bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells
Authors: Ross Anna Laura , Cannou Claude , Barré-Sinoussi Françoise , Menu Elisabeth 
Published: May 2009

Abstract

Background
The human placenta-derived cell line BeWo has been demonstrated to be restrictive to cell-free HIV-1 infection. BeWo cells are however permissive to infection by VSV-G pseudotyped HIV-1, which enters cells by a receptor-independent mechanism, and to infection by HIV-1 via a cell-to-cell route.

Results
Here we analysed viral entry in wild type BeWo (CCR5+, CXCR4+) and BeWo-CD4+ (CD4+, CCR5+, CXCR4+) cells. We report that HIV-1 internalisation is not restricted in either cell line. Levels of internalised p24 antigen between VSV-G HIV-1 pseudotypes and R5 or X4 virions were comparable. We next analysed the fate of internalised virions; X4 and R5 HIV-1 virions were less stable over time in BeWo cells than VSV-G HIV-1 pseudotypes. We then investigated the role of the proteasome in restricting cell-free HIV-1 infection in BeWo cells using proteasome inhibitors. We observed an increase in the levels of VSV-G pseudotyped HIV-1 infection in proteasome-inhibitor treated cells, but the infection by R5-Env or X4-Env pseudotyped virions remains restricted.

Conclusion
Collectively these results suggest that cell-free HIV-1 infection encounters a surface block leading to a non-productive entry route, which either actively targets incoming virions for non-proteasomal degradation, and impedes their release into the cytoplasm, or causes the inactivation of mechanisms essential for viral replication.
Presence of necrotic strains of Potato virus Y in Mexican potatoes
Authors: Ramírez-Rodríguez Victoriano Roberto , Aviña-Padilla Katia , Frías-Treviño Gustavo , Silva-Rosales Laura , Martínez-Soriano Juan Pablo 
Published: May 2009

Abstract
As part of a routine screening for the possible presence of the necrotic strains of potato virus Y affecting potatoes in Mexico, five PVY isolates were submitted to biological and molecular analysis. Considering their serological properties, two belong to the common strain (O) and three to the necrotic strain (N). All the isolates induced vein necrosis in Nicotiana tabacum. To characterize the isolates, 5' NTR and P1 genes were sequenced and compared with sequences from GenBank database. Nucleotide sequence similarity ranged from 47–100% in the 5' NTR and from 63–100% in the P1 coding region. The lowest amino acid similarity between sequences of P1 gene was 55%. In phylogenetic trees of 5'NTR analysis, two PVYO Mexican isolates clustered with other PVYO isolates. In turn, the three PVYN isolates grouped with PVYN-NTN isolates. The phylogenetic analysis of P1 sequences (nucleotide and amino acid) showed two PVYO isolates grouping next to N-NTN cluster. A detailed analysis of the PVYO isolates showed two potential recombination regions in the P1 gene, in contrast to 5'NTR where no recombination was detected.
Association of the Aromatase Gene Alleles With BMD:Epidemiological and Functional Evidence
Authors: Riancho José A , Sañudo Carolina , Valero Carmen , Pipaón Carlos , Olmos José M , Mijares Verónica , Fernández-Luna José L , Zarrabeitia María T 
Published: May 2009

Abstract
BMD has a strong heritable component. Estrogen activity depends on the aromatization of androgenic precursors in nongonadal tissues both in postmenopausal women and men. Therefore, aromatase is an appealing candidate gene to explain, in part, the genetic component of BMD. In fact, an association between aromatase polymorphisms and BMD has been previously reported in some relatively small groups. In this study, we explored the relationship between several SNPs in the aromatase region and hip BMD in 1163 postmenopausal women. We found significant differences across genotypes, particularly in older women. The BMD differences between homozygous women with opposing genotypes were 4.2% in the whole group and 7.3% in women &gt;67 yr of age. Body weight was significantly associated with BMD also, but there was no evidence for a statistically significant interaction between body weight and aromatase polymorphisms. Electrophoretic mobility shift assays suggested the binding of the CEBPβ transcription factor to the C/G rs1062033 locus, located ∼12 kb upstream of the translation start site. Experiments of transient transfection of osteoblastic cells with luciferase reporters showed differences in the transcriptional activity of alleles C and G at this locus, with different responses to the co-transfection of a CEBPβ expression vector. Furthermore, evidence for differential allelic expression was found in bone tissue samples. In conclusion, polymorphisms in a 12-kb region of the aromatase gene are associated with BMD in postmenopausal women, particularly during the late postmenopausal period. In vitro functional studies point to rs1062033 as a true regulatory polymorphism.
Bone and Muscle Development During Puberty in Girls: A Seven-Year Longitudinal Study
Authors: Xu Leiting , Nicholson Patrick , Wang Qingju , Alén Markku , Cheng Sulin 
Published: May 2009

