bluuebunny/crossref_metadata_2025 huggingface dataset:
Imputation aware meta‐analysis of genome‐wide association studies
Authors: Zaitlen Noah , Eskin Eleazar
Published: August 2010

Genome‐wide association studies have recently identified many new loci associated with human complex diseases. These newly discovered variants typically have weak effects requiring studies with large numbers of individuals to achieve the statistical power necessary to identify them. Likely, there exist even more associated variants, which remain to be found if even larger association studies can be assembled. Meta‐analysis provides a straightforward means of increasing study sample sizes without collecting new samples by combining existing data sets. One obstacle to combining studies is that they are often performed on platforms with different marker sets. Current studies overcome this issue by imputing genotypes missing from each of the studies and then performing standard meta‐analysis techniques. We show that this approach may result in a loss of power since errors in imputation are not accounted for. We present a new method for performing meta‐analysis over imputed single nucleotide polymorphisms, show that it is optimal with respect to power, and discuss practical implementation issues. Through simulation experiments, we show that our imputation aware meta‐analysis approach outperforms or matches standard meta‐analysis approaches. Genet. Epidemiol. 34: 537–542, 2010. © 2010 Wiley‐Liss, Inc.
On the genome‐wide analysis of copy number variants in family‐based designs: methods for combining family‐based and population‐based information for testing dichotomous or quantitative traits, or completely ascertained samples
Authors: Murphy Amy , Won Sungho , Rogers Angela , Chu Jen‐Hwa , Raby Benjamin A. , Lange Christoph
Published: August 2010

We propose a new approach for the analysis of copy number variants (CNVs)for genome‐wide association studies in family‐based designs. Our new overall association test combines the between‐family component and the within‐family component of the family‐based data so that the new test statistic is fully efficient and, at the same time, maintains robustness against population‐admixture and stratification, like classical family‐based association tests that are based only on the within‐family component. Although all data are incorporated into the test statistic, an adjustment for genetic confounding is not needed, even for the between‐family component. The new test statistic is valid for testing either quantitative or dichotomous phenotypes. If external CNV data are available, the approach can also be applied to completely ascertained samples. Similar to the approach by Ionita‐Laza et al. ([2008]. Genet Epidemiol 32:273–284), the proposed test statistic does not require a CNV‐calling algorithm and is based directly on the CNV probe intensities. We show, via simulation studies, that our methodology increases the power of the FBAT statistic to levels comparable to those of population‐based designs. The advantages of the approach in practice are demonstrated by an application to a genome‐wide association study for body mass index. Genet. Epidemiol. 34: 582–590, 2010. © 2010 Wiley‐Liss, Inc.
Variation in folate pathway genes contributes to risk of congenital heart defects among individuals with Down syndrome
Authors: Locke Adam E. , Dooley Kenneth J. , Tinker Stuart W. , Cheong Soo Yeon , Feingold Eleanor , Allen Emily G. , Freeman Sallie B. , Torfs Claudine P. , Cua Clifford L. , Epstein Michael P. , Wu Michael C. , Lin Xihong , Capone George , Sherman Stephanie L. , Bean Lora J.H.
Published: August 2010

Cardiac abnormalities are one of the most common congenital defects observed in individuals with Down syndrome. Considerable research has implicated both folate deficiency and genetic variation in folate pathway genes with birth defects, including both congenital heart defects (CHD) and Down syndrome (DS). Here, we test variation in folate pathway genes for a role in the major DS‐associated CHD atrioventricular septal defect (AVSD). In a group of 121 case families (mother, father, and proband with DS and AVSD) and 122 control families (mother, father, and proband with DS and no CHD), tag SNPs were genotyped in and around five folate pathway genes: 5,10‐methylenetetrahyrdofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), cystathionine β‐synthase (CBS), and the reduced folate carrier (SLC19A1, RFC1). SLC19A1 was found to be associated with AVSD using a multilocus allele‐sharing test. Individual SNP tests also showed nominally significant associations with odds ratios of between 1.34 and 3.78, depending on the SNP and genetic model. Interestingly, all marginally significant SNPs in SLC19A1 are in strong linkage disequilibrium (r2≥0.8) with the nonsynonymous coding SNP rs1051266 (c.80A>G), which has previously been associated with nonsyndromic cases of CHD. In addition to SLC19A1, the known functional polymorphism MTHFR c.1298A was over‐transmitted to cases with AVSD (P=0.05) and under‐transmitted to controls (P=0.02). We conclude, therefore, that disruption of the folate pathway contributes to the incidence of AVSD among individuals with DS. Genet. Epidemiol. 34: 603–612, 2010. © 2010 Wiley‐Liss, Inc.
Three New Paeonidanin‐Type Monoterpene Glycosides from Paeonia suffruticosaAndr.
Authors: Yang Yu , Hu Hong‐Yu , Yu Neng‐Jiang , Zhang Yang , Zhao Yi‐Min
Published: August 2010

Three new paeonidanin‐type monoterpene glycosides, named suffrupaeonidanins A–C, were isolated as minor components from the root cortex of Paeonia suffruticosa Andr. Their structures were elucidated by a combination of 1D‐ and 2D‐NMR, and mass spectral techniques.
A New Nortriterpene from the Root of Celastrus hypoleucus
Authors: Wang Hong , Tian Xuan , Ying Guo Qing
Published: August 2010

A new nortriterpene, 2‐hydroxy‐3‐methyl‐21‐oxo‐12,24‐dinor‐D : B‐friedooleana‐1,3,5(10),7‐tetraen‐29‐oic acid (1), was isolated from the root of Celastrus hypoleucus, together with the two known compounds, celastorol (2) and pristimerine (3). Their structures were elucidated on the basis of spectroscopic analyses. Compounds 1–3 exhibited in vitro significant antioxidant (against lipid peroxidation; by the TBARS method) and antitumor activities (against cancer cell lines P‐388, A‐549, HL‐60, and BEL‐7402).
Enantioselective Synthesis of Herbarumin III by Using a Chelation‐Controlled Reduction
Authors: Sabitha Gowravaram , Srinivas Chitti , Maruthi Chittapragada , Yadav Jhillu Singh
Published: August 2010

