bluuebunny/crossref_metadata_2025 huggingface dataset:
Vacuolar H+ ATPase expression and activity is required for Rab27B‐dependent invasive growth and metastasis of breast cancer
Authors: Hendrix An , Sormunen Raija , Westbroek Wendy , Lambein Kathleen , Denys Hannelore , Sys Gwen , Braems Geert , Van den Broecke Rudy , Cocquyt Veronique , Gespach Christian , Bracke Marc , De Wever Olivier
Published: February 2013

The secretory Rab27B small GTPase promotes invasive growth and metastasis in estrogen receptor (ER) α‐positive breast cancer cells by orchestrating the peripheral targeting of vesicles secreting proinvasive growth regulators. Increased Rab27B expression is associated with poor prognosis in breast cancer patients. The molecular mechanisms of peripheral Rab27B secretory vesicle distribution are poorly understood. Mass spectrometry analysis on green fluorescent protein (GFP)‐Rab27B vesicles prepared from GFP‐Rab27B transfected MCF‐7 human breast cancer cells detected eight subunits of the vacuolar H(+)‐ATPase (V‐ATPase) and the presence of V0a1 and V0d1 subunits was confirmed by Western blot analysis. Reversible inhibition of V‐ATPase activity by bafilomycin A1 or transient silencing of V0a1 or V0d1 subunits demonstrated that V‐ATPase controls peripheral localization and size of Rab27B vesicles. V‐ATPase expression and activity further controls Rab27B‐induced collagen type I invasion, cell‐cycle progression and invasive growth in the chorioallantoic membrane assay. In agreement, Rab27B‐dependent extracellular heat shock protein90α release and matrix metalloprotease‐2 activation is markedly reduced by bafilomycin A1 and transient silencing of V0a1 and V0d1 subunits. Poor prognosis ERα‐positive primary breast tumors expressing high levels of Rab27B also expressed multiple V‐ATPase subunits and showed a strong cytoplasmic and peripheral V‐ATPase V1E expression. In conclusion, inhibiting V‐ATPase activity by interfering agents and drugs might be an effective strategy for blocking Rab27B‐dependent proinvasive secretory vesicle trafficking in ERα‐positive breast cancer patients.
Neoadjuvant epirubicin, gemcitabine and docetaxel for primary breast cancer: Long‐term survival data and major prognostic factors based on two consecutive neoadjuvant phase I/II trials
Authors: Marmé Frederik , Aigner Julia , Lorenzo Bermejo Justo , Sinn Peter , Sohn Christof , Jäger Dirk , Schneeweiss Andreas
Published: February 2013

We previously reported primary endpoints of two consecutive phase I/II trials, evaluating different schedules of neoadjuvant epirubicin (E), gemcitabine (G) and docetaxel (Doc) for primary breast cancer (PBC). Here, we report mature survival data and prognostic factors. One hundred fifty‐one patients were recruited into two consecutive phase I/II trials of neoadjuvant chemotherapy for T2–4 N0–2 M0 PBC. Patients received six cycles of G/E/Doc every 3 weeks with G repeated on d8 (GEDoc, n = 84) or five cycles of G/E followed by four cycles of Doc all given every two weeks (GEsDoc, n = 67). Prognostic factors were investigated using univariate and multivariate analyses. No survival differences by treatment were found. Among reported predictive factors for pathologic complete response (pCR), oestrogen receptor (ER) status was the only relevant factor in the multivariate analysis. Unexpectedly, pCR resulted in poorer survival (univariate HR for overall survival [OS] 3.11, p = 0.007). Multivariate analyses identified molecular subtype and tumour size as the most relevant prognostic factors for OS. HER2‐receptor status and the CPS‐EG score (Mittendorf et al., J Clin Oncol 2011;29:1956–62), based on clinical and pathological stage, ER‐status and tumour grade, were particularly relevant in disease‐free survival. Our findings cast doubt on the reliability of pCR as single marker for prognosis of this unselected breast cancer cohort, with an abundance of luminal subtypes. These results underline the significance of additional molecular characteristics for breast cancer survival.
Expression of NTRK1/TrkA affects immunogenicity of neuroblastoma cells
Authors: Pajtler Kristian W. , Rebmann Vera , Lindemann Monika , Schulte Johannes H. , Schulte Stefanie , Stauder Michael , Leuschner Ivo , Schmid Kurt‐Werner , Köhl Ulrike , Schramm Alexander , Eggert Angelika
Published: February 2013

High levels of the NTRK1/TrkA receptor are expressed in low‐stage neuroblastomas, which are characterized by a good patient prognosis and often undergo spontaneous regression. In addition to apoptosis, tumor‐immune responses might contribute to this regression. We hypothesized that TrkA expression might enhance the immune response to neuroblastomas. Immunohistochemistry on neuroblastoma tissue microarrays confirmed significantly higher lymphocyte infiltration in low‐stage compared with high‐stage tumors. Flow cytometry of human SH‐SY5Y cells stably transfected with NTRK1/TrkA cDNA revealed significant upregulation of major histocompatibility complex (MHC) class I complexes on TrkA‐expressing cells. Corresponding to this upregulation, T cell activity and cytoxicity was enhanced in the presence of SY5Y‐TrkA cells or by medium conditioned by them, suggesting the existence of additional soluble factors stimulating the T cell response. Activation of natural killer (NK) cells was only increased in the presence of SY5Y‐TrkA conditioned medium (CM) and not in co‐culture assays, suggesting a dominant inhibitory effect of upregulated MHC class I as the primary NK cell escape mechanism of TrkA‐expressing neuroblastomas. We reanalyzed gene expression data obtained from the cell culture model to identify additional genes involved in the TrkA‐mediated modulation of immune responses. Upregulation of selected target genes in SY5Y‐TrkA cells was confirmed on transcript and protein levels. However, none of the proteins were detected in medium conditioned by SY5Y‐TrkA cells, arguing against these factors as soluble mediators of the TrkA‐induced immune response. We here provide evidence that TrkA expression in neuroblastoma leads to an increased immunogenicity that may contribute to a less malignant phenotype and/or spontaneous regression of neuroblastoma cells.
Genetic Loci That Control the Loss and Regain of Trabecular Bone During Unloading and Reambulation
Authors: Judex Stefan , Zhang Weidong , Donahue Leah Rae , Ozcivici Engin
Published: February 2013

