bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline and somatic DNA methylation and epigenetic regulation of KILLIN in renal cell carcinoma
Authors: Bennett Kristi L. , Campbell Rebecca , Ganapathi Shireen , Zhou Ming , Rini Brian , Ganapathi Ram , Neumann Hartmut P.H. , Eng Charis 
Published: May 2011

AbstractWe recently identified germline methylation of KILLIN, a novel p53‐regulated tumor suppressor proximal to PTEN, in >1/3 Cowden or Cowden syndrome‐like (CS/CSL) individuals who are PTEN mutation negative. Individuals with germline KILLIN methylation had increased risks of renal cell carcinoma (RCC) over those with PTEN mutations. Therefore, we tested the hypothesis that KILLIN may be a RCC susceptibility gene, silenced by germline methylation. We found germline hypermethylation by combined bisulfite restriction analysis in at least one of the four CpG‐rich regions in 23/41 (56%) RCC patients compared to 0/50 controls (P < 0.0001). Of the 23, 11 (48%) demonstrated methylation in the −598 to −890 bp region in respect to the KILLIN transcription start site. Furthermore, 19 of 20 advanced RCC showed somatic hypermethylation upstream of KILLIN, with the majority hypermethylated at more than one CpG island (13/19 vs. 3/23 with germline methylation, P < 0.0001). qRT‐PCR revealed that methylation significantly downregulates KILLIN expression (P = 0.05), and demethylation treatment by 5‐aza‐2′deoxycytidine significantly increased KILLIN expression in all RCC cell lines while only increasing PTEN expression in one line. Furthermore, targeted in vitro methylation revealed a significant decrease in KILLIN promoter activity only. These data reveal differential epigenetic regulation by DNA promoter methylation of this bidirectional promoter. In summary, we have identified KILLIN as a potential novel cancer predisposition gene for nonsyndromic clear‐cell RCC, and the epigenetic mechanism of KILLIN inactivation in both the germline and somatic setting suggests the potential for treatment with demethylating agents. © 2011 Wiley‐Liss, Inc.
Maffucci syndrome: A genome‐wide analysis using high resolution single nucleotide polymorphism and expression arrays on four cases
Authors: Pansuriya Twinkal C. , Oosting Jan , Verdegaal Suzan H. M. , Flanagan Adrienne M. , Sciot Raf , Kindblom Lars‐Gunnar , Hogendoorn Pancras C. W. , Szuhai Karoly , Bovée Judith V. M. G. 
Published: May 2011

AbstractOllier disease and Maffucci syndrome are rare, nonhereditary skeletal disorders characterized by the presence of multiple enchondromas with (Maffucci) or without (Ollier) co‐existing multiple hemangiomas of soft tissue. Enchondromas can progress toward central chondrosarcomas. PTH1R mutations are found in a small subset of Ollier patients. The genetic deficit in Maffucci syndrome is unknown. Here, we report the first genome‐wide analysis using Affymetrix SNP 6.0 array on Maffucci enchondromas (n = 4) and chondrosarcomas (n = 2) from four cases. Results were compared to a previously studied cohort of Ollier patients (n = 37). We found no loss of heterozygosity (LOH) or common copy number alterations shared by all enchondromas, with the exception of some copy number variations. As expected, chondrosarcomas were found to have multiple genomic imbalances. This is similar to conventional solitary and Ollier‐related enchondromas and chondrosarcomas and supports the multistep genetic progression model. Expression profiling using Illumina BeadArray‐v3 chip revealed that cartilaginous tumors in Maffucci patients are more similar to such tumors in Ollier patients than to sporadic cartilage tumors. Point mutations in a single gene or other copy number neutral genomic changes might play a role in enchondromagenesis. © 2011 Wiley‐Liss, Inc.
Quality of life for patients requiring surgical resection and reconstruction for mandibular osteoradionecrosis: 10‐year experience at the university of California San Francisco
Authors: Chang Edward I. , Leon Pablo , Hoffman William Y. , Schmidt Brian L. 
Published: May 2011

