bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-Induced Hypophosphatemic Rickets in an Adolescent Boy—Clinical Presentation, Diagnosis, and Histological Findings in Growth Plate and Muscle Tissue
Authors: Haeusler G. , Freilinger M. , Dominkus M. , Egerbacher M. , Amann G. , Kolb A. , Schlegel W. , Raimann A. , Staudenherz A. 
Published: July 2010

Context: The mechanism behind disabling muscle weakness in tumor-induced hypophosphatemic rickets is obscure. Histological investigation of growth plate tissue of patients with tumor-induced osteomalacia has so far not been reported.Patient: A mesenchymal tumor was detected in the left distal fibula by 68Ga-DOTATOC in a 17-yr-old boy with adolescent onset of severe hypophosphatemic rickets. Disabling muscle weakness improved within days after surgery, and normal mobility was restored within months.Methods and Results: The resected tissue included part of the growth plate allowing immunohistochemical investigation. Positive staining of FGF23 was found in the tumor cells and in hypertrophic chondrocytes, osteoblasts, and osteoclasts of the adjacent growth plate. This distribution matched that found in growth plate tissue of a healthy control. We found positive staining for the somatostatin receptor not only in the tumor but also within the growth plate and adjacent bony tissue in the patient and the healthy control. Muscle tissue provided evidence for a partial defect in respiratory chain complexes I-IV. Biochemical markers were nearly or completely restored to normal 12 months after surgery.Conclusions: Hypertrophic growth plate chondrocytes are a target or source of FGF23 in tumor-induced osteomalacia. Low serum phosphate, FGF23, or other factors produced by the tumor may interfere with mitochondrial function.
Discovery of Glucocorticoid Receptor-β in Mice with a Role in Metabolism
Authors: Hinds Terry D. , Ramakrishnan Sadeesh , Cash Harrison A. , Stechschulte Lance A. , Heinrich Garrett , Najjar Sonia M. , Sanchez Edwin R. 
Published: July 2010

AbstractGlucocorticoid hormones control diverse physiological processes, including metabolism and immunity, by activating the major glucocorticoid receptor (GR) isoform, GRα. However, humans express an alternative isoform, human (h)GRβ, that acts as an inhibitor of hGRα to produce a state of glucocorticoid resistance. Indeed, evidence exists that hGRβ contributes to many diseases and resistance to glucocorticoid hormone therapy. However, rigorous testing of the GRβ contribution has not been possible, because rodents, especially mice, are not thought to express the β-isoform. Here, we report expression of GRβ mRNA and protein in the mouse. The mGRβ isoform arises from a distinct alternative splicing mechanism utilizing intron 8, rather than exon 9 as in humans. The splicing event produces a form of β that is similar in structure and functionality to hGRβ. Mouse (m)GRβ has a degenerate C-terminal region that is the same size as hGRβ. Using a variety of newly developed tools, such as a mGRβ-specific antibody and constructs for overexpression and short hairpin RNA knockdown, we demonstrate that mGRβ cannot bind dexamethasone agonist, is inhibitory of mGRα, and is up-regulated by inflammatory signals. These properties are the same as reported for hGRβ. Additionally, novel data is presented that mGRβ is involved in metabolism. When murine tissue culture cells are treated with insulin, no effect on mGRα expression was observed, but GRβ was elevated. In mice subjected to fasting-refeeding, a large increase of GRβ was seen in the liver, whereas mGRα was unchanged. This work uncovers the much-needed rodent model of GRβ for investigations of physiology and disease.
Human Chorionic Gonadotropin Stimulates Theca-Interstitial Cell Proliferation and Cell Cycle Regulatory Proteins by a cAMP-Dependent Activation of AKT/mTORC1 Signaling Pathway
Authors: Palaniappan Murugesan , Menon K.M.J. 
Published: July 2010

