bluuebunny/crossref_metadata_2025 huggingface dataset:
Polypyrrole‐silk electro‐conductive composite fabric byin situchemical polymerization
Authors: Malhotra Urvashi , Maity Subhankar , Chatterjee Arobindo
Published: August 2014

This article describes the preparation of polypyrrole‐silk composite fabric byin situchemical polymerization of pyrrole.In situpolymerization process has been optimized by employing Box‐Behnken response surface design. The effect of process parameters on surface resistivity of the fabric has been statistically analyzed. Most significant process parameter and interaction effects have been identified. Thermal, electrical, and morphological properties of the composite fabric have been studied. Surface resistivity of the fabric obtained is 636.33 Ω. The fabric composite shows a linerV–Icharacteristic like an Ohmic conductor. An exponential rise of surface temperature of the fabric is observed by the application of DC voltage across it. Optical microscopic and SEM studies reveal uniform and even coating of polypyrrole on silk surface. FTIR studies indicate a possible chemical interaction between polypyrrole and silk. The polypyrrole‐treated composite fabric exhibits enhanced thermal stability as is evidenced from DSC and TGA result. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2015,132, 41336.
Rheology, morphology, and mechanical properties of HMSPP/POE blends and its alternate layered foam
Authors: Zhao Tianbao , Zhang Xianlong , Wu Hong , Guo Shaoyun , Sun Xiaojie , Liang Wenbin
Published: August 2014

In this article, the multilayered foaming sheet with alternate layered structure was successfully prepared through multilayer co‐extrusion. The high melt strength polypropylene (HMSPP)/poly (ethylene‐co‐octene) (POE) blend and POE were designed as foaming layers and film layers, respectively. POE was added into HMSPP to reduce the crystalline degree and improve the processing performance. The rheological results indicated that the addition of POE had a little effect on relaxation process and the strain hardening behavior of HMSPP when the POE content was lower than 50%. The results of the foam morphology showed that the cell size and its distribution of the multilayered foaming sheet with alternate layers were better than that with single layer. In addition, the cell size reduced and the cell density increased with increasing the number of layers from 4 to 32. The mechanical properties of the multilayered foaming sheet with alternate layers also could be improved through assembling of foaming layers and film layers. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41339.
Residual charge and filtration efficiency of polycarbonate fibrous membranes prepared by electrospinning
Authors: Cho Byoung Min , Nam Young Sik , Cheon Ja Young , Park Won Ho
Published: August 2014

Polycarbonate (PC) ultrafine fiber membranes with benzyl triethylammonium chloride (BTEAC) were prepared by electrospinning of PC/chloroform solution with different BTEAC contents. In the presence of BTEAC additive, the PC solution showed a better electrospinnability and led to thinner fibers with uniformity than the neat PC solution. The charge retention of the electrospun PC fibrous membranes with BTEAC was investigated in terms of additive content, membrane thickness and storage condition. The residual charge on the PC fibrous membrane was increased to 1 wt % BTEAC content, but thereafter gradually decreased up to 10 wt % BTEAC. In addition, the residual charge on the membrane was increased with increasing the membrane thickness, but was rapidly decreased at a high humidity condition in comparison with a low humidity. The filtration efficiency was examined for the fibrous membranes with or without BTEAC. The PC membrane with BTEAC had higher filtration efficiency than one without BTEAC, not affecting the pressure drop. The filtration efficiency between the PC membranes with or without residual charge was also compared. When the residual charge existed on the membrane, the membrane showed higher filter efficiency because of the enhanced filtration effect by an electrostatic attraction. Therefore, the PC fibrous membranes with BTEAC have a great potential as an electrets filter for air filtration. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41340.
Effect of surfactant on EG dispersion in EVA and thermal and mechanical properties of the system
Authors: Sefadi Shale J. , Luyt Adriaan S. , Pionteck Jürgen
Published: August 2014

The influence of expanded graphite (EG) and sodium dodecyl sulfate (SDS) modified EG on the structure, thermal stability, and mechanical properties of ethylene vinyl acetate (EVA) was investigated in this study. The EVA filled with EG platelets, with and without anionic SDS modification, was prepared by melt mixing using a Brabender Plastograph mixer. The extent of dispersion and morphology of the composites were characterized using scanning electron microscopy (SEM), optical microscopy (OM), and X‐ray diffraction (XRD). The optical microscopy results show better distribution of the modified EG platelets in the EVA matrix, while the SEM results show an improved interfacial adhesion between the polymer and the SDS‐EG particles. Both the EVA18 copolymer and the EG platelets have monoclinic phases, and both EG and SDS do not seem to have any influence on the melting and crystallization behavior of the EVA18. The addition of EG enhanced the thermal stability of EVA18, and this stabilizing influence was further improved when the EG was treated with SDS. All the tensile properties of EVA/EG improved after surface modification. The storage modulus of EVA generally increased with increasing both the unmodified EG and the SDS modified EG content. There was a shift in the Tg to higher temperatures with an increase in both the EG and modified EG content. The α‐relaxation peak in the SDS modified EG curves was less intense than the β‐relaxation peak, even for the untreated EG composites. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41352.
The Nasal Complex of Neanderthals: An Entry Portal to their Place in Human Ancestry
Authors: Márquez Samuel , Pagano Anthony S. , Delson Eric , Lawson William , Laitman Jeffrey T.
Published: August 2014

