bluuebunny/crossref_metadata_2025 huggingface dataset:
Semisynthetic Latrunculin Derivatives as Inhibitors of Metastatic Breast Cancer: Biological Evaluations, Preliminary Structure–Activity Relationship and Molecular Modeling Studies
Authors: Khanfar Mohammad A. , Youssef Diaa T. A. , El Sayed Khalid A.
Published: December 2009

The microfilament cytoskeleton protein actin plays an important role in cell biology and affects cytokinesis, morphogenesis, and cell migration. These functions usually fail and become abnormal in cancer cells. The marine‐derived macrolides latrunculins A and B, from the Red Sea sponge Negombata magnifica, are known to reversibly bind actin monomers, forming 1:1 stoichiometric complexes with G‐actin, disrupting its polymerization. To identify novel therapeutic agents for effective treatment of metastatic breast cancer, several semisynthetic derivatives of latrunculin A with diverse steric, electrostatic, and hydrogen bond donor and acceptor properties were rationally prepared. Analogues were designed to modulate the binding affinity toward G‐actin. Examples of these reactions are esterification, acetylation, and N‐alkylation. Semisynthetic latrunculins were then tested for their ability to inhibit pyrene‐conjugated actin polymerization, and subsequently assayed for their antiproliferative and anti‐invasive properties against MCF7 and MDA‐MB‐231 cells using MTT and invasion assays, respectively.
Pancreatic cysts
Authors: Pitman Martha Bishop , Lewandrowski Kent , Shen Jian , Sahani Dushyant , Brugge William , Fernandez‐del Castillo Carlos
Published: December 2009

Preoperative diagnosis of pancreatic cysts benefits from integrating the clinical, radiological, and cytological features. As patient management algorithms evolve to increasingly nonsurgical options, accuracy in distinguishing mucinous from nonmucinous and benign from malignant mucinous cysts is important. This review focuses on pseudocysts, serous cystadenomas, intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms. Patients with pseudocysts almost always present with pancreatitis and are usually medically managed. Radiological studies reveal a unilocular cyst mostly in the pancreatic tail. Cyst fluid is thin, with high amylase but low carcinoembryonic antigen (CEA) levels. DNA mutations are absent. Serous cystadenomas are benign and do not require resection. Patients are usually asymptomatic and have microcystic or macrocystic masses anywhere in the pancreas. Cytology is frequently nondiagnostic. CEA and amylase levels are low. DNA analysis may reveal loss of heterozygosity (LOH) at 3p if associated with Von Hippel‐Lindau disease. Neoplastic mucinous cysts are highly variable in their presentation. Most are resected. Mucinous cystic neoplasms typically arise in the body or tail of the pancreas of middle‐aged women and demonstrate a septated cyst without dilatation of the main pancreatic duct. Branch duct IPMNs are more common in the pancreatic head of elderly men. Main duct dilatation correlates with main duct or combined type IPMN. Both types of mucinous cysts produce variable amounts of mucin. Cytologically nonmalignant but atypical epithelial cells, even when scant, are an indication of a high risk for malignancy. High CEA level supports a mucinous cyst, as do KRAS mutation and good quality DNA levels. KRAS mutation and multiple LOH support malignancy. Cancer (Cancer Cytopathol) 2010. © 2009 American Cancer Society.
Coadsorption of Hydrogen and CO on Hydrogen Pre‐Covered PtRu/Ru(0001) Surface Alloys
Authors: Diemant Thomas , Bansmann Joachim , Rauscher Hubert
Published: December 2009

The influence of pre‐adsorbed hydrogen on the adsorption of CO on well‐defined PtRu/Ru(0001) surface alloys and the modification of the adsorption properties of both adsorbate species due to coadsorption was studied by a combination of temperature‐programmed desorption and infrared spectroscopic measurements. The hydrogen binding strength is weakened both by surface alloy formation and by CO coadsorption. In the densely packed coadsorbate layers, which can be formed after CO post‐adsorption, the adsorption properties of the adsorbed CO molecules are also affected significantly. Depending on the Pt surface concentration, the CO adsorption process on hydrogen pre‐covered surfaces is blocked to a different extent with a decreasing blocking tendency for Pt‐rich alloys.
Palladium Catalyzed Direct 3‐Arylation of Benzofurans using Low Catalyst Loadings
Authors: Ionita Marina , Roger Julien , Doucet Henri
Published: December 2009

The palladium‐catalyzed direct 3‐arylation of benzofurans provides a cost‐effective and environmentally attractive route for the preparation of 3‐arylbenzofuran derivatives. The reactions were carried out using a wide variety of electronically and sterically diverse aryl or heteroaryl bromides with low catalyst loadings. In the presence of only 0.1–0.5 mol % catalyst, products in moderate to good yields were obtained. The aryl bromide reactants were able to tolerate a wide range of functionalities, such as acetyl, propionyl, formyl, ester, nitrile, trifluoromethyl, or fluoro groups. Higher yields were obtained using electron‐deficient aryl bromides as reactants compared to using electron‐rich aryl bromides. Functionalized benzofuran derivatives, bearing formyl or hydroxymethyl on C2, were also successfully employed.
ALDH+/CD44+/CD24− expression in cells from body cavity fluids
Authors: Krishan Awtar , Sharma Deepti , Sharma Siddharth , Hamelik Ronald M. , Ganjei‐Azar Parvin , Nadji Mehrdad
Published: December 2009

Background:

Enhanced expression of aldehyde dehydrogenase 1 (ALDH1) and phenotypic markers (CD44+/CD24−) in stem cells from breast tumors has been reported. This study was undertaken to monitor expression of these markers in cells from body cavity fluids of female patients suspected to have a malignancy.