The total synthesis of herbarumin III (1) was achieved via an alkynide ion addition onto a chiral aldehyde and LiAlH4/LiI reduction as key steps (Scheme 2).
One‐Step Synthesis of 1‐(4,5‐Diphenylpyrimidin‐2‐yl)thiourea
Authors: Han Wen‐Yong , Zhang Zun‐Ting , Zhang Ying‐Chun , Xue Dong , Li Gang
Published: August 2010

A simple and straightforward methodology toward the synthesis of novel 1‐(4,5‐diphenylpyrimidin‐2‐yl)thiourea has been developed by a one‐step reaction of isoflavones with amidinothiourea. A series of 16 new compounds was synthesized. All compounds were characterized by FT‐IR, NMR, and elemental analysis. The structure of a typical compound was established by X‐ray diffraction. A variety of substrates can participate in the process with good yields and high purities, making this methodology suitable for library synthesis in drug discovery.
A New Method for the Synthesis of Nonsymmetrically Substituted Bis(azulen‐1‐yl) Ketones
Authors: Sigrist Rolf , Hansen Hans‐Jürgen
Published: August 2010

The 1‐(3‐methylazulen‐1‐yl)alkan‐1‐ones, when oxidized with excess 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (=4,5‐dichloro‐3,6‐dioxocyclohexa‐1,4‐diene‐1,2‐dicarbonitrile; DDQ) in aqueous acetone in the presence of 1‐(3‐demethylazulen‐1‐yl)alkan‐1‐ones, form the corresponding unsymmetrically substituted bis(3‐acylazulen‐1‐yl)methanones in good to excellent yields (Schemes 4, 5, 7, and 10). Intermediates are the corresponding disubstituted methane derivatives, which are formed by radical and radical‐cation recombination (Scheme 6). The 1‐(3‐methylazulen‐1‐yl)alkan‐1‐ones can as well be coupled oxidatively with azulene itself, benz[a]azulene, or 1,3‐dimethoxybenzene (Schemes 9–11).
Analysis of unsupervised learning techniques for face recognition
Authors: Kumar Dinesh , Rai C. S. , Kumar Shakti
Published: August 2010

Face recognition has always been a potential research area because of its demand for reliable identification of a human being especially in government and commercial sectors, such as security systems, criminal identification, border control, etc. where a large number of people interact with each other and/or with the system. The last two decades have witnessed many supervised and unsupervised learning techniques proposed by different researchers for the face recognition system. Principal component analysis (PCA), self‐organizing map (SOM), and independent component analysis (ICA) are the most widely used unsupervised learning techniques reported by research community. This article presents an analysis and comparison of these techniques. The article also includes two SOM processing methods global SOM (GSOM) and local SOM (LSOM) for performance evaluation along with PCA and ICA. We have used two different databases for our analysis. The simulation result establishes the supremacy of GSOM in general among all the unsupervised techniques. © 2010 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 20, 261–267, 2010
RTN3 and RTN4: Candidate modulators in vascular cell apoptosis and atherosclerosis
Authors: Chen Yaqin , Zhao Shuiping , Xiang Rong
Published: August 2010

The vascular cell apoptosis may play an important role in the development of atherosclerosis. Reticulons, the only molecular so far to participate in all three apoptosis signaling pathways, may be a novel player in the progress of AS. We presumes that reticulons may belong to the principle node of apoptosis pathway and be the candidate factor linking apoptosis and AS. J. Cell. Biochem. 111: 797–800, 2010. © 2010 Wiley‐Liss, Inc.
Microarray Profile of Gene Expression During Osteoclast Differentiation in Modelled Microgravity
Authors: Sambandam Yuvaraj , Blanchard Jeremy J. , Daughtridge Giffin , Kolb Robert J. , Shanmugarajan Srinivasan , Pandruvada Subramanya N. M. , Bateman Ted A. , Reddy Sakamuri V.
Published: August 2010

Microgravity (µXg) leads to a 10–15% loss of bone mass in astronauts during space flight. Osteoclast (OCL) is the multinucleated bone‐resorbing cell. In this study, we used the NASA developed ground‐based rotating wall vessel bioreactor (RWV), rotary cell culture system (RCCS) to simulate µXg conditions and demonstrated a significant increase (2‐fold) in osteoclastogenesis compared to normal gravity control (Xg). Gene expression profiling of RAW 264.7 OCL progenitor cells in modelled µXg by Agilent microarray analysis revealed significantly increased expression of critical molecules such as cytokines/growth factors, proteases and signalling proteins, which play an important role in enhanced OCL differentiation/function. Transcription factors such as c‐Jun, MITF and CREB implicated in OCL differentiation are upregulated; however no significant change in the levels of NFATc1 expression in preosteoclast cells subjected to modelled µXg. We also identified high‐level expression of calcium‐binding protein, S100A8 (calcium‐binding protein molecule A8/calgranulin A) in preosteoclast cells under µXg. Furthermore, modelled µXg stimulated RAW 264.7 cells showed elevated cytosolic calcium (Ca2+) levels/oscillations compared to Xg cells. siRNA knock‐down of S100A8 expression in RAW 264.7 cells resulted in a significant decrease in modelled µXg stimulated OCL differentiation. We also identified elevated levels of phospho‐CREB in preosteoclast cells subjected to modelled µXg compared to Xg. Thus, modelled µXg regulated gene expression profiling in preosteoclast cells provide new insights into molecular mechanisms and therapeutic targets of enhanced OCL differentiation/activation to prevent bone loss and fracture risk in astronauts during space flight missions. J. Cell. Biochem. 111: 1179–1187, 2010. © 2010 Wiley‐Liss, Inc.
Both FGF23 and extracellular phosphate activate Raf/MEK/ERK pathway via FGF receptors in HEK293 cells
Authors: Yamazaki Miwa , Ozono Keiichi , Okada Tomoko , Tachikawa Kanako , Kondou Hiroki , Ohata Yasuhisa , Michigami Toshimi
Published: August 2010