Neanderthals are one of the most intensely studied groups of extinct humans, as aspects of their phylogeny and functional morphology remain controversial. They have long been described as cold adapted but recent analyses of their nasal anatomy suggest that traits formerly considered adaptations may be the result of genetic drift. This study performs quantitative and qualitative analysis of aspects of the nasal complex (NC) in Neanderthals and other later Pleistocene fossils from Europe and Africa. A geographically diverse sample of modern human crania was used to establish an anatomical baseline for populations inhabiting cold and tropical climates. Nasofrontal angle, piriform aperture dimensions, and relative maxillary sinus volume were analyzed along with qualitative features of the piriform aperture rim. Results indicate that Neanderthals and other later Pleistocene Homo possessed NC's that align them with tropical modern humans. Thus comparison of Neanderthal nasal morphology with that of modern humans from cold climates may not be appropriate as differences in overall craniofacial architecture may constrain the narrowing of the piriform apertures in Neanderthals. They retain primitively long, low crania, large maxillary sinuses, and large piriform aperture area similar to mid‐Pleistocene Homo specimens such as Petralona 1 and Kabwe 1. Adaptation to cold climate may have necessitated other adaptations such as bony medial projections at the piriform aperture rim and, potentially, midfacial prognathism. Nasal complex components of the upper respiratory tract remain a critical but poorly understood area that may yet offer novel insight into one of the greatest continuing controversies in paleoanthropology. Anat Rec, 297:2121–2137, 2014. © 2014 Wiley Periodicals, Inc.
Incisor Crown Bending Strength Correlates With Diet and Incisor Curvature in Anthropoid Primates
Authors: Deane Andrew S.
Published: August 2014

Anthropoid incisors are large relative to the postcanine dentition and function in the preprocessing of food items. Previous analyses of anthropoid incisor allometry and shape demonstrate that incisor morphology is correlated with preferred foods and that more frugivorous anthropoids have larger and more curved incisors. Although the relationship between incisal crown curvature and preferred foods has been well documented in extant and fossil anthropoids, the functional significance of curvature variation has yet to be conclusively established. Given that an increase in crown curvature will increase maximum linear crown dimensions, and bending resistance is a function of linear crown dimensions, it is hypothesized that incisor crown curvature functons to increase incisor crown resistance to bending forces. This study uses beam theory to calculate the mesiodistal and labiolingual bending strengths of the maxillary and mandibular incisors of hominoid and platyrrhine taxa with differing diets and variable degrees of incisal curvature. Results indicate that bending strength correlates with incisal curvature and that frugivores have elevated incisor bending resistance relative to folivores. Maxillary central incisor bending strengths further discriminate platyrrhine and hominoid hard‐ and soft‐object frugivores suggesting this crown is subjected to elevated occlusal loading relative to other incisors. These results are consistent with the hypothesis that incisor crown curvature functions to increase incisor crown resistance to bending forces but does not preclude the possibility that incisor bending strength is a composite function of multiple dentognathic variables including, but not limited to, incisor crown curvature. Anat Rec, 298:463–478, 2015. © 2014 Wiley Periodicals, Inc.
Chaotification of Switching Control Systems via Dwell Time Approach
Authors: Zhang Yuping , Liu Xinzhi , Zhu Hong , Zeng Yong
Published: August 2014

In this paper, a class of switching control systems is investigated, and a novel switching control method is developed, which can be applied to generating chaos dynamics from switching control systems through dwell time restriction. A numerical example is given to illustrate the generated chaotic dynamic behavior of the systems, and the corresponding bifurcation diagram is sketched. Then, the validity of the main results is verified together with other phase portraits.
Robust Position Stabilization of Underactuated Surface Vessels With Unknown Modeling Parameters Via Simple P/D‐Like Feedback: The Center Manifold Approach
Authors: Wen‐Jing Xie , Bao‐Li Ma
Published: August 2014

In this work, two smooth time‐invariant control laws are proposed to achieve asymptotic position stabilization of underactuated surface vessels despite modeling parameter uncertainties. The proposed control laws take a strikingly simple linear proportional derivative (PD)‐like feedback form or just a simplest proportional (P)‐like one, where the former relies on measuring the relative position error and surge/yaw velocity and the latter relies on measuring only the relative position error, decreasing or minimizing the sensing cost. The stabilities of the closed‐loop systems for the both control laws are strictly proved via the center manifold approach despite the unknown model parameters. The effectiveness of the proposed control laws is verified by simulation examples.
Putative roles of organic anion transporting polypeptides (OATPs) in cell survival and progression of human cancers
Authors: Nakanishi Takeo , Tamai Ikumi
Published: August 2014

Transporter proteins classified into the solute carrier (SLC) transporter superfamily are essential for the import of nutrients required for cell survival in organisms. Various SLC transporters are differentially upregulated in cancer cells, and among them, polyspecific organic anion‐transporting polypeptides (OATPs) have been proposed to have pathophysiological significance in cancer. This review will briefly introduce OATPs and summarize their proposed roles in cancer, focusing particularly on hormone‐dependent breast and prostate cancers. Over the past two decades, compelling evidence has also accumulated that SLC transporters, including OATPs, interact with clinically important anticancer agents and influence their pharmacokinetics, particularly the processes of absorption, elimination and distribution. Therefore, a better understanding of not only the pathophysiological roles, but also the pharmacological effects of OATPs in cancer cells should be helpful in combating human malignant tumors. Copyright © 2014 John Wiley & Sons, Ltd.
Deciphering the unusual HLA‐A2/Melan‐A/MART‐1‐specific TCR repertoire in humans
Authors: Romero Pedro , Speiser Daniel E. , Rufer Nathalie
Published: August 2014