AbstractBackgroundMandibular osteoradionecrosis is the most devastating complication after radiation therapy for head and neck malignancies. Quality of life (QOL) after surgical treatment is unclear.MethodsA retrospective cohort analysis (1997–2007) was conducted of all patients treated at our institution for stage II and III mandibular osteoradionecrosis. Nineteen of 35 patients responded to a modified University of Washington QOL questionnaire. Twenty had undergone reconstruction using free flaps, and the remainder with plates, plates and local flaps, or debridement alone.ResultsComplications included 3 infections, 5 with hardware, 5 flap‐specific, and 1 nonunion. Four patients had recurrent squamous cell carcinoma (SCC). The factors of greatest concern to patients were appearance, swallowing, and chewing. Average overall QOL was good to very good, and very good compared to preoperative.ConclusionDespite a 37% complication rate, a multidisciplinary team approach with adequate debridement, resection, and reconstruction can greatly improve QOL. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Primary Succession of Soil Rotifers in Clays of Brown Coal Post‐Mining Dumps
Authors: Devetter Miloslav , Frouz Jan 
Published: May 2011

AbstractChanges in rotifer soil communities along a primary succession chronosequence was studied on brown coal post mining areas near Sokolov, NW part of the Czech Republic. The chronosequence of unreclaimed plots was 2, 11, 14, 20, 43 years old. The rotifers were extracted from soil samples using a modification of the Baermann funnel method with combined light and temperature gradients.In total, 34 taxa of soil rotifers were identified throughout the study. The most common species wereEncentrum arvicola, Adineta vaga, A. steineri, Habrotrocha rosa, H. elegans, H. filum, Macrotrachela quadricorniferaandM. nana. Rotifer abundance varied from 4 ± 2 · 103to 516 ± 488 · 103individuals m–2. Species number per sample increased with age of the plot (r= 0.45,P= 0.003). The most important environmental variables which significantly affected rotifer community were wood cover, sodium concentration and age of the plot. Pioneer plant species occupied 2 and 11 year old plots, 14–20 year old plots were covered bySalix capreashrubs and a forest formed byBetula pendulaandPopulus tremuloidesdeveloped on the 43 year old plot. Some species were ubiquitous and present throughout the chronosequence (Macrotrachela quadricornifera). Among the pioneer species wereEncentrum incisum, Habrotrocha rosaandMacrotrachela papillosa, 14–20 years old plots were preferred byAdineta vaga, E. arvicola, H. filumandM. nana, while the oldest plot was dominated byAdineta steineriandEncentrum mucronatum. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Role of Cell Hydrophobicity on Colony Formation in Microcystis (Cyanobacteria)
Authors: Yang Hualin , Cai Yuanfeng , Xia Meng , Wang Xingyu , Shi Limei , Li Pengfu , Kong Fanxiang 
Published: May 2011

AbstractColony formation is highly import ant for the competitive advantage of the cyanobacterium Microcystis over other phytoplankton species. The laboratory‐grown colonial Microcystis strains isolated from Lake Taihu (China) maintained colonial forms under the low light condition (10 μE m–2 s–1). The cell surface hydrophobicities of the Microcystis colonies were measured by cyanobacterial adherence to xylene in comparison with unicellular Microcystis strains. The cells of the tested colonial strains were all hydrophobic, while the cells of the tested unicellular strains were all hydrophilic. Incubation under the higher light condition (75 μE m–2 s–1) leaded to the significant decrease in the cell hydrophobicities of the colonial Microcystis and the transition from colonial forms to unicellular forms. These findings indicated that the cell hydrophobicity of Microcystis may play a role in cell‐cell adherence and colony formation. Phosphate‐limitation, nitrate‐limitation and pH did not affect cell hydrophobicities of colonial Microcystis. Treatment with proteolytic enzymes had no effect on the cell hydrophobicity, indicating that cell surface proteins did not contribute to high cell hydrophobicity. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Relationship of testosterone and osteocalcin levels during growth
Authors: Kirmani Salman , Atkinson Elizabeth J , Melton L Joseph , Riggs B Lawrence , Amin Shreyasee , Khosla Sundeep 
Published: May 2011

