bluuebunny/crossref_metadata_2025 huggingface dataset:
Array comparative genomic hybridization identifies a distinct DNA copy number profile in renal cell cancer associated with hereditary leiomyomatosis and renal cell cancer
Authors: Koski Taru A. , Lehtonen Heli J. , Jee Kowan J. , Ninomiya Shinsuke , Joosse Simon A. , Vahteristo Pia , Kiuru Maija , Karhu Auli , Sammalkorpi Heli , Vanharanta Sakari , Lehtonen Rainer , Edgren Henrik , Nederlof Petra M. , Hietala Marja , Aittomäki Kristiina , Herva Riitta , Knuutila Sakari , Aaltonen Lauri A. , Launonen Virpi
Published: April 2009

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumor predisposition syndrome with cutaneous and uterine leiomyomatosis as well as renal cell cancer (RCC) as its clinical manifestations. HLRCC is caused by heterozygous germline mutations in the fumarate hydratase (fumarase) gene. In this study, we used array comparative genomic hybridization to identify the specific copy number changes characterizing the HLRCC‐associated RCCs. The study material comprised formalin‐fixed paraffin‐embedded renal tumors obtained from Finnish patients with HLRCC. All 11 investigated tumors displayed the papillary type 2 histopathology typical for HLRCC renal tumors. The most frequent copy number changes detected in at least 3/11 (27%) of the tumors were gains in chromosomes 2, 7, and 17, and losses in 13q12.3‐q21.1, 14, 18, and X. These findings provide genetic evidence for a distinct copy number profile in HLRCC renal tumors compared with sporadic RCC tumors of the same histopathological subtype, and delineate chromosomal regions that associate with this very aggressive form of RCC. © 2009 Wiley‐Liss, Inc.
Do microsatellite instability profiles really differ between colorectal and endometrial tumors?
Authors: Ferreira Ana M. , Westers Helga , Wu Ying , Niessen Renée C. , Olderode‐Berends Maran , van der Sluis Tineke , van der Zee Ate G. , Hollema Harry , Kleibeuker Jan H. , Sijmons Rolf H. , Hofstra Robert M. W.
Published: April 2009

Microsatellite instability (MSI) occurs in more than 90% of the tumors of Lynch syndrome patients, and in 15–25% of sporadic colorectal (CRC) and endometrial carcinomas (EC). Previous studies comparing EC and CRC using BAT markers showed that the frequency of unstable markers is lower in EC, and that the size of the mutations is smaller in EC. In the present study, we analyzed the type (insertions/deletions), size, and frequency of mutations occurring at three BAT and three dinucleotide markers in CRC and EC, to elucidate whether it is possible to establish different MSI profiles in carcinomas of different tissue origin. We show that mononucleotide markers nearly always become shorter whereas dinucleotide markers can become shorter or longer, in both CRC and EC. We therefore conclude that the type of mutation is a marker‐dependent feature rather than tissue‐dependent. However, we observed that the size of the deletions/insertions differs between CRC and EC, with EC having shorter alterations. The frequency of mono‐ and dinucleotide instability found in both tissues is comparable, with mononucleotide and dinucleotide markers being affected at similar rates. We conclude that it is not possible to define clearly different MSI profiles that could distinguish MSI‐high in CRC and EC. We propose that the differences observed might indicate different durations of tumor development and/or differences in tissue turnover between colorectal and endometrial epithelium, rather than reflecting truly different MSI profiles. We therefore suggest that the same MSI tests can be used for both tumor types. © 2009 Wiley‐Liss, Inc.
Spontaneous regression of Merkel cell carcinoma of the nose
Authors: Karkos Petros D. , Sastry Anand , Hampal Sucha , Al‐Jafari Mohammad
Published: April 2009

Background.

Merkel Cell Carcinoma (MCC) is a rare neurendocrine tumor of cutaneous origin.

Methods and Results.

A 79‐year‐old woman was seen with a neck lump and a lesion in the left nasal vestibule. Biopsy of the lesion revealed a primary neurendocrine MCC of the skin of the nasal vestibule with metastases to the cervical lymph nodes. The patient decided against any further active treatment. Follow‐up of patient for 30 months showed spontaneous regression of the lesions without any active treatment.

Conclusions.

Although spontaneous resolution of MCC has been described for other head neck sites, there has not been any published case of nasal MCC regression. We present this rare case of nasal MCC with neck metastases and its regression. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Significance of stromal desmoplasia and myofibroblast appearance at the invasive front in squamous cell carcinoma of the oral cavity
Authors: Kawashiri Shuichi , Tanaka Akira , Noguchi Natsuyo , Hase Takashi , Nakaya Hiromitsu , Ohara Teruhisa , Kato Koroku , Yamamoto Etsuhide
Published: April 2009

Background.

Tumor invasion involves complex interactions between tumor and stromal cells. We examined the extent of connective tissue in the tumor stroma and whether myofibroblasts play a role in assisting cancer invasion and metastasis.

Methods.

Biopsy materials from 84 patients with oral squamous cell carcinoma (SCC) were used. We compared data from intrastromal collagen fibers using Azan staining, immunohistochemical identification of myofibroblasts by cytoskeletal markers, α‐smooth muscle actin, vimentin, desmin, and clinicopathological parameters. Clinical outcome was compared by 5‐year survival rate.

Results.

There were high levels of stromal collagen fibers in invasive tumors. Myofibroblast appearance increased with increasing tumor invasiveness. Lymph node metastasis occurred more frequently in the myofibroblast‐positive group, and the survival rate was significantly poorer in this group.