Changes in trabecular morphology during unloading and reloading are marked by large variations between individuals, implying that there is a strong genetic influence on the magnitude of the response. Here, we subjected more than 350 second-generation (BALBxC3H) 4-month-old adult female mice to 3 weeks of hindlimb unloading followed by 3 weeks of reambulation to identify the quantitative trait loci (QTLs) that define an individual's propensity to either lose trabecular bone when weight bearing is removed or to gain trabecular bone when weight bearing is reintroduced. Longitudinal in vivo micro–computed tomography (µCT) scans demonstrated that individual mice lost between 15% and 71% in trabecular bone volume fraction (BV/TV) in the distal femur during unloading (average: −43%). Changes in trabecular BV/TV during the 3-week reambulation period ranged from a continuation of bone loss (−18%) to large additions (56%) of tissue (average: +10%). During unloading, six QTLs accounted for 21% of the total variability in changes in BV/TV whereas one QTL accounted for 6% of the variability in changes in BV/TV during reambulation. QTLs were also identified for changes in trabecular architecture. Most of the QTLs defining morphologic changes during unloading or reambulation did not overlap with those QTLs identified at baseline, suggesting that these QTLs harbor genes that are specific for sensing changes in the levels of weight bearing. The lack of overlap in QTLs between unloading and reambulation also emphasizes that the genes modulating the trabecular response to unloading are distinct from those regulating tissue recovery during reloading. The identified QTLs contain the regulatory genes underlying the strong genetic regulation of trabecular bone's sensitivity to weight bearing and may help to identify individuals that are most susceptible to unloading-induced bone loss and/or the least capable of recovering.
A universal fluid cell for the imaging of biological specimens in the atomic force microscope
Authors: Kasas Sandor , Radotic Ksenja , Longo Giovanni , Saha Bashkar , Alonso‐Sarduy Livan , Dietler Giovanni , Roduit Charles
Published: February 2013

Recently, atomic force microscope (AFM) manufacturers have begun producing instruments specifically designed to image biological specimens. In most instances, they are integrated with an inverted optical microscope, which permits concurrent optical and AFM imaging. An important component of the set‐up is the imaging chamber, whose design determines the nature of the experiments that can be conducted. Many different imaging chamber designs are available, usually designed to optimize a single parameter, such as the dimensions of the substrate or the volume of fluid that can be used throughout the experiment. In this report, we present a universal fluid cell, which simultaneously optimizes all of the parameters that are important for the imaging of biological specimens in the AFM. This novel imaging chamber has been successfully tested using mammalian, plant, and microbial cells. Microsc. Res. Tech. 76:357–363, 2013. © 2013 Wiley Periodicals, Inc.
Differential expression and regulation of PNA and UEA‐1 bindings in rabbit uterus during preimplantation period
Authors: Guo Bin , Duan Cui‐Cui , Wang Qu‐Yuan , Yue Zhan‐Peng
Published: February 2013

Peanut agglutinin (PNA) and Ulex europaeus agglutinin‐1 (UEA‐1) were used as probes to study the distribution of β‐gal (1→3) ga1Nac and α‐l‐Fucose in rabbit uterus during early pregnancy. PNA binding was mainly localized on the surface of uterine glandular and luminal epithelium. There were no positive signals on day 1 of pregnancy. PNA binding gradually increased from day 2 and reached its highest level on days 3 and 4. The distribution of PNA binding gradually declined from day 5 and reached a low level on day 7. However, UEA‐1 binding was only localized on the luminal epithelial during early pregnancy. A high level of UEA‐1 binding had been found on the luminal epithelium on day 1 of pregnancy and low level of positive signals had been found in the uterus on days 2 and 3. UEA‐1 binding increased gradually and reached its highest level on day 4. Then the distribution of UEA‐1 binding sharply declined and no positive signals were found on days 5–7. The distribution of PNA and UEA‐1 bindings in pseudopregnant uterus was similar to that in normal pregnant uterus. During estrus cycle, there was no detectable PNA binding signal in uterus. But, a high level of UEA‐1 binding was found in the luminal epithelium of estrus uterus. In ovariectomized rabbit uterus, progesterone significantly induced the expression of PNA binding, while estrogen stimulated UEA‐1 binding expression. These results suggested that the distribution of PNA and UEA‐1 bindings in rabbit uterus may be related to rabbit implantation. Microsc. Res. Tech. 76:398–403, 2013. © 2013 Wiley Periodicals, Inc.
Daily mean air temperature estimation from MODIS land surface temperature products based on M5 model tree
Authors: Emamifar Saeed , Rahimikhoob Ali , Noroozi Ali Akbar
Published: February 2013