Abstract
Recent studies in mice have demonstrated that osteocalcin (OCN) regulates testosterone (T) production in males but not in females. We hypothesized that this novel bone-testis axis may be most relevant during rapid skeletal growth to help maximize bone size. Thus we measured serum T, total and undercarboxylated (UC) OCN, and periosteal circumference at the radius in 56 boys (bone age 4 to 20 years). T was correlated with OCN (bone-age-adjusted r = 0.30, p = .024), with a similar trend for UC OCN. T began to increase in the boys at bone age 11 years, and OCN peaked at bone age 14 years. Thus we divided the boys into three groups: 4 to 10 years (n = 16), 11 to 14 years (n = 18), and 15 to 20 years (n = 22). In boys of bone age 11 to 14 years (but not the other two groups), OCN was correlated with T (r = 0.57, p = .013), with a similar trend for UC OCN; T, in turn, was correlated with periosteal circumference (r = 0.75, p &lt; .001). Collectively, these findings support the recent observations in mice of a novel bone-testis axis. Moreover, our data suggest that in human males, this axis may be most relevant during rapid skeletal growth, when T levels are rising under the influence of the hypothalamic-pituitary axis and OCN is increasing due to skeletal growth. During this phase, OCN may further stimulate testicular T production, which, in turn, contributes to an increase in bone size. © 2011 American Society for Bone and Mineral Research
Concerted actions of insulin-like growth factor 1, testosterone, and estradiol on peripubertal bone growth: A 7-year longitudinal study
Authors: Xu Leiting , Wang Qin , Wang Qingju , Lyytikäinen Arja , Mikkola Tuija , Völgyi Eszter , Cheng Shumei , Wiklund Petri , Munukka Eveliina , Nicholson Patrick , Alén Markku , Cheng Sulin 
Published: May 2011

Abstract
A better understanding of how bone growth is regulated during peripuberty is important for optimizing the attainment of peak bone mass and for the prevention of osteoporosis in later life. In this report we used hierarchical models to evaluate the associations of insulin-like growth factor 1 (IGF-1), estradiol (E2), and testosterone (T) with peripubertal bone growth in a 7-year longitudinal study. Two-hundred and fifty-eight healthy girls were assessed at baseline (mean age 11.2 years) and at 1, 2, 3.5, and 7 years. Serum concentrations of IGF-1, E2, and T were determined. Musculoskeletal properties in the left lower leg were measured using peripheral quantitative computed tomography (pQCT). Serum levels of IGF-1, E2, and T increased dramatically before menarche, whereas they decreased, plateaued, or increased at a lower rate, respectively, after menarche. IGF-1 level was positively associated with periosteal circumference (PC) and total bone mineral content (tBMC) throughout peripuberty but not after adjustment for muscle cross-sectional area (mCSA). On the other hand, IGF-1 was associated with tibial length (TL) independently of mCSA before menarche. T was positively associated with TL, PC, tBMC, and cortical volumetric bone mineral density, independent of mCSA, before menarche but not after. E2 was associated with TL positively before menarche but negatively after menarche. These findings suggest that during puberty, circulating IGF-1 promotes bone periosteal apposition and mass accrual indirectly, probably through stimulating muscle growth, whereas the effects of sex steroids on bone growth differ before and after menarche, presenting a biphasic pattern. Hence the concerted actions of these hormones are essential for optimal bone development in peripuberty. © 2011 American Society for Bone and Mineral Research
Simultaneous screening for osteoporosis at CT colonography: Bone mineral density assessment using MDCT attenuation techniques compared with the DXA reference standard
Authors: Pickhardt Perry J , Lee Lawrence J , Muñoz del Rio Alejandro , Lauder Travis , Bruce Richard J , Summers Ron M , Pooler B Dustin , Binkley Neil 
Published: May 2011

Abstract
The purpose of this study was to evaluate the utility of lumbar spine attenuation measurement for bone mineral density (BMD) assessment at screening computed tomographic colonography (CTC) using central dual-energy X-ray absorptiometry (DXA) as the reference standard. Two-hundred and fifty-two adults (240 women and 12 men; mean age 58.9 years) underwent CTC screening and central DXA BMD measurement within 2 months (mean interval 25.0 days). The lowest DXA T-score between the spine and hip served as the reference standard, with low BMD defined per World Health Organization as osteoporosis (DXA T-score ≤ −2.5) or osteopenia (DXA T-score between −1.0 and −2.4). Both phantomless quantitative computed tomography (QCT) and simple nonangled region-of-interest (ROI) multi-detector CT (MDCT) attenuation measurements were applied to the T12–L5 levels. The ability to predict osteoporosis and low BMD (osteoporosis or osteopenia) by DXA was assessed. A BMD cut-off of 90 mg/mL at phantomless QCT yielded 100% sensitivity for osteoporosis (29 of 29) and a specificity of 63.8% (143 of 224); 87.2% (96 of 110) below this threshold had low BMD and 49.6% (69 of 139) above this threshold had normal BMD at DXA. At L1, a trabecular ROI attenuation cut-off of 160 HU was 100% sensitive for osteoporosis (29 of 29), with a specificity of 46.4% (104 of 224); 83.9% (125 of 149) below this threshold had low BMD and 57.5% (59/103) above had normal BMD at DXA. ROI performance was similar at all individual T12–L5 levels. At ROC analysis, AUC for osteoporosis was 0.888 for phantomless QCT [95% confidence interval (CI) 0.780–0.946] and ranged from 0.825 to 0.853 using trabecular ROIs at single lumbar levels (0.864; 95% CI 0.752–0.930 at multivariate analysis). Supine-prone reproducibility was better with the simple ROI method compared with QCT. It is concluded that both phantomless QCT and simple ROI attenuation measurements of the lumbar spine are effective for BMD screening at CTC with high sensitivity for osteoporosis, as defined by the DXA T-score. © 2011 American Society for Bone and Mineral Research
The effects of a two-year randomized, controlled trial of whey protein supplementation on bone structure, IGF-1, and urinary calcium excretion in older postmenopausal women
Authors: Zhu Kun , Meng Xingqiong , Kerr Deborah A , Devine Amanda , Solah Vicky , Binns Colin W , Prince Richard L 
Published: May 2011

