bluuebunny/crossref_metadata_2025_split huggingface dataset:
Origin of mitochondrial DNA diversity of domestic yaks
Authors: Guo Songchang , Savolainen Peter , Su Jianping , Zhang Qian , Qi Delin , Zhou Jie , Zhong Yang , Zhao Xinquan , Liu Jianquan 
Published: September 2006

Abstract

Background
The domestication of plants and animals was extremely important anthropologically. Previous studies have revealed a general tendency for populations of livestock species to include deeply divergent maternal lineages, indicating that they were domesticated in multiple, independent events from genetically discrete wild populations. However, in water buffalo, there are suggestions that a similar deep maternal bifurcation may have originated from a single population. These hypotheses have rarely been rigorously tested because of a lack of sufficient wild samples. To investigate the origin of the domestic yak (Poephagus grunnies), we analyzed 637 bp of maternal inherited mtDNA from 13 wild yaks (including eight wild yaks from a small population in west Qinghai) and 250 domesticated yaks from major herding regions.

Results
The domestic yak populations had two deeply divergent phylogenetic groups with a divergence time of > 100,000 yrs BP. We here show that haplotypes clustering with two deeply divergent maternal lineages in domesticated yaks occur in a single, small, wild population. This finding suggests that all domestic yaks are derived from a single wild gene pool. However, there is no clear correlation of the mtDNA phylogenetic clades and the 10 morphological types of sampled yaks indicating that the latter diversified recently. Relatively high diversity was found in Qinghai and Tibet around the current wild distribution, in accordance with previous suggestions that the earliest domestications occurred in this region. Conventional molecular clock estimation led to an unrealistic early dating of the start of the domestication. However, Bayesian estimation of the coalescence time allowing a relaxation of the mutation rate are better in agreement with a domestication during the Holocene as supported by archeological records.

Conclusion
The information gathered here and the previous studies of other animals show that the demographic histories of domestication of livestock species were highly diverse despite the common general feature of deeply divergent maternal lineages. The results further suggest that domestication of local wild prey ungulate animals was a common occurrence during the development of human civilization following the postglacial colonization in different locations of the world, including the high, arid Qinghai-Tibetan Plateau.
Human fetal neuroblast and neuroblastoma transcriptome analysis confirms neuroblast origin and highlights neuroblastoma candidate genes
Authors: De Preter Katleen , Vandesompele Jo , Heimann Pierre , Yigit Nurten , Beckman Siv , Schramm Alexander , Eggert Angelika , Stallings Raymond L , Benoit Yves , Renard Marleen , Paepe Anne De , Laureys Geneviève , Påhlman Sven , Speleman Frank 
Published: September 2006

Abstract
Background
Neuroblastoma tumor cells are assumed to originate from primitive neuroblasts giving rise to the sympathetic nervous system. Because these precursor cells are not detectable in postnatal life, their transcription profile has remained inaccessible for comparative data mining strategies in neuroblastoma. This study provides the first genome-wide mRNA expression profile of these human fetal sympathetic neuroblasts. To this purpose, small islets of normal neuroblasts were isolated by laser microdissection from human fetal adrenal glands.

Results
Expression of catecholamine metabolism genes, and neuronal and neuroendocrine markers in the neuroblasts indicated that the proper cells were microdissected. The similarities in expression profile between normal neuroblasts and malignant neuroblastomas provided strong evidence for the neuroblast origin hypothesis of neuroblastoma. Next, supervised feature selection was used to identify the genes that are differentially expressed in normal neuroblasts versus neuroblastoma tumors. This approach efficiently sifted out genes previously reported in neuroblastoma expression profiling studies; most importantly, it also highlighted a series of genes and pathways previously not mentioned in neuroblastoma biology but that were assumed to be involved in neuroblastoma pathogenesis.