The Melan‐A/MART‐126‐35 antigenic peptide is one of the best studied human tumor‐associated antigens. It is expressed in healthy melanocytes and malignant melanoma and is recognized by CD8+ T cells in the context of the MHC class I molecule HLA‐A*0201. While an unusually large repertoire of CD8+ T cells specific for this antigen has been documented, the reasons for its generation have remained elusive. In this issue of the European Journal of Immunology, Pinto et al. [Eur. J. Immunol. 2014. 44: 2811–2821] uncover one important mechanism by comparing the thymic expression of the Melan‐A gene to that in the melanocyte lineage. This study shows that medullary thymic epithelial cells (mTECs) dominantly express a truncated Melan‐A transcript, the product of misinitiation of transcription. Consequently, the protein product in mTECs lacks the immunodominant epitope spanning residues 26–35, thus precluding central tolerance to this antigen. In contrast, melanocytes and melanoma tumor cells express almost exclusively the full‐length Melan‐A transcript, thus providing the target antigen for efficient recognition by HLA‐A2‐restricted CD8+ T cells. The frequency of these alternative gene transcription modes may be more common than previously appreciated and may represent an important factor modulating the efficiency of central tolerance induction in the thymus.
Discoidin domain receptor 1 is a novel transcriptional target of ZEB1 in breast epithelial cells undergoing H‐Ras‐induced epithelial to mesenchymal transition
Authors: Koh Minsoo , Woo Yunjung , Valiathan Rajeshwari R. , Jung Hae Yoen , Park So Yeon , Kim Yong Nyun , Kim Hyeong‐Reh Choi , Fridman Rafael , Moon Aree
Published: August 2014

The epithelial‐to‐mesenchymal transition (EMT) process allows carcinoma cells to dissociate from the primary tumor thereby facilitating tumor cell invasion and metastasis. Ras‐dependent hyperactive signaling is commonly associated with tumorigenesis, invasion, EMT, and metastasis. However, the downstream effectors by which Ras regulates EMT remain ill defined. In this study, we show that the H‐Ras pathway leads to mesenchymal‐like phenotypic changes in human breast epithelial cells by controlling the ZEB1/microRNA−200c axis. Moreover, H‐Ras suppresses the expression of the discoidin domain receptor 1 (DDR1), a collagen receptor tyrosine kinase, via ZEB1, thus identifying ZEB1 as a novel transcriptional repressor of DDR1. Mutation studies on the putative promoter of the DDR1 gene revealed that bipartite Z‐ and E‐box elements play a key role in transcriptional repression of DDR1 in Hs578T and MDA‐MB‐231 breast carcinoma cell lines by ZEB1. Furthermore, we found an inverse correlation between ZEB1 and DDR1 expression in various cancer cell lines and in human breast carcinoma tissues. Consistently, overexpression of DDR1 reduced the invasive phenotype of mesenchymal‐like triple‐negative breast cancer cells in 3D cultures and in vivo. Thus, ZEB1's role in maintenance of EMT in breast carcinoma cells is mediated in part by its ability to suppress DDR1 expression and consequently contribute to the activation of the invasive phenotype. Taken together, our results unveil a novel H‐Ras/ZEB1/DDR1 network that contributes to breast cancer progression in triple‐negative breast cancers.
Metastasis blood test by flow cytometry: In vivo cancer spheroids and the role of hypoxia
Authors: Denes Viktoria , Lakk Monika , Makarovskiy Andrew , Jakso Pal , Szappanos Szabolcs , Graf Laszlo , Mandel Laszlo , Karadi Istvan , Geck Peter
Published: August 2014

Cancer hypoxia correlates with therapeutic resistance and metastasis, suggesting that hypoxic adaptation is a critical survival advantage for cancer stem cells (CSCs). Hypoxic metabolism, however, may be a disadvantage in aerobic circulation as the extremely low incidence of metastasis—compared to the high circulating tumor‐cell numbers (CTCs)—appears to suggest. As rare metastatic CSCs still survive, we searched for a mechanism that protects them from oxygen in circulation. CSCs form multicellular spheroids in vitro from virtually all cancers tested. We asked, therefore, whether cancers also form spheroids in vivo and whether circulating spheroids play a role in metastasis. We used metabolic, apoptotic and hypoxia assays, we measured aerobic barriers and calculated hypoxia vs. spheroid‐size correlations. We detected metabolic/oxidative stress in spheroids, we found correlation between stem cell presence and hypoxia and we showed that the size of hypoxic spheroids is compatible with circulation. To detect spheroids in patients, we worked out a new light‐scatter flow cytometry blood test and assayed 67 metastatic and control cases. We found in vivo spheroids with positive stem cell markers in cancer blood and they showed exclusive correlation with metastasis. In conclusion, our data suggest that metastatic success depends on CSC‐association with in vivo spheroids. We propose that the mechanism involves a portable “micro‐niche” in spheroids that may support CSC‐survival/adaptation in circulation. The new assay may establish a potential early marker of metastatic progression.
Treatment of oral leukoplakia with a low‐dose of beta‐carotene and vitamin C supplements: A randomized controlled trial
Authors: Nagao Toru , Warnakulasuriya Saman , Nakamura Tomoyasu , Kato Shinichiro , Yamamoto Keiichi , Fukano Hideo , Suzuki Koji , Shimozato Kazuo , Hashimoto Shuji
Published: August 2014