The use of satellite data to estimate air temperature (Ta) near the Earth's surface has become an effective way for a large area with high spatial and temporal resolution. In this study, M5 model tree was used to estimate Ta in Khuzestan province (in the southwest of Iran) using satellite remotely sensed land surface temperature (Ts) data acquired by the MODerate Resolution Imaging Spectroradiometer (MODIS)‐Terra sensor. The input variables for the M5 model tree were the daytime and nighttime MODIS Ts, extraterrestrial solar radiation and Julian day. A total of 365 images of MOD11A1 Ts product for the year 2007, covering the area of this study were collected from the Land Processes Distributed Active Archive Center (LP DAAC). The results of this study showed that mean daily Ta can be estimated with acceptable levels of the statistical indicators from MODIS data and from the two geographic parameters using the M5 model. Root mean square error and R2 for the comparison between observed and estimated Ta for the tested data are 2.3 and 0.96 °C, respectively.
Influence of autochthonous adjunct cultures on ripening parameters of Argentinean goat's milk cheeses
Authors: Oliszewski Rubén , Wolf I Verónica , Bergamini Carina V , Candioti Mario , Perotti María C
Published: February 2013

Background

Argentinean semi‐hard goat's cheeses manufactured with and without the addition of autochthonous adjunct cultures of Lactobacillus plantarum ETC17, Lactobacillus rhamnosus ETC14 and Enterococcus faecium ETC3 were analysed to evaluate the effect of these strains on ripening parameters.

Results

Gross composition was similar among cheeses. Microbiological analysis indicated that lactic acid bacteria added to cheeses reached high levels. None of the strains assayed affected the primary proteolysis. Overall, E. faecium had a clearer effect on the peptide and lipolysis profiles of cheeses. Analysis of the volatile fraction of cheeses indicated that the levels of several compounds involved in the overall flavour of goat's cheeses were affected by the presence of E. faecium. This could explain the differences detected in the global perception of cheeses made with this strain compared with control cheeses.

Conclusion

The present work represents a first contribution to knowledge of the ripening process of Argentinean goat's cheeses made with the addition of autochthonous adjunct cultures. The results suggest that E. faecium ETC3 showed a significant effect during ripening, which was reflected both in the profiles of proteolysis, lipolysis and volatile compounds and in the global sensory perception of cheeses. © 2013 Society of Chemical Industry
Beneficial effects of Allium sativum L. stem extract on lipid metabolism and antioxidant status in obese mice fed a high‐fat diet
Authors: Kim Inhye , Kim Haeng‐Ran , Kim Jae‐Hyun , Om Ae‐Son
Published: February 2013

BACKGROUND

This study was designed to examine the potential health benefits of Allium sativum L. (garlic) stem extract (ASSE) on obesity and related disorders in high‐fat diet‐induced obese mice. Obese mice were orally administered ASSE at doses of 100, 250 and 500 mg kg−1 body weight day−1 for 4 weeks.

RESULTS

Consumption of ASSE significantly suppressed body weight gain and white adipose tissue (WAT) weight regardless of daily food intake. Obese mice fed ASSE also exhibited a significant decrease in WAT cell size. The decreased level of adiponectin and increased level of leptin in obese mice reverted to near normal mice levels in ASSE‐treated mice. ASSE administration significantly improved lipid parameters of the serum and liver and inhibited fat accumulation in the liver by modulating the activities of hepatic lipid‐regulating enzymes in obese mice. Administration of ASSE also led to significant increases in antioxidant enzymes and suppressed glutathione depletion and lipid peroxidation in hepatic tissue.

CONCLUSION

These results suggest that ASSE may ameliorate obesity, insulin resistance and oxidative damage in high‐fat diet‐induced obese mice. © 2013 Society of Chemical Industry
Stereocomplex Crystallization Behavior and Physical Properties of Linear 1‐Arm, 2‐Arm, and Branched 4‐Arm Poly(L‐lactide)/Poly(D‐lactide) Blends: Effects of Chain Directional Change and Branching
Authors: Sakamoto Yuzuru , Tsuji Hideto
Published: February 2013

For number‐average molecular weight (Mn) below 1 × 104 g mol−1, the comparison of cold crystallization temperature and spherulite growth rate and crystallinity of linear 1‐arm, 2‐arm, and branched 4‐arm poly(L‐lactide)/poly(D‐lactide) blends exhibits that the effects of chain directional change and branching significantly disturb stereocomplex crystallization. In contrast, the comparison of glass transition and melting temperatures of linear 1‐arm, 2‐arm, and branched 4‐arm poly(L‐lactide)/poly(D‐lactide) blends indicates that the effects of chain directional change and branching insignificantly alter and largely increase the segmental mobility of the blends, respectively, and the crystalline thickness of the blends is determined by Mn per one arm not by Mn and is not affected by the molecular architecture.

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Characterization of peripheral hematopoietic stem cells and monocytes in Parkinson's disease
Authors: Funk Natalja , Wieghofer Peter , Grimm Sabrina , Schaefer Richard , Bühring Hans‐Jörg , Gasser Thomas , Biskup Saskia
Published: February 2013

Background

Emerging evidence has highlighted the pivotal role of the immune system in neurodegenerative diseases. This study investigated the impact of progressive neurodegeneration on the differentiation and development of hematopoietic stem cells in the peripheral blood of Parkinson's patients. Methods: A colony‐forming cell assay was established to study hematopoietic stem cells from venous blood of Parkinson's patients, and flow cytometry was used to analyze the expression of chemokine receptors on monocytes.

Results

We demonstrate that there is strong upregulation in the percentage of monocyte precursors in the peripheral blood of Parkinson's patients and asymptomatic high‐risk individuals. We identify the receptor CCR2 as undergoing strong upregulation on the surface of classical monocytes in Parkinson's patients.