Conclusion
This unique dataset adds power to ongoing and future gene expression studies in neuroblastoma and will facilitate the identification of molecular targets for novel therapies. In addition, this neuroblast transcriptome resource could prove useful for the further study of human sympathoadrenal biogenesis.
Screening for abdominal aortic aneurysm by general practitioners and practice-based ultrasonographers
Authors: Laws Catharine , Eastman Jo 
Published: September 2006

Aim: To find out if aortic aneurysm screening could be successfully organized from a general practice with ultrasound facilities, and to offer a screening service to surrounding general practices within a primary health care trust (PHCT) in Surrey. Methods: The study screened men between the ages of 65 and 80 years for abdominal aortic aneurysm (AAA). The screening project was set up and carried out entirely in primary care (in local practices). Funding was received from the PHCT; the costs of the screening programme had to fit within this budget. Results: There was a 71.7% attendance rate and 4.1% of the screened population had an AAA. The screens cost approximately £17.39 per scan. Conclusions: The costs for the screening programme were low, although it is hard to find direct comparisons. The attendance rate could be improved, but the prevalence of AAA in this study was comparable to those found in hospital-led screening trials.
Atrophy of the stria vascularis, a common cause for hearing loss.
Authors: Schuknecht Harold F. , Watanuki Kozo , Takahashi Tadahiko , Aziz Belal A. , Kimura Robert S. , Jones Diane Deleo , Ota Carol Y. 
Published: September 2006

AbstractAtrophy of the stria vascularis is a genetically determined deafness of aging characterized by a bilateral symmetrical sensori‐neural hearing loss showing flat audiometric patterns and excellent speech discrimination. The temporal bones of individuals exhibiting this type of hearing loss were studied by serial sections and surface preparations for light microscopy and by electron microscopy. The atrophic changes are most severe in the apical regions of the cochleas and involve the marginal, intermediate and basal cells in that order of severity. It seems probable that atrophy of the stria vascularis causes some deficiency in the quality of endolymph throughout the cochlear duct, regardless of the location of the atrophy. Typically all other structures of the cochlear duct are normal, and the sense organ when stimulated within its sensitivity range is capable of normal stimulus coding, thus accounting for the usually excellent speech discrimination.
Surveillance for Early Detection of Aggressive Parathyroid Disease: Carcinoma and Atypical Adenoma in Familial Isolated Hyperparathyroidism Associated With a Germline HRPT2 Mutation
Authors: Kelly Thomas G , Shattuck Trisha M , Reyes-Mugica Miguel , Stewart Andrew F , Simonds William F , Udelsman Robert , Arnold Andrew , Carpenter Thomas O 
Published: September 2006

Abstract
Familial hyperparathyroid syndromes involving mutations of HRPT2 (also CDC73), a tumor suppressor, are important to identify because the relatively high incidence of parathyroid malignancy associated with such mutations warrants a specific surveillance strategy. However, there is a dearth of reports describing experience with surveillance and early detection informed by genetic insight into this disorder.
Introduction: Familial isolated hyperparathyroidism (FIHP) is a rare cause of parathyroid (PT) tumors without other neoplasms or endocrinopathies. Germline mutations in CASR, MEN1, and rarely, HRPT2 have been identified in kindreds with FIHP. HRPT2 mutations may be enriched in FIHP families with PT carcinoma, underscoring the importance of identifying causative mutations.
Materials and Methods: A 13-year-old boy, whose father had died of PT carcinoma, developed primary hyperparathyroidism. A left superior PT mass was identified by ultrasonography and removed surgically. Aggressive histological features of the boy's tumor included fibrous trabeculae, mitoses, and microscopic capsular infiltration. Two years later, under close biochemical surveillance, primary hyperparathyroidism recurred 5 months after documentation of normocalcemia and normal parathyroid status. Ultrasound and MRI identified a newly enlarged right superior PT gland but indicated no recurrent disease in the left neck. Histologic features typical of a benign adenoma were evident after surgical extirpation of the gland.
Results: Leukocyte DNA analysis revealed a frameshift mutation in exon 2 of HRPT2. The initial tumor manifested the expected germline HRPT2 mutation, plus a distinct somatic frameshift mutation, consistent with the Knudson “two hit” concept of biallelic inactivation of a classic tumor suppressor gene. Genetic screening of the patient's 7 asymptomatic and previously normocalcemic siblings revealed three with the same germline HRPT2 mutation. One of the siblings newly identified as mutation-positive was noted to be hypercalcemic at the time of the genetic screening. He was found to have a PT adenoma with aggressive features. Two of the five children of another mutation-positive sibling also carry the same HRPT2 mutation.
Conclusions: Despite the reported rarity of HRPT2 mutations in FIHP, a personal or family history of PT carcinoma in FIHP mandates serious consideration of germline HRPT2 mutation status. This information can be used in diagnostic and management considerations, leading to early detection and removal of potentially malignant parathyroid tumors.
Adiponectin Stimulates RANKL and Inhibits OPG Expression in Human Osteoblasts Through the MAPK Signaling Pathway
Authors: Luo Xiang-Hang , Guo Li-Juan , Xie Hui , Yuan Ling-Qing , Wu Xian-Ping , Zhou Hou-De , Liao Er-Yuan 
Published: September 2006

