four previously detected QTL were confirmed at a 5% genomewide significance level, and FIA gave strong evidence (P < 0.01) for two of these QTL to be segregating within the founder lines. FIA was also extended to account for epistasis and using simulations we show that the method provides good estimates of epistatic QTL variance even for segregating QTL. Extensions of FIA and its applications on other intercross populations including backcrosses, advanced intercross lines, and heterogeneous stocks are also discussed.
Molecular Characterization of Lal2, an SRK-Like Gene Linked to the S-Locus in the Wild Mustard Leavenworthia alabamica
Authors: Busch Jeremiah W , Sharma Julia , Schoen Daniel J
Published: April 2008

Single-locus sporophytic self-incompatibility inhibits inbreeding in many members of the mustard family (Brassicaceae). To investigate the genetics of self-incompatibility in the wild mustard Leavenworthia alabamica, diallel crosses were conducted between full siblings. Patterns of incompatibility were consistent with the action of single-locus sporophytic self-incompatibility. DNA sequences related to S-locus receptor kinase (SRK), the gene involved in self-pollen recognition in mustards, were cloned and sequenced. A single sequence with high identity to SRK and several other groups of sequences (Lal1, Lal2, Lal3, Lal8, and Lal14) were isolated from L. alabamica. We propose that either Lal2 sequences are divergent alleles of SRK or Lal2 is in tight linkage with SRK because (1) Lal2 alleles cosegregate with S-alleles inferred from dialleles in all 97 cases tested in five families; (2) Lal2 sequences are highly diverse at both synonymous and nonsynonymous sites and exhibit patterns of selective constraint similar to those observed at SRK in Brassica and Arabidopsis; and (3) transcripts of one Lal2 allele were detected in leaves and the styles of open flowers, but were most abundant in the stigmas of maturing buds. We discuss the utility of the S-linked polymorphism at Lal2 for studying the evolutionary forces acting on self-incompatibility in Leavenworthia.
Reproducing Kernel Hilbert Spaces Regression Methods for Genomic Assisted Prediction of Quantitative Traits
Authors: Gianola Daniel , van Kaam Johannes B C H M
Published: April 2008

Reproducing kernel Hilbert spaces regression procedures for prediction of total genetic value for quantitative traits, which make use of phenotypic and genomic data simultaneously, are discussed from a theoretical perspective. It is argued that a nonparametric treatment may be needed for capturing the multiple and complex interactions potentially arising in whole-genome models, i.e., those based on thousands of single-nucleotide polymorphism (SNP) markers. After a review of reproducing kernel Hilbert spaces regression, it is shown that the statistical specification admits a standard mixed-effects linear model representation, with smoothing parameters treated as variance components. Models for capturing different forms of interaction, e.g., chromosome-specific, are presented. Implementations can be carried out using software for likelihood-based or Bayesian inference.
Nonparametric Methods for Incorporating Genomic Information Into Genetic Evaluations: An Application to Mortality in Broilers
Authors: González-Recio Oscar , Gianola Daniel , Long Nanye , Weigel Kent A , Rosa Guilherme J M , Avendaño Santiago
Published: April 2008

Four approaches using single-nucleotide polymorphism (SNP) information (F∞-metric model, kernel regression, reproducing kernel Hilbert spaces (RKHS) regression, and a Bayesian regression) were compared with a standard procedure of genetic evaluation (E-BLUP) of sires using mortality rates in broilers as a response variable, working in a Bayesian framework. Late mortality (14–42 days of age) records on 12,167 progeny of 200 sires were precorrected for fixed and random (nongenetic) effects used in the model for genetic evaluation and for the mate effect. The average of the corrected records was computed for each sire. Twenty-four SNPs seemingly associated with late mortality were included in three methods used for genomic assisted evaluations. One thousand SNPs were included in the Bayesian regression, to account for markers along the whole genome. The posterior mean of heritability of mortality was 0.02 in the E-BLUP approach, suggesting that genetic evaluation could be improved if suitable molecular markers were available. Estimates of posterior means and standard deviations of the residual variance were 24.38 (3.88), 29.97 (3.22), 17.07 (3.02), and 20.74 (2.87) for E-BLUP, the linear model on SNPs, RKHS regression, and the Bayesian regression, respectively, suggesting that RKHS accounted for more variance in the data. The two nonparametric methods (kernel and RKHS regression) fitted the data better, having a lower residual sum of squares. Predictive ability, assessed by cross-validation, indicated advantages of the RKHS approach, where accuracy was increased from 25 to 150%, relative to other methods.
Pleiotropic Patterns of Quantitative Trait Loci for 70 Murine Skeletal Traits
Authors: Kenney-Hunt Jane P , Wang Bing , Norgard Elizabeth A , Fawcett Gloria , Falk Doug , Pletscher L Susan , Jarvis Joseph P , Roseman Charles , Wolf Jason , Cheverud James M
Published: April 2008