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone produced by bone and exerts its function in the target organs by binding the FGF receptor (FGFR) and Klotho. Since recent studies suggested that extracellular inorganic phosphate (Pi) itself triggers signal transduction and regulates gene expression in some cell types, we tested the notion that extracellular Pi induces signal transduction in the target cells of FGF23 also and influences its signaling, utilizing a human embryonic kidney cell line HEK293. HEK293 cells expressed low levels of klotho, and treatment with a recombinant FGF23[R179Q], a proteolysis‐resistant mutant of FGF23, resulted in phosphorylation of ERK1/2 and induction of early growth response‐1 (EGR1) expression. Interestingly, increased extracellular Pi resulted in activation of the Raf/MEK/ERK pathway and expression of EGR1, which involved type III sodium/phosphate (Na+/Pi) cotransporter PiT‐1. Since the effects of an inhibitor of Na+/Pi cotransporter on FGF23 signaling suggested that the signaling triggered by increased extracellular Pi shares the same downstream cascade as FGF23 signaling, we further investigated their convergence point. Increasing the extracellular Pi concentration resulted in the phosphorylation of FGF receptor substrate 2α (FRS2α), as did treatment with FGF23. Knockdown of FGFR1 expression diminished the phosphorylation of both FRS2α and ERK1/2 induced by the Pi. Moreover, overexpression of FGFR1 rescued the decrease in Pi‐induced phosphorylation of ERK1/2 in the cells where the expression of PiT‐1 was knocked down. These results suggest that increased extracellular Pi triggers signal transduction via PiT‐1 and FGFR and influences FGF23 signaling in HEK293 cells. J. Cell. Biochem. 111: 1210–1221, 2010. © 2010 Wiley‐Liss, Inc.
Flow cytometric sorting of neuronal and glial nuclei from central nervous system tissue
Authors: Okada Seiji , Saiwai Hirokazu , Kumamaru Hiromi , Kubota Kensuke , Harada Akihito , Yamaguchi Masahiro , Iwamoto Yukihide , Ohkawa Yasuyuki
Published: August 2010

Due to the complex cellular heterogeneity of the central nervous system (CNS), it is relatively difficult to reliably obtain molecular descriptions with cell‐type specificity. In particular, comparative analysis of epigenetic regulation or molecular profiles is hampered by the lack of adequate methodology for selective purification of defined cell populations from CNS tissue. Here, we developed a direct purification strategy of neural nuclei from CNS tissue based on fluorescence‐activated cell sorting (FACS). We successfully fractionated nuclei from complex tissues such as brain, spinal cord, liver, kidney, and skeletal muscle extruded mechanically or chemically, and fractionated nuclei were structurally maintained and contained nucleoproteins and nuclear DNA/RNA. We collected sufficient numbers of nuclei from neurons and oligodendrocytes using FACS with immunolabeling for nucleoproteins or from genetically labeled transgenic mice. In addition, the use of Fab fragments isolated from papain antibody digests, which effectively enriched the specialized cell populations, significantly enhanced the immunolabeling efficacy. This methodology can be applied to a wide variety of heterogeneous tissues and is crucial for understanding the cell‐specific information about chromatin dynamics, nucleoproteins, protein–DNA/RNA interactions, and transcriptomes retained in the nucleus, such as non‐coding RNAs. J. Cell. Physiol. 226: 552–558, 2011. © 2010 Wiley‐Liss, Inc.
Characterization of GFP‐tagged GnRH‐containing terminalis neurons in transgenic zebrafish
Authors: Wang Xiaokai , Huang Luoxiu , Li Yue , Li Xinle , Li Ping , Ray John , Li Lei
Published: August 2010

The terminalis nerve (TN) has been described in all vertebrate species, in which it plays important roles in animal behavior and physiology. In teleost fish, the TN is located in the olfactory bulb and in its nerve tract. Here, we report a study on the characterization of the TN cell development, axon projection and physiology in zebrafish (Danio rerio). We have generated several lines of transgenic zebrafish [Tg (GnRH‐3::GFP)] that express GFP in the TN cells. The transgenes are expressed under the transcriptional control of the zebrafish GnRH‐3 promoter. During development, the first GFP‐positive TN cell was identified at approximately 34 h post‐fertilization (hpf). By 38 hpf, several clusters of TN cells were identified in the olfactory bulb and olfactory nerve tract. In the olfactory bulb, the TN cells projected axons caudally. In the forebrain, some of the TN axons extended caudally, but most crossed the midline of the brain at the commissural anterior. In the midbrain, some of the TN axons extended dorsally towards the tectum, whereas other axons extended caudally, or extended ventrally to the optic nerve where they entered the neural retina. We also examined the cell membrane property of the TN cells. Using patch‐clamp techniques, we recorded spontaneous and evoked action potentials from isolated TN cells. We examined the expression of glutamate receptors in the TN cells. The data shed light on the mechanisms of TN function in the nervous system and in the regulation of animal physiology. J. Cell. Physiol. 226: 608–615, 2011. © 2010 Wiley‐Liss, Inc.
Involvement of β1‐integrin via PIP complex and FAK/paxillin in dexamethasone‐induced human mesenchymal stem cells migration
Authors: Yun Seung Pil , Ryu Jung Min , Han Ho Jae
Published: August 2010