Conclusions

The association between blood cell development and progressive cell death in the brain of Parkinson's patients should be further investigated as a potential dynamic biomarker and indicator of disease progression. © 2013 Movement Disorder Society
Surgical treatment of myoclonus dystonia syndrome
Authors: Rughani Anand I. , Lozano Andres M.
Published: February 2013

Myoclonus dystonia (M‐D) syndrome is a heritable movement disorder characterized by myoclonic jerks and dystonia primarily of the upper extremities. M‐D remains poorly responsive to pharmacological treatment. Emerging reports suggest good response to DBS of the internal globus pallidus (GPi) and ventral intermediate nucleus (VIM) of the thalamus. This study aimed to appraise the value of these two DBS targets by evaluating reports available in the literature. A systematic search of published case reports and case series was performed on Medline and Embase. Responses to DBS were evaluated. Myoclonus was assessed with the Unified Myoclonus Rating Scale (UMRS) and dystonia by the Burke‐Fahn‐Marsden dystonia rating scale (BFMDRS). The primary outcome of interest was the relative improvements noted with GPi, compared to VIM stimulation. A total of 17 publications yielded 40 unique cases, with mean follow‐up of 27.2 months. All patients demonstrated improvements in myoclonus scores, with 93.5% showing at least a 50% improvement in UMRS. The mean improvement in myoclonus scores was 72.6%. In contrast, dystonia scores were improved in 87.9% of patients, with 72.7% reporting at least a 50% improvement in BFMDRS. The mean improvement in dystonia scores was 52.6%. Improvements in myoclonus scores were similar for both GPi (75.7%) and VIM (70.4%; P = 0.27). However, the improvements in dystonia scores were greater with GPi (60.2%), compared to VIM (33.3%; P = 0.03). Although both targets achieve similar improvements in myoclonus, GPi stimulation may be a preferred target because it may achieve greater improvements in dystonia, compared to VIM stimulation. © 2013 Movement Disorder Society
Structure‐Activity Relationship Analysis of the Thermal Stabilities of Nitroaromatic Compounds Following Different Decomposition Mechanisms
Authors: Li Jiazhong , Liu Huanxiang , Huo Xing , Gramatica Paola
Published: February 2013

The decomposition behavior of energetic materials is very important for the safety problems concerning their production, transportation, use and storage, because molecular decomposition is intimately connected to their explosive properties. Nitroaromatic compounds, particularly nitrobenzene derivatives, are often considered as prototypical energetic molecules, and some of them are commonly used as high explosives. Quantitative structure‐activity relationship (QSAR) represents a potential tool for predicting the thermal stability properties of energetic materials. But it is reported that constructing general reliable models to predict their stability and their potential explosive properties is a very difficult task. In this work, we make our efforts to investigate the relationship between the molecular structures and corresponding thermal stabilities of 77 nitrobenzene derivatives with various substituent functional groups (in ortho, meta and/or para positions). The proposed best MLR model, developed by the new software QSARINS, based on Genetic Algorithm for variable selection and with various validation tools, is robust, stable and predictive with R2 of 0.86, QLOO2 of 0.79 and CCC of 0.90. The results indicated that, though difficult, it is possible to build predictive, externally validated QSAR models to estimate the thermal stability of nitroaromatic compounds.
Novel retrospective, respiratory‐gating method enables 3D, high resolution, dynamic imaging of the upper airway during tidal breathing
Authors: Wagshul Mark E. , Sin Sanghun , Lipton Michael L. , Shifteh Keivan , Arens Raanan
Published: February 2013

Purpose

A retrospective, respiratory‐gated technique for measuring dynamic changes in the upper airway over the respiratory cycle was developed, with the ultimate goal of constructing anatomically and functionally accurate upper airway models in obstructive sleep apnea patients.

Methods

Three‐dimensional cine, retrospective respiratory‐gated, gradient echo imaging was performed in six adolescents being evaluated for polycystic ovary syndrome, a disorder with a high obstructive sleep apnea prevalence. A novel retrospective gating scheme, synchronized to flow from a nasal cannula, limited image acquisition to predefined physiological ranges. Images were evaluated with respect to contrast, airway signal leakage, and demonstration of dynamic airway area changes.

Results

Two patients were diagnosed with obstructive sleep apnea. Motion artifacts were absent in all image sets. Scan efficiency ranged from 48 to 88%. Soft tissue‐to‐airway contrast‐to‐noise ratio varied from 6.1 to 9.6. Airway signal leakage varied between 10 and 17% of soft tissue signal. Automated segmentation allowed calculation of airway area changes over the respiratory cycle. In one severe apnea patient, the technique allowed demonstration of asynchronous airway expansion and contraction above and below a severe constriction.

Conclusions

Retrospective, respiratory gated imaging of the upper airway has been demonstrated, utilizing a gating algorithm to ensure acquisition over specified ranges of respiratory rate and tidal volume. Magn Reson Med 70:1580–1590, 2013. © 2013 Wiley Periodicals, Inc.
Effects of image reconstruction on fiber orientation mapping from multichannel diffusion MRI: Reducing the noise floor using SENSE
Authors: Sotiropoulos S. N. , Moeller S. , Jbabdi S. , Xu J. , Andersson J. L. , Auerbach E. J. , Yacoub E. , Feinberg D. , Setsompop K. , Wald L. L. , Behrens T. E. J. , Ugurbil K. , Lenglet C.
Published: February 2013

Purpose

To examine the effects of the reconstruction algorithm of magnitude images from multichannel diffusion MRI on fiber orientation estimation.

Theory and Methods

It is well established that the method used to combine signals from different coil elements in multichannel MRI can have an impact on the properties of the reconstructed magnitude image. Using a root‐sum‐of‐squares approach results in a magnitude signal that follows an effective noncentral‐χ distribution. As a result, the noise floor, the minimum measurable in the absence of any true signal, is elevated. This is particularly relevant for diffusion‐weighted MRI, where the signal attenuation is of interest.