Abstract
Our study indicates that recombinant adiponectin induced RANKL and inhibited OPG expression in human osteoblasts through the AdipoR1/p38 MAPK pathway, and these responses contributed to the adiponectin-induced osteoclasts formation in the co-culture of osteoblast and peripheral blood monocytes systems. These findings showed that adiponectin increased osteoclast formation indirectly through stimulating RANKL and inhibiting OPG production in osteoblasts. It also suggests the pharmacological nature of recombinant adiponectin that indirectly induces osteoclasts formation.
Introduction: Recently, adiponectin has emerged as an element in the regulation of bone metabolism, but the mechanism remains. This study was undertaken to investigate the action of adiponectin on osteoclastogenesis through revealing RANKL and osteoprotegerin (OPG) expression in osteoblasts and osteoclast formation.
Materials and Methods: Real-time quantitative PCR and ELISA were used to detect RANKL and OPG mRNA and protein expression in cultured human osteoblasts. The involved signal pathway was studied using mitogen-activated protein kinase (MAPK) inhibitor and adiponectin receptor 1 (AdipoR1) siRNA. The effects of recombinant adiponectin on osteoclasts formation also were examined in the co-culture systems of osteoblast and peripheral blood monocytes (PBMCs) systems or purified CD14 + PBMCs cultures.
Results: Our study showed that recombinant adiponectin induced RANKL and inhibited OPG mRNA expression in human osteoblasts in a dose- and time-dependent manner. Adiponectin also increased soluble RANKL and decreased OPG secretion in osteoblasts conditioned media. Suppression of AdipoR1 with siRNA abolished the adiponectin-regulated RANKL and OPG mRNA expression in osteoblasts. Furthermore, pretreatment of osteoblasts with the MAPK inhibitor SB203580 abolished adiponectin-regulated RANKL and OPG mRNA expression. Adiponectin induced osteoclast formation in the co-culture systems of osteoblast and PBMCs systems, and OPG entirely blocked this response. However, adiponectin had no direct effect on the differentiation of osteoclast precursor purified CD14 + PBMCs.
Conclusions: These data indicate that recombinant adiponectin induced RANKL and inhibited OPG expression in human osteoblasts through the AdipoR1/p38 MAPK pathway, and these responses contributed to the adiponectin-induced osteoclast formation in the co-culture of osteoblast and PBMCs systems. These findings showed that adiponectin increased osteoclast formation indirectly through stimulating RANKL and inhibiting OPG production in osteoblasts. It suggests the pharmacological nature of recombinant adiponectin that indirectly induces osteoclasts formation.
BMD and Risk of Hip and Nonvertebral Fractures in Older Men:A Prospective Study and Comparison With Older Women
Authors: Cummings Steven R , Cawthon Peggy M , Ensrud Kristine E , Cauley Jane A , Fink Howard A , Orwoll Eric S 
Published: September 2006