Quantitative trait locus (QTL) studies of a skeletal trait or a few related skeletal components are becoming commonplace, but as yet there has been no investigation of pleiotropic patterns throughout the skeleton. We present a comprehensive survey of pleiotropic patterns affecting mouse skeletal morphology in an intercross of LG/J and SM/J inbred strains (N = 1040), using QTL analysis on 70 skeletal traits. We identify 798 single-trait QTL, coalescing to 105 loci that affect on average 7–8 traits each. The number of traits affected per locus ranges from only 1 trait to 30 traits. Individual traits average 11 QTL each, ranging from 4 to 20. Skeletal traits are affected by many, small-effect loci. Significant additive genotypic values average 0.23 standard deviation (SD) units. Fifty percent of loci show codominance with heterozygotes having intermediate phenotypic values. When dominance does occur, the LG/J allele tends to be dominant to the SM/J allele (30% vs. 8%). Over- and underdominance are relatively rare (12%). Approximately one-fifth of QTL are sex specific, including many for pelvic traits. Evaluating the pleiotropic relationships of skeletal traits is important in understanding the role of genetic variation in the growth and development of the skeleton.
Wispy, the Drosophila Homolog of GLD-2, Is Required During Oogenesis and Egg Activation
Authors: Cui Jun , Sackton Katharine L , Horner Vanessa L , Kumar Kritika E , Wolfner Mariana F
Published: April 2008

Egg activation is the process that modifies mature, arrested oocytes so that embryo development can proceed. One key aspect of egg activation is the cytoplasmic polyadenylation of certain maternal mRNAs to permit or enhance their translation. wispy (wisp) maternal-effect mutations in Drosophila block development during the egg-to-embryo transition. We show here that the wisp gene encodes a member of the GLD-2 family of cytoplasmic poly(A) polymerases (PAPs). The WISP protein is required for poly(A) tail elongation of bicoid, Toll, and torso mRNAs upon egg activation. In Drosophila, WISP and Smaug (SMG) have previously been reported to be required to trigger the destabilization of maternal mRNAs during egg activation. SMG is the major regulator of this activity. We report here that SMG is still translated in activated eggs from wisp mutant mothers, indicating that WISP does not regulate mRNA stability by controlling the translation of smg mRNA. We have also analyzed in detail the very early developmental arrest associated with wisp mutations. Pronuclear migration does not occur in activated eggs laid by wisp mutant females. Finally, we find that WISP function is also needed during oogenesis to regulate the poly(A) tail length of dmos during oocyte maturation and to maintain a high level of active (phospho-) mitogen-activated protein kinases (MAPKs).
Genetic Dissociation of Ethanol Sensitivity and Memory Formation in Drosophila melanogaster
Authors: LaFerriere Holly , Guarnieri Douglas J , Sitaraman Divya , Diegelmann Soeren , Heberlein Ulrike , Zars Troy
Published: April 2008

The ad hoc genetic correlation between ethanol sensitivity and learning mechanisms in Drosophila could overemphasize a common process supporting both behaviors. To challenge directly the hypothesis that these mechanisms are singular, we examined the learning phenotypes of 10 new strains. Five of these have increased ethanol sensitivity, and the other 5 do not. We tested place and olfactory memory in each of these lines and found two new learning mutations. In one case, altering the tribbles gene, flies have a significantly reduced place memory, elevated olfactory memory, and normal ethanol response. In the second case, mutation of a gene we name ethanol sensitive with low memory (elm), place memory was not altered, olfactory memory was sharply reduced, and sensitivity to ethanol was increased. In sum, however, we found no overall correlation between ethanol sensitivity and place memory in the 10 lines tested. Furthermore, there was a weak but nonsignificant correlation between ethanol sensitivity and olfactory learning. Thus, mutations that alter learning and sensitivity to ethanol can occur independently of each other and this implies that the set of genes important for both ethanol sensitivity and learning is likely a subset of the genes important for either process.
Estimation of Pairwise Identity by Descent From Dense Genetic Marker Data in a Population Sample of Haplotypes
Authors: Browning Sharon R
Published: April 2008