Methods:

Cells from peritoneal and pleural fluids of 100 female patients were examined by diagnostic cytology and analyzed by laser flow cytometry for enhanced ALDH1 expression. Cells from 36 body cavity fluids with ALDH1bright fluorescence were then analyzed for the expression of CD44 and CD24 markers.

Results:

In samples positive for malignancy, ALDH1bright cells with both SSClow and SSChigh were seen. In 15 body cavity fluids positive for malignancy, the percentage of ALDH1bright cells ranged from 0.26 to 6.34% of the total cells. The percentage of ALDH1bright cells with CD44+/CD24− expression in these samples ranged from 0.02 to 3.66%. ALDH1bright cells with CD44+/CD24− expression were also present in body cavity fluids of patients in whom diagnostic cytology could not detect any malignancy. However, the percentage of ALDH1bright and CD44+/CD24− cells amongst the 21 body cavity fluids with negative cytology was lower than that of samples with malignancy.

Conclusions:

Expression of ALDH1bright and the CD44+/CD24− phenotype in body cavity fluids in which diagnostic cytology could not find any malignant cells suggests that this phenotype may not be restricted to the putative breast tumor stem cells. It is possible that only subsets of cells with this phenotype are the putative breast tumor stem cells. © 2010 Clinical Cytometry Society
Transitional cell carcinoma of renal allograft associated with BK virus infection
Authors: Saquib Rehana , Barri Yousri M. , Saad Rana , Savino Daniel A. , Rice Kim M. , Hays Steven R. , Melton Larry B.
Published: December 2009

BK virus (BKV) has oncogenic properties and has been associated with different malignancies. However, reports of malignancy in renal transplant recipients are scarce and circumstantial. We report on a renal transplant recipient with a diagnosis of BKV nephropathy for several years, who subsequently developed a renal allograft mass. Renal allograft mass biopsy revealed a high‐grade transitional cell carcinoma. The patient underwent a renal allograft nephrectomy and returned to hemodialysis. Neoplastic tissue was positive for BKV DNA by polymerase chain reaction (PCR) and large T‐antigen (TAg) by immunohistochemical staining. In contrast, BKV DNA by PCR was negative in non‐neoplastic tissue. The presence of BKV DNA and TAg exclusively in the neoplastic tissue, suggest that malignancy was induced by BKV. Of note, JC virus DNA by PCR was negative in the neoplastic tissue. BKV is associated with transitional cell carcinoma of the allograft renal pelvis and that warrants monitoring these patients for this possibility.
CD14‐independent responses induced by a synthetic lipid A mimetic
Authors: Legat Amandine , Thomas Séverine , Hermand Philippe , Van Mechelen Marcelle , Goldman Michel , De Wit Dominique
Published: December 2009

CRX‐527 belongs to a new family of synthetic lipid A mimetics, the aminoalkyl glucosaminide 4‐phosphates, which are considered as potential vaccine adjuvants or stand‐alone immunotherapeutics to harness innate immune defenses. Since natural lipid A from bacterial LPS depends on membrane‐bound (mCD14) or soluble CD14 for its TLR4 ligand activity, we investigated the involvement of both forms of CD14 in the responses elicited by CRX‐527. First, we found that CRX‐527 induces NF‐κB and interferon regulatory factor‐3 (IRF‐3) activation in human embryonic kidney cells transfected with TLR4 and MD‐2 genes alone, whereas the responses to LPS require either co‐transfection of the gene encoding mCD14 or addition of soluble CD14. We then observed that monocyte‐derived DC, which are devoid of mCD14 respond to CRX‐527 but not to LPS in serum‐free medium. Furthermore, we found that, in contrast to LPS, CRX‐527 induces the production of cytokines in whole blood of a patient with paroxysmal nocturnal hemoglobinuria, a disease in which mCD14‐dependent responses are defective. Finally, we demonstrated that splenocytes from CD14‐deficient mice produce cytokines in response to CRX‐527 but not to LPS. We conclude that the lipid A mimetic CRX‐527 does not require the CD14 co‐receptor to elicit TLR4‐mediated responses.
Mast cells in innate and adaptive immunity to infection
Authors: Palker Thomas J. , Dong Gang , Leitner Wolfgang W.
Published: December 2009

In June 2009, the National Institute of Allergy and Infectious Diseases (NIAID), Division of Allergy, Immunology and Transplantation (DAIT), sponsored a workshop entitled Mast Cells in Innate and Adaptive Immunity. International experts in mast cell biology discussed recent advances in the field and future areas of research aimed at advancing our understanding of the importance of mast cells in shaping nonallergic, adaptive immunity to infection.
Cover Picture: Eur. J. Immunol. 1/10
Authors: Nakhaei‐Nejad Maryam , Zhang Qiu‐Xia , Murray Allan G.
Published: December 2009

This issue's cover image shows immunofluorescent staining of endothelial cells for microtubules (red) and vascular endothelial cadherin (green). The image was taken from the article Endothelial IQGAP1 regulates efficient lymphocyte transendothelial migration by Nakhaei‐Nejad et al. (pp. 204–213), in which the authors examine the role of IQGAP1, an adaptor protein that binds to filamentous‐actin and microtubules at interendothelial junctions, during lymphocyte transendothelial migration.
Use of CE for the determination of binding constants
Authors: Jiang Chunxia , Armstrong Daniel W.
Published: December 2009