Although glucocorticoids strongly affect numerous biological processes including cell growth, development, and homeostasis, their effects on migration of human mesenchymal stem cells (hMSCs) are unclear. Therefore, we investigated the role of dexamethasone (DEX) and its related signaling pathways on migration of hMSCs. We found that DEX, at 10−8 to 10−6 M, significantly increased migration after a 24 h incubation, and DEX (10−6 M) increased migration at >12 h. Moreover, DEX (10−6 M) increased the level of glucocorticoid receptor (GR)‐α mRNA and protein expression, but not GR‐β mRNA. The increases in DEX‐induced migration were inhibited by the GR antagonist mifepristone (10−7 M). In addition, DEX increased integrin‐linked kinase (ILK) and α‐parvin expression but did not change PINCH‐1/2 expression in lysate. DEX also increased formations of complex with ILK and α‐parvin, and ILK and PINCH‐1/2 as shown by immunoprecipitation, which were all inhibited by mifepristone. DEX‐induced migration was blocked by ILK and α‐parvin small interfering(si)RNAs. In addition, DEX increased focal adhesion kinase (FAK) and paxillin expression, which were attenuated by ILK and α‐parvin siRNAs. DEX‐induced cell migration was inhibited by FAK/paxillin siRNAs. DEX also increased β1‐integrin expression, which was blocked by FAK/paxillin siRNAs. In addition, DEX‐induced cell migration was inhibited by β1‐integrin siRNA. Downregulation of ILK, α‐parvin, FAK/paxillin and β1‐integrin expression by siRNAs decreased DEX‐induced filamentous(F)‐actin organization and migration of hMSCs. In conclusion, DEX partially stimulates hMSC migration by the expression of β1‐integrin through formation of a PINCH‐1/2/ILK/α‐parvin complex (PIP complex), and FAK and paxillin expression. J. Cell. Physiol. 226: 683–692, 2011. © 2010 Wiley‐Liss, Inc.
Exercise training reduces insulin resistance and upregulates the mTOR/p70S6k pathway in cardiac muscle of diet‐induced obesity rats
Authors: Medeiros Cleber , Frederico Marisa J. , da Luz Gabrielle , Pauli José R. , Silva Adelino S.R. , Pinho Ricardo A. , Velloso Lício A. , Ropelle Eduardo R. , De Souza Cláudio T.
Published: August 2010

Obesity and insulin resistance are rapidly expanding public health problems. These disturbances are related to many diseases, including heart pathology. Acting through the Akt/mTOR pathway, insulin has numerous and important physiological functions, such as the induction of growth and survival of many cell types and cardiac hypertrophy. However, obesity and insulin resistance can alter mTOR/p70S6k. Exercise training is known to induce this pathway, but never in the heart of diet‐induced obesity subjects. To evaluate the effect of exercise training on mTOR/p70S6k in the heart of obese Wistar rats, we analyzed the effects of 12 weeks of swimming on obese rats, induced by a high‐fat diet. Exercise training reduced epididymal fat, fasting serum insulin and plasma glucose disappearance. Western blot analyses showed that exercise training increased the ability of insulin to phosphorylate intracellular molecules such as Akt (2.3‐fold) and Foxo1 (1.7‐fold). Moreover, reduced activities and expressions of proteins, induced by the high‐fat diet in rats, such as phospho‐JNK (1.9‐fold), NF‐kB (1.6‐fold) and PTP‐1B (1.5‐fold), were observed. Finally, exercise training increased the activities of the transduction pathways of insulin‐dependent protein synthesis, as shown by increases in Raptor phosphorylation (1.7‐fold), p70S6k phosphorylation (1.9‐fold), and 4E‐BP1 phosphorylation (1.4‐fold) and a reduction in atrogin‐1 expression (2.1‐fold). Results demonstrate a pivotal regulatory role of exercise training on the Akt/mTOR pathway, in turn, promoting protein synthesis and antagonizing protein degradation. J. Cell. Physiol. 226: 666–674, 2011. © 2010 Wiley‐Liss, Inc.
Resveratrol induces apoptosis of human nasopharyngeal carcinoma cells via activation of multiple apoptotic pathways
Authors: Huang Tsung‐Teng , Lin Hung‐Chi , Chen Chang‐Chieh , Lu Chia‐Chen , Wei Chia‐Fong , Wu Ting‐Shu , Liu Fu‐Guo , Lai Hsin‐Chih
Published: August 2010

Resveratrol, a naturally occurring dietary compound with chemopreventive properties has been reported to trigger a variety of cancer cell types to apoptosis. Whether resveratrol shows any activity on human nasopharyngeal carcinoma (NPC) cells remained to be determined. The aim of this study was to investigate the effect and mechanism of resveratrol on human NPC cells. Treatment of resveratrol resulted in significant decrease in cell viability of NPC cell lines in a dose‐ and time‐dependent manner. A dose‐dependent apoptotic cell death was also measured by flow cytometery analysis. Molecular mechanistic studies of apoptosis unraveled resveratrol treatment resulted in a significant loss of mitochondrial transmembrane potential, release of cytochrome c, enhanced expression of Fas ligand (FasL), and suppression of glucose‐regulated protein 78 kDa (GRP78). These were followed by activation of caspases‐9, ‐8, ‐4, and ‐3, subsequently leading to DNA fragmentation and cell apoptosis. Furthermore, up‐regulation of proapoptotic Bax and down‐regulation of antiapoptotic Bcl‐2 protein were also observed. Taken together, resveratrol induces apoptosis in human NPC cells through regulation of multiple apoptotic pathways, including death receptor, mitochondria, and endoplasmic reticulum (ER) stress. Resveratrol can be developed as an effective compound for human NPC treatment. J. Cell. Physiol. 226: 720–728, 2011. © 2010 Wiley‐Liss, Inc.
Dexamethasone modulates osteogenesis and adipogenesis with regulation of osterix expression in rat calvaria‐derived cells
Authors: Mikami Yoshikazu , Lee Mio , Irie Seiko , Honda Masaki J.
Published: August 2010