Abstract
The effects of dietary protein on bone structure and metabolism have been controversial, with evidence for and against beneficial effects. Because no long-term randomized, controlled studies have been performed, a two-year study of protein supplementation in 219 healthy ambulant women aged 70 to 80 years was undertaken. Participants were randomized to either a high-protein drink containing 30 g of whey protein (n = 109) or a placebo drink identical in energy content, appearance, and taste containing 2.1 g of protein (n = 110). Both drinks provided 600 mg of calcium. Dual-energy X-ray absorptiometric (DXA) hip areal bone mineral density (aBMD), 24-hour urinary calcium excretion, and serum insulin-like growth factor 1 (IGF-1) were measured at baseline and at 1 and 2 years. Quantitative computed tomographic (QCT) hip volumetric bone mineral density (vBMD) and a femoral neck engineering strength analysis were undertaken at baseline and at 2 years. Baseline average protein intake was 1.1 g/kg of body weight per day. There was a significant decrease in hip DXA aBMD and QCT vBMD over 2 years with no between-group differences. Femoral neck strength was unchanged in either group over time. The 24-hour urinary calcium excretion increased significantly from baseline in both groups at 1 year but returned to baseline in the placebo group at 2 years, at which time the protein group had a marginally higher value. Compared with the placebo group, the protein group had significantly higher serum IGF-1 level at 1 and 2 years (7.3% to 8.0%, p &lt; .05). Our study showed that in protein-replete healthy ambulant women, 30 g of extra protein increased IGF-1 but did not have beneficial or deleterious effects on bone mass or strength. The effect of protein supplementation in populations with low dietary protein intake requires urgent attention. © 2011 American Society for Bone and Mineral Research
Mediation of Rac1 activation by kindlin‐2: An essential function in osteoblast adhesion, spreading, and proliferation
Authors: Jung Gil‐Yong , Park Yoon‐Jeong , Han Jung‐Suk 
Published: May 2011

AbstractKindlins are focal adhesion proteins that regulate integrin signaling. Although integrin activation is critical for bone development, little is known about the expression and role of kindlins in osteoblasts. We therefore investigated the function of kindlin‐2 in osteoblast adhesion, spreading, and proliferation using small interfering RNA. In MC3T3‐E1 cells, only kindlin‐2 is highly expressed and localizes to focal adhesion. We found that kindlin‐2 was involved in integrin activation in MC3T3‐E1 cells and that kindlin‐2 knockdown osteoblasts resulted in diminished cell adhesion, spreading, and proliferation. In this process, kindlin‐2 knockdown impaired transient Rac1 activation, influencing Akt activation and AP‐1 activity. In agreement with these data, pharmacological inhibition of Rac1 reduced MC3T3‐E1 cell adhesion, spreading, and proliferation. Overall, these findings demonstrated that kindlin‐2 governs Rac1 activation, which controls osteoblast function. Our findings provide the first insights concerning the function of kindlin‐2 in osteoblast, and suggest that kindlin‐2 is a critical mediator for osteoblast physiology. J. Cell. Biochem. 112: 2541–2548, 2011. © 2011 Wiley‐Liss, Inc.
IL‐8 increases integrin expression and cell motility in human chondrosarcoma cells
Authors: Lee Chun‐Yi , Huang Chun‐Yin , Chen Meng‐Yi , Lin Ching‐Yuang , Hsu Horng‐Chaung , Tang Chih‐Hsin 
Published: May 2011

AbstractChondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. Interleukin‐8 (IL‐8), a chemokine with a defining CXC amino acid motif, is known to possess tumorigenic and proangiogenic properties. Over‐expression of IL‐8 has been detected in many human tumors. However, the effects of IL‐8 in migration and integrin expression in chondrosarcoma cells are largely unknown. In this study, we found that IL‐8 increased the migration and the expression of αvβ3 integrin in human chondrosarcoma cells. Activations of phosphatidylinositol 3‐kinase (PI3K), Akt, and AP‐1 pathways after IL‐8 treatment were demonstrated, and IL‐8‐induced expression of integrin and migration activity was inhibited by the specific inhibitor and mutant of PI3K, Akt, and AP‐1 cascades. Taken together, our results indicated that IL‐8 enhances the migration of chondrosarcoma cells by increasing αvβ3 integrin expression through the PI3K/Akt/AP‐1 signal transduction pathway. J. Cell. Biochem. 112: 2549–2557, 2011. © 2011 Wiley‐Liss, Inc.
Development of a successive targeting liposome with multi‐ligand for efficient targeting gene delivery
Authors: Ma Kun , Shen Haijun , Shen Song , Xie Men , Mao Chuanbin , Qiu Liyan , Jin Yi 
Published: May 2011

AbstractBackgroundA successful gene delivery system needs to breakthrough several barriers to allow efficient transgenic expression. In the present study, successive targeting liposomes (STL) were constructed by integrating various targeting groups into a nanoparticle to address this issue.MethodsPolyethylenimine (PEI) 1800‐triamcinolone acetonide (TA) with nuclear targeting capability was synthesized by a two‐step reaction. Lactobionic acid was connected with cholesterol to obtain a compound of [(2‐lactoylamido) ethylamino]formic acid cholesterol ester (CHEDLA) with hepatocyte‐targeting capability. The liposome was modified with PEI 1800‐TA and CHEDLA to prepare successive targeting liposome (STL). Its physicochemical properties and transfection efficiency were investigated both in vitro and in vivo.ResultsThe diameter of STL was approximately 100 nm with 20 mV of potential. The confocal microscopy observation and potential assay verified that lipid bilayer of STL was decorated with PEI 1800‐TA. Cytotoxicity of STL was significantly lower than that of PEI 1800‐TA and PEI 25K. The transfection efficiency of 10% CHEDLA STL in HepG2 cells was the higher than of the latter two with serum. Its transfection efficiency was greatly reduced with excessive free galactose, indicating that STL was absorbed via galactose receptor‐mediated endocytosis. The in vivo study in mice showed that 10% CHEDLA STL had better transgenic expression in liver than the other carriers.ConclusionsSTL with multi‐ligand was able to overcome the various barriers to target nucleus and special cells and present distinctive transgenic expression. Therefore, it has a great potential for gene therapy as a nonviral carrier. Copyright © 2011 John Wiley & Sons, Ltd.
Spatial patterns and regimes of daily precipitation in Iran in relation to large‐scale atmospheric circulation
Authors: Raziei Tayeb , Mofidi Abbas , Santos João A. , Bordi Isabella 
Published: May 2011

AbstractThe relationships between large‐scale atmospheric circulation types and seasonal regimes of daily precipitation over Iran are assessed using daily precipitation from a high‐resolution gridded dataset provided by the Asian Precipitation‐Highly Resolved Observational Data Integration Towards the Evaluation of Water Resources (APHRODITE) Project. Regional spatial modes of daily precipitation variability were identified by S‐mode Principal Component Analysis (PCA) with Varimax rotation, applied to the subset of days when at least 10% of all grid‐points over Iran received precipitation ≥ 5 mm. The study refers to the period 1961–2004 and is carried out for each season (excluding summer) separately. To characterize the dynamical features associated with each regional precipitation regime (PR), composites of daily atmospheric fields are computed by only averaging days with rotated PCA scores ≥ 1.5 (strong positive phase). In autumn and winter, Iran is divided into five PRs, while four PRs are identified in spring. Results suggest that the spatial distribution of precipitation over Iran is largely governed by the geographical position of both the mid‐tropospheric trough over the Middle East and the Arabian anticyclone. In fact, in almost all PRs, the trough, as a pre‐conditioning factor, leads to regional‐scale ascending motions, whereas the Arabian anticyclone induces low‐tropospheric moisture transports from southern water bodies into the cyclonic systems near Iran, triggering rain‐generating conditions. Copyright © 2011 Royal Meteorological Society