Abstract
The growth of lean mass precedes that of bone mass, suggesting that muscle plays an important role in the growth of bone. However, to date, no study has directly followed the growth of bone and muscle size through puberty and into adulthood. This study aimed to test the hypothesis that the growth of muscle size precedes that of bone size (width and length) and mass during puberty. Bone and muscle properties were measured using pQCT and DXA in 258 healthy girls at baseline (mean age, 11.2 yr) and 1-, 2-, 3–4- and 7-yr follow-up. Growth trends as a function of time relative to menarche were determined from prepuberty to early adulthood for tibial length (TL), total cross-sectional area (tCSA), cortical CSA (cCSA), total BMC (tBMC), cortical volumetric BMD (cBMD), and muscle CSA (mCSA) in hierarchical models. The timings of the peak growth velocities for these variables were calculated. Seventy premenopausal adults, comprising a subset of the girl's mothers (mean age, 41.5 yr), were included for comparative purposes. In contrast to our hypothesis, the growth velocity of mCSA peaked 1 yr later than that of tibial outer dimensions (TL and tCSA) and slightly earlier than tBMC. Whereas TL ceased to increase 2 yr after menarche, tCSA, cCSA, tBMC, and mCSA continued to increase and were still significantly lower than adult values at the age of 18 yr (all p &lt; 0.01). The results do not support the view that muscle force drives the growth of bone size during puberty.
Bone Health in Children and Adolescents After Renal Transplantation
Authors: Valta Helena , Mäkitie Outi , Rönnholm Kai , Jalanko Hannu 
Published: May 2009

Abstract
The basis for lifelong bone health is established in childhood and adolescence. Whereas pediatric renal transplant (RTx) patients are at risk for impaired bone mass gain and fractures, scarce data on this subject are available. We performed a cross-sectional and longitudinal study of bone health in a national cohort of 106 pediatric RTx patients (median age, 12.6 yr; median follow-up, 5.1 yr after RTx). The patients underwent clinical evaluation, DXA for BMD, and spinal imaging for vertebral fractures. In longitudinal analysis, the median lumbar spine BMD Z-score was lowest (median, −1.0) at 1 yr postoperatively but increased to a peak value of −0.2 at 5 yr. In boys, the lumbar spine BMD Z-score increased also during puberty but decreased in girls. In cross-sectional analysis, the lumbar spine, hip, and whole body BMD Z-scores were &lt; −2 SD in 4%, 6%, and 6% of the patients, respectively. Sixteen percent had sustained peripheral fractures, and 8% had vertebral fractures. Female sex and age &gt;15 yr (OR, 56.26; 95% CI, 5.17–611.82; p = 0.0007) as well as high plasma PTH levels (OR, 4.03; 95% CI, 1.37–11.85; p = 0.009) were significant predictors for low BMD. Three-year cumulative glucocorticoid dose, outside the immediate post-RTx years, was not associated with BMD parameters. The observed BMD results were satisfactory. However, the high (8%) prevalence of vertebral fractures warrants careful evaluation of bone health in these patients.
Sclerostin Mediates Bone Response to Mechanical Unloading Through Antagonizing Wnt/β-Catenin Signaling
Authors: Lin Chuwen , Jiang Xuan , Dai Zhongquan , Guo Xizhi , Weng Tujun , Wang Jun , Li Yinghui , Feng Guoyin , Gao Xiang , He Lin 
Published: May 2009