Conclusions.

Fibrous stroma in SCC appeared to have a desmoplastic response. However, an independent invasive mechanism may regulate the stroma, with tumor desmoplasia occurring in highly developed, invasive tumors. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Early oral feeding after salvage laryngectomy
Authors: Eustaquio Marcia , Medina Jesus E. , Krempl Greg A. , Hales Nathan
Published: April 2009

Background.

Our aim was to determine the feasibility and safety of initiating early oral feeding in patients who underwent salvage laryngectomy on postoperative day 5 and to review the rate of pharyngocutaneous fistula formation.

Methods.

A retrospective review of 29 patients who underwent salvage laryngectomy was completed. Patients included in the study had radiation therapy ± chemotherapy for laryngeal squamous cell carcinoma with subsequent total laryngectomy. Patients were excluded from analysis if they were reliant on a gastrostomy tube preoperatively, had a concurrent complete glossectomy, or developed a fistula before beginning oral feedings. Early oral feeding was initiated on postoperative day 5.

Results.

Twenty patients met complete inclusion criteria. Pharyngocutaneous fistula occurred in 10% (2/20) of the patients. Patients without postoperative complications on an average remained in the hospital for 7 days.

Conclusions.

The risk of fistula formation is not increased and the duration of hospital stay may be shortened in patients who were given early postoperative feeds. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Trigeminal nerve palsy in nasopharyngeal carcinoma: Correlation between clinical findings and magnetic resonance imaging
Authors: Cui Chunyan , Liu Lizhi , Ma Jun , Liang Shaobo , Tian Li , Tang Linglong , Li Li
Published: April 2009

Background.

Our aim was to document the relationship between clinical and MRI evidence of trigeminal nerve involvement.

Methods.

The MRI and medical records of 924 consecutive patients with newly diagnosed nasopharyngeal carcinoma (NPC) were reviewed retrospectively.

Results.

A total of 92 divisions of palsied trigeminal nerves were found clinically in 46 patients (5.0%). The involved trigeminal nerve was ophthalmic nerve (V1; n = 21), the maxillary division (V2; n = 41), and the mandibular division (V3; n = 30). Of the 316 patients with MRI‐demonstrated trigeminal nerve involvements, the symptoms were lacking in 270 patients (85.4%). Of the 92 clinical palsied trigeminal nerve divisions, 91 nerves (98.9%) showed MRI evidence of 1 or more trigeminal nerve involvements. Of the 91 palsied trigeminal nerve with MRI evidence, 85 divisions (93.4%) were found with intracranial or orbital segment involvement, 6 (6.6%) divisions were found only basicranial evidence, and 83 (91.2%) divisions were found with cavernous sinus invasion.

Conclusion.

The incidence of MRI‐evidenced trigeminal nerve involvement is high and often asymptomatic in NPC. Almost all patients with clinical trigeminal nerve palsies had MRI evidence of trigeminal nerve involvement in intracranial or orbital segment, especially in cavernous sinus. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Streamflow response to Pinus plantation harvesting: Canobolas State forest, southeastern Australia
Authors: Webb Ashley A.
Published: April 2009

Streamflows were measured in two Pinus radiata plantation catchments and one native eucalypt forest catchment in Canobolas State forest from 1999 to 2007. In 2002/2003, clearfall harvesting of 43·2 and 40·3% of two plantation catchments occurred, respectively. Water yields increased by 54 mm (52%), 71 mm (35%) and 50 mm (19%) in the first three years post‐harvest in treated catchment A and by 103 mm (118%), 157 mm (82%) and 119 mm (48%) in treated catchment B relative to the native forest control catchment. In the fourth post‐harvest water year annual rainfall was only 488 mm, which resulted in negligible run‐off in all catchments, regardless of forest cover. In both plantation catchments, monthly streamflows increased significantly (p = 0·01, p < 0·001) due to a significant increase in baseflows (p < 0·001) after harvesting. Monthly stormflows were not significantly affected by harvesting. Flow duration curve analyses indicated a variable response between the two plantation catchments. Treated catchment A was converted from an ephemeral stream flowing 42% of the time pre‐harvest to a temporary stream flowing 82% of the time post‐harvest. These changes occurred throughout all seasons of the year but were most pronounced during summer and autumn when baseflows were maintained post‐harvest but were not observed under native forest or mature pine plantations. By contrast, flow duration increased in treated catchment B from 12% of the time pre‐harvest to 38% of the time post‐harvest with the greatest changes measured during the winter and spring months when streamflow would normally occur under native forest conditions. These observations have important implications for the development of models of plantation water use to be utilized in water resource planning in Australia. Copyright © 2009 John Wiley & Sons, Ltd.
Low and high flow analyses and wavelet application for characterization of the Blue Nile River system
Authors: Melesse Assefa , Abtew Wossenu , Dessalegne Tibebe , Wang Xixi
Published: April 2009