Management of oral leukoplakia—a potentially malignant disorder—is currently not evidence‐based. Of the few randomized trials that have been reported, most have negative data. Therefore, a multi‐centre, randomized, double‐blind controlled trial (RCT) was undertaken to evaluate the use of low‐dose beta‐carotene combined with vitamin C supplements for the treatment and to prevent malignant transformation of oral leukoplakia. 46 Japanese participants with oral leukoplakia were allocated randomly either to an experimental arm (10 mg day−1 of beta‐carotene and 500 mg day−1 of vitamin C) or placebo arm (50 mg day−1 of vitamin C). Current or ex‐smokers within 3 months of cessation were excluded. The supplements were continued over a period of 1 year. The primary endpoint was clinical remission at 1‐year and the likelihood of malignant transformation during a 5‐year follow‐up period as a secondary endpoint. The overall clinical response rate in the experimental arm was 17.4% (4/23) and 4.3% (1/23) in the placebo arm (p = 0.346). During the median 60‐month follow‐up period, two subjects in the experimental arm and three in the control arm developed oral cancer. Under the intention‐to‐treat principle, relative risk by supplementing with beta‐carotene and vitamin C was 0.77 (95%CI: 0.28–1.89) (p = 0.580) by the Cox proportional hazards model. No unfavorable side‐effects were noted. Beta‐carotene (10 mg day−1) and vitamin C were neither effective for clinical remission, nor for protection against the development of cancer. Data from this RCT does not support the hypothesis that chemoprevention with this treatment is effective for oral leukoplakia.
Sweat but no gain: Inhibiting proliferation of multidrug resistant cancer cells with “ersatzdroges”
Authors: Kam Yoonseok , Das Tuhin , Tian Haibin , Foroutan Parastou , Ruiz Epifanio , Martinez Gary , Minton Susan , Gillies Robert J. , Gatenby Robert A.
Published: August 2014

ATP‐binding cassette (ABC) drug transporters consuming ATPs for drug efflux is a common mechanism by which clinical cancers develop multidrug resistance (MDR). We hypothesized that MDR phenotypes could be suppressed by administration of “ersatzdroges,” nonchemotherapy drugs that are, nevertheless, ABC substrates. We reasoned that, through prolonged activation of the ABC pumps, ersatzdroges will force MDR cells to divert limited resources from proliferation and invasion thus delaying disease progression. We evaluated ABC substrates as ersatzdroge by comparing their effects on proliferation and survival of MDR cell lines (MCF‐7/Dox and 8226/Dox40) with the effects on the drug‐sensitive parental lines (MCF‐7 and 8226/s, respectively) in glucose‐limited condition. The changes in glucose and energy demands were also examined in vitro and in vivo. MCF‐7/Dox showed higher ATP demand and susceptibility to glucose resource limitation. Ersatzdroges significantly decreased proliferation of MCF‐7/Dox when the culture media contained physiological glucose concentrations (1.0 g/L) or less, but had no effect on MCF‐7. Similar evidence was obtained from 8226/Dox40 and 8226/s comparison. In vivo 18F‐FDG‐PET imaging demonstrated that glucose uptake was increased by systemic administration of an ersatzdroge in tumors composed of MDR. These results suggest that administration of ersatzdroges, by increasing the metabolic cost of resistance, can suppress proliferation of drug‐resistance phenotypes. This provides a novel and relatively simple application model of evolution‐based strategy, which can exploit the cost of resistance to delay proliferation of drug‐resistant cancer phenotypes. Furthermore, suggested is the potential of ersatzdroges to identify tumors or regions of tumors that express the MDR phenotype.
Novel functions and targets of miR‐944 in human cervical cancer cells
Authors: Xie Hong , Lee Linkiat , Scicluna Patrick , Kavak Ersen , Larsson Catharina , Sandberg Rickard , Lui Weng‐Onn
Published: August 2014

Altered expression of specific microRNAs (miRNAs) has been observed in human cervical cancer. However, the biological functions of many of these miRNAs are yet to be discovered. We previously showed that miR‐944 is significantly more abundant in cervical cancer tissues than their normal counterparts. In this study, we investigated the functions and targets of miR‐944 in human cervical cancer cells. MiR‐944 is located in the intron of the tumor protein p63 (TP63) gene, which is frequently overexpressed in cervical carcinomas. Using gain‐ and loss‐of‐function experiments in vitro, we demonstrate that miR‐944 promotes cell proliferation, migration and invasion, but has no effect on apoptosis, in human cervical cancer cells. To identify the targets of miR‐944, we performed photoactivatable‐ribonucleoside‐enhanced crosslinking and immunoprecipitation followed by deep sequencing. Among the candidate targets, we validated HECW2 (HECT domain ligase W2) and S100PBP (S100P binding protein) as direct targets of miR‐944 using luciferase reporter assays and western blot analysis. Our findings reveal novel functions and targets of miR‐944 in human cervical cancer cells, which may provide new insights of its role in cervical carcinogenesis.
Cell crowding induces interferon regulatory factor 9, which confers resistance to chemotherapeutic drugs
Authors: Kolosenko Iryna , Fryknäs Mårten , Forsberg Sofi , Johnsson Per , Cheon HyeonJoo , Holvey‐Bates Elise G. , Edsbäcker Elin , Pellegrini Paola , Rassoolzadeh Hanif , Brnjic Slavica , Larsson Rolf , Stark George R. , Grandér Dan , Linder Stig , Tamm Katja Pokrovskaja , De Milito Angelo
Published: August 2014