Abstract
In a prospective study of 5384 older men, hip BMD was a very strong predictor of hip fracture, much stronger than spine BMD. The relationship between hip BMD and hip fracture risk seemed to be stronger than observed in a large prospective study of women. Hip BMD is an excellent test for predicting fracture risk in men.
Introduction: There have been few studies of the relationship between BMD and risk of fractures in men and none for the association between lumbar spine BMD and risk of hip and nonvertebral fractures. There is also controversy about whether the associations between BMD and risk of fracture are the same in men and women.
Materials and Methods: We measured proximal femur and lumbar spine BMD in 5384 men, ≥65 years of age. We compared the results to the very similar cohort of 7871 women ≥65 of age. During 4.4 years of 99% complete follow-up, we validated 317 nonvertebral (59 hip) fractures in men and 1169 nonvertebral (208 hip) fractures in women.
Results: Total hip BMD was very strongly associated with risk hip fracture in men (3.2-fold increased risk per sex-specific SD decrease in BMD; 95% CI, 2.4–4.1). The association was stronger than observed in SOF (2.1; 95% CI, 1.8, 2.4; p &lt; 0.001 for interaction). Among the men, lumbar spine BMD was weakly associated with risk of hip fracture (relative risk [RR] per sex-specific SD decrease in BMD: 1.5; 95% CI, 1.2, 2.0). The association between total hip BMD and risk of nonvertebral fractures was somewhat stronger for men (RR = 1.6; 95% CI, 1.5, 1.8) than found for women (p = 0.01 for interaction). The risk of nonvertebral fracture was substantially higher in women than in men for all T scores of hip BMD, regardless of whether sex-specific or female reference values were used.
Conclusions: Hip BMD is strongly associated with risk of nonvertebral, and especially hip fracture, in older men. These associations are at least as strong as in women. As in women, lumbar spine BMD in men is only weakly associated with risk of hip fracture. Regardless of whether sex-specific or female reference values were used, T scores indicated different risks of fractures in men than in women.
Vitamin D Action and Regulation of Bone Remodeling: Suppression of Osteoclastogenesis by the Mature Osteoblast
Authors: Baldock Paul A , Thomas Gethin P , Hodge Jason M , Baker Sara UK , Dressel Uwe , O'Loughlin Peter D , Nicholson Geoffrey C , Briffa Kathy H , Eisman John A , Gardiner Edith M 
Published: September 2006

Abstract
Vitamin D acts through the immature osteoblast to stimulate osteoclastogenesis. Transgenic elevation of VDR in mature osteoblasts was found to inhibit osteoclastogenesis associated with an altered OPG response. This inhibition was confined to cancellous bone. This study indicates that vitamin D–mediated osteoclastogenesis is regulated locally by OPG production in the mature osteoblast.
Introduction: Vitamin D stimulates osteoclastogenesis acting through its nuclear receptor (VDR) in immature osteoblast/stromal cells. This mobilization of calcium stores does not occur in a random manner, with bone preferentially removed from cancellous bone. The process whereby the systemic, humoral regulator is targeted to a particular region of the skeleton is unclear.
Materials and Methods: Bone resorption was assessed in mice with vitamin D receptor transgenically elevated in mature osteoblasts (OSVDR). Vitamin D–mediated osteoclastogenesis was examined in vitro using OSVDR osteoblasts and osteoblastic RANKL: osteoprotegerin (OPG) examined in vivo and in vitro after vitamin D treatment.
Results: Vitamin D–mediated osteoclastogenesis was reduced in OSVDR mice on chow and calcium-restricted diets, with effects confined to cancellous bone. OSVDR osteoblasts had a reduced capacity to support osteoclastogenesis in culture. The vitamin D–mediated reduction in OPG expression was reduced in OSVDR osteoblasts in vivo and in vitro, resulting in a reduced RANKL/OPG ratio in OSVDR compared with wildtype, after exposure to vitamin D.
Conclusions: Mature osteoblasts play an inhibitory role in bone resorption, with active vitamin D metabolites acting through the VDR to increase OPG. This inhibition is less active in cancellous bone, effectively targeting this region for resorption after the systemic release of activated vitamin D metabolites.
Fracture Incidence and Characterization in Patients on Osteoporosis Treatment: The ICARO Study
Authors: Adami Silvano , Isaia Giancarlo , Luisetto Giovanni , Minisola Salvatore , Sinigaglia Luigi , Gentilella Raffaella , Agnusdei Donato , Iori Nicoletta , Nuti Ranuccio 
Published: September 2006