Abstract
Reduced mechanical stress leads to bone loss, as evidenced by disuse osteoporosis in bedridden patients and astronauts. Osteocytes have been identified as major cells responsible for mechanotransduction; however, the mechanism underlying the response of bone to mechanical unloading remains poorly understood. In this study, we found that mechanical unloading of wildtype mice caused decrease of Wnt/β-catenin signaling activity accompanied by upregulation of Sost. To further analyze the causal relationship among these events, Sost gene targeting mice were generated. We showed that sclerostin selectively inhibited Wnt/β-catenin in vivo, and sclerostin suppressed the activity of osteoblast and viability of osteoblasts and osteocytes. Interestingly, Sost−/− mice were resistant to mechanical unloading-induced bone loss. Reduction in bone formation in response to unloading was also abrogated in the mutant mice. Moreover, in contrast to wildtype mice, Wnt/β-catenin signaling was not altered by unloading in Sost−/− mice. Those data implied that sclerostin played an essential role in mediating bone response to mechanical unloading, likely through Wnt/β-catenin signaling. Our findings also indicated sclerostin is a promising target for preventing disuse osteoporosis.
Use of FTIR Spectroscopic Imaging to Identify Parameters Associated With Fragility Fracture
Authors: Gourion-Arsiquaud Samuel , Faibish Dan , Myers Elizabeth , Spevak Lyudmila , Compston Juliet , Hodsman Anthony , Shane Elizabeth , Recker Robert R , Boskey Elizabeth R , Boskey Adele L 
Published: May 2009

Abstract
BMD does not entirely explain an individual's risk of fracture. The purpose of this study was to assess whether specific differences in spatially resolved bone composition also contribute to fracture risk. These differences were assessed using Fourier transform infrared spectroscopic imaging (FTIRI) and analyzed through multiple logistic regression. Models were constructed to determine whether FTIRI measured parameters describing mineral content, mineral crystal size and perfection, and collagen maturity were associated with fracture. Cortical and cancellous bone were independently evaluated in iliac crest biopsies from 54 women (32 with fractures, 22 without) who had significantly different spine but not hip BMDs and ranged in age from 30 to 83 yr. The parameters that were significantly associated with fracture in the model were cortical and cancellous collagen maturity (increased with increased fracture risk), cortical mineral/matrix ratio (higher with increased fracture risk), and cancellous crystallinity (increased with increased fracture risk). As expected, because of its correlation with cortical but not cancellous bone density, hip BMD was significantly associated with fracture risk in the cortical but not the cancellous model. This research suggests that additional parameters associated with fracture risk should be targeted for therapies for osteoporosis.
New Variants in the Enpp1 and Ptpn6 Genes Cause Low BMD, Crystal-Related Arthropathy, and Vascular Calcification
Authors: Babij Philip , Roudier Martine , Graves Tom , Han Chun-Ya E , Chhoa Mark , Li Chi-Ming , Juan Todd , Morony Sean , Grisanti Mario , Li Xiaodong , Yu Longchuan , Dwyer Denise , Lloyd David J , Bass Michael B , Richards William G , Ebeling Christine , Amato Julie , Carlson George 
Published: May 2009

Abstract
A large genome-wide, recessive, N-ethyl-N-nitrosourea (ENU)-induced mutagenesis screen was performed on a mixed C57BL/6J and C3H.SW-H2/SnJ mouse background to identify genes regulating bone mass. Approximately 6500 male and female G3 hybrid mice were phenotyped at 8 and 10 wk of age by DXA analysis for evidence of changes in unadjusted or body weight–adjusted BMD or BMC. Phenodeviant lines were identified based on statistical criteria that included a false discovery rate (FDR) &lt;20% and Z-score &gt;2.8. Genome-wide mapping scans were initiated on 22 lines, with evidence of high or low BMD or BMC that deviated by approximately −30% to +50% from the means. Several lines were discontinued as showing lack of heritability, but two heritable lines were identified with narrow chromosomal regions that allowed sequencing of potential mutant candidate genes. Novel mutations were identified in the Enpp1 (C397S) gene on chromosome 10 (line 4482) and the Ptpn6 (I482F) gene on chromosome 6 (line 4489) that were both associated with low bone mass. In addition, the phenotype of the Enpp1 mice showed a striking joint disease and calcification of blood vessels including the aorta, myocardium, and renal arteries and capillaries. These results support a role for the Enpp1 gene in the pathogenesis associated with mineralization of articular cartilage and vascular calcification. This work confirms the utility of the chemical mutagenesis approach for identification of potential disease genes and confirms the role of Enpp1 and Ptpn6 in regulating mineralization and skeletal bone mass.
Dose-Dependent Effects of Runx2 on Bone Development
Authors: Zhang Shiqin , Xiao Zhousheng , Luo Junming , He Nan , Mahlios Josh , Quarles L Darryl 
Published: May 2009