AbstractIn addition to playing a cardinal role in androgen production, LH also regulates growth and proliferation of theca-interstitial (T-I) cells. Here, we show for the first time that LH/human chorionic gonadotropin (hCG) regulates T-I cell proliferation via the mammalian target of rapamycin complex 1 (mTORC1) signaling network. LH/hCG treatment showed a time-dependent stimulation of T-I cell proliferation and phosphorylation of protein kinase B (AKT), ERK1/2, and ribosomal protein (rp)S6 kinase 1 (S6K1), and its downstream effector, rpS6. Pharmacological inhibition of ERK1/2 signaling did not block the hCG-induced phosphorylation of tuberin, the upstream regulator of mTORC1 or S6K1, the downstream target of mTORC1. However, inhibition of AKT signaling completely blocked the hCG response. Furthermore, the AKT-specific inhibitor abolished forskolin (FSK)-stimulated phosphorylation of AKT, tuberin, S6K1, and rpS6. Human CG and FSK-mediated phosphorylation of AKT and downstream targets of mTORC1 were attenuated by inhibition of adenylyl cyclase. Pharmacologic targeting of mTORC1 with rapamycin also abrogated hCG or FSK-induced phosphorylation of S6K1, rpS6, and eukaryotic initiation factor 4E binding protein 1. In addition, hCG or FSK-mediated up-regulation of the cell cycle regulatory proteins cyclin-dependent kinase 4, cyclin D3, and proliferating cell nuclear antigen was blocked by rapamycin. These results were further confirmed by demonstrating that knockdown of mTORC1 using small interfering RNA abolished hCG-mediated increases in cell proliferation and the expression of cyclin D3 and proliferating cell nuclear antigen. Taken together, the present studies show a novel intracellular signaling pathway for T-I cell proliferation involving LH/hCG-mediated activation of the AKT/mTORC1 signaling cascade.
AMPK Regulates Metabolic Actions of Glucocorticoids by Phosphorylating the Glucocorticoid Receptor through p38 MAPK
Authors: Nader Nancy , Ng Sinnie Sin Man , Lambrou George I. , Pervanidou Panagiota , Wang Yonghong , Chrousos George P. , Kino Tomoshige 
Published: July 2010

Abstract
Glucocorticoids play central roles in the regulation of energy metabolism by shifting it toward catabolism, whereas AMP-activated protein kinase (AMPK) is the master regulator of energy homeostasis, sensing energy depletion and stimulating pathways of increasing fuel uptake and saving on peripheral supplies. We showed here that AMPK regulates glucocorticoid actions on carbohydrate metabolism by targeting the glucocorticoid receptor (GR) and modifying transcription of glucocorticoid-responsive genes in a tissue- and promoter-specific fashion. Activation of AMPK in rats reversed glucocorticoid-induced hepatic steatosis and suppressed glucocorticoid-mediated stimulation of glucose metabolism. Transcriptomic analysis in the liver suggested marked overlaps between the AMPK and glucocorticoid signaling pathways directed mostly from AMPK to glucocorticoid actions. AMPK accomplishes this by phosphorylating serine 211 of the human GR indirectly through phosphorylation and consequent activation of p38 MAPK and by altering attraction of transcriptional coregulators to DNA-bound GR. In human peripheral mononuclear cells, AMPK mRNA expression positively correlated with that of glucocorticoid-responsive glucocorticoid-inducible leucine zipper protein, which correlated also positively with the body mass index of subjects. These results indicate that the AMPK-mediated energy control system modulates glucocorticoid action at target tissues. Because increased action of glucocorticoids is associated with the development of metabolic disorders, activation of AMPK could be a promising target for developing pharmacological interventions to these pathologies.
Molecular bases of neuroserpin function and pathology
Authors: Caccia Sonia , Ricagno Stefano , Bolognesi Martino 
Published: July 2010

AbstractSerpins build a large and evolutionary widespread protein superfamily, hosting members that are mainly Ser-protease inhibitors. Typically, serpins display a conserved core domain composed of three main β-sheets and 9–10 α-helices, for a total of approximately 350 amino acids. Neuroserpin (NS) is mostly expressed in neurons and in the central and peripheral nervous systems, where it targets tissue-type plasminogen activator. NS activity is relevant for axogenesis, synaptogenesis and synaptic plasticity. Five (single amino acid) NS mutations are associated with severe neurodegenerative disease in man, leading to early onset dementia, epilepsy and neuronal death. The functional aspects of NS protease inhibition are linked to the presence of a long exposed loop (reactive center loop, RCL) that acts as bait for the incoming partner protease. Large NS conformational changes, associated with the cleavage of the RCL, trap the protease in an acyl-enzyme complex. Contrary to other serpins, this complex has a half-life of approximately 10 min. Conformational flexibility is held to be at the bases of NS polymerization leading to Collins bodies intracellular deposition and neuronal damage in the pathological NS variants. Two main general mechanisms of serpin polymerization are currently discussed. Both models require the swapping of the RCL among neighboring serpin molecules. Specific differences in the size of swapped regions, as well as differences in the folding stage at which polymerization can occur, distinguish the two models. The results provided by recent crystallographic and biophysical studies allow rationalization of the functional and pathological roles played by NS based on the analysis of four three-dimensional structures.
Alternative Procedure for Determination of Hot Mix Asphalt Creep Compliance
Authors: Zofka Adam , Yut Iliya 
Published: July 2010