Results

In this study, we illustrate problems that such image reconstruction characteristics may cause in the estimation of fiber orientations, both for model‐based and model‐free approaches, when modern 32‐channel coils are used. We further propose an alternative image reconstruction method that is based on sensitivity encoding (SENSE) and preserves the Rician nature of the single‐channel, magnitude MR signal. We show that for the same k‐space data, root‐sum‐of‐squares can cause excessive overfitting and reduced precision in orientation estimation compared with the SENSE‐based approach.

Conclusion

These results highlight the importance of choosing the appropriate image reconstruction method for tractography studies that use multichannel receiver coils for diffusion MRI acquisition. Magn Reson Med 70:1682–1689, 2013. © 2013 Wiley Periodicals, Inc.
Principal component analysis enhances SNR for dynamic electron paramagnetic resonance oxygen imaging of cycling hypoxia in vivo
Authors: Redler Gage , Epel Boris , Halpern Howard J.
Published: February 2013

Purpose

Low oxygen concentration (hypoxia) in tumors strongly affects their malignant state and resistance to therapy. These effects may be more deleterious in regions undergoing cycling hypoxia. Electron paramagnetic resonance imaging (EPRI) has provided a noninvasive, quantitative imaging modality to investigate static pO2 in vivo. However, to image changing hypoxia, EPRI images with better temporal resolution may be required. The tradeoff between temporal resolution and signal‐to‐noise ratio (SNR) results in lower SNR for EPRI images with imaging time short enough to resolve cycling hypoxia.

Methods

Principal component analysis allows for accelerated image acquisition with acceptable SNR by filtering noise in projection data, from which pO2 images are reconstructed. Principal component analysis is used as a denoising technique by including only low‐order components to approximate the EPRI projection data.

Results

Simulated and experimental studies show that principal component analysis filtering increases SNR, particularly for small numbers of sub‐volumes with changing pO2, enabling an order of magnitude increase in temporal resolution with minimal deterioration in spatial resolution or image quality.

Conclusion

The SNR necessary for dynamic EPRI studies with temporal resolution required to investigate cycling hypoxia and its physiological implications is enabled by principal component analysis filtering. Magn Reson Med 71:440–450, 2014. © 2013 Wiley Periodicals, Inc.
TSC1 involvement in bladder cancer: diverse effects and therapeutic implications
Authors: Guo Yanan , Chekaluk Yvonne , Zhang Jianming , Du Jinyan , Gray Nathanael S , Wu Chin‐Lee , Kwiatkowski David J
Published: February 2013

TSC1 is often mutated in bladder cancer. However the importance of this event in disease pathogenesis and its implications for therapy are uncertain. We used genomic sequencing to examine the involvement of TSC1 in bladder cancer, and signalling pathway analysis and small‐molecule screening to identify targeted therapeutic strategies in TSC1 mutant bladder cancer cell lines. TSC1 loss of heterozygosity was seen in 54% of bladder cancers. Two (4.9%) of these 41 bladder cancers had TSC1 mutations by exon‐based sequencing. Analysis of 27 bladder cancer cell lines demonstrated inactivating TSC1 mutations in three: RT‐4, HCV29, 97–1. Interestingly, only RT‐4 showed classic feedback inhibition of AKT, and was highly sensitive to treatment with mTOR inhibitors rapamycin and Torin1. 97–1 cells showed constitutive EGFR activation, and were highly sensitive to combined treatment with the mTOR inhibitor Torin1 and EGFR inhibitors Lapatinib or Afatinib. A BRAF missense mutation G469V was found in HCV29 cells, and AKT activation was dependent on BRAF, but independent of ERK. A kinase inhibitor screen of HCV29 cells showed strong growth inhibition by the Hsp90 inhibitor NVP‐AUY922, and we then found synergistic inhibitory effects of NVP‐AUY922 combined with either Torin1 or rapamycin on cell survival for both HCV29 and 97–1 cells. In aggregate, these findings indicate that there are highly variable mutation profiles and signalling pathway activation in TSC1‐mutant bladder cancer. Furthermore, combined Hsp90/mTOR inhibition is a promising therapeutic approach for TSC1 mutant bladder cancer. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Essential role of stem cell factor–c‐Kit signalling pathway in bleomycin‐induced pulmonary fibrosis
Authors: Ding Lin , Dolgachev Vladilsav , Wu Zhuang , Liu Tianju , Nakashima Taku , Wu Zhe , Ullenbruch Matthew , Lukacs Nicholas W , Chen Zidi , Phan Sem H
Published: February 2013

Stem cell factor (SCF) and its receptor c‐Kit have been implicated in tissue remodelling and fibrosis. Alveolar fibroblasts from patients with diffuse interstitial fibrosis secrete more SCF. However, its precise role remains unclear. In this study the potential role of the SCF–c‐Kit axis in pulmonary fibrosis was examined. Fibrosis was induced by intratracheal instillation of bleomycin (BLM), which caused increased SCF levels in plasma, bronchoalveolar lavage fluid (BALF) and lung tissue, as well as increased expression by lung fibroblasts. These changes were accompanied by increased numbers of bone marrow‐derived c‐Kit+ cells in the lung, with corresponding depletion in bone marrow. Both recombinant SCF and lung extracts from BLM‐treated animals induced bone‐marrow cell migration, which was blocked by c‐Kit inhibitor. The migrated cells promoted myofibroblast differentiation when co‐cultured with fibroblasts, suggesting a paracrine pathogenic role. Interestingly, lung fibroblast cultures contained a subpopulation of cells that expressed functionally active c‐Kit, which were significantly greater and more responsive to SCF induction when isolated from fibrotic lungs, including those from patients with idiopathic pulmonary fibrosis (IPF). This c‐Kit+ subpopulation was αSMA‐negative and expressed lower levels of collagen I but significantly higher levels of TGFβ than c‐Kit‐negative cells. SCF deficiency achieved by intratracheal treatment with neutralizing anti‐SCF antibody or by use of KitlSl/KitlSl‐d mutant mice in vivo resulted in significant reduction in pulmonary fibrosis. Taken together, the SCF–c‐Kit pathway was activated in BLM‐injured lung and might play a direct role in pulmonary fibrosis by the recruitment of bone marrow progenitor cells capable of promoting lung myofibroblast differentiation. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Behavior of high density polyethylene and its nanocomposites under static and dynamic compression loadings
Authors: Hu Y. , Liu T. , Ding J.L. , Zhong W.H.
Published: February 2013