Osteoblasts and adipocytes originate from common mesenchymal progenitor cells and although a number of compounds can induce osteoblastic and adipogenic differentiation from progenitor cells, the underlying mechanisms have not been elucidated. The present study examined the synergistic effects of dexamethasone (Dex) and bone morphogenetic protein (BMP)‐2 on the differentiation of clonal mesenchymal progenitor cells isolated from rat calvaria into osteoblasts and adipocytes, as well as the effects of the timing of treatment. Cells were cultured for various periods of time in the presence of Dex and/or BMP‐2. When cells were treated with Dex + BMP‐2 during the early phase of differentiation, they differentiated into adipocytes. However, when cells were treated with Dex + BMP‐2 during the late phase of differentiation, a synergistic effect on in vitro matrix mineralization was observed. To examine differences between the early and late phases of differentiation, ALP activity was measured in the presence of BMP‐2. ALP activity increased markedly on Day 9, corresponding to the onset of the synergistic effect of Dex. Dex treatment inhibited osterix (OSX) expression in cells committed to adipogenic differentiation, but not in cells committed to osteogenic differentiation following BMP‐2 treatment. The isoform2 OSX promoter region was found to be involved in the effects of Dex on cells during the early phase of differentiation. Furthermore, cells stably expressing OSX (isoform2) formed mineralized nodules even though they had been treated with Dex + BMP‐2 during the early phase of differentiation. It appears that Dex modulates osteogenesis and adipogenesis in mesenchymal stem cells by regulating OSX expression. J. Cell. Physiol. 226: 739–748, 2011. © 2010 Wiley‐Liss, Inc.
Regulation of UDP‐glucose dehydrogenase is sufficient to modulate hyaluronan production and release, control sulfated GAG synthesis, and promote chondrogenesis
Authors: Clarkin Claire E. , Allen Steve , Kuiper Nikki J. , Wheeler Benjamin T. , Wheeler‐Jones Caroline P. , Pitsillides Andrew A.
Published: August 2010

Glycosaminoglycans (GAGs) are critical for extracellular matrix (ECM) integrity in cartilage but mechanisms regulating their synthesis are not defined. UDP‐glucose dehydrogenase (UGDH) catalyses UDP‐glucose oxidation to UDP‐glucuronic acid, an essential monosaccharide in many GAGs. Our previous studies in articular surface (AS) cells from embryonic joints have established pivotal roles for mitogen‐activated protein kinases (MAPK) in synthesis of the unsulfated GAG, hyaluronan (HA). We investigated the functional significance of UGDH in GAG production and chondrogenesis, and determined roles for MEK–ERK and p38MAPK pathways in regulating UGDH expression and function. Inhibitors of MEK and p38MAPK reduced UGDH protein in AS cells. Treatment with TGF‐β (archetypal growth factor) increased UGDH expression, sulfated (s)‐GAG/HA release and pericellular matrix formation in a p38MAPK‐dependent manner. Retroviral overexpression of UGDH augmented HA/sGAG release and pericellular matrix elaboration, which were blocked by inhibiting MEK but not p38MAPK. UGDH overexpression increased cartilage nodule size in bone marrow culture, promoted chondrogenesis in limb bud micromass culture and selectively suppressed medium HA levels and modified GAG sulfation, as assessed by FACE analysis. Our data provide evidence that: (i) TGF‐β regulates UGDH expression via p38MAPK to modulate sGAG/HA secretion, (ii) MEK–ERK, but not p38MAPK facilitates UGDH‐induced HA and sGAG release, and (iii) increased UGDH expression promotes chondrogenesis directly and differential modifies GAG levels and sulfation. These results indicate a more diverse role for UGDH in the support of selective GAG production than previously described. Factors regulating UGDH may provide novel candidates for restoring ECM integrity in degenerative cartilage diseases, such as osteoarthritis.Arthritis Research Campaign. J. Cell. Physiol. 226: 749–761, 2011. © 2010 Wiley‐Liss, Inc.
Induction of small G protein RhoB by non‐genotoxic stress inhibits apoptosis and activates NF‐κB
Authors: Li Yi‐Dong , Liu Ya‐Ping , Cao Dong‐Mei , Yan Ya‐Min , Hou You‐Na , Zhao Jie‐Ying , Yang Rui , Xia Zhao‐Fan , Lu Jian
Published: August 2010

It has been reported by us and other groups that the expression of small GTP binding protein RhoB can be induced by genotoxic stressors and glucocorticoid (GC), a stress hormone that plays a key role in stress response. Until now stress‐induced genes that confer cytoprotection under stressed conditions are largely unknown. In this study, we investigated the effects and mechanism of non‐genotoxic stressors, including scalding in vivo and heat stress in vitro on the expression of RhoB. We found for the first time that both scalding, which could induce typical neuroendocrine responses of acute stress and cellular heat stress significantly increased the expression of RhoB at mRNA and protein levels. Moreover, in vitro experiments in human lung epithelial cells (A549) showed that induction of RhoB by heat stress was in a glucocorticoid receptor (GR)‐independent manner and through multiple pathways including stabilization of RhoB mRNA and activation of p38 MAPK. Further experiments demonstrated that up‐regulation of RhoB significantly inhibited heat stress‐induced apoptosis and elevated transcriptional activity of NF‐κB, but did not affect the expression of Hsp70 in A549 cells. In conclusion, we showed for the first time that RhoB was up‐regulated by scalding in vivo and heat stress in vitro and played an important cytoprotective role during heat stress‐induced apoptotic cell death. J. Cell. Physiol. 226: 729–738, 2011. © 2010 Wiley‐Liss, Inc.
PLGA based drug delivery systems (DDS) for the sustained release of insulin: insight into the protein/polyester interactions and the insulin release behavior
Authors: Lassalle Verónica , Ferreira María Luján
Published: August 2010

BACKGROUND: Drug delivery systems (DDS) were designed using insulin as model drug and poly (lactic–co‐glycolic) copolymers (PLGA) as polymeric matrix. The carriers were synthesized by direct self‐assembly of the insulin and the polyester under mild conditions.