The low and high flow characteristic of the Blue Nile River (BNR) basin is presented. The study discusses low and high flow, flow duration curve (FDC) and trend analysis of the BNR and its major tributaries. Different probability density functions were fitted to better describe the low and high flows of the BNR and major tributaries in the basin. Wavelet analysis was used in understanding the variance and frequency‐time localization and detection of dominant oscillations in rainfall and flow. FDCs were developed, and low flow (below 50% exceedance) and high flow (over 75% exceedance) of the curves were analysed and compared. The Gravity Recovery and Climate Experiment (GRACE) satellite‐based maps of monthly changes in gravity converted to water equivalents from 2003 to 2006 for February, May and September showed an increase in the moisture influx in the BNR basin for the month of September, and loss of moisture in February and May. It was also shown that 2004 and 2005 were drier with less moisture influx compared to 2003 and 2006. On the basis of the Kolmogorov‐Smirnov, Anderson‐Darling and Chi‐square tests, Gen. Pareto, Frechet 3P, Log‐normal, Log‐logistics, Fatigue Life and Phased Bi‐Weibull distributions best describe the low and high flows within the BNR basin. This will be beneficial in developing flow hydrographs for similar ungauged watersheds within the BNR basin. The below 50% and above 75% exceedance on the FDC for five major rivers in addition to the BNR showed different characteristics depending on size, land cover, topography and other factors. The low flow frequency analysis of the BNR at Bahir Dar showed 0·55 m3/s as the monthly low flow with recurrence interval of 10 years. The wavelet analysis of the rainfall (at Bahir Dar and basin‐wide) and flows at three selected stations shows inter‐ and intra‐annual variability of rainfall and flows at various scales. Copyright © 2009 John Wiley & Sons, Ltd.
Forecasting US output growth using leading indicators: an appraisal using MIDAS models
Authors: Clements Michael P. , Galvão Ana Beatriz
Published: April 2009

We evaluate the predictive power of leading indicators for output growth at horizons up to 1 year. We use the MIDAS regression approach as this allows us to combine multiple individual leading indicators in a parsimonious way and to directly exploit the information content of the monthly series to predict quarterly output growth. When we use real‐time vintage data, the indicators are found to have significant predictive ability, and this is further enhanced by the use of monthly data on the quarter at the time the forecast is made. Copyright © 2009 John Wiley & Sons, Ltd.
Raman spectroscopy of DNA packaging in individual human sperm cells distinguishes normal from abnormal cells
Authors: Huser Thomas , Orme Christine A. , Hollars Christopher W. , Corzett Michele H. , Balhorn Rod
Published: April 2009

Healthy human males produce sperm cells of which about 25–40% have abnormal head shapes. Increases in the percentage of sperm exhibiting aberrant sperm head morphologies have been correlated with male infertility, and biochemical studies of pooled sperm have suggested that sperm with abnormal shape may contain DNA that has not been properly repackaged by protamine during spermatid development. We have used micro‐Raman spectroscopy to obtain Raman spectra from individual human sperm cells and examined how differences in the Raman spectra of sperm chromatin correlate with cell shape. We show that Raman spectra of individual sperm cells contain vibrational marker modes that can be used to assess the efficiency of DNA‐packaging for each cell. Raman spectra obtained from sperm cells with normal shape provide evidence that DNA in these sperm is very efficiently packaged. We find, however, that the relative protein content per cell and DNA packaging efficiencies are distributed over a relatively wide range for sperm cells with both normal and abnormal shape. These findings indicate that single cell Raman spectroscopy should be a valuable tool in assessing the quality of sperm cells for in‐vitro fertilization. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
New therapeutic targets for the treatment of high‐risk neuroblastoma
Authors: Wagner Lars M. , Danks Mary K.
Published: April 2009

High‐risk neuroblastoma remains a major problem in pediatric oncology, accounting for 15% of childhood cancer deaths. Although incremental improvements in outcome have been achieved with the intensification of conventional chemotherapy agents and the addition of 13‐cis‐retinoic acid, only one‐third of children with high‐risk disease are expected to be long‐term survivors when treated with current regimens. In addition, the cost of cure can be quite high, as surviving children remain at risk for additional health problems related to long‐term toxicities of treatment. Further advances in therapy will require the targeting of tumor cells in a more selective and efficient way so that survival can be improved without substantially increasing toxicity. In this review we summarize ongoing clinical trials and highlight new developments in our understanding of the molecular biology of neuroblastoma, emphasizing potential targets or pathways that may be exploitable therapeutically. J. Cell. Biochem. 107: 46–57, 2009. © 2009 Wiley‐Liss, Inc.
Insulin receptor kinase‐independent signaling via tyrosine phosphorylation of phosphatase PHLPP1
Authors: Zhang Manchao , Riedel Heimo
Published: April 2009

Most insulin responses correlate well with insulin receptor (IR) Tyr kinase activation; however, critical exceptions to this concept have been presented. Specific IR mutants and stimulatory IR antibodies demonstrate a lack of correlation between IR kinase activity and specific insulin responses in numerous independent studies. IR conformation changes in response to insulin observed with various IR antibodies define an IR kinase‐independent signal that alters the C‐terminus. IR‐related receptors in lower eukaryotes that lack a Tyr kinase point to an alternative mechanism of IR signaling earlier in evolution. However, the implied IR kinase‐independent signaling mechanism remained obscure at the molecular level. Here we begin to define the molecular basis of an IR‐dependent but IR kinase‐independent insulin signal that is equally transmitted by a kinase‐inactive mutant IR. This insulin signal results in Tyr phosphorylation and catalytic activation of phosphatase PHLPP1 via a PI 3‐kinase‐independent, wortmannin‐insensitive signaling pathway. Dimerized SH2B1/PSM is a critical activator of the IR kinase and the resulting established insulin signal. In contrast it is an inhibitor of the IR kinase‐independent insulin signal and disruption of SH2B1/PSM dimer binding to IR potentiates this signal. Dephosphorylation of Akt2 by PHLPP1 provides an alternative, SH2B1/PSM‐regulated insulin‐signaling pathway from IR to Akt2 of opposite polarity and distinct from the established PI 3‐kinase‐dependent signaling pathway via IRS proteins. In combination, both pathways should allow the opposing regulation of Akt2 activity at two phosphorylation sites to specifically define the insulin signal in the background of interfering Akt‐regulating signals, such as those controlling cell proliferation and survival. J. Cell. Biochem. 107: 65–75, 2009. © 2009 Wiley‐Liss, Inc.
Down‐regulating cold shock protein genes impairs cancer cell survival and enhances chemosensitivity
Authors: Zeng Yu , Kulkarni Prakash , Inoue Takahiro , Getzenberg Robert H.
Published: April 2009