In this study, the deformation behavior of high density polyethylene (HDPE) and its nanocomposites under uniaxial static and dynamic compression loadings were experimentally investigated. The nanofillers used were carbon nanofibers (CNF) with surface treatments and pristine graphite nanoplatelets (GNP) respectively. The dynamic tests were performed at the strain rates of 1 × 103, 4 × 103, and 7 × 103/s using the split Hopkinson pressure bar and the static tests were done at the strain rate of 1 × 10−2/s. In addition, microstructual examinations were performed to gain insights into the observed macroscopic behavior. It was observed that all the materials showed appreciable strain‐rate sensitivity. CNF‐based nanocomposites exhibited higher strength compared to that of the HDPE matrix material. However, the strength enhancement by GNP was very limited. The lower strength in HDPE/GNP relative to that of HDPE/CNF is likely due to the defect formation around the poor interface between polyethylene matrix and GNP reinforcement. Furthermore, the GNP with lamellate structure is also likely to create two‐dimensional interfacial cracks between the two phases, and hence weaken the strength and stability of the composites. It was also observed that for HDPE/CNF composites, different surface treatments did not seem to show significant effects on material strength. POLYM. COMPOS., 2013 © 2013 Society of Plastics Engineers
Characterization of in situ prepared nanocomposites of PS and TIO2 nanoparticles surface modified with alkyl gallates: Effect of alkyl chain length
Authors: Džunuzović Enis S. , Džunuzović Jasna V. , Radoman Tijana S. , Marinović‐Cincović Milena T. , Nikolić Ljubiša B. , Jeremić Katarina B. , Nedeljković Jovan M.
Published: February 2013

Incorporation of surface modified TiO2 nanoparticles into polystyrene (PS) matrix was achieved by in situ bulk radical polymerization of styrene. The surface of TiO2 nanoparticles was modified with four amphiphilic esters of the gallic acid (octyl, decyl, lauryl and cetyl gallate), which have different lengths of hydrophobic alkyl chain (C8–C16). FTIR and UV‐Vis spectroscopy measurements confirmed the formation of a charge transfer complex between surface Ti atoms and gallic esters. Microstructural characterization of the synthesized nanocomposites revealed that the best dispersion of TiO2 nanoparticles in PS was achieved when the TiO2 surface was modified with octyl gallate. The presence of surface modified TiO2 nanoparticles by different alkyl gallates does not have an influence on the molecular weight and glass transition temperature of PS matrix. On the other hand, thermal and thermo‐oxidative stability of PS were significantly improved by incorporation of surface modified TiO2 nanoparticles. The most pronounced improvement of thermal and thermo‐oxidative stability was observed for TiO2 nanoparticles surface modified with octyl gallate. POLYM. COMPOS., 2013. © 2013 Society of Plastics Engineers
PARENT ATTACHMENT AND EARLY ADOLESCENTS’ LIFE SATISFACTION: THE MEDIATING EFFECT OF HOPE
Authors: Jiang Xu , Huebner E. Scott , Hills Kimberly J.
Published: February 2013

Research using an attachment theory framework has provided evidence that parent attachment is one of the crucial determinants of psychological adjustment in adolescents, including global life satisfaction (LS). This study investigated the interrelationships among parent attachment, hope, and LS during early adolescence, including the mediation effect of hope in the relationship between parent attachment and LS. A sample of 565 middle‐school students in Grades 6 through 8 participated. Results showed statistically significant relationships among all three variables, and hope partially mediated the relationship between parent attachment and LS. Implications of the findings are discussed.
1:2‐sequence‐regulated radical copolymerization of naturally occurring terpenes with maleimide derivatives in fluorinated alcohol
Authors: Matsuda Masaru , Satoh Kotaro , Kamigaito Masami
Published: February 2013