The mechanism of multicellular drug resistance, defined as the reduced efficacy of chemotherapeutic drugs in solid tumors is incompletely understood. Here we report that colon carcinoma cells cultured as 3D microtissues (spheroids) display dramatic increases in the expression of a subset of type I interferon‐(IFN)‐stimulated genes (ISGs). A similar gene signature was associated previously with resistance to radiation and chemotherapy, prompting us to examine the underlying biological mechanisms. Analysis of spheroids formed by different tumor cell lines and studies using knock‐down of gene expression showed that cell crowding leads to the induction of IFN regulatory factor‐9 (IRF9) which together with STAT2 and independently of IFNs, is necessary for ISG upregulation. Increased expression of IRF9 alone was sufficient to induce the ISG subset in monolayer cells and to confer increased resistance to clinically used cytotoxic drugs. Our data reveal a novel mechanism of regulation of a subset of ISGs, leading to drug resistance in solid tumors.
Hyperpolarized [1,3‐13C2]ethyl acetoacetate is a novel diagnostic metabolic marker of liver cancer
Authors: Jensen Pernille R. , Serra Sonia Colombo , Miragoli Luigi , Karlsson Magnus , Cabella Claudia , Poggi Luisa , Venturi Luca , Tedoldi Fabio , Lerche Mathilde H.
Published: August 2014

An increased prevalence of liver diseases such as hepatitis C and nonalcoholic fatty liver results in an augmented incidence of the most common form of liver cancer, hepatocellular carcinoma (HCC). HCC is most often found in the cirrhotic liver and it can therefore be challenging to rely on anatomical information alone when diagnosing HCC. Valuable information on specific cellular metabolism can be obtained with high sensitivity thanks to an emerging magnetic resonance (MR) technique that uses 13C labeled hyperpolarized molecules. Our interest was to explore potential new high contrast metabolic markers of HCC using hyperpolarized 13C‐MR. This work led to the identification of a class of substrates, low molecular weight ethyl‐esters, which showed high specificity for carboxyl esterases and proved in many cases to possess good properties for signal enhancement. In particular, hyperpolarized [1,3‐13C2]ethyl acetoacetate (EAA) was shown to provide a metabolic fingerprint of HCC. Using this substrate a liver cancer implanted in rats was diagnosed as a consequence of an ∼4 times higher metabolic substrate‐to‐product ratio than in the surrounding healthy tissue, (p = 0.009). Unregulated cellular uptake as well as cosubstrate independent enzymatic conversion of EAA, made this substrate highly useful as a hyperpolarized 13C‐MR marker. This could be appreciated by the signal‐to‐noise (SNR) obtained from EAA, which was comparable to the SNR reported in a literature liver cancer study with state‐of‐the‐art hyperpolarized substrate, [1‐13C]pyruvate. Also, the contrast‐to‐noise (CNR) in the EAA based metabolic ratio images was significantly improved compared with the CNR in equivalent images reported using [1‐13C]pyruvate.
Combination therapy of oncolytic herpes simplex virus HF10 and bevacizumab against experimental model of human breast carcinoma xenograft
Authors: Tan Gewen , Kasuya Hideki , Sahin Tevfik Tolga , Yamamura Kazuo , Wu Zhiwen , Koide Yusuke , Hotta Yoshihiro , Shikano Toshio , Yamada Suguru , Kanzaki Akiyuki , Fujii Tsutomu , Sugimoto Hiroyuki , Nomoto Shuji , Nishikawa Yoko , Tanaka Maki , Tsurumaru Naoko , Kuwahara Toshie , Fukuda Saori , Ichinose Toru , Kikumori Toyone , Takeda Shin , Nakao Akimasa , Kodera Yasuhiro
Published: August 2014

Breast cancer is one of the most common and feared cancers faced by women. The prognosis of patients with advanced or recurrent breast cancer remains poor despite refinements in multimodality therapies involving chemotherapeutic and hormonal agents. Multimodal therapy with more specific and effective strategy is urgently needed. The oncolytic herpes simplex virus (HSV) has potential to become a new effective treatment option because of its broad host range and tumor selective viral distribution. Bevacizumab is a monoclonal antibody against VEGFA, which inhibits angiogenesis and therefore tumor growth. Our approach to enhance the antitumor effect of the oncolytic HSV is to combine oncolytic HSV HF10 and bevacizumab in the treatment of breast cancer. Our results showed that bevacizumab enhanced viral distribution as well as tumor hypoxia and expanded the population of apoptotic cells and therefore induced a synergistic antitumor effect. HF10 is expected to be a promising agent in combination with bevacizumab in the anticancer treatment.
Prostate cancer cells home to bone using a novel in vivo model: Modulation by the integrin antagonist GLPG0187
Authors: Reeves Kimberley J. , Hurrell Jack E. , Cecchini Marco , van der Pluijm Gabri , Down Jenny M. , Eaton Colby L. , Hamdy Freddie , Clement‐Lacroix Philippe , Brown Nicola J.
Published: August 2014

Micrometastasis is a barrier to the development of effective cancer therapies for prostate cancer metastasis to bone. The mechanisms remain incompletely characterised, primarily due to an inability to adequately monitor the initial metastatic events in vivo. This study aimed to establish a new model, allowing the tracking of prostate cancer cells homing to bone, and furthermore, to evaluate the response of this approach to therapeutic modulation, using the integrin antagonist GLPG0187. A single murine metatarsal was engrafted into a dorsal skinfold chamber implanted on a SCID mouse. Fluorescently‐labeled human prostate (PC3‐GFP) or oral (SCC4‐GFP) cancer cells were administered via intracardiac (i.c) injection, with simultaneous daily GLPG0187 or vehicle‐control treatment (i.p. 100 mg/kg/day) for the experimental duration. Metatarsal recordings were taken every 48 h for up to 4 weeks. Tissue was harvested and processed for microCT, multiphoton analysis, histology and immunohistochemistry. Cell viability, proliferation and migration in vitro were also quantified following treatment with GLPG0187. Metatarsals rapidly revascularised by inosculation with the host vasculature (day 5–7). PC3‐GFP cells adhered to the microvascular endothelium and/or metatarsal matrix 3 days after administration, with adhesion maintained for the experimental duration. GLPG0187 treatment significantly (p < 0.05) reduced PC3 cell number within the metatarsal in vivo and reduced migration (p < 0.05) and proliferation (p < 0.05) but not cell viability in vitro. This new model allows evaluation of the early events of tumour‐cell homing and localisation to the bone microenvironment, in addition to determining responses to therapeutic interventions.
Chronic Exposure to Low‐Dose Arsenic Modulates Lipogenic Gene Expression in Mice
Authors: Adebayo Adeola O. , Zandbergen Fokko , Kozul‐Horvath Courtney D. , Gruppuso Philip A. , Hamilton Joshua W.
Published: August 2014