In the past two decades, CE has been used frequently for the measurement of apparent binding/association constants. CE has numerous advantages, including short analysis times, low sample consumption, simplicity of operation, etc. This review provides a fundamental introduction to binding theory and then summarizes recent applications and advances in the field of CE‐based methods for the evaluation of molecular association. The time period for this survey is from 2002 (when our previous review was published) to the present.
CEC of phytochemical bioactive compounds
Authors: Yang Feng‐qing , Zhao Jing , Li Shao‐ping
Published: December 2009

Although there are many publications related to technological or methodological developments of CEC, few focus on the analysis of natural products, especially phytochemical bioactive compounds. This review summarized the application of CEC in the analysis of phytochemical bioactive components, including flavonoids, nucleosides, steroids, lignans, quinones and coumarins, as well as fingerprint analysis of herbs. The strategies for optimization of CEC conditions and detection were also discussed.
Soil erosion resistance effects on rill and gully initiation points and dimensions
Authors: Knapen A. , Poesen J.
Published: December 2009

Recent research has indicated the large spatial and temporal variation in soil erosion resistance against concentrated flow (SER). This study analyzes this variability in relation to rill and gully initiation locations on slopes and the downslope eroded volumes. The soil erodibility (Kc) and critical flow shear stress (τcr), were estimated from topsoil properties and correlated to eroded rill and gully volumes and their initiation points on slopes in the Belgian loess belt. Therefore, concentrated flow paths and topsoil properties were measured in their vicinity. The results show that rill and gully initiation points, and hence the lengths of concentrated flow paths, depend on τcr, which is controlled by soil surface conditions and can be predicted from saturated soil shear strength. Soil erosion control measures that increase soil shear strength (e.g. thalweg compaction), can therefore decrease rill and gully lengths. Once a rill or an ephemeral gully is initiated, its cross‐section was found to depend on Kc, which can be estimated from the soil water content, dry bulk density, and the dry density of roots and crop residues incorporated in the topsoil. 74% of the variation in the channel cross‐sectional area measured in the study area could be predicted from the combined effect of flow intensity and these three soil properties, whereas flow intensity alone could only account for 31% of the variation. Soil conservation measures affecting one of the soil properties that control Kc (e.g. double drilling of the thalweg, conservation tillage) can therefore decrease the cross‐sections of the concentrated flow paths. These findings also indicate that rill and gully initiation points are not only topographically controlled but also depend on the SER, which in turn determines the dimensions of these concentrated flow paths. Hence, knowledge of the variability in SER is indispensable. Copyright © 2009 John Wiley & Sons, Ltd.
Survey data as coincident or leading indicators
Authors: Frale Cecilia , Marcellino Massimiliano , Mazzi Gian Luigi , Proietti Tommaso
Published: December 2009

In this paper we propose a monthly measure for the euro area gross domestic product (GDP) based on a small‐scale factor model for mixed‐frequency data, featuring two factors: the first is driven by hard data, whereas the second captures the contribution of survey variables as coincident indicators. Within this framework we evaluate both the in‐sample contribution of the second survey‐based factor, and the short‐term forecasting performance of the model in a pseudo‐real‐time experiment. We find that the survey‐based factor plays a significant role for two components of GDP: industrial value added and exports. Moreover, the two‐factor model outperforms in terms of out‐of‐sample forecasting accuracy the traditional autoregressive distributed lags (ADL) specifications and the single‐factor model, with few exceptions. Copyright © 2009 John Wiley & Sons, Ltd.
The local quadratic trend model
Authors: Harvey Andrew
Published: December 2009

The local quadratic trend model provides a flexible response to underlying movements in a macroeconomic time series in its estimates of level and change. If the underlying movements are thought of as a trend plus cycle, an estimate of the cycle may be obtained from the quadratic term. Estimating the cycle in this way may offer a useful alternative to other model‐based methods of signal extraction, particularly when the series is short. The properties of the filter used to extract the cycle are analysed in the frequency domain and the technique is illustrated with macroeconomic time series from several countries. Copyright © 2009 John Wiley & Sons, Ltd.
Business cycles in the euro area defined with coincident economic indicators and predicted with leading economic indicators
Authors: Ozyildirim Ataman , Schaitkin Brian , Zarnowitz Victor
Published: December 2009

Clusters of cyclical turning points in the coincident indicators help us identify and date euro area recessions and recoveries in the past several decades. In the USA and some other countries, composite indexes of coincident indicators (CEI) are used to date classical business cycle turning points; also indexes of leading indicators (LEI) are used to help in the difficult task of predicting these turning points. This paper reviews a selection of the available data for monthly and quarterly euro area coincident and leading indicators. From these data, we develop composite indexes using methods analogous to those tested in the US CEI and LEI published by The Conference Board. We compare the resulting business cycle chronology with the existing alternatives and evaluate our selection of leading indicators in the context of how well they predict current economic activity and its major fluctuations for the euro area. Copyright © 2009 John Wiley & Sons, Ltd.
GDP nowcasting with ragged‐edge data: a semi‐parametric modeling
Authors: Ferrara Laurent , Guégan Dominique , Rakotomarolahy Patrick
Published: December 2009

This paper formalizes the process of forecasting unbalanced monthly datasets in order to obtain robust nowcasts and forecasts of quarterly gross domestic product (GDP) growth rate through a semi‐parametric modeling. This innovative approach lies in the use of non‐parametric methods, based on nearest neighbors and on radial basis function approaches, to forecast the monthly variables involved in the parametric modeling of GDP using bridge equations. A real‐time experience is carried out on euro area vintage data in order to anticipate, with an advance ranging from 6 to 1 months, the GDP flash estimate for the whole zone. Copyright © 2009 John Wiley & Sons, Ltd.
Dynamic probit models and financial variables in recession forecasting
Authors: Nyberg Henri
Published: December 2009