Naturally occurring bulky terpenes, such as (+)‐ and (–)‐limonene and (–)‐β‐pinene, were quantitatively copolymerized with maleimide (MI) derivatives (i.e., phenyl‐, cyclohexyl‐, ethyl‐, and unsubstituted‐MI) in PhC(CF3)2OH solvent via selective 1:2‐alternating propagation governed by the penultimate effect, which resulted in 1:2‐sequence regulated polymers with relatively high glass transition temperatures and optical activities. Similar petroleum‐derived bulky olefins possessing cyclohexenyl, cyclohexyl, or additional α‐methyl substituents were copolymerized with phenylmaleimide via preferential 1:2‐alternating propagation with a slightly lower selectivity. A further decrease in the bulkiness of nonpolar olefins increased the 1:1‐alternating sequence. The copolymerization of limonene and acrylonitrile also proceeded approximately via 1:1‐alternating propagation, in which the penultimate effect was less observable. Furthermore, when methylene chloride was used instead of fluorinated alcohol for the copolymerization of limonene and phenylmaleimide, the length of the sequence of MI units increased. Thus, in addition to the characteristic MI skeleton, the bulky and rather specific structure of either limonene or β‐pinene induces 1:2‐selective propagation via the penultimate effect, whereas the fluoroalcohol diminishes the homopropagation of MI via a hydrogen bonding interaction with the MI unit. RAFT copolymerization of limonene and various MI derivatives in PhC(CF3)2OH successfully proceeded to give the end‐to‐end 1:2‐sequence‐regulated copolymer with a selective initiating sequence and predominant capping sequence using an appropriate RAFT agent. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
In situ nitroxide‐mediated polymerization of styrene promoted by the N‐tert‐butyl‐α‐isopropylnitrone/bpo pair: ESR investigations
Authors: Detrembleur Christophe , Clément Jean‐Louis , Sciannaméa Valérie , Jérôme Christine , Catala Jean‐Marie , Gigmes Didier , Autissier Laurent , Botek Edith , Zarycz Natalia , Champagne Benoît
Published: February 2013

The styrene polymerization initiated by benzoyl peroxide (BPO) in the presence of N‐tert‐butyl‐α‐isopropylnitrone as nitroxide precursor is well‐controlled provided that a prereaction between the nitrone and BPO is carried out in suitable conditions prior to polymerization at a higher temperature. Electron spin resonance (ESR) spectroscopy was implemented to probe the nitroxides formed during both steps, that is, the prereaction and polymerization, and to get crucial information regarding the structure of the nitroxides responsible for the polymerization control. ESR studies combined with first principles calculations have evidenced that nitroxides observed during the prereaction in the presence of styrene and during the polymerization steps consist of a mixture of two macronitroxides. One is formed by the addition of a growing polystyrene chain to the nitrone as would be expected. However, the second one results from the addition of a polystyrene chain to tert‐butyl nitroso that is in situ formed presumably by decomposition of the first macronitroxide type. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
In situ polymerization and characterization of graphene oxide‐co‐poly(phenylene benzobisoxazole) copolymer fibers derived from composite inner salts
Authors: Li Yanwei , Li Jun , Song Yuanjun , Hu Zhen , Zhao Feng , Huang Yudong
Published: February 2013

A facile and efficient strategy for preparing well dispersed graphene oxide (GO)‐co‐Poly(phenylene benzobisoxazole) (PBO) copolymer fibers was carried out by direct in situ polycondensation of composite inner salts. The composite inner salts were achieved to improve the dispersivity, solubility, reactivity, and interfacial adhesion of GO in PBO polymer matrix. The structure and morphology of GO‐co‐PBO copolymer fibers have been characterized. It was demonstrated that GO were covalently incorporated with PBO molecular chains and dispersed considerably well in PBO fiber even the GO reach to 3 wt %. Meanwhile, the tensile modulus, tensile strength and thermal stability of GO‐co‐PBO copolymer fibers increased considerably with GO. The mechanism and theoretical calculation of GO enhanced PBO fiber were also discussed. The main reasons for the improvement on performance of PBO fiber should be attributed to good dispersion GO in PBO matrix and covalent bonding networks at the interface between GO and PBO molecular chains. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
Synthesis of a well‐defined polyallene‐based amphiphilic graft copolymer via sequential living coordination polymerization and SET‐LRP
Authors: Lu Guolin , Li Yongjun , Dai Bin , Xu Caixia , Huang Xiaoyu
Published: February 2013

A well‐defined amphiphilic graft copolymer, poly(6‐methyl‐1,2‐heptadien‐4‐ol)‐g‐poly(2‐(dimethylamino)ethyl methacrylate) (PMHDO‐g‐PDMAEMA), has been synthesized by the combination of living coordination polymerization, single electron transfer‐living radical polymerization (SET‐LRP), and the grafting‐from strategy. PMHDO backbone containing double bonds and pendant hydroxyls was first prepared by [(η3‐allyl)NiOCOCF3]2‐initiated living coordination polymerization of 6‐methyl‐1,2‐heptadien‐4‐ol (MHDO) followed by treating the pendant hydroxyls with 2‐chloropropionyl chloride to give PMHDO‐Cl macroinitiator. SET‐LRP of 2‐(dimethylamino)ethyl methacrylate (DMAEMA) was performed in THF/H2O using PMHDO‐Cl as macroinitiator and CuCl/Me6TREN as catalytic system to afford the well‐defined PMHDO‐g‐PDMAEMA graft copolymer with a narrow molecular weight distribution (Mw/Mn = 1.28). The grafting density was as high as 92%. The critical micelle concentration (cmc) in water was determined by fluorescence probe technique and the micellar morphology was preliminarily explored by transmission electron microscopy. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
Tuning the frontier molecular orbital energy levels of n‐type conjugated copolymers by using angular‐shaped naphthalene tetracarboxylic diimides, and their use in all‐polymer solar cells with high open‐circuit voltages
Authors: Chen Shan‐Ci , Zheng Qingdong , Zhang Qikai , Cai Dongdong , Wang Jinyun , Yin Zhigang , Tang Changquan
Published: February 2013