The microenvironment of the cancer cell is pivotal to its phenotypic regulation. One of the central components of the microenvironment is temperature. An elevation in environmental temperature has been shown to increase the cancer cell's susceptibility to chemo‐ and radiation therapy. The goal of the studies described here was to identify some of the pathways that are modified by a mild increase in temperature in cancer cells. Using prostate cancer cells as a model system we found that in addition to the well described and anticipated up‐regulation of the heat shock family of proteins, there is a significant down‐regulation of certain members of the “cold shock” family of proteins such as, RNA binding motif protein 3 (RBM3) and cold inducible RNA binding protein (CIRBP). siRNA‐mediated down‐regulation of the cold shock protein (CSP) encoding mRNAs dramatically attenuates cell survival in the absence of any heat application. Furthermore, we also demonstrate that knocking down the CSPs can enhance the therapeutic response of prostate cancer cells to chemotherapy. Our findings suggest that down‐regulating CSPs in cancer cells may “mimic” the stress response the cells experience when exposed to heat treatment rendering them more susceptible to therapy. Thus, the pharmacological modulation of RBM3 and CIRBP may represent novel therapeutic approaches for prostate cancer. J. Cell. Biochem. 107: 179–188, 2009. © 2009 Wiley‐Liss, Inc.
First‐principles study of molecular hydrogen dissociation on doped Al12X (X = B, Al, C, Si, P, Mg, and Ca) clusters
Authors: Wang Lu , Zhao Jijun , Zhou Zhen , Zhang S. B. , Chen Zhongfang
Published: April 2009

Inspired by the concept of superatom via substitutionally doping an Al13 magic cluster, we investigated the H2 molecule dissociation on the doped icosahedral Al12X (X = B, Al, C, Si, P, Mg, and Ca) clusters by means of density functional theory. The computed reaction energies and activation barriers show that the concept of superatom is still valid for the catalysis behavior of doped metal clusters. The hydrogen dissociation behavior on metal clusters characterized by the activation barrier and reaction energy can be tuned by controllable doping. Thus, doped Al12X clusters might serve as highly efficient and low‐cost catalysts for hydrogen dissociation. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009
Unorthodox uses of Bennett's acceptance ratio method
Authors: König Gerhard , Bruckner Stefan , Boresch Stefan
Published: April 2009

We illustrate the application of Bennett's acceptance ratio method (BAR) to problems in which standard methods to compute free energy differences (thermodynamic integration, exponential formula) are not practical. Our starting point is the observation that BAR can often compute the free energy difference between two states without the need for intermediate states usually employed (and necessary) in alchemical free energy simulations. This is demonstrated first for the free energy difference between ethane and methanol in aqueous solution. We then show how BAR can be used to compute directly rather unusual free energy differences, such as the free energy difference resulting from changing the treatment of electrostatic interactions, from switching the force field, or from using an implicit solvent model. Calculations of this kind should prove useful for force field development and the validation of implicit solvent methods. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009
QSPR modeling of enthalpies of formation for organometallic compounds by SMART‐based optimal descriptors
Authors: Toropov Andrey A. , Toropova Alla P. , Benfenati Emilio , Manganaro Alberto
Published: April 2009

A quantitative structure‐property relationship (QSPR) model for the prediction of gas‐phase enthalpy of formation has been developed, using as chemical information descriptors based on the SMART notation, which is an alternative to SMILES. The model is one‐variable equation. The SMART‐based descriptors are calculated with correlation weights of SMART attributes which are obtained by the Monte Carlo method. The model addressed organometallic compounds. Statistical characteristics of the model are the following: n = 104, r2 = 0.9944, s = 19.6 (kJ/mol), F = 18,269 (training set) and n = 28, r2 = 0.9909, s = 28.8 (kJ/mol), F = 2832 (test set). © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009
Linear response theory in dihedral angle space for protein structural change upon ligand binding
Authors: Omori Satoshi , Fuchigami Sotaro , Ikeguchi Mitsunori , Kidera Akinori
Published: April 2009

Coupling between proteins motion and ligand binding can be well explained by the linear response theory (Ikeguchi, M.; Ueno, J.; Sato, M.; Kidera, A. Phys Rev Lett 2005, 94, 078102.), in which the structural change is treated as a response to ligand binding. The prediction accuracy of structural change upon ligand binding has been improved by replacing the variables in the linear response theory from Cartesian coordinates to dihedral angles. The dihedral angle theory can more accurately describe the rotational motions of protein domains compared with the Cartesian theory, which tends to shift the coordinate to the tangential direction of the domain rotation. In this study, the ligand‐bound form of Ferric‐binding protein was predicted from its ligand‐free form using the dihedral linear response theory. When the variance–covariance matrix, the key component in the linear response theory, was derived by linear conversion from Cartesian coordinates to dihedral angles, the dihedral linear response theory gave an improvement in the prediction. Therefore, the description of the rotational motion by dihedral angles is crucial for accurate prediction of protein structural change. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009
Extension of QM/MM docking and its applications to metalloproteins
Authors: Cho Art E. , Rinaldo David
Published: April 2009