RESULTS: The kind and level of association between the protein and the polymer were studied using computational methods (combined MM2/PM3) and spectroscopic tools (Fourier transform infrared (FTIR), energy dispersive X‐ray (EDX) and X‐ray fluorescence spectroscopy (XFS)). The effect of the number average molecular weight (Mn) of the copolymer on the association efficiency (AE) drug–polymer as well as on the release profile has been explored. Mathematical models were used to predict the insulin release kinetic and mechanism.

CONCLUSIONS: Satisfactory protein/PLGA association efficiencies (between 77 and 99%) were registered depending on the Mn of the PLGA. Hydrophobic and hydrophilic interactions were detected between the protein and the polymeric network by computational analysis. In vitro release studies demonstrated that copolyesters of about 8600 and 1500 Da were suitable for the gradual release of insulin while PLGA oligomers of average molecular weight between 700 and 800 Da were unsuitable as DDS. The insulin release kinetics fits well with the Korsmeyer model, following the anomalous transport mechanism. Copyright © 2010 Society of Chemical Industry
Solvent‐free synthesis of glycerol carbonate and glycidol from 3‐chloro‐1,2‐propanediol and potassium (hydrogen) carbonate
Authors: Gómez‐Jiménez‐Aberasturi Olga , Ochoa‐Gómez José R. , Pesquera‐Rodríguez Amaia , Ramírez‐López Camilo , Alonso‐Vicario Ainhoa , Torrecilla‐Soria Jesús
Published: August 2010

BACKGROUND: An indirect solvent‐free synthetic approach for obtaining glycerol carbonate and glycidol from glycerol and CO2 through their more reactive and easily synthesizable derivatives 3‐chloro‐1,2‐propanediol (HAL) and potassium (hydrogen) carbonate has been studied.

RESULTS: The reaction is fast with source of carbonation and temperature having a strong influence on the results. A yield of 80% glycerol carbonate together with a simultaneous substantial production of glycidol (0.56 mol mol−1 glycerol carbonate) are obtained using K2CO3 as the carbonation source at 80 °C, a reaction time of 30 min and a 3:1 HAL/K2CO3 molar ratio. A lower yield of glycerol carbonate (60%) is obtained from KHCO3 after 50 min with the other experimental conditions remaining unchanged. In this case, glycidol formation is zero or insignificant. Glycerol is also obtained in high yields, although in much lower amounts from KHCO3 (∼0.59 mol mol−1 glycerol carbonate independent of operating conditions) than from K2CO3 (0.84–1.1 mol mol−1 glycerol carbonate, depending on experimental conditions).

CONCLUSIONS: The proposed synthetic strategy overcomes the currently difficult direct reaction between glycerol and CO2, leading to the simultaneous synthesis of two valuable chemicals: glycerol carbonate and glycidol. However, glycerol is also obtained in substantial amounts thus decreasing the overall yield of the process. Thus, methods for preventing its formation must be developed for industrial feasibility. Copyright © 2010 Society of Chemical Industry
Differences in Brachypelma albopilosa (theraphosidae) hemolymph proteome between subadult and adult females
Authors: Trabalon Marie , Carapito Christine , Voinot Florian , Martrette Jean‐Marc , Van Dorsselaer Alain , Gilbert Caroline , Bertile Fabrice
Published: August 2010

The changes in the hemolymph proteome of mygalomorph Brachypelma albopilosa females were examined for the first time in relation to their developmental stage (subadult and adult period). Seven distinct subunits of hemocyanin (a, b, c, d, e, f, and g chains), as well as actin were clearly identified and their sequence partly characterized using a combination of one‐ and two‐dimensional gel electrophoresis and mass spectrometry. The different structures determined along with possible post‐translational modifications may reflect a role of hemocyanin in molting, immunity, and reproduction. In addition, despite no precise identification, additional peptide sequences from eight protein bands (four bands >200 kDa and four bands in the 95–200 kDa mass range) were determined. As reported in other spider species, the putative corresponding structures are the coagulogen protein and/or lipoproteins (HDL‐1, HDL‐2, VHDL) for which quantitative differences between adult and subadult individuals could be related to the molting process and/or cuticle lipid and protein composition according to the developmental stage. J. Exp. Zool. 313A:651–659, 2010. © 2010 Wiley‐Liss, Inc.
Effectiveness of an inpatient smoking cessation program
Authors: Gadomski Anne M. , Gavett Jessie , Krupa Nicole , Tallman Nancy , Jenkins Paul
Published: August 2010

BACKGROUND:

Inpatient smoking cessation may increase the success of quitting smoking post‐hospital discharge.

METHODS:

Using a quasiexperimental study design, use of cessation methods, mortality, self‐reported abstinence, and quit status 6 months post–hospital discharge were measured to assess the effectiveness of an inpatient smoking cessation program. Subjects were interviewed by telephone 6 months post‐hospital discharge. Outcomes for patients who were seen by the inpatient smoking cessation counselor were compared to consecutive patients who were not seen by the counselor. Electronic medical records (EMRs) and administrative data were used to construct baseline measures, comorbidity covariates, pharmaceutical use rates during hospitalization, readmission, and mortality outcomes. Multivariate methods included logistic regression and survival analysis.

RESULTS:

At baseline, the study groups varied by mean age, length of stay (LOS), comorbidity index, cardiovascular diagnosis, and acuity. At 6 months post–hospital discharge, the intent to treat estimate for point prevalence abstinence was 16% in the intervention group compared to 10% in the comparison group (P = 0.02) while self‐reported quit status in the intervention group was 44% vs. 30% in the comparison group (P = 0.00). The intervention group used more nicotine replacement therapy (NRT) than the comparison group both in‐hospital and following discharge. Crude post–hospital discharge mortality was significantly less in the intervention group (0.02) than in the comparison group (0.04). A multivariate survival model, controlling for baseline imbalances, showed a significantly reduced mortality in the intervention group (hazard ratio [HR] = 0.37; P = 0.04).