In this paper, various financial variables are examined as predictors of the probability of a recession in the USA and Germany. We propose a new dynamic probit model that outperforms the standard static model, giving accurate out‐of‐sample forecasts in both countries for the recession period that began in 2001, as well as the beginning of the recession in 2008. In accordance with previous findings, the domestic term spread proves to be an important predictive variable, but stock market returns and the foreign term spread also have predictive power in both countries. In the case of Germany, the interest rate differential between the USA and Germany is also a useful additional predictor. Copyright © 2009 John Wiley & Sons, Ltd.
Matrix metalloproteinase‐9 reversibly affects the time course of NMDA‐induced currents in cultured rat hippocampal neurons
Authors: Gorkiewicz Tomasz , Szczuraszek Katarzyna , Wyrembek Paulina , Michaluk Piotr , Kaczmarek Leszek , Mozrzymas Jerzy W.
Published: December 2009

Matrix Metalloproteinase 9 (MMP‐9) has been demonstrated to play a crucial role in maintenance of NMDA receptor‐dependent LTP and in lateral mobility of these receptors. However, the effect of MMP‐9 on NMDA receptor (NMDAR) functional properties is unknown. For this purpose we have investigated the impact of recombinant MMP‐9 on the whole‐cell NMDAR‐mediated current responses in cultured hippocampal neurons. Treatment with MMP‐9 induced a reversible acceleration of desensitization and deactivation kinetics but had no effect on current amplitude. Interestingly, phorbol ester, a PKC activator known to enhance NMDAR lateral mobility, induced kinetic changes of currents similar to those produced by MMP‐9. In conclusion, our results show that MMP‐9 reversibly modulates the NMDAR kinetics and raise a possibility that this modulation could be related to the lateral mobility of these receptors. © 2009 Wiley‐Liss, Inc.
Acute stress disrupts paired pulse facilitation and long‐term potentiation in rat dorsal hippocampus through activation of glucocorticoid receptors
Authors: Cazakoff Brittany N. , Howland John G.
Published: December 2009

Cognitive functions such as learning and memory are widely believed to depend on patterns of short‐ and long‐term synaptic plasticity. Factors, such as acute stress, which affect learning and memory, may do so by altering patterns of synaptic plasticity in distinct neural circuits. Numerous studies have examined the effects of acute stress on long‐term synaptic plasticity; however, few have examined its influence on short‐term plasticity. The present experiments directly assessed the effects of acute stress on short‐term synaptic plasticity as measured by paired pulse facilitation (PPF) of excitatory postsynaptic potentials recorded from rat dorsal hippocampus (dHip) in vivo. Long‐term potentiation (LTP) was also examined. Acute stress induced by exposure to an elevated platform impaired PPF and LTP in the dHip. Pretreatment of rats exposed to stress with mifepristone (RU38486; 10 mg kg−1) blocked the stress‐induced impairment of both PPF and LTP. These data demonstrate that activation of glucocorticoid receptors during acute stress disrupts normal patterns of both PPF and LTP in the dHip. © 2009 Wiley‐Liss, Inc.
Tuning afferent synapses of hippocampal interneurons by neuropeptide Y
Authors: Ledri Marco , Sørensen Andreas Toft , Erdelyi Ferenc , Szabo Gabor , Kokaia Merab
Published: December 2009

Cholecystokinin (CCK)‐expressing basket cells encompass a subclass of inhibitory GABAergic interneurons that regulate memory‐forming oscillatory network activity of the hippocampal formation in accordance to the emotional and motivational state of the animal, conveyed onto these cells by respective extrahippocampal afferents. Various excitatory and inhibitory afferent and efferent synapses of the hippocampal CCK basket cells express serotoninergic, cholinergic, cannabinoid, and benzodiazepine sensitive receptors, all contributing to their functional plasticity. We explored whether CCK basket cells are modulated by neuropeptide Y (NPY), one of the major local neuropeptides that strongly inhibits hippocampal excitability and has significant effect on its memory function. Here, using GAD65‐GFP transgenic mice for prospective identification of CCK basket cells and whole‐cell patch‐clamp recordings, we show for the first time that excitatory and inhibitory inputs onto CCK basket cells in the dentate gyrus of the hippocampus are modulated by NPY through activation of NPY Y2 receptors. The frequency of spontaneous and miniature EPSCs, as well as the amplitudes of stimulation‐evoked EPSCs were decreased. Similarly, the frequency of both spontaneous and miniature IPSCs, and the amplitudes of stimulation‐evoked IPSCs were decreased after NPY application. Most of the effects of NPY could be attributed to a presynaptic site of action. Our data provide the first evidence that the excitatory and inhibitory inputs onto the CCK basket cells could be modulated by local levels of NPY, and may change the way these cells process extrahippocampal afferent information, influencing hippocampal function and its network excitability during normal and pathological oscillatory activities. © 2009 Wiley‐Liss, Inc.
Differential regulation of synaptic plasticity of the hippocampal and the hypothalamic inputs to the anterior thalamus
Authors: Tsanov Marian , Vann Seralynne D. , Erichsen Jonathan T. , Wright Nick , Aggleton John P. , O'Mara Shane M.
Published: December 2009