Abstract
Creep compliance function is one of the fundamental properties of viscoelastic materials. In asphalt research, creep compliance is used in the prediction of low-temperature cracking, which is a prevalent distress in asphalt pavements in northern parts of the United States and Canada. The thermal cracking prediction model included in the current version of the Mechanistic-Empirical Pavement Design Guide requires the creep compliance of hot mix asphalt (HMA) materials as a primary input. The current AASHTO procedure for determining creep compliance of HMA is based on the indirect tension (IDT) test. The IDT test is performed on relatively thick cylindrical specimens, which makes this test unsuitable for field cores from thin layers and construction lifts. In addition, thick specimens do not allow for investigation of the gradual aging that occurs in asphalt layers due to oxidation and volatilization. This paper outlines the procedure that uses the bending beam rheometer (BBR) as an alternative to the IDT test to determine the low-temperature creep compliance of HMA using thin beam specimens. Twenty different HMA mixtures are tested at three temperature levels using both the IDT and the BBR instruments. The analysis of test results is presented in two parts. First, the variability in creep compliance values obtained from the IDT and the BBR tests is discussed. Next, the artificial neural networks (ANNs) are trained to (1) predict IDT results from BBR measurements using design parameters of HMA mixture and testing temperature as the model inputs and (2) backcalculate HMA creep compliance from the binder creep compliance and vice versa. It is concluded that testing HMA beams can be used instead of IDT specimens for the low-temperature characterization of HMA mixtures, and the ANN can be successfully used for the backcalculation of the creep compliance measured by both IDT and BBR devices.
Primary tumour size is a prognostic parameter in patients suffering from differentiated thyroid carcinoma with extrathyroidal growth: results of the MSDS trial
Authors: Krämer Jan Alexander , Schmid Kurt Werner , Dralle Henning , Dietlein Markus , Schicha Harald , Lerch Hartmut , Gerss Joachim , Frankewitsch Thomas , Schober Otmar , Riemann Burkhard 
Published: July 2010

ObjectiveThe Multicentre Study Differentiated Thyroid Cancer (MSDS) collective represents a well-defined group of patients with thyroid carcinomas with extrathyroidal extension. The aim of the present study was to evaluate the relationship of the primary tumour size with clinicopathological features as well as the outcome of patients with minimum and extensive extrathyroidal growth (pT3b- and pT4a-tumours; UICC 2002/2003, 6th ed).MethodsThe tumour diameter was available in 324 out of 351 MSDS patients (244 females, 80 males). Mean age of patients was 47.7±12.0 years (range, 20.1–69.8 years), and the median follow-up was 6.2 years. The relationship between primary tumour size and the following clinicopathological data was investigated: age, gender, histological tumour type (papillary thyroid carcinomas (PTC) versus follicular thyroid carcinomas (FTC)) and UICC/AJCC TNM classification. In addition, the correlation between primary tumour size and event-free and overall survival was assessed.ResultsThe FTC of our series were significantly larger than PTC (3.46 vs 1.84 cm;P<0.001). Patients suffering from pT3b-tumours presented with significantly smaller tumour size than those with extensive extrathyroidal growth (pT4a-tumours) (1.9 vs 3.0 cm;P<0.01). All patients with distant metastases suffered from tumours >2 cm. Furthermore, event-free and overall survival were significantly correlated with increasing tumour size (P<0.05). Using multivariate analysis, a pT4a-category and a tumour diameter >2 cm remained independent predictors of survival.ConclusionsIn patients suffering from differentiated thyroid carcinoma with extrathyroidal growth (pT3b and pT4a), the tumour size is an independent predictor of event-free and overall survival.
In the News
Authors: Jacobs William , Nicogossian Arnauld 
Published: July 2010

AbstractIn the Editors' opinion, the materials summarized in this section have the potential for the development of health policies and standards; or for use in the daily practice and counseling of patients in preventative care. For additional information, readers might wish to visit Internet‐based medical news websites, some free of charge, such as MedScape, Stone Heart, American College of Physicians, and the World Medical Association.
Deconstructing Sport: When Philosophy and Education Meet in Derrida's Thought
Authors: Isidori Emanuele 
Published: July 2010