CONCLUSIONS:

Inpatient smoking cessation programs effectively improve quit outcomes, NRT use, and mortality post–hospital discharge. Journal of Hospital Medicine 2011. © 2010 Society of Hospital Medicine.
Cognitive error as the most frequent contributory factor in cases of medical injury: A study on verdict's judgment among closed claims in Japan
Authors: Tokuda Yasuharu , Kishida Naoki , Konishi Ryota , Koizumi Shunzo
Published: August 2010

BACKGROUND:

Cognitive errors in the course of clinical decision‐making are prevalent in many cases of medical injury. We used information on verdict's judgment from closed claims files to determine the important cognitive factors associated with cases of medical injury.

METHODS:

Data were collected from claims closed between 2001 to 2005 at district courts in Tokyo and Osaka, Japan. In each case, we recorded all the contributory cognitive, systemic, and patient‐related factors judged in the verdicts to be causally related to the medical injury. We also analyzed the association between cognitive factors and cases involving paid compensation using a multivariable logistic regression model.

RESULTS:

Among 274 cases (mean age 49 years old; 45% women), there were 122 (45%) deaths and 67 (24%) major injuries (incomplete recovery within a year). In 103 cases (38%), the verdicts ordered hospitals to pay compensation (median; 8,000,000 Japanese Yen). An error in judgment (199/274, 73%) and failure of vigilance (177/274, 65%) were the most prevalent causative cognitive factors, and error in judgment was also significantly associated with paid compensation (odds ratio, 1.9; 95% confidence interval [CI], 1.0‐3.4). Systemic causative factors including poor teamwork (11/274, 4%) and technology failure (5/274, 2%) were less common.

CONCLUSIONS:

The closed claims analysis based on verdict's judgment showed that cognitive errors were common in cases of medical injury, with an error in judgment being most prevalent and closely associated with compensation payment. Reduction of this type of error is required to produce safer healthcare. Journal of Hospital Medicine 2010. © 2010 Society of Hospital Medicine.
Organic soil phosphorus considerably contributes to plant nutrition but is neglected by routine soil‐testing methods
Authors: Steffens Diedrich , Leppin Thomas , Luschin‐Ebengreuth Nora , Min Yang Zhi , Schubert Sven
Published: August 2010

In upper layer of arable soils, the percentage of organically bound phosphorus (P) can range from 20% to 80% of total P concentration. Approximately 40% of organic soil P is in the inositol‐P fraction. The objective of our study was to evaluate various soil‐testing methods in measuring phytate soil P as an important source of organic soil P, and to determine the bioavailability of phytate soil P for summer wheat (Triticum aestivum L.), rape (Brassica napus L.), sugar beet (Beta vulgaris L. var. altissima Döll), phacelia (Phacelia tanacetifolia L.), maize (Zea mays L.), white lupin (Lupinus albus L.), Mexican sunflower (Tithonia diversifolia Hemsley Gray), summer rye (Secale cereale L.), buckwheat (Fagopyrum esculentum L.), and pigeon pea (Cajanus cajan L.). Plants were cultivated in a growth chamber on a subsoil as a substrate with very low organic‐matter content and negligible microbial activity in order to restrict the contribution of mycorrhiza and soil microbial activity for organic–soil P mobilization. Application of organic P (100 mg P [kg soil]–1 as Na‐hexaphytate, C6H6O24P6Na12) did not result in a significant increase of extractable soil P measured with routine soil‐testing methods (CAL, DL, NaHCO3, EUF, Me‐III) although the applied organic P was available for all tested plant species. The relative P‐uptake efficiency for Na‐hexaphytate compared to Ca(H2PO4)2 was for rape, pigeon pea, and phacelia approximately 100%, for white lupin and maize 80%, for sugar beet, Mexican sunflower, wheat, and buckwheat approximately 60%, and for rye 35%. The results indicate that the bioavailability of organic soil P is not taken into account by routine soil‐testing methods.
Effects of tannic acid on gluten protein structure, dough properties and bread quality of Chinese wheat
Authors: Zhang Li , Cheng Libao , Jiang Lijun , Wang Yuesheng , Yang Guangxiao , He Guangyuan
Published: August 2010

BACKGROUND: The effects of tannic acid, which is present in many plants, on the structure of gluten proteins and the properties of dough and bread were studied. Tannic acid was added at levels of 0.01, 0.02 and 0.03 g kg−1 during the dough‐making process.

RESULTS: The added tannic acid acted negatively on disulfide bond formation but interacted with gluten proteins via other covalent bonds, as detected by UV spectroscopy and dynamic rheometry. Rheological properties and texture of the bread were measured by farinograph, extensograph and texture profile analyser. Texture analysis indicated little change in adhesiveness and resilience of the bread at all three levels of tannic acid compared with the control, but changes in hardness and chewiness of the bread made with added tannic acid indicated that tannic acid could delay bread staling.

CONCLUSION: The effect of tannic acid on flour and dough is different from that of other flour redox agents. It breaks down disulfide bonds but also has positive effects on dough properties and bread quality. Disulfide bonds are commonly considered to be the most important factor affecting changes in the quality of bread. However, this study presents the new concept that other covalent bonds can also improve the quality of flour and bread and uses this property to investigate new, safe and efficient flour additives. Copyright © 2010 Society of Chemical Industry
Anatomical considerations for endoscopic endonasal skull base surgery in pediatric patients
Authors: Tatreau Jason R. , Patel Mihir R. , Shah Rupali N. , McKinney Kibwei A. , Wheless Stephen A. , Senior Brent A. , Ewend Matthew G. , Germanwala Anand V. , Ebert Charles S. , Zanation Adam M.
Published: August 2010

Objectives/Hypothesis:

Pediatric skull base surgery is limited by several boney sinonasal landmarks that must be overcome prior to tumor dissection. When approaching a sellar or parasellar tumor, the piriform aperture, sphenoid sinus pneumatization, and intercarotid distances are areas of potential limitation. Quantitative pediatric anatomical measurements relevant to skull base approaches are lacking. Our goal was to use radio‐anatomic analysis of computed tomography scans to determine anatomical limitations for trans‐sphenoidal approaches in pediatric skull base surgery.