The hippocampus projects to the anterior thalamic nuclei both directly and indirectly via the mammillary bodies, but little is known about the electrophysiological properties of these convergent pathways. Here we demonstrate, for the first time, the presence of long‐term plasticity in anterior thalamic nuclei synapses in response to high‐ and low‐frequency stimulation (LFS) in urethane‐anesthetized rats. We compared the synaptic changes evoked via the direct vs. the indirect hippocampal pathways to the anterior thalamus, and found that long‐term potentiation (LTP) of the thalamic field response is induced predominantly through the direct hippocampal projections. Furthermore, we have estimated that that long‐term depression (LTD) can be induced only after stimulation of the indirect connections carried by the mammillothalamic tract. Interestingly, basal synaptic transmission mediated by the mammillothalamic tract undergoes use‐dependent, BDNF‐mediated potentiation, revealing a distinct form of plasticity specific to the diencephalic region. Our data indicate that the thalamus does not passively relay incoming information, but rather acts as a synaptic network, where the ability to integrate hippocampal and mammillary body inputs is dynamically modified as a result of previous activity in the circuit. The complementary properties of these two parallel pathways upon anterior thalamic activity reveal that they do not have duplicate functions. © 2009 Wiley‐Liss, Inc.
IGF1, IGFBP1, and IGFBP3 genes and mammographic density: The Multiethnic Cohort
Authors: Verheus Martijn , Maskarinec Gertraud , Woolcott Christy G. , Haiman Christopher A. , Le Marchand Loïc , Henderson Brian E. , Cheng Iona , Kolonel Laurence N.
Published: December 2009

Insulin‐like growth factor‐I (IGF‐I) has mitogenic properties and stimulates cell growth. In this analysis, we investigated the relation between common genetic variation in IGF1, IGFBP1, and IGFBP3, and mammographic density among 819 women of Hawaiian, European, and Japanese ancestry from the Multiethnic Cohort Study. Mammographic density was assessed using a quantitative computer‐assisted method. Previously identified tag single nucleotide polymorphisms (SNPs) for IGF1 (26 tag SNPs) and IGFBP1/IGFBP3 (22 tag SNPs) were genotyped among the 819 women. Mixed models were conducted to evaluate the associations between genetic variation and mammographic density. Two SNPs were borderline statistical significantly associated with mammographic density: rs35539615 on IGFBP1 (p = 0.05) and rs2453839 on IGFBP3 (p = 0.01). Rs35767on IGF1 (p = 0.03) was also associated with mammographic density, although in opposite direction of what was expected from previous findings with IGF‐I levels. The majority of SNPs were, however, not associated with mammographic density. Analyses stratified by ethnicity showed similar results as the overall analyses for IGF1 and IGFBP1. However, for 4 SNPs in the IGFBP3 gene, the minor allele was associated with lower mammographic density in Japanese Americans and higher mammographic density in Caucasians. Given the large number of SNPs tested and the few borderline significant results, we only found weak evidence that genetic variations in IGFBP1 or IGFBP3 may be related to mammographic density. Ethnicity may modify these relations.
Functional screening identifies a microRNA, miR‐491 that induces apoptosis by targeting Bcl‐XL in colorectal cancer cells
Authors: Nakano Haruo , Miyazawa Tatsuya , Kinoshita Keita , Yamada Yoji , Yoshida Tetsuo
Published: December 2009

MicroRNAs (miRNAs) are a class of small noncoding RNAs that negatively regulate expression of target mRNA. They are involved in many biological processes, including cell proliferation, apoptosis and differentiation, and considered as new therapeutic targets for cancers. In our study, we performed a gain‐of‐function screen using 319 miRNAs to identify those affecting cell proliferation and death in human colorectal cancer cells (DLD‐1). We discovered a number of miRNAs that increased or decreased cell viability in DLD‐1. They included known oncogenic miRNAs such as miR‐372 and miR‐373, and tumor suppressive miRNAs such as miR‐124a, but also some for which this information was novel. Among them, miR‐491 markedly decreased cell viability by inducing apoptosis. We demonstrated that Bcl‐XL was a direct target of miR‐491, and its silencing contributed to miR‐491‐induced apoptosis. Moreover, treatment of miR‐491 suppressed in vivo tumor growth of DLD‐1 in nude mice. Our study provides a new regulation of Bcl‐XL by miR‐491 in colorectal cancer cells, and suggests a therapeutic potential of miRNAs for treating colorectal cancer by targeting Bcl‐XL.
Fluorescent imaging of high‐grade bladder cancer using a specific antagonist for chemokine receptor CXCR4
Authors: Nishizawa Koji , Nishiyama Hiroyuki , Oishi Shinya , Tanahara Noriko , Kotani Hirokazu , Mikami Yoshiki , Toda Yoshinobu , Evans Barry J. , Peiper Stephen C. , Saito Ryoichi , Watanabe Jun , Fujii Nobutaka , Ogawa Osamu
Published: December 2009

We previously reported that the expression of CXC chemokine receptor‐4 (CXCR4) was upregulated in invasive bladder cancers and that the small peptide T140 was a highly sensitive antagonist for CXCR4. In this study, we identified that CXCR4 expression was induced in high‐grade superficial bladder tumors, including carcinoma in situ and invasive bladder tumors. To visualize the bladder cancer cells using urinary sediments from the patients and chemically induced mouse bladder cancer model, a novel fluorescent CXCR4 antagonist TY14003 was developed, that is a T140 derivative. TY14003 could label bladder cancer cell lines expressing CXCR4, whereas negative‐control fluorescent peptides did not label them. When labeling urinary sediments from patients with invasive bladder cancer, positive‐stained cells were identified in all patients with bladder cancer and positive urine cytology but not in controls. Although white blood cells in urine were also labeled with TY14003, they could be easily discriminated from urothelial cells by their shape and size. Finally, intravesical instillation of TY14003 into mouse bladder, using N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine (BBN)‐induced bladder cancer model, demonstrated that fluorescent signals were detected in the focal areas of bladder of all mice examined at 12 weeks of BBN drinking by confocal microscopy and fluorescent endoscopy. On the contrary, all the normal bladders were found to be negative for TY14003 staining. In conclusion, these results indicate that TY14003 is a promising diagnostic tool to visualize small or flat high‐grade superficial bladder cancer.
Differentiation of mouse embryonic stem cells into hepatocytes induced by a combination of cytokines and sodium butyrate
Authors: Zhou Mingming , Li Ping , Tan Li , Qu Su , Ying Qi‐Long , Song Houyan
Published: December 2009