Deconstructing Sport: When Philosophy and Education Meet in Derrida's ThoughtJacques Derrida (1930-2004), master of the deconstructionist method and recognized as one of the greatest thinkers of our time, was in his youth, before beginning his career as a philosopher, a footballer who played this game with the Italian prisoners in Algiers, his birthplace, during World War II. In a 1991 interview, when he was 60, Derrida narrated in detail his childhood dream of becoming a professional football player, confiding that all of his philosophy and thought had been inspired by sport and the game of football. Starting from this biographical note, the aim of my study is to demonstrate, first of all, how Derrida's whole philosophy and technique of deconstruction really has its roots in the concept of sport. The French-Algerian philosopher understood sport as a cultural structure based on the concepts of play, game, body, rules, and all of the oppositional pairs deriving from différance and from the tensions it generates. Secondly, the study tries to show how sport is for Derrida a metaphor of life and its meaning, suspended between being and nothingness; a place and a field in which human beings act, learn and educate themselves, deconstructing, as in a text, the values and prejudices of their lives and understanding, through sport itself, their roles and responsibility toward themselves and the community in which they live.
The Relationship of Management Style and Job Satisfaction among PE Teachers
Authors: Ehsani Mohammad 
Published: July 2010

The Relationship of Management Style and Job Satisfaction among PE TeachersThe present study was conducted with the purpose of determining the relationship between management style of physical education responsibilities with job satisfaction of sport teachers and determination of the relationship between transformational and transactional leadership of physical education authorities with job satisfaction of sport instructors.After recognition of relationships between management style and leadership with job satisfaction, a step is taken towards recognition of effective factors for improvement of organization; therefore, such research is considered as optimized and appropriate solutions for recognition of the management and organization's problems and difficulties, for presenting guidance.This study is based on the opinions of 181 male and female physical education teachers from five districts of the education and instruction department of Esfahan, in which the type of management style of physical education authorities of all five districts of education and instruction of Esfahan and job-satisfaction of the teacher were evaluated through two questionnaires, the confidentiality of which was computed via Cronbach's alpha-coefficient.Results of the study showed that the relationship between management style and leadership of physical education authorities and sport teachers' job-satisfaction with P<0.01 level has been positive and significant. Also, the relationship between transformational and transactional management style of physical education authorities and job-satisfaction of teachers with p<0.01 level has been positive and significant too. Amongst other results of this study with regard to e.g. sex, age, marital status, field of education, educational degree, and previous work-record of P.E teachers and their job-satisfaction, the relationship for those with p<0.01 level has not been significant.
Value Priorities in Connection to Sport Participation
Authors: Perényi Szilvia 
Published: July 2010

Value Priorities in Connection to Sport ParticipationSport participation is not only a token for the general physical health of youth and future generations, but also a fundamental element of youth socialisation and value transfer. This study is based on Youth2004©, which contains a nationwide, randomly selected representative sample of 15 to 29 year old subjects (N=8000). The purpose of this study was to analyse the layout of value preferences of sport participant and non-participant Hungarian youth by using the same methods of analysis that were applied to the data of the first edition of the Youth research series in year 2000. The goals are to analyse whether similar values would connect to sport participation, taking the time element into consideration, and to review how sport participation is associated with the layout of values, examining the socio-demographic determination of both sport participation and value orientation. For data analysis Mean and non-parametric Mann & Whitney U test was applied. It was found that, similarly to previous results, the majority of values associated with sport participation fall under the self-direction, stimulation value dimensions of Schwartz (1994). However, the higher importance given to the materialistic value of ‘wealth/richness’ by the non-participants in the first set of data (Perényi 2008), was not traceable four years later. Furthermore, the continuing democratisation of society and sport provided for the inclusion of wider societal segments, which can also be tracked by the wider portfolio of preferred values by sporting participants. Values like appreciation of ‘tradition’ and ‘national identity’, however, may also have more association to other socio-demographic factors and, as a consequence, to life circumstances, such as size of settlement or level of education.
Heterointegration of Pt/Si/Ag Nanowire Photodiodes and Their Photocatalytic Properties
Authors: Qu Yongquan , Xue Teng , Zhong Xing , Lin Yung‐Chen , Liao Lei , Choi Jina , Duan Xiangfeng 
Published: July 2010