To overcome the limitation of conventional docking methods which assume fixed charge model from force field parameters, combined quantum mechanics/molecular mechanics (QM/MM) method has been applied to docking as a variable charge model and shown to exhibit improvement on the docking accuracy over fixed charge based methods. However, it has also been shown that there are a number of examples for which adoption of variable‐charge model fails to reproduce the native binding modes. In particular, for metalloproteins, previously implemented method of QM/MM docking failed most often. This class of proteins has highly polarized binding sites at which high‐coordinate‐numbered metal ions reside. We extend the QM/MM docking method so that protein atoms surrounding the binding site along with metal ions are included as quantum region, as opposed to only ligand atoms. This extension facilitates the required scaling of partial charges on metal ions leading to prediction of correct binding modes in metalloproteins. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009
Inhibition of RelB by 1,25‐dihydroxyvitamin D3 promotes sensitivity of breast cancer cells to radiation
Authors: Mineva Nora D. , Wang Xiaobo , Yang Sanghwa , Ying Haoqiang , Xiao Zhi‐Xiong J. , Holick Michael F. , Sonenshein Gail E.
Published: April 2009

Aberrant constitutive expression of the NF‐κB c‐Rel and RelA subunits in breast cancer cells was shown to promote their survival. Recently, we demonstrated that aggressive breast cancers constitutively express high levels of the RelB subunit, which promotes their more invasive phenotype via induction of the BCL2 gene. As these cancers are frequently resistant to therapy, here we tested the hypothesis that RelB promotes their survival. High RelB expressing Hs578T and MDA‐MB‐231 breast cancer cells were more resistant to γ‐radiation than MCF7 and ZR‐75 cells, which express lower RelB levels. Knockdown of RelB in Hs578T led to decreased survival in response to γ‐irradiation, while conversely ectopic expression of RelB in MCF7 cells protected these cells from radiation. Similar data were obtained upon treatment of Hs578T or MCF7 cells with the chemotherapeutic agent doxorubicin. High serum levels of 25‐hydroxyvitamin D are associated with decreased breast cancer risk and mortality, although, the mechanisms of its protective actions have not been fully elucidated. Treatment of Hs578T and Her‐2/neu‐driven NF639 cells with 1,25‐dihydroxyvitamin D3 decreased RelB/RELB gene expression and levels of pro‐survival targets Survivin, MnSOD and Bcl‐2, while increasing their sensitivity to γ‐irradiation. Thus, RelB, which promotes survival and a more highly invasive phenotype of breast cancer cells, is a target of 1,25‐dihydroxyvitamin D3, providing one mechanism for the observed protective role of 25‐hydroxyvitamin D in patients with breast cancer. J. Cell. Physiol. 220: 593–599, 2009. © 2009 Wiley‐Liss, Inc.
Modulation of HSP27 alters hypoxia‐induced endothelial permeability and related signaling pathways
Authors: Liu Tiegang , Guevara Oscar E. , Warburton Rod R. , Hill Nicholas S. , Gaestel Matthias , Kayyali Usamah S.
Published: April 2009

This manuscript describes how the permeability of pulmonary artery microvascular endothelial cell (RPMEC) monolayer is elevated by hypoxia and the role played by HSP27 phosphorylation. p38 MAP kinase activation leading to HSP27 phosphorylation was previously shown by our laboratory to alter the actin cytoskeleton and tethering properties of RPMEC. This effect was independent of hypoxia‐induced contractility which was ROCK‐dependent rather than HSP27‐dependent. Results described here show that increased HSP27 phosphorylation not only does not underlie hypoxia‐induced permeability, but may actually augment the endothelial barrier. Hypoxia causes gap formation between RPMEC and increases MLC2 phosphorylation. The phosphorylation of MYPT1, which inhibits MLC2 phosphatase, is also increased in hypoxia. In addition, FAK phosphorylation, which alters focal adhesion signaling, is increased in hypoxia. Overexpressing phosphomimicking HSP27 (pmHSP27), which induces significant actin stress fiber formation, surprisingly renders RPMEC resistant to hypoxia‐ or TGFβ‐induced permeability. siRNA against pmHSP27 reverses the increased actin stress fiber formation in pmHSP27‐overexpressing cells, and disrupting actin stress fibers in pmHSP27‐overexpressing RPMEC renders them more susceptible to hypoxia. Finally, hypoxia‐induced gap formation, as well as phosphorylation of MLC2, MYPT1 and FAK are almost abolished by overexpressing pmHSP27 in RPMEC. These effects of pmHSP27 overexpression might represent decreased cytoskeletal plasticity and increased tethering which counteracts permeability‐inducing contractility. Thus hypoxia activates two pathways one leading to contractility and increased permeability, the other leading to actin stress fibers, stronger adhesion, and reduced permeability. Altering HSP27 phosphorylation, which tips the balance towards decreased permeability, might be targeted in managing endothelial barrier dysfunction. J. Cell. Physiol. 220: 600–610, 2009. © 2009 Wiley‐Liss, Inc.
Acrosomal exocytosis of mouse sperm progresses in a consistent direction in response to zona pellucida
Authors: Buffone Mariano G. , Rodriguez‐Miranda Esmeralda , Storey Bayard T. , Gerton George L.
Published: April 2009