I present a new approach for calculating probabilities of identity by descent for pairs of haplotypes. The approach is based on a joint hidden Markov model for haplotype frequencies and identity by descent (IBD). This model allows for linkage disequilibrium, and the method can be applied to very dense marker data. The method has high power for detecting IBD tracts of genetic length of 1 cM, with the use of sufficiently dense markers. This enables detection of pairwise IBD between haplotypes from individuals whose most recent common ancestor lived up to 50 generations ago.
Fine Mapping of Quantitative Trait Loci Affecting Female Fertility in Dairy Cattle on BTA03 Using a Dense Single-Nucleotide Polymorphism Map
Authors: Druet Tom , Fritz Sébastien , Boussaha Mekki , Ben-Jemaa Slim , Guillaume François , Derbala David , Zelenika Diana , Lechner Doris , Charon Céline , Boichard Didier , Gut Ivo G , Eggen André , Gautier Mathieu
Published: April 2008

Fertility quantitative trait loci (QTL) are of high interest in dairy cattle since insemination failure has dramatically increased in some breeds such as Holstein. High-throughput SNP analysis and SNP microarrays give the opportunity to genotype many animals for hundreds SNPs per chromosome. In this study, due to these techniques a dense SNP marker map was used to fine map a QTL underlying nonreturn rate measured 90 days after artificial insemination previously detected with a low-density microsatellite marker map. A granddaughter design with 17 Holstein half-sib families (926 offspring) was genotyped for a set of 437 SNPs mapping to BTA3. Linkage analysis was performed by both regression and variance components analysis. An additional analysis combining both linkage analysis and linkage-disequilibrium information was applied. This method first estimated identity-by-descent probabilities among base haplotypes. These probabilities were then used to group the base haplotypes in different clusters. A QTL explaining 14% of the genetic variance was found with high significance (P < 0.001) at position 19 cM with the linkage analysis and four sires were estimated to be heterozygous (P < 0.05). Addition of linkage-disequilibrium information refined the QTL position to a set of narrow peaks. The use of the haplotypes of heterozygous sires offered the possibility to give confidence in some peaks while others could be discarded. Two peaks with high likelihood-ratio test values in the region of which heterozygous sires shared a common haplotype appeared particularly interesting. Despite the fact that the analysis did not fine map the QTL in a unique narrow region, the method proved to be able to handle efficiently and automatically a large amount of information and to refine the QTL position to a small set of narrow intervals. In addition, the QTL identified was confirmed to have a large effect (explaining 13.8% of the genetic variance) on dairy cow fertility as estimated by nonreturn rate at 90 days.
Patterns of Molecular Evolution in Caenorhabditis Preclude Ancient Origins of Selfing
Authors: Cutter Asher D , Wasmuth James D , Washington Nicole L
Published: April 2008

The evolution of self-fertilization can mediate pronounced changes in genomes as a by-product of a drastic reduction in effective population size and the concomitant accumulation of slightly deleterious mutations by genetic drift. In the nematode genus Caenorhabditis, a highly selfing lifestyle has evolved twice independently, thus permitting an opportunity to test for the effects of mode of reproduction on patterns of molecular evolution on a genomic scale. Here we contrast rates of nucleotide substitution and codon usage bias among thousands of orthologous groups of genes in six species of Caenorhabditis, including the classic model organism Caenorhabditis elegans. Despite evidence that weak selection on synonymous codon usage is pervasive in the history of all species in this genus, we find little difference among species in the patterns of codon usage bias and in replacement-site substitution. Applying a model of relaxed selection on codon usage to the C. elegans and C. briggsae lineages suggests that self-fertilization is unlikely to have evolved more than ∼4 million years ago, which is less than a quarter of the time since they shared a common ancestor with outcrossing species. We conclude that the profound changes in mating behavior, physiology, and developmental mechanisms that accompanied the transition from an obligately outcrossing to a primarily selfing mode of reproduction evolved in the not-too-distant past.
Raw Mediates Antagonism of AP-1 Activity in Drosophila
Authors: Bates Katherine L , Higley Matthew , Letsou Anthea
Published: April 2008

High baselines of transcription factor activities represent fundamental obstacles to regulated signaling. Here we show that in Drosophila, quenching of basal activator protein 1 (AP-1) transcription factor activity serves as a prerequisite to its tight spatial and temporal control by the JNK (Jun N-terminal kinase) signaling cascade. Our studies indicate that the novel raw gene product is required to limit AP-1 activity to leading edge epidermal cells during embryonic dorsal closure. In addition, we provide the first evidence that the epidermis has a Basket JNK-independent capacity to activate AP-1 targets and that raw function is required broadly throughout the epidermis to antagonize this activity. Finally, our mechanistic studies of the three dorsal-open group genes [raw, ribbon (rib), and puckered (puc)] indicate that these gene products provide at least two tiers of JNK/AP-1 regulation. In addition to Puckered phosphatase function in leading edge epidermal cells as a negative-feedback regulator of JNK signaling, the three dorsal-open group gene products (Raw, Ribbon, and Puckered) are required more broadly in the dorsolateral epidermis to quench a basal, signaling-independent activity of the AP-1 transcription factor.