Study Design:

A radio‐anatomic cross‐sectional survey.

Methods:

Measurements included the diameter of the piriform aperture, posterior extent of sphenoid sinus pneumatization, and intercarotid distances on fine‐cut, age‐stratified maxillofacial scans. Fifty pediatric (<18 years of age) and 10 adult patients were equally subdivided into seven age groups and compared to determine age‐related differences in sphenoid sinus pneumatization, skull base thicknesses, and intercarotid distances.

Results:

Piriform aperture width was significantly greater in adults than in patients under age 7 years (P ≤ .002). Three fourths of the planum and sellar face and one half of the sellar floor were pneumatized by ages 6 to 7 years. Superior clival pneumatization was not evident until 12 years of age. Clival intercarotid distances were not different among groups. Drilling distances for trans‐planar, trans‐sellar, and trans‐clival approaches are described.

Conclusions:

Several potential anatomic limits must be considered in pediatric skull base surgery, and these vary according to age. Piriform aperture is likely a limit only in the youngest patients (under 2 years). Sphenoid pneumatization to the planum and sella start at 3 years and complete by age 10 years. Clival intercarotid distances do not change significantly and are not prohibitively narrow in any age group. Laryngoscope, 2010
Systemic steroid reduces long‐term hearing loss in experimental pneumococcal meningitis
Authors: Worsøe Lise , Brandt Christian Thomas , Lund Søren Peter , Østergaard Christian , Thomsen Jens , Cayé‐Thomasen Per
Published: August 2010

Objectives/Hypothesis:

Sensorineural hearing loss is a common complication of pneumococcal meningitis. Treatment with corticosteroids reduces inflammatory response and may thereby reduce hearing loss. However, both experimental studies and clinical trials investigating the effect of corticosteroids on hearing loss have generated conflicting results. The objective of the present study was to determine whether systemic steroid treatment had an effect on hearing loss and cochlear damage in a rat model of pneumococcal meningitis.

Study Design:

Controlled animal study of acute bacterial meningitis.

Methods:

Adult rats were randomly assigned to two experimental treatment groups: a group treated with systemic steroid (n = 13) and a control group treated with saline (n = 13). Treatment was initiated 21 hours after infection and repeated once a day for three days. Hearing loss and cochlear damage were assessed by distortion product otoacoustic emissions (DPOAE), auditory brainstem response (ABR) at 16 kHz, and spiral ganglion neuron density.

Results:

Fifty‐six days after infection, steroid treatment significantly reduced hearing loss assessed by DPOAE (P < .05; Mann‐Whitney) and showed a trend toward reducing loss of viable neurons in the spiral ganglion (P = .0513; Mann‐Whitney). After pooling data from day 22 with data from day 56, we found that systemic steroid treatment significantly reduced loss of spiral ganglion neurons (P = .0098; Mann‐Whitney test).

Conclusions:

Systemic steroid treatment reduces long‐term hearing loss and loss of spiral ganglion neurons in experimental pneumococcal meningitis in adult rats. The findings support a beneficial role of anti‐inflammatory agents in reducing hearing loss and cochlear damage in meningitis. Laryngoscope, 2010
Selective neck dissection and deintensified postoperative radiation and chemotherapy for oropharyngeal cancer: A subset analysis of the university of pennsylvania transoral robotic surgery trial
Authors: Weinstein Gregory S. , Quon Harry , O'Malley Bert W. , Kim Grace G. , Cohen Marc A.
Published: August 2010

Objectives/Hypothesis:

The purpose of this study was to determine the regional recurrence rate of node‐positive oropharyngeal squamous cell carcinoma (OPSCC) in patients undergoing transoral robotic surgery (TORS) and selective neck dissection (SND) followed by observation, radiation, or concurrent chemoradiation.

Study Design:

A prospective, phase I, single‐arm study was conducted. All OPSCC patients who voluntarily participated in a surgical trial with TORS and SND at an academic tertiary referral center from May 2005 to July 2007 were included.

Methods:

Thirty‐one patients with previously untreated OPSCC undergoing TORS and SND (29 unilateral and two bilateral) were included. There were 29 males and two females, with ages ranging from 36 to 76 years (median = 55 years) with one palate, one lateral wall, 17 tonsil, 11 base of tongue, and one vallecula primary tumor classified as follows: T1 (n = 9, 29%), T2 (n = 15, 48.4%), T3 (n = 7, 22.6%), N0 (n = 6, 19.4%), N1 (n = 15, 48.4%), N2b (n = 10, 32.3%), and N2c (n = 1, 3.2%). There were three stage I (9.7%), two stage II (6.5%), 15 stage III (48.4%) and 11 stage IVa (35.5%) patients. Twenty‐two patients were treated postoperatively with adjuvant therapy (12 radiation alone and 12 combined radiation and chemotherapy). Primary outcome measured was regional recurrence rate.

Results:

There was one regional recurrence on the contralateral, non‐operated neck and one distant recurrence among the 31 patients who underwent SND.

Conclusions:

SND after TORS resection of primary OPSCC enables the use of selective and deintensified adjuvant therapy to reduce regional recurrence rates. Laryngoscope, 2010
Simultaneous involvement of larynx and middle ear in pulmonary tuberculosis
Authors: Parab Sapna R. , Khan Mubarak M. , Ghaisas Virendra S.
Published: August 2010

We present a rare case of simultaneous involvement of larynx and ear in a patient with pulmonary tuberculosis. The aim of this article is to create an awareness of Ear Nose Throat tuberculosis, and to consider tuberculosis in the differential diagnosis of ear and laryngeal diseases. Laryngoscope, 2010