Sperm acrosomal exocytosis is essential for successful fertilization, and the zona pellucida (ZP) has been classically considered as the primary initiator in vivo. At present, following what is referred to as primary binding of the sperm to the ZP, the acrosome reaction paradigm posits that the outer acrosomal membrane and plasma membrane fuse at random points, releasing the contents of the acrosome. It is then assumed that the inner acrosomal membrane mediates secondary binding of the sperm to the ZP. In the present work we used a live fluorescence imaging system and mouse sperm containing enhanced green fluorescent protein (EGFP) in their acrosomes. We compared the processes of acrosomal exocytosis stimulated by the calcium ionophore ionomycin or by solubilized ZP. As monitored by the loss of EGFP from the sperm, acrosomal exocytosis driven by these two agents occurred differently. When ionomycin was used, exocytosis started randomly (no preference for the anterior, middle or posterior acrosomal regions). In contrast, following treatment with solubilized ZP, the loss of acrosomal components always started at the posterior zone of the acrosome and progressed in an anterograde direction. The exocytosis was slower when stimulated with ZP and on the order of 10 sec, which is in accordance with other reports. These results demonstrate that ZP stimulates acrosomal exocytosis in an orderly manner and suggest that a receptor‐mediated event controls this process of membrane fusion and release of acrosomal components. These findings are incorporated into a model. J. Cell. Physiol. 220: 611–620, 2009. © 2009 Wiley‐Liss, Inc.
Utilization of organically stabilized proteinous solid waste for the treatment of coloured waste‐water
Authors: Fathima N Nishad , Aravindhan R , Rao J Raghava , Nair BU
Published: April 2009

BACKGROUND: Solid waste emanating from tanneries contains a high percentage of protein with raw trimmings from hides constituting a significant percentage of the solid waste. In this study, organically stabilized trimmings (OST) have been used as an adsorbent material for removal of colour from waste‐water.

RESULTS: Various parameters such as adsorbent dosage, dye concentration and pH have been optimized. The effect of neutral salts on the dye adsorption capacity of OST has also been studied. The adsorption of dye by OST follows the Freundlich isotherm. More than 99% removal of colour has been achieved. Commercial trials prove the potential use of organically stabilized trimmings for the treatment of colored wastewater.

CONCLUSIONS: Dye loaded OSTs have been employed in the manufacture of a tanning salt, which can be used in the leather industry. Thus, a holistic solution to the challenging solid waste disposal problem has been developed. Copyright © 2009 Society of Chemical Industry
Uncovering genetic regulatory network divergence between duplicate genes using yeast eQTL landscape
Authors: Zou Yangyun , Su Zhixi , Yang Jian , Zeng Yanwu , Gu Xun
Published: April 2009

Genetical genomics, a novel approach combining microarray technology and quantitative genetic analysis, aims to identify the expression quantitative trait loci (eQTLs), which may regulate the genome‐wide expression pattern. In this article, we have studied yeast genomic eQTL data to investigate how the genetic eQTL regulation of ancestral gene has diverged since gene duplication. Our findings are as follows: (i) Duplicate genes have higher heritability for gene expression than single‐copy genes, but little difference in their epistasis and directional effect. (ii) The divergence of trans‐acting eQTLs between duplicate pairs increases with the evolutionary time since gene duplication. (iii) Trans‐acting eQTL divergence can explain about 21% of the variation in expression divergence between duplicate pairs with KS<2.0, which increases to 27% when the transcription factor (TF)–target interaction divergence is combined. Moreover, under the partial correlation analysis, trans‐acting eQTL divergence seems make a bigger contribution to expression divergence than does TF divergence. (iv) Trans‐acting eQTL divergence between duplicate pairs is correlated with gene ontology categories “Biological processes” and “Cellular components,” but not with “Molecular functions,” and is related to fitness defect under treatment conditions, but not with fitness under normal condition. We conclude that eQTL analysis provides a novel approach to explore the effect of gene duplications on the genetic regulatory network. J. Exp. Zool. (Mol. Dev. Evol.) 312B:722–733, 2009. © 2009 Wiley‐Liss, Inc.
The multi‐color Ramsey number of an odd cycle
Authors: Li Yusheng
Published: April 2009

Let rk(G) be the k‐color Ramsey number of a graph G. It is shown that
$r_{k}(C_{5})\le \sqrt{18^{k}\,k!}$ for k⩾2 and that rk(C2m+ 1)⩽(ckk!)1/m if the Ramsey graphs of rk(C2m+ 1) are not far away from being regular. © 2009 Wiley Periodicals, Inc. J Graph Theory 62: 324–328, 2009
Label‐free determination of protein–ligand binding constants using mass spectrometry and validation using surface plasmon resonance and isothermal titration calorimetry
Authors: Jecklin Matthias C. , Schauer Stefan , Dumelin Christoph E. , Zenobi Renato
Published: April 2009