There is increasing evidence to suggest that embryonic stem cells (ESCs) are capable of differentiating into hepatocytes in vitro. In this study, we used a combination of cytokines and sodium butyrate in a novel three‐step procedure to efficiently direct the differentiation of mouse ESCs into hepatocytes. Mouse ESCs were first differentiated into definitive endoderm cells by 3 days of treatment with Activin A. The definitive endoderm cells were then differentiated into hepatocytes by the addition of acidic fibroblast growth factor (aFGF) and sodium butyrate to the culture medium for 5 days. After 10 days of further in vitro maturation, the morphological and phenotypic markers of hepatocytes were characterized using immunohistochemistry, immunoblotting, and reverse transcription‐polymerase chain reaction (RT‐PCR). Furthermore, the cells were tested for functions associated with mature hepatocytes, including glycogen storage and indocyanine green uptake and release, and the ratio of hepatic differentiation was determined by counting the percentage of albumin‐positive cells. In the presence of medium containing cytokines and sodium butyrate, numerous epithelial cells resembling hepatocytes were observed, and ∼74% of the cells expressed the hepatic marker, albumin, after 18 days in culture. RT‐PCR analysis and immunohistochemistry showed that these cells expressed adult liver cell markers, and had the abilities of glycogen storage and indocyanine green uptake and release. We have developed an efficient method for directing the differentiation of mouse ESCs into cells that exhibit the characteristics of mature hepatocytes. This technique will be useful for research into the molecular mechanisms underlying liver development, and could provide a source of hepatocytes for transplantation therapy and drug screening. J. Cell. Biochem. 109: 606–614, 2010. © 2009 Wiley‐Liss, Inc.
Bone morphogenic protein 2 directly enhances differentiation of murine osteoclast precursors
Authors: Jensen Eric D. , Pham Lan , Billington Charles J. , Espe Kelly , Carlson Ann E. , Westendorf Jennifer J. , Petryk Anna , Gopalakrishnan Rajaram , Mansky Kim
Published: December 2009

Previous studies found that bone morphogenic proteins (BMPs) support osteoclast formation, but it is not clear whether this is a direct effect on osteoclasts or mediated indirectly through osteoblasts. We have shown that a mouse deficient for the BMP antagonist Twisted gastrulation suggested a direct positive role for BMPs on osteoclastogenesis. In this report, we further determine the significance of BMP signaling on osteoclast formation in vitro. We find that BMP2 synergizes with suboptimal levels of receptor activator of NF‐κB ligand (RANKL) to enhance in vitro differentiation of osteoclast‐like cells. The enhancement by BMP2 is not a result of changes in the rate of proliferation or survival of the bone marrow‐derived cultures, but is accompanied by an increase in expression of genes involved in osteoclast differentiation and fusion. Treatment with BMP2 did not significantly alter expression of RANKL or OPG in our osteoclast cultures, suggesting that the enhancement of osteoclastogenesis is not mediated indirectly through osteoblasts or stromal cells. Consistent with this, we detected phosphorylated SMAD1,5,8 (p‐SMAD) in the nuclei of mononuclear and multinucleated cells in osteoclast cultures. Levels of p‐SMAD, BMP2, and BMP receptors increased during differentiation. RNAi suppression of Type II BMP receptor inhibited RANKL‐stimulated formation of multinuclear TRAP‐positive cells. The BMP antagonist noggin inhibited RANKL‐mediated osteoclast differentiation when added prior to day 3, while addition of noggin on day 3 or later failed to inhibit their differentiation. Taken together, these data indicate that osteoclasts express BMP2 and BMP receptors, and that autocrine BMP signaling directly promotes the differentiation of osteoclasts‐like cells. J. Cell. Biochem. 109: 672–682, 2010. © 2009 Wiley‐Liss, Inc.
T‐cadherin modulates endothelial barrier function
Authors: Andreeva Alexandra V. , Han Jingyan , Kutuzov Mikhail A. , Profirovic Jasmina , Tkachuk Vsevolod A. , Voyno‐Yasenetskaya Tatyana A.
Published: December 2009

T‐cadherin is an atypical member of the cadherin family, which lacks the transmembrane and intracellular domains and is attached to the plasma membrane via a glycosylphosphatidylinositol anchor. Unlike canonical cadherins, it is believed to function primarily as a signaling molecule. T‐cadherin is highly expressed in endothelium. Using transendothelial electrical resistance measurements and siRNA‐mediated depletion of T‐cadherin in human umbilical vein endothelial cells, we examined its involvement in regulation of endothelial barrier. We found that in resting confluent monolayers adjusted either to 1% or 10% serum, T‐cadherin depletion modestly, but consistently reduced transendothelial resistance. This was accompanied by increased phosphorylation of Akt and LIM kinase, reduced phosphorylation of p38 MAP kinase, but no difference in tubulin acetylation and in phosphorylation of an actin filament severing protein cofilin and myosin light chain kinase. Serum stimulation elicited a biphasic increase in resistance with peaks at 0.5 and 4–5 h, which was suppressed by a PI3 kinase/Akt inhibitor wortmannin and a p38 inhibitor SB 239063. T‐cadherin depletion increased transendothelial resistance between the two peaks and reduced the amplitude of the second peak. T‐cadherin depletion abrogated serum‐induced Akt phosphorylation at Thr308 and reduced phosphorylation at Ser473, reduced phosphorylation of cofilin, and accelerated tubulin deacetylation. Adiponectin slightly improved transendothelial resistance irrespectively of T‐cadherin depletion. T‐cadherin depletion also resulted in a reduced sensitivity and delayed responses to thrombin. These data implicate T‐cadherin in regulation of endothelial barrier function, and suggest a complex signaling network that links T‐cadherin and regulation of barrier function. J. Cell. Physiol. 223: 94–102, 2010. © 2009 Wiley‐Liss, Inc.
Heat shock but not cold shock leads to disturbed intracellular zinc homeostasis
Authors: Pirev Elvis , Ince Yasemin , Sies Helmut , Kröncke Klaus D.
Published: December 2009