Arsenic, a ubiquitous environmental toxicant, can affect lipid metabolism through mechanisms that are not well understood. We studied the effect of arsenic on serum lipids, lipid‐regulating genes, and transcriptional regulator sterol regulatory element binding protein 1c (SREBP‐1c). C57BL/6 mice were administered 0 or 100 ppb sodium arsenite in drinking water for 5 weeks. Arsenic exposure was associated with decreased liver weight but no change in body weight. Serum triglycerides level fell in arsenic‐exposed animals, but not in fed animals, after short‐term fasting. Hepatic expression of SREBP‐1c was reduced in arsenic‐exposed fed animals, with a 16‐fold change in reduction. Similar effects were seen for SREBP‐1c in white adipose tissue. However, fasting resulted in dissociation of the expression of SREBP‐1c and its targets, and SREBP‐1c protein content could not be shown to correlate with its mRNA expression. We conclude that arsenic modulates hepatic expression of genes involved in lipid regulation through mechanisms that are independent of SREBP‐1c expression.
Evolutionary morphology of the organ systems in squat lobsters and porcelain crabs (Crustacea: Decapoda: Anomala): An insight into carcinization
Authors: Keiler Jonas , Richter Stefan , Wirkner Christian S.
Published: August 2014

Porcelain crabs (Porcellanidae) are one of three taxa within anomuran crustaceans (Anomala) which possess a crab‐like body form. Curiously, these three lineages evolved this shape independently from true crabs (Brachyura) in the course of the evolutionary process termed carcinization. The entire pleon in porcelain crabs is flexed under the cephalothorax and the carapace is approximately as broad as long. Despite their crab‐like habitus, porcelain crabs are phylogenetically nested within squat lobsters (Munidopsidae, Munididae, Galatheidae). With a pleon which is only partly flexed under the cephalothorax and a cephalothorax which is longer than it is broad, squat lobsters represent morphologically intermediate forms between lobster‐like and crab‐like body shapes. Carcinization has so far mostly been studied with respect to outer morphology; however, it is evident that internal anatomical features are influenced through this change of body shape too. In this paper, the situation in Galatheoidea is elucidated by adding more taxa to existing descriptions of the hemolymph vascular systems and associated structures and organs. Micro‐computer tomography and 3D reconstruction provide new insights. Autapomorphic states of various internal anatomical characters are present in nearly all the studied species, also reflecting some degree of anatomical disparity found within Galatheoidea. The ventral vessel system of porcelain crabs differs distinctly from that of squat lobsters. The differences in question are coherent (i.e. structural dependent) with morphological transformations in the integument, such as the shortening of the sternal plastron, which evolved in the course of carcinization. Shifts in the gonads and the pleonal neuromeres are coherent with the loss of the caridoid escape reaction, which in turn is a consequence of carcinization. The arterial transformations, however, are minor compared to other instances of carcinization in anomuran crustaceans since the last common ancestor of squat lobsters and porcelain crabs was already “half carcinized”. J. Morphol. 276:1–21, 2015. © 2014 Wiley Periodicals, Inc.
MRI of the Hip for the evaluation of femoroacetabular impingement; past, present, and future
Authors: Riley Geoffrey M. , McWalter Emily J. , Stevens Kathryn J. , Safran Marc R. , Lattanzi Riccardo , Gold Garry E.
Published: August 2014

The concept of femoroacetabular impingement (FAI) has, in a relatively short time, come to the forefront of orthopedic imaging. In just a few short years MRI findings that were in the past ascribed to degenerative change, normal variation, or other pathologies must now be described and included in radiology reports, as they have been shown, or are suspected to be related to, FAI. Crucial questions have come up in this time, including: what is the relationship of bony morphology to subsequent cartilage and labral damage, and most importantly, how is this morphology related to the development of osteoarthritis? In this review, we attempt to place a historical perspective on the controversy, provide guidelines for interpretation of MRI examinations of patients with suspected FAI, and offer a glimpse into the future of MRI of this complex condition. J. Magn. Reson. Imaging 2015;41:558–572. © 2014 Wiley Periodicals, Inc.
Diffusion tensor imaging of patients with proteolipid protein 1 gene mutations
Authors: Laukka Jeremy J. , Makki Malek I. , Lafleur Tori , Stanley Jeffrey , Kamholz John , Garbern James Y.
Published: August 2014