We performed a systematic comparison of three label‐free methods for quantitative assessment of binding strengths of proteins interacting with small molecule ligands. The performance of (1) nanoelectrospray ionization mass spectrometry (nESI‐MS), (2) surface plasmon resonance (SPR), and (3) isothermal titration calorimetry (ITC) was compared for the determination of dissociation constants (KD). The model system studied for this purpose was the human carbonic anhydrase I (hCAI) with eight known and well characterized sulfonamide inhibitors (Krishnamurthyet al.,Chem. Rev.2008, 108: 946–1051). The binding affinities of the inhibitors chosen vary by more than four orders of magnitude e.g., theKDvalue determined for ethoxzolamide by nESI‐MS was 5 ± 1 nM and theKDvalue for sulfanilamide was 145.7 ± 10.0 µM. The agreement of the determinedKDvalues by the three methods investigated was excellent for ethoxzolamide and benzenesulfonamide (variation with experimental error), good for acetazolamide and 4‐carboxybenzenesulfonamide (variation by ∼ one order of magnitude), but poor for others e.g., sulpiride. The accuracies of theKDvalues are determined, and advantages and drawbacks of the individual methods are discussed. Moreover, we critically evaluate the three examined methods in terms of ease of the measurement, sample consumption, time requirement, and discuss their limitations. Copyright © 2009 John Wiley & Sons, Ltd.
Emerging drugs: mechanism of action, mass spectrometry and doping control analysis
Authors: Thevis Mario , Thomas Andreas , Kohler Maxie , Beuck Simon , Schänzer Wilhelm
Published: April 2009

The number of compounds and doping methods in sports is in a state of constant flux. In addition to ‘traditional’ doping agents, such as anabolic androgenic steroids or erythropoietin, new therapeutics and emerging drugs have considerable potential for misuse in elite sport. Such compounds are commonly based on new chemical structures, and the mechanisms underlying their modes of action represent new therapeutic approaches arising from recent advances in medical research; therefore, sports drug testing procedures need to be continuously modified and complementary methods developed, preferably based on mass spectrometry, to enable comprehensive doping controls. This tutorial not only discusses emerging drugs that can be categorized as anabolic agents (selective androgen receptor modulators, SARMs), gene doping [hypoxia‐inducible factor stabilizers, peroxisome‐proliferator‐activated receptor (PPAR)δ‐agonists] and erythropoietin‐mimetics (Hematide) but also compounds with potentially performance‐enhancing properties that are not classified in the current list of the World Anti‐Doping Agency. Compounds such as ryanodine‐calstabin‐complex modulators (benzothiazepines) are included, their mass spectrometric properties discussed, and current approaches in sports drug testing outlined. Copyright © 2009 John Wiley & Sons, Ltd.
Qualitative and quantitative comparison of N‐glycans between pig endothelial and islet cells by high‐performance liquid chromatography and mass spectrometry‐based strategy
Authors: Kim Yun‐Gon , Gil Geun‐Cheol , Jang Kyung‐Soon , Lee Sukmook , Kim Hyoung‐Il , Kim Jung‐Sik , Chung Junho , Park Chung‐Gyu , Harvey David J. , Kim Byung‐Gee
Published: April 2009

N‐glycan structures released from miniature pig endothelial and islet cells were determined by matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF), negative ion electrospray ionization (ESI) MS/MS and normal‐phase high performance liquid chromatography (NP‐HPLC) combined with exoglycosidase digestion. Totally, the identified structures were 181 N‐glycans including 129 sialylated and 18 α‐galactosylated glycans from pig endothelial cells and 80 N‐glycans including 41 sialylated and one α‐galactosylated glycans from pig islet cells. The quantity of the α‐galactosylated glycans from pig islet cells was certainly neglectable compared to pig endothelial cells. A number of NeuGc‐terminated N‐glycans (80 from pig endothelial cells and 13 from pig islet cells) are newly detected by our mass spectrometric strategies. The detailed structural information will be a matter of great interest in organ or cell xenotransplantation using α 1,3‐galactosyltransferase gene‐knockout (GalT‐KO) pig. Copyright © 2009 John Wiley & Sons, Ltd.
Antioxidant compounds in green and red peppers as affected by irrigation frequency, salinity and nutrient solution composition
Authors: Marín Alicia , Rubio José S. , Martínez Vicente , Gil María I
Published: April 2009

BACKGROUND: There is a need to encourage more sustainable agricultural practices, reducing inputs of water and fertilisers while minimising any negative impact on fruit quality. The effect of irrigation frequency, salinity and potassium and calcium fertilisation on the content of bioactive compounds and quality attributes of green and red peppers grown with and without substrate was evaluated.

RESULTS: Low irrigation frequency and salinity improved the quality attributes (dry matter, soluble solids content and titratable acidity) of pepper. Low irrigation frequency increased vitamin C content by 23% in green peppers, while in red fruits it was not affected. In contrast, total carotenoids and provitamin A only increased in red fruits by 30% and 15%, respectively, as a consequence of low irrigation frequency. When the effect of potassium and calcium doses was investigated, it was shown that a high proportion of potassium increased the vitamin C, provitamin A and total phenolic content of red and green peppers, whereas pepper grown at low calcium doses, presented the highest content in carotenoids and provitamin A.

CONCLUSION: Low irrigation frequency and fertilisation with high potassium and low calcium doses improved pepper quality increasing the content of bioactive compounds. Copyright © 2009 Society of Chemical Industry
Compensatory growth in slaughter pigs reared under organic conditions
Authors: Fernández José Adalberto , Nørgaard Jan Værum
Published: April 2009

BACKGROUND:Compensatory growth is the physiological process leading to accelerated growth following a period of growth retardation. This study assessed different feeding strategies that may induce compensatory growth. Pigs from two sire breeds, reared under organic conditions, were subjected to: (1)ad libitumfeeding; (2) 0.7×ad libitumfeeding; (3) 0.7×ad libitumfeeding for 25 days followed byad libitumfeeding to slaughter; and (4) as (3) but finished with an energy‐ and vitamin E‐enriched diet.