Abstract
None of the available osteoporosis therapies have been shown to completely abolish the risk of fractures. In clinical practice, the outcome may be even poorer. In 880 patients prescribed with antiresorptives (alendronate, risedronate, and raloxifene) for &gt;1 year, a fragility fracture was recorded in 8.9%/year of them. This incidence is considerably higher than that observed in randomized clinical trials, and it was significantly related to poor compliance and lack of supplementation with calcium and vitamin D.
Introduction: Osteoporotic fracture is one of the most important public health concerns among the elderly. Currently available therapies have been shown to significantly decrease the risk of fracture, although none of them completely abolishes this risk. In clinical practice, poor treatment response may also result from a number of other factors.
Materials and Methods: The Incidence and ChAracterization of inadequate clinical Responders in Osteoporosis (ICARO) is a multicenter, observational study carried out in Italy. It aimed to analyze, in postmenopausal women with established osteoporosis, the risk factors for an “inadequate clinical response” to drug therapy, defined as the occurrence of new vertebral or nonvertebral fragility fractures in patients prescribed, for at least 1 year, alendronate, risedronate, or raloxifene, with a compliance &gt;50%.
Results: In 880 patients treated with antiresorptive agents for a median of 2.0 years (95% CI: 1.0–4.5) years, the “inadequate clinical responder (ICR)” subjects over the observation period were 220 (25%), with an annual incidence of 8.9%. ICRs, compared with “adequate clinical responders (ACRs),” had more pretreatment fractures and were treated longer (2.8 versus 1.8 years; p &lt; 0.001). After multiple adjustment for these confounding factors, significant determinants of inadequate clinical response were a poorer treatment compliance and a less frequent co-administration of calcium and vitamin D supplements.
Conclusions: The incidence of fractures during treatment with antiresorptive agents in a clinical setting is considerably higher than that observed in randomized clinical trials. Inadequate compliance to treatment and lack of supplementation of calcium and vitamin D are major determinants of this poor response.
Detection of Exon Deletions within an Entire Gene (CFTR) by Relative Quantification on the LightCycler
Authors: Schneider Mircea , Joncourt Franziska , Sanz Javier , von Känel Thomas , Gallati Sabina 
Published: September 2006

AbstractBackground: Cystic fibrosis (CF) is associated with at least 1 pathogen point sequence variant on each CFTR allele. Some symptomatic patients, however, have only 1 detectable pathogen sequence variant and carry, on the other allele, a large deletion that is not detected by conventional screening methods.Methods: For relative quantitative real-time PCR detection of large deletions in the CFTR gene, we designed DNA-specific primers for each exon of the gene and primers for a reference gene (β2-microglobulin). For PCR we used a LightCycler system (Roche) and calculated the gene-dosage ratio of CFTR to β2-microglobulin. We tested the method by screening all 27 exons in 3 healthy individuals and 2 patients with only 1 pathogen sequence variant. We then performed specific deletion screenings in 10 CF patients with known large deletions and a blinded analysis in which we screened 24 individuals for large deletions by testing 8 of 27 exons.Results: None of the ratios for control samples were false positive (for deletions or duplications); moreover, for all samples from patients with known large deletions, the calculated ratios for deleted exons were close to 0.5. In addition, the results from the blinded analysis demonstrated that our method can also be used for the screening of single individuals.Conclusions: The LightCycler assay allows reliable and rapid screening for large deletions in the CFTR gene and detects the copy number of all 27 exons.
Rapid Detection and Identification of Clinically Important Bacteria by High-Resolution Melting Analysis after Broad-Range Ribosomal RNA Real-Time PCR
Authors: Cheng Ju-Chien , Huang Chien-Ling , Lin Chung-Ching , Chen Chi-Ching , Chang Yi-Chih , Chang Shy-Shin , Tseng Ching-Ping 
Published: September 2006

AbstractBackground: Broad-range PCR provides valuable information for detecting bacterial infections. This study assesses the combined use of broad-range real-time PCR and high-resolution melting analysis for rapid detection and identification of clinically important bacteria.Methods: We subjected 46 bacterial culture colonies representing 25 clinically important bacterial species to LightCycler real-time PCR amplification of the 16S rRNA gene in the presence of LCGreen I fluorescent dye. We performed high-resolution melting analysis of the PCR products with the HR-1 instrument and used melting profiles as molecular fingerprints for bacterial species identification. We validated this method via assessment of 54 consecutive bacteria culture colonies obtained from a clinical microbiology laboratory.Results: The 16S rRNA gene of all 25 bacterial species was amplifiable by this method, with PCR product lengths of 216 or 217 bp. Of the 25 bacterial species, we identified 11 via a 1-step post-PCR high-resolution melting analysis. The remaining bacterial species were identified via the high-resolution melting plots obtained by heteroduplex formation between the PCR products of the tested and reference bacterial species or by a 2nd real-time PCR targeting a different region of the 16S rRNA gene. A high-resolution melting database and a working protocol were established for identifying these 25 bacterial species. In the validation assay, a 94% accuracy rate was achieved when the bacterial species were in the high-resolution melting database.Conclusions: This assay requires no multiplexing or hybridization probes and provides a new approach for bacterial species identification in a molecular diagnostic laboratory.