Pelizaeus‐Merzbacher disease (PMD) is an X‐linked disorder of the central nervous system (CNS) caused by a wide variety of mutations affecting proteolipid protein 1 (PLP1). We assessed the effects of PLP1 mutations on water diffusion in CNS white matter by using diffusion tensor imaging. Twelve patients with different PLP1 point mutations encompassing a range of clinical phenotypes were analyzed, and the results were compared with a group of 12 age‐matched controls. The parallel (λ//), perpendicular (λ⊥), and apparent diffusion coefficients (ADC) and fractional anisotropy were measured in both limbs of the internal capsule, the genu and splenium of corpus callosum, the base of the pons, and the cerebral peduncles. The mean ADC and λ⊥ in the PMD patient group were both significantly increased in all selected structures, except for the base of the pons, compared with controls. PMD patients with the most severe disease, however, had a significant increase of both λ// and λ⊥. In contrast, more mildly affected patients had much smaller changes in λ// and λ⊥. These data suggest that myelin, the structure responsible in part for the λ⊥ barrier, is the major site of disease pathogenesis in this heterogeneous group of patients. Axons, in contrast, the structures mainly responsible for λ//, are much less affected, except within the subgroup of patients with the most severe disease. Clinical disability in patients with PLP1 point mutation is thus likely determined by the extent of pathological involvement of both myelin and axons, with alterations of both structures causing the most severe disease. © 2014 Wiley Periodicals, Inc.
Endogenous functional compounds in Korean native chicken meat are dependent on sex, thermal processing and meat cut
Authors: Jayasena Dinesh D , Jung Samooel , Kim Sun Hyo , Kim Hyun Joo , Alahakoon Amali U , Lee Jun Heon , Jo Cheorun
Published: August 2014

BACKGROUND

In this study the effects of sex, meat cut and thermal processing on the carnosine, anserine, creatine, betaine and carnitine contents of Korean native chicken (KNC) meat were determined. Forty 1‐day‐old chicks (20 chicks of each sex) from a commercial KNC strain (Woorimatdag™) were reared under similar standard commercial conditions with similar diets, and ten birds of each sex were randomly selected and slaughtered at 14 weeks of age. Raw and cooked meat samples were prepared from both breast and leg meats and analyzed for the aforementioned functional compounds.

RESULTS

Female KNCs had significantly higher betaine and creatine contents. The breast meat showed significantly higher carnosine and anserine contents, whereas the leg meat had a higher betaine and carnitine content. The content of all functional compounds was significantly depleted by thermal processing.

CONCLUSION

This study confirms that KNC meat is a good source of the above‐mentioned functional compounds, which can be considered attractive nutritional quality factors. However, their concentrations were significantly affected by thermal processing conditions, meat cut and sex. Further experiments are needed to select the best thermal processing method to preserve these functional compounds. © 2014 Society of Chemical Industry
The effect of salt replacers and flavor enhancer on the processing characteristics and consumer acceptance of turkey sausages
Authors: Pietrasik Zeb , Gaudette Nicole J
Published: August 2014

BACKGROUND

Producing high‐quality processed meats that contain reduced amounts of sodium chloride is a major challenge facing industry owing to the importance of sodium chloride toward the functional, microbial stability and sensory properties of these products. In order to create reduced sodium alternatives, a number of commercial salt replacers and flavor enhancers have entered the market; however, their ability to be applied in processed meats requires investigation. In this study, two salt replacers (Ocean's Flavor – OF45, OF60) and one flavor enhancer (Fonterra™ Savoury Powder – SP) were evaluated for their ability to effectively reduce sodium while maintaining the functional and sensory properties of turkey sausages. Functionality via instrumental measures (yield, purge loss, pH, expressible moisture, proximate composition, sodium content, color, texture), safety (microbiological assessment) and consumer acceptability were obtained on all samples.

RESULTS

All non‐control treatments resulted in products with sodium chloride contents below Canada's Health Check™ Program target for processed meats. There was no detrimental effect on water binding and texture in treatments when NaCl was substituted with OF60 sea salt replacers. Sodium reduction had no negative effect on the shelf life of the turkey sausages with up to 60 days of refrigerated storage. Consumer acceptability for all attributes did not differ significantly, except for aftertaste, which scored lowest for OF45 compared with the control (regular NaCl content).

CONCLUSION

This work demonstrated that salt replacers could potentially substitute for NaCl in smoked turkey sausages; however, further flavor optimization may be required to suppress undesirable levels of bitterness elicited by some of these ingredients. © 2014 Society of Chemical Industry
Efficiency of irrigation water application in sugarcane cultivation in Pakistan
Authors: Watto Muhammad Arif , Mugera Amin W.
Published: August 2014

BACKGROUND

Diminishing irrigation water supplies are threatening the sustainability of irrigated agriculture in Pakistan. Within the context of dwindling water resources and low agricultural water productivity, it is imperative to improve efficiency in agricultural production and to make efficient use of available water resources. This study employs a non‐parametric approach to estimate the extent of technical and irrigation water efficiency in sugarcane cultivation in Pakistan.

RESULTS

The mean technical efficiency score is 0.96 for tube‐well owners whereas it is 0.94 for water buyers. The mean irrigation water efficiency score is 0.86 for tube‐well owners whereas it is 0.72 for water buyers. We find that across all farms, 59% of the tube‐well owners and 45% of the water buyers are fully technically efficient, whereas only 36% of the tube‐well owners and 30% of the water buyer are fully efficient in irrigation water use.