An angular‐shaped naphthalene tetracarboxylic diimide (NDI) was designed and synthesized as a new building block for n‐type conjugated polymers to tune their energy levels. Three n‐type copolymers incorporating this angular‐shaped NDI as the acceptor moiety were obtained by Stille coupling reactions and had number average molecular weights of 18.7–73.0 kDa. All‐polymer bulk‐heterojunction solar cells made from blends of these polymers with poly(3‐hexylthiophene) gave a power conversion efficiency up to 0.32% and exhibited an open‐circuit voltage (Voc) up to 0.94 V due to their relative high‐lying lowest unoccupied molecular orbital energy levels. The high Voc of 0.94 V is higher than that of solar cells based on linear‐shaped NDI‐containing polymers (<0.6 V). The results indicate that the angular‐shaped NDI is a promising building block for constructing nonfullerene polymer acceptors for solar cells with high open‐circuit voltages. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
Poly‐L‐Arginine Grafted Silica Mesoporous Nanoparticles for Enhanced Cellular Uptake and their Application in DNA Delivery and Controlled Drug Release
Authors: Kar Mrityunjoy , Tiwari Neha , Tiwari Mitali , Lahiri Mayurika , Gupta Sayam Sen
Published: February 2013

Mesoporous silica nanoparticles (MSNs), that are capable of delivering gene and drugs to organisms in an effective and selective way have attracted much attention lately for its potential in the treatment of cancer. However, the successful application of MSNs for delivery of plasmid DNA or drugs requires surface modification of the silica with positively charged functional groups so that it binds to the negatively charged nucleic acids and also helps it penetrate through the cell membrane. We report for the first time the synthesis of a hybrid MSN where the cell penetrating cationic polypeptide poly‐L‐arginine synthesized by NCA polymerization is grafted onto the external surface of MSN using click chemistry. These poly‐L‐arginine grafted MSNs show low cytotoxity (85% cell viability at 100 μg/mL MSN concentration) and high cellular uptake by both HeLa and A549 (>90%). The poly‐L‐arginine grafted MSNs were used effectively to deliver mCherry DNA plasmid into cells leading to expression of the protein mCherry inside the cells (transfection efficiency 60%). In contrast, poly‐L‐arginine grafted non‐porous silica nanoparticles were unable to express the protein mCherry inside the cells although their uptake into the cells was as efficient as with poly‐L‐arginine grafted MSNs. We also show preliminary results to demonstrate that these hybrid MSNs can be used as a delivery vehicle for the anticancer drug Doxorubicin towards cancerous cells HeLa and A549. The biocompatibility of poly‐L‐arginine and its cell penetrating ability are expected to make these MSN conjugates very useful carriers for the delivery of genes and drugs into cancer cells.
Assembly of anthrax toxin pore: Lethal‐factor complexes into lipid nanodiscs
Authors: Akkaladevi N. , Hinton‐Chollet L. , Katayama H. , Mitchell J. , Szerszen L. , Mukherjee S. , Gogol E. P. , Pentelute B. L. , Collier R. J. , Fisher M. T.
Published: February 2013

We have devised a procedure to incorporate the anthrax protective antigen (PA) pore complexed with the N‐terminal domain of anthrax lethal factor (LFN) into lipid nanodiscs and analyzed the resulting complexes by negative‐stain electron microscopy. Insertion into nanodiscs was performed without relying on primary and secondary detergent screens. The preparations were relatively pure, and the percentage of PA pore inserted into nanodiscs on EM grids was high (∼43%). Three‐dimensional analysis of negatively stained single particles revealed the LFN‐PA nanodisc complex mirroring the previous unliganded PA pore nanodisc structure, but with additional protein density consistent with multiple bound LFN molecules on the PA cap region. The assembly procedure will facilitate collection of higher resolution cryo‐EM LFN‐PA nanodisc structures and use of advanced automated particle selection methods.
Effective antimicrobial activity of Cbf‐K16 and Cbf‐A7A13 against NDM‐1‐carrying Escherichia coli by DNA binding after penetrating the cytoplasmic membrane in vitro
Authors: Hao Qingru , Wang Hui , Wang Jing , Dou Jie , Zhang Min , Zhou Weidong , Zhou Changlin
Published: February 2013

New Delhi metallo‐beta‐lactamase‐1(NDM‐1)‐carrying isolates, which are resistant to most clinical used antibiotics except for tigecycline and colistin, have been found worldwide. Cathelicidin‐BF (BF‐30) is found in the venom of the snake Bungarus fasciatus and exhibits broad antimicrobial activity. Cbf‐K16 and Cbf‐A7A13 were obtained by mutating Lys16, Ala7, and Ala13 of BF‐30, respectively. To investigate their antimicrobial activities against NDM‐1 carrying bacteria, recombinant Escherichia coli BL21 (DE3)‐NDM‐1 with high NDM‐1 activity was constructed by inserting the Klebsiella pneumoniae NDM‐1 gene (GenBank accession no. HQ328085) into a pET28a vector and transforming it into E. coli BL21 (DE3). The peptides showed effective antimicrobial activities against NDM‐1‐carrying E. coli, and the minimum inhibitory concentrations of Cbf‐K16 and Cbf‐A7A13 were only 4 and 8 µg/ml, whereas those of minimum bactericidal concentrations were 8 and 16 µg/ml, respectively. A time course experiment showed that colony forming unit counts rapidly decreased, and bacteria were thoroughly eliminated within 3 and 6 h by the Cbf‐K16 and Cbf‐A7A13 treatments, respectively. The peptides penetrated the bacterial cell membrane and enabled β‐galactosidase leakage, and caused the cytoplasmic membrane to become permeable, and finally bound to the DNA. The genomic DNA of E. coli was completely unable to migrate on an agarose gel after Cbf‐K16 treatment (8 µg/ml). These data demonstrated that Cbf‐K16 and Cbf‐A7A13 possess effective antimicrobial activity against drug‐resistant strains, including NDM‐1 carrying E. coli BL21 (DE3)‐NDM‐1, by binding to DNA after penetrating the cytoplasmic membrane in vitro, which may have potential therapeutic value for the treatment of NDM‐1‐carrying bacterial infections. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.