The heat shock response is a highly conserved process essential for surviving environmental stress, including extremes of temperature. To investigate whether heat shock has an impact on intracellular Zn2+ homeostasis, cells were subjected to heat shock, and subsequently the intracellular free zinc concentration was investigated. Sublethal heat shock induced a temperature‐dependent and transient intracellular Zn2+ release that was repeatable after 24 h. The free zinc was localized in round‐shaped nuclear bodies identified as nucleoli. Metallothionein, the main cellular zinc storing protein, was found to be not functionally essential for this heat‐shock‐induced effect. No significant oxidative stress within the cells was detected after heat shock. Cold shock and subsequent rewarming did not result in disturbed intracellular zinc homeostasis. These results show that heat shock and cold shock differ with respect to intracellular Zn2+ release. A role for zinc as signaling ion during fever is conceivable. J. Cell. Physiol. 223: 103–109, 2010. © 2009 Wiley‐Liss, Inc.
Surgical management for a malignant bowel obstruction with recurrent gastrointestinal carcinoma
Authors: Amikura Katsumi , Sakamoto Hirohiko , Yatsuoka Toshimasa , Kawashima Yoshiyuki , Nishimura Yoji , Tanaka Yoichi
Published: December 2009

Background

A malignant bowel obstruction (MBO) is a common clinical complication in patients with recurrent gastrointestinal carcinoma, which has a poor prognosis and a limited life expectancy. This study considered the effectiveness of surgical management for MBO.

Methods

This study reviewed the clinical course of 70 patients who underwent surgery for MBO and compared the outcomes in three groups: patients with (A) peritonitis carcinomatosis without manifest ascites, (B) peritonitis carcinomatosis with ascites, (C) local recurrence without peritonitis carcinomatosis.

Results

The 1‐year survival rate and median survival time (MST) in the patients in group A were 33.3% and 228 days, which was statistically longer than those (6.7% and 46 days) in the patients in group B (P = 0.026). The rate of the patients with possible oral intake of solid meals for 6 months and median oral intake periods were 45.4% and 161 days in patients in group A and 28.0% and 93 days in patients in group C. In contrast, 66.7% in group B could not take solid meals for more than 1 month, and five patients could not take solid meals at all.

Conclusion

Palliative operations for the patients with manifest ascites of MBO are risky and rarely effectively improve oral intake, but this is not considered to be a contraindication for surgical management. Informed consent is therefore important in the surgical management of MBO. J. Surg. Oncol. 2010; 101: 228–232. © 2009 Wiley‐Liss, Inc.
Growth hormone and gene expression of in vitro‐matured rhesus macaque oocytes
Authors: Nyholt de Prada Jenna K. , Kellam Lori D. , Patel Bela G. , Latham Keith E. , VandeVoort Catherine A.
Published: December 2009

Growth hormone (GH) in rhesus macaque in vitro oocyte maturation (IVM) has been shown to increase cumulus expansion and development of embryos to the 9–16 cell stage in response to 100 ng/ml recombinant human GH (r‐hGH) supplementation during IVM. Although developmental endpoints for metaphase II (MII) oocytes and embryos are limited in the macaque, gene expression analysis can provide a mechanism to explore GH action on IVM. In addition, gene expression analysis may allow molecular events associated with improved cytoplasmic maturation to be detected. In this study, gene expression of specific mRNAs in MII oocytes and cumulus cells that have or have not been exposed to r‐hGH during IVM was compared. In addition, mRNA expression was compared between in vitro and in vivo‐matured metaphase II (MII) oocytes and germinal vesicle (GV)‐stage oocytes. Only 2 of 17 genes, insulin‐like growth factor 2 (IGF2) and steroidogenic acute regulator (STAR), showed increased mRNA expression in MII oocytes from the 100 ng/ml r‐hGH treatment group compared with other IVM treatment groups, implicating insulin‐like growth factor (IGF) and steroidogenesis pathways in the oocyte response to GH. The importance of IGF2 is notable, as expression of IGF1 was not detected in macaque GV‐stage or MII oocytes or cumulus cells. Mol. Reprod. Dev. 77: 353–362, 2010. © 2009 Wiley‐Liss, Inc.
A posteriori error analysis for the Morley plate element with general boundary conditions
Authors: Beirão da Veiga L. , Niiranen J. , Stenberg R.
Published: December 2009