AbstractPhotocatalyst mediated photoelectrochemical processes can make use of the photogenerated electrons and holes onsite for photocatalytic redox reactions, and enable the harness and conversion of solar energy into chemical energy, in analogy to natural photosynthesis. However, the photocatalysts available to date are limited by either poor efficiency in the visible light range or insufficient photoelectrochemical stability. Here, it is shown that a Pt/Si/Ag nanowire heterostructure can be rationally synthesized to integrate a nanoscale metal‐semiconductor Schottky diode encased in a protective insulating shell with two exposed metal catalysts. The synthesis of Pt/Si/Ag nanowire diodes involves a scalable process including the formation of silicon nanowire array through wet chemical etching, electrodeposition of platinum and photoreduction of silver. The Pt/Si/Ag diodes exhibit highly efficient photocatalytic activity for a wide range of applications including environmental remediation and solar fuel production in the visible range. In this article, photodegradation of indigo carmine and 4‐nitrophenol are used to evaluate the photoactivity of Pt/Si/Ag diodes. The Pt/Si/Ag diodes also show high activity for photoconversion of formic acid into carbon dioxide and hydrogen.
A Fluorescence‐Activated Cell Sorter Analysis of the Relationship Between Protein Kinase G and Endothelial Nitric Oxide Synthase
Authors: John Theresa A. , Raj J. Usha 
Published: July 2010

AbstractThe process of regulation of NOS after production of nitric oxide is not yet delineated. Protein kinase G may exert a feedback regulation of this enzyme. We used diaminofluorescein assays to detect changes in basal nitric oxide production caused by modulators of protein kinase G activity in freshly isolated ovine lung microvascular endothelial cells. We also used fluorescence activated cell sorter analysis (FACS) to determine molecular and phosphorylation changes caused by PKG activation with 8‐Br‐cGMP. The PKG activator, 8‐Br‐cGMP (100 μM) produced a shift in the basal NO production curve downward. The inhibition began within 5 min and was sustained over 4.5 hr. The two protein kinase G inhibitors 100 μM Rp‐8‐Br‐PET‐cGMPS and 50 nM guanosine 3′‐5′‐cyclic monophosphoro thionate‐8‐Br‐Rp isomer Na salt and the cGMP inhibitor 4 μM Rp‐8‐pCPT‐cGMPS all enhanced NO production as seen by the upward shift in the basal NO curve. Conversely, the PKG activator drug, 100 μM guanosine‐3′‐5′‐cyclic monophosphate‐β‐phenyl‐1NF‐ethano‐8‐bromo sodium salt decreased NO production causing a downward shift in the basal curve. FACS analysis revealed that 5 μM 8‐Br‐cGMP in <5 min caused an increase in N‐terminal labeling of NOS and a decrease in both C‐terminal and serine 1177 labeling of NOS. 8‐Br‐cGMP appeared to increase PKG 1α and to decrease PKG 1β labeling. Changes in other phosphorylation sites were less consistent but overall mean channel fluorescence increased from 19.92 to 217.36 for serine 116 and decreased from 329.27 to 254.03 for threonine 495 phosphorylation. Data indicated that PKG caused both molecular and phosphorylation changes in NOS. Anat Rec 293:1755–1765, 2010. © 2010 Wiley‐Liss, Inc.
Hepatic Stellate Cells in Inflammation‐Fibrosis‐Carcinoma Axis
Authors: Wang Bin‐Bin , Cheng Jun‐Yao , Gao Hong‐Hao , Zhang Yang , Chen Zhi‐Nan , Bian Huijie 
Published: July 2010

AbstractAlmost 80% of hepatocellular carcinoma (HCC) cases are associated with chronic hepatitis and cirrhosis resulting from inflammation and fibrosis. A three‐step process of “inflammation‐fibrosis‐carcinoma” is believed to be involved in hepatocarcinogenesis. The activation of hepatic stellate cells (HSCs) may serve as an important mediator in the process of inflammation‐fibrosis‐carcinoma axis, even in tumor metastasis. A remarkable knowledge of activated HSCs in the pathology of HCC development is mostly focused on the liver fibrosis. The molecular links that connects inflammation and cancer in the activation of HSC are not completely known. This highlights urgent need to increase our understanding of the cellular and molecular mechanisms, by which activation of HSCs is involved in the hepatic inflammation, carcinogenesis, and metastasis. Anat Rec 293:1492–1496, 2010. © 2010 Wiley‐Liss, Inc.