RESULTS:Compared to the performance ofad libitumfed pigs, re‐alimentation was not capable of fully compensating the effect of the imposed feed restriction either in the number of days used to reach the same slaughter weight (+4% to 7%) or in the slaughter weight achieved in the same number of feeding days (−0.5% to 2.0%,P= 0.65 and 0.11).

CONCLUSION:It is reasonable to propose that although compensatory growth does occur by re‐alimentation after feed restriction, the compensation is far from always complete. The latter is a crucial aspect that has to be taken into account when considering the application of feeding strategies expected to lead to compensatory growth in organic pig production. The expectation of compensatory growth alone does not necessarily justify the application of these strategies. Copyright © 2009 Society of Chemical Industry
Young age is not associated with increased local recurrence for DCIS treated by breast‐conserving surgery and radiation
Authors: Turaka Aruna , Freedman Gary M. , Li Tianyu , Anderson Penny R. , Swaby Ramona , Nicolaou Nicos , Goldstein Lori , Sigurdson Elin R. , Bleicher Richard J.
Published: April 2009

Background

We report local recurrence (LR) after breast‐conserving surgery and radiation (BCS + RT) for ductal carcinoma in situ (DCIS) to determine outcomes for patients aged ≤40 years compared with older women.

Methods

The study included 440 women with DCIS treated from 1978 to 2007. All patients received whole‐breast radiotherapy with a boost in 95% of cases. Demographics, characteristics, surgical, and adjuvant treatments were analyzed for an effect on LR.

Results

Median age was 56.5 years with 24 patients aged ≤40. Median DCIS size was 0.8 cm. Re‐excision was required in 62% of patients, and in 75% of those aged ≤40. Tamoxifen was used in 22%, but only one patient aged ≤40. Median follow‐up was 6.8 years. Actuarial LR was 7% (95% confidence interval of 4–11%) at 10 years and 8% (5–14%) at 15 years. There was no difference in LR by age (P = 0.76).

Conclusions

The long‐term risk of LR after BCS + RT for DCIS is low, even in patients ≤40 years. This may be due to patient selection for small size, high utilization of re‐excision, and radiation boost. Young age may be a smaller contributor to LR risk in DCIS than previously suggested. J. Surg. Oncol. 2009;100:25–31. © 2009 Wiley‐Liss, Inc.
Endoscopic clipping of duodenal stump leakage after Billroth II gastrectomy in gastric cancer patient
Authors: Lee Jong Yeul , Ryu Keun Won , Cho Soo‐Jeong , Kim Chan Gyoo , Choi Il Ju , Kim Min Ju , Lee Jong Seok , Kim Hyun Beom , Lee Jun Ho , Kim Young Woo
Published: April 2009

Various gastrointestinal anastomotic breakdown has been reported to be closed by endoscopic clipping. However, no report has been issued on the control of duodenal stump leakage after Billroth II gastrectomy by endoscopic clipping. The authors describe successful endoscopic clipping in a case of duodenal stump leakage. J. Surg. Oncol. 2009;100:80–81. © 2009 Wiley‐Liss, Inc.
Nutritional management during neoadjuvant therapy for esophageal cancer
Authors: Bower Matthew R. , Martin Robert C.G.
Published: April 2009

Patients undergoing neoadjuvant therapy for esophageal cancer are at a high risk for malnutrition due to the effects of chemoradiation, dysphagia, and malignancy induced cachexia. Preparation for esophagectomy requires careful assessment of nutritional risk and adequate supplementation as indicated. Supplementation via the enteral route is preferred to the parenteral route but requires feeding tube placement. Endoscopically placed silicone stents have also shown promise as a means to alleviate malnutrition and avoid invasive feeding tubes. J. Surg. Oncol. 2009;100:82–87. © 2009 Wiley‐Liss, Inc.
Middle ear cancer: A population‐based study
Authors: Gurgel Richard K. , Karnell Lucy H. , Hansen Marlan R.
Published: April 2009

Objectives/Hypothesis:

Primary carcinoma of the middle ear is a rare clinical entity, best suited for evaluation using a population‐based database. The objective of this study was to utilize the Surveillance, Epidemiology, and End Results (SEER) database to determine the incidence, treatment, and survival of middle ear carcinoma.

Study Design:

Analysis of national cancer database.

Method:

Using SEER*Stat software, records for patients diagnosed with middle ear carcinoma between 1973 and 2004 were extracted from the SEER database. Five‐year, observed survival was analyzed, with significant differences determined by the Wilcoxon statistic.

Results:

The 5‐year observed survival rate for the 215 patients in this study was 36.4%. Histologic subtypes included squamous cell carcinoma (62.8%), adenocarcinoma (18.2%), other carcinomas (13.0%), and noncarcinomas (6.0%), with 5‐year survival rates of 23.9%, 65.0%, 60.0%, and 38.6%, respectively (P = .003). Of the 123 patients with known stage, 23.6% had local, 69.1% had regional, and 7.3% had distant disease, with their 5‐year survival rates being 64.9%, 34.2%, and 0%, respectively (P < .001). Treatment included surgery (31.2%), radiation (16.3%), surgery and radiation (38.6%), or no treatment (8.4%) with 5‐year survival of 69.2%, 14.6%, 26.4%, and 0%, respectively (P < .001).

Conclusions:

Patients with primary middle ear carcinoma have a relatively poor prognosis. However, subsets of patients, such as those with adenocarcinomas and with localized tumors, demonstrated significantly better survival. Surgery alone had significantly better survival than the other treatment groups, presumably due to less advanced disease in this treatment group. These data are useful in counseling patients and understanding the natural history of middle ear carcinoma. Laryngoscope, 2009