This paper introduces and analyses a local, residual‐based a posteriori error indicator for the Morley finite element method of the biharmonic Kirchhoff plate bending problem. In the theoretical part of the paper, a recent approach presented by the authors for clamped boundaries is extended to general boundary conditions. The error indicator is proven to be both reliable and efficient. The numerical part of the paper presents a set of results on various benchmark computations with different kinds of domains and boundary conditions. These tests verify the reliability and efficiency of the error estimator and illustrate the robustness of the method for adaptive mesh refinements. Copyright © 2009 John Wiley & Sons, Ltd.
Short‐term in‐home intervention reduces depressive symptoms in Early Head Start Latina mothers of infants and toddlers
Authors: Beeber Linda S. , Holditch‐Davis Diane , Perreira Krista , A. Schwartz Todd , Lewis Virginia , Blanchard Hjordis , Canuso Regina , Goldman Barbara Davis
Published: December 2009

Depressive symptoms may compromise the ability of low‐income Latina mothers with limited English language proficiency to parent their infants or toddlers. Eighty Early Head Start Latina mothers with limited English language proficiency were randomized to an advanced practice nurse‐delivered, culturally tailored, in‐home psychotherapy intervention, or to usual care. Repeated measures regression analysis showed a significantly greater decrease in depressive symptoms for intervention mothers compared to the usual care group at 22 and 26 weeks (4 weeks post intervention). Intervention mothers' reports of their child's aggression diminished significantly from T1 to T4 compared to usual care mothers (p = .03). Self‐efficacy appeared to only partially mediate the intervention effect, and maternal health moderated the intervention impact. Results indicate that the intervention reduced depressive symptoms and, compared to previous studies in this population, retention of mothers in both intervention and control conditions was improved. © 2009 Wiley Periodicals, Inc. Res Nurs Health 33:60–76, 2010
Proton conducting grafted/crosslinked membranes prepared from poly(vinylidene fluoride‐co‐chlorotrifluoroethylene) copolymer
Authors: Seo Jin Ah , Kim Yong Woo , Roh Dong Kyu , Shul Yong Gun , Kim Jong Hak
Published: December 2009

Poly(vinylidene fluoride‐co‐chlorotrifluoroethylene) (P(VDF‐co‐CTFE)) backbone was grafted with crosslinkable chains of poly(hydroxyl ethyl acrylate) (PHEA) and proton conducting chains of poly(styrene sulfonic acid) (PSSA) to produce amphiphilic P(VDF‐co‐CTFE)‐g‐P(HEA‐co‐SSA) graft copolymer via atom transfer radical polymerization (ATRP). Successful synthesis and microphase‐separated structure of the copolymer were confirmed by 1H NMR, FT‐IR spectroscopy, and TEM analysis. Furthermore, this graft copolymer was thermally crosslinked with sulfosuccinic acid (SA) to produce grafted/crosslinked membranes. Ion exchange capacity (IEC) increased continuously with increasing SA contents but the water uptake increased up to 6 wt% of SA concentration, above which it decreased monotonically. The membrane also exhibited a maximum proton conductivity of 0.062 S/cm at 6 wt% of SA concentration, resulting from competitive effect between the increase of ionic groups and the degree of crosslinking. XRD patterns also revealed that the crystalline structures of P(VDF‐co‐CTFE) disrupted upon graft polymerization and crosslinking. These membranes exhibited good thermal stability at least up to 250°C, as revealed by TGA. Copyright © 2009 John Wiley & Sons, Ltd.
Morphology of blends containing high concentrations of POSS nanoparticles in different polymer matrices
Authors: Li Shuyan , Simon George P. , Matisons Janis G.
Published: December 2009

This article reports an investigation into the miscibility and morphology of octaisobutyl‐substituted polyhedral oligomeric silsesquioxane (ibPOSS) nanocages over a wide concentration range (25–75 wt%) in polymer matrices, produced by solution blending. Three different, strategically chosen polymers were used: polystyrene (PS), poly(isobutyl methacrylate) (PIBMA), and poly(methyl methacrylate) (PMMA), to allow the effect of matrix structure and polarity on miscibility to be investigated. Differential scanning calorimetry, dynamic mechanical analysis, X‐ray diffraction, and scanning electron microscopy were used to characterize the composite systems. The Tg of PMMA and PIBMA were found to increase with introduction of ibPOSS, whereas PS did not show any significant change of Tg with increasing POSS content, indicating differing degrees of interaction. The phase separation has been found and a cubic POSS crystal structure has been observed in all blends with different size. The glass transition increased with concentration, even though all compositions were predominantly phase‐separated, and we suggest that this is due to the influence of the external face of the crystalline units on the polymer chains, and possibly some polymer contained within the crystalline POSS phase. POLYM. ENG. SCI., 2010. © 2009 Society of Plastics Engineers
‘And then one day they all moved to Leicester’: the relocation of Somalis from the Netherlands to the UK explained
Authors: van Liempt Ilse
Published: December 2009

Since 2000 it is estimated that between 10,000 and 20,000 Somali immigrants have left the Netherlands for the UK. This exceptionally high level of intra‐European Union (EU) mobility is in contrast with the general trend of very low levels of intra‐EU mobility. Based on 33 in‐depth interviews with Dutch Somalis in London and Leicester this paper tries to explain the relocation of Somalis from the Netherlands to the UK. The presence of a large Somali community in the UK, economic and educational opportunities in the UK, and differences in integration policies have influenced Dutch Somalis' decision to relocate. It is argued, however, that the wider context in which these movements take place should be taken into account as well. Immigrants may (initially) not always be in a position to move where they want to move. As such, Somalis' relocation from the Netherlands to the UK could also be seen as a follow‐up to an earlier movement that was interrupted along the way. Dutch Somalis' narratives about their onward move provide us with a comparison of the Netherlands and the UK as countries of settlement. At the same time, these stories also challenge the binary oppositions that have tended to inform how we think about migration in a static and often linear way. Copyright © 2009 John Wiley & Sons, Ltd.