Abstract
Runx2 controls the commitment of mesenchymal cells to the osteoblastic lineage. Distinct promoters, designated P1 and P2, give rise to functionally similar Runx2-II and Runx2-I isoforms. We postulate that this dual promoter gene structure permits temporal and spatial adjustments in the amount of Runx2 isoforms necessary for optimal bone development. To evaluate the gene dose-dependent effect of Runx2 isoforms on bone development, we intercrossed selective Runx2-II+/− with nonselective Runx2-II+/−/Runx2-I+/− mice to create compound mutant mice: Runx2-II+/−, Runx2-II+/−/Runx2-I+/−, Runx2-II−/−, Runx2-II−/−/Runx2-I+/−, Runx2-II−/−/Runx2-I−/−. Analysis of the different Runx2-deficient genotypes showed gene dose-dependent differences in the level of expression of the Runx2 isoforms. In addition, we found that Runx2-I is predominately expressed in the perichondrium and proliferating chondrocytes, whereas Runx2-II is expressed in hypertrophic chondrocytes and metaphyseal osteoblasts. Newborn mice showed impaired development of a mineralized skeleton, bone length, and widening of the hypertrophic zone that were proportionate to the reduction in total Runx2 protein expression. Osteoblast differentiation ex vivo was also proportionate to total amount of Runx2 expression that correlated with reduced Runx2 binding to the osteocalcin promoter by quantitative chromatin immunoprecipitation analysis. Functional analysis of P1 and P2 promoters showed differential regulation of the two promoters in osteoblastic cell lines. These findings support the possibility that the total amount of Runx2 derived from two isoforms and the P1 and P2 promoters, by regulating the time, place, and amount of Runx2 in response to changing environmental cues, impacts on bone development.
Effect of Adherence on Lifetime Fractures in Osteoporotic Women Treated With Daily and Weekly Bisphosphonates
Authors: Danese Mark D. , Badamgarav Enkhe , Bauer Douglas C. 
Published: May 2009

Abstract
Patients miss doses of their osteoporosis medications, or stop taking them altogether, for a variety of reasons. Whereas the reasons have been well-studied, their consequences, at the population level, have not. The goal of this study was to estimate the number of fractures that could be prevented with optimal adherence compared with usual adherence to daily and weekly bisphosphonates in the United States (US). We developed a simulation of adherence to bisphosphonate therapy in the US. The model samples women by age and BMD from nationally representative US distributions, and tracks them over time assuming they are treated with a daily or weekly bisphosphonate. The model simulates two adherence scenarios: usual adherence and optimal adherence. The differences in fracture rates between these scenarios, as well as the medication and fracture costs, are estimated with the model. Approximately 258 (95% interval, 194–324) lifetime fractures can be prevented with optimal adherence per 1,000 bisphosphonate-treated women. For optimal adherence, these results translate to an additional lifetime medication cost of $3,800 and a lifetime savings in fracture-related costs of $2,100, for an expected net cost of $1,700 (95% interval, −$4,100 to $3,300) per woman over her lifetime. These results suggest that in patients taking daily or weekly bisphosphonate therapy, a substantial number of fractures occur that are attributable to less than optimal adherence. These results show that there is implicit value to improving adherence, both from a financial and clinical perspective.
Meta-Analysis of the Effect of the Acid-Ash Hypothesis of Osteoporosis on Calcium Balance
Authors: Fenton Tanis R. , Lyon Andrew W. , Eliasziw Michael , Tough Suzanne C. , Hanley David A. 
Published: May 2009

Abstract
The acid-ash hypothesis posits that protein and grain foods, with a low potassium intake, produce a diet acid load, net acid excretion (NAE), increased urine calcium, and release of calcium from the skeleton, leading to osteoporosis. The objectives of this meta-analysis were to assess the effect of changes in NAE, by manipulation of healthy adult subjects' acid-base intakes, on urine calcium, calcium balance, and a marker of bone metabolism, N-telopeptides. This meta-analysis was limited to studies that used superior methodological quality for the study of calcium metabolism. We systematically searched the literature and included studies if subjects were randomized to the interventions and followed the recommendations of the Institute of Medicine's Panel on Calcium and Related Nutrients for calcium studies. Five of 16 studies met the inclusion criteria. The studies altered the amount and/or type of protein. Despite a significant linear relationship between an increase in NAE and urinary calcium (p &lt; 0.0001), there was no relationship between a change of NAE and a change of calcium balance (p = 0.38; power = 94%). There was no relationship between a change of NAE and a change in the marker of bone metabolism, N-telopeptides (p = 0.95). In conclusion, this meta-analysis does not support the concept that the calciuria associated with higher NAE reflects a net loss of whole body calcium. There is no evidence from superior quality balance studies that increasing the diet acid load promotes skeletal bone mineral loss or osteoporosis. Changes of urine calcium do not accurately represent calcium balance. Promotion of the “alkaline diet” to prevent calcium loss is not justified.
Klotho Variants and Chronic Hemodialysis Mortality
Authors: Friedman David J. , Afkarian Maryam , Tamez Hector , Bhan Ishir , Isakova Tamara , Wolf Myles , Ankers Elizabeth , Ye Jun , Tonelli Marcello , Zoccali Carmine , Kuro-o Makoto , Moe Orson , Karumanchi S. Ananth , Thadhani Ravi 
Published: May 2009

Abstract
Patients with end-stage renal disease (ESRD) suffer exceptionally high mortality rates in their first year of chronic hemodialysis. Both vitamin D and fibroblast growth factor (FGF)-23 levels correlate with survival in these patients. Klotho is a protein in the vitamin D/FGF-23 signaling pathway that has been linked with accelerated aging and early mortality in animal models. We therefore hypothesized that genetic variation in the Klotho gene might be associated with survival in subjects with ESRD. We tested the association between 12 single nucleotide polymorphisms (SNPs) in the Klotho gene and mortality in a cohort of ESRD patients during their first year on hemodialysis (n = 1307 white and Asian). We found a significant association between the CC genotype of one tag SNP, rs577912, and increased risk for 1-yr mortality (RR, 1.76; 95% CI, 1.19–2.59; p = 0.003). This effect was even more marked among patients who were not treated with activated vitamin D supplementation (HR, 2.51; 95% CI, 1.18–5.34; p = 0.005). In lymphoblastoid cell lines derived from HapMap subjects, the CC genotype was associated with a 16–21% lower Klotho expression compared with the AA/AC genotype. Our data suggest that a specific Klotho variant (rs577912) is linked to survival in ESRD patients initiating chronic hemodialysis and that therapy with activated vitamin D may modify this risk.
Elastic T-Stress Solutions of Embedded Elliptical Cracks Subjected to Uniaxial and Biaxial Loadings
Authors: Qu J , Wang X 
Published: May 2009

Abstract
The elastic T-stress has been found to be an important parameter in characterizing the near crack tip elastic-plastic stress states of 2-D and 3-D crack problems. In addition to the J-integral, the T-stress provides an effective two-parameter characterization of 2-D and 3-D elastic-plastic crack tip fields in a variety of crack configurations under small scale yielding conditions. Embedded elliptical crack in an infinite solid subjected to uniaxial or biaxial tension conditions represents an excellent model for many engineering components with embedded cracks. Although extensive analyses are available for stress intensity factors (SIFs) for embedded elliptical cracks, to date no analytical T-stress solutions are available. This paper presents the exact close form solutions for elastic T-stress of an embedded elliptical crack in an infinite body under remote uniaxial or biaxial tension. The foundation of the derivation is based on the potential method for three-dimensional elasticity. Solutions of stress components parallel to and perpendicular to the cracked plane are derived first. T-stress is then obtained from the asymptotic stress field near the crack front. Complete solutions of T-stress along the crack front are established. Further, three-dimensional finite element analyses are conducted to verify the derived solutions; excellent agreements are achieved. When combined with the corresponding K or J solutions, these T-stress solutions are suitable for the analysis of constraint effects for embedded elliptical shaped cracks in engineering components.
Calculation of Neutron Fluxes for Radioactive Inventory Assessment of Magnox Power Plant
Authors: Allen DA , Thiruarooran C , Thornton DA , Fletcher AL , Bird AJ , Rycroft S , Wright GA 
Published: May 2009

Abstract
This paper describes the methodology and results of Monte Carlo neutron transport calculations performed to determine the neutron fluxes required for assessments of radioactive inventories of Magnox power plant. Use has been made of existing validated Monte Carlo models of the plant, which have been extended to include details beyond the pressure vessels to the outer surface of the biological shield.