CONCLUSIONS

This study finds that sugarcane growers are operating at fairly high technical efficiency levels. But, there is considerable potential to improve irrigation water efficiency. This study proposes expanding the role of agricultural extension services from merely agronomic grounds to guide farmers to undertake cost benefit analysis of the available production technology, would help achieve higher efficiency levels. © 2014 Society of Chemical Industry
Dishevelled‐3 activates p65 to upregulate p120‐catenin transcription via a p38‐dependent pathway in non‐small cell lung cancer
Authors: Zhao Huanyu , Zhao Yue , Jiang Guiyang , Zhang Xiupeng , Zhang Yijun , Dong Qianze , Luan Lan , Papavassiliou Paulie , Wang Endi , Wang Enhua
Published: August 2014

Dishevelled‐3 (Dvl‐3) and p120‐catenin (p120ctn) have abnormal expression in non‐small cell lung cancer (NSCLC), which is associated with poor prognosis. Dvl‐3 upregulates p120ctn transcription in NSCLC cells, but the mechanism is unknown. Here we transiently transfected Dvl‐3 cDNA to NSCLC cells. Dvl‐3 transfection is sufficient for induction of p38 signaling. In turn, Dvl‐3 induces p38‐mediated activation of the p65 so as to facilitate its nuclear translocation. Treatment with SB203580 (p38 inhibitor) or BAY 11‐7082 (IκB‐α phosphorylation inhibitor) suppresses Dvl‐3 induced activation of p65. The results further show that active p65 interacts with PAX2 promoter to increase the expression of PAX2 and then PAX2 binds to p120ctn promoter so as to upregulate p120ctn gene transcription. Moreover, Dvl‐3 transfection enhanced the binding of active p65 to Sp1 so as to decrease the binding of Sp1 to p120ctn promoter. The above‐mentioned effects are linked to biological behavior of non‐small cell lung cancer cells. These findings confirm that p38 and PAX2 are important for the Dvl‐3 induced upregulation of p120ctn. Dvl‐3 activates a p38 → p65 → PAX2 → p120ctn pathway to affect biological behavior of NSCLC cells. © 2014 Wiley Periodicals, Inc.
Decrease of 5‐hydroxymethylcytosine in rat liver with subchronic exposure to genotoxic carcinogens riddelliine and aristolochic acid
Authors: Lian Christine Guo , Xu Shuyun , Guo Weimin , Yan Jian , Frank Maximilian Y.M. , Liu Robert , Liu Cynthia , Chen Ying , Murphy George F. , Chen Tao
Published: August 2014

The level of 5‐hydroxymethylcytosine (5‐hmC) converted by ten‐eleven translocation (TET) family is decreased in cancers. However, whether 5‐hmC level is perturbed in early stages of carcinogenesis caused by genotoxic carcinogens is not defined. 5‐hmC levels and TET2 expression were measured in liver of rats treated with genotoxic carcinogens, riddelliine, or aristolochic acid. Levels of 5‐hmC and TET2 expression decreased in the liver of the carcinogens‐treated rats. Loss of 5‐hmC correlates well with documented induction of genetic mutations by the carcinogens, suggesting that TET2‐mediated 5‐hydroxymethylation plays an epigenetic role in early state of carcinogenesis. © 2014 Wiley Periodicals, Inc.
Oxidative stress, mammospheres and Nrf2–new implication for breast cancer therapy?
Authors: Wu Tongde , Harder Bryan G. , Wong Pak K. , Lang Julie E. , Zhang Donna D.
Published: August 2014

Mammosphere culture of breast cancer cell lines is an important approach used for enrichment of cancer stem cells (CSCs), which exhibit high tumorigenicity and chemoresistance features. Evidence shows that CSCs maintain lower ROS levels due to elevated expression of ROS‐scavenging molecules and antioxidative enzymes, which favors the survival of the CSCs and their chemoresistance. The transcription factor NF‐E2‐related factor 2 (Nrf2) has emerged as the master regulator of cellular redox homeostasis, by up‐regulating antioxidant response element (ARE)‐bearing genes products. Although Nrf2 has long‐term been regarded as a beneficial defense mechanism, accumulating studies have revealed the “dark side” of Nrf2. High constitutive levels of Nrf2 was observed in many types of tumors and cancer cell lines promoting their resistance to chemotherapeutics. In this study, we report a high expression of Nrf2 and its target genes in mammospheres compared to corresponding adherent cells. In MCF‐7 and MDA‐MB‐231 mammmosphere cells, the Nrf2‐mediated cellular protective response is significantly elevated which is associated with increased resistance to taxol and anchorage‐independent growth. Brusatol, an inhibitor of the Nrf2 pathway, suppressed the protein level of Nrf2 and its target genes, enhanced intracellular ROS and sensitized mammospheres to taxol, and reduced the anchorage‐independent growth. These results suggest that mammospheres rely on abnormal up‐regulation of Nrf2 to maintain low intracellular ROS levels. Nrf2 inhibitors, such as brusatol, have the potential to be developed into novel adjuvant chemotherapeutic drug combinations in order to combat refractory tumor initiating CSCs. © 2014 Wiley Periodicals, Inc.
Phosphorylation of the N‐terminal domain of p48 Ebp1 by CDK2 is required for tumorigenic function of p48
Authors: Ko Hyo Rim , Kim Chung Kwon , Ahn Jee‐Yin
Published: August 2014

The long isoform of ErbB3 binding protein 1 (Ebp1), p48, strongly promotes tumorigenesis of glioblastoma, accelerating cell proliferation and transformation, while the short isoform, p42, which lacks the N‐terminal 54 amino acids, inhibits tumor growth. However, it is unclear if the N‐terminal domain of p48 regulates the oncogenic function of p48. Here, we show that p48, but not p42, interacts with cyclin‐dependent kinase 2 (CDK2) through its N‐terminal domain, resulting in the specific phosphorylation of serine 34 of p48. Overexpression of wild‐type p48 greatly enhanced tumor cell growth, whereas phospho‐ablated mutant S34A of p48, which is mutated at the CDK2 phosphorylation site, antagonizes cell proliferation and transformation. Moreover, phospho‐ablated mutant S34A abrogated the ability of p48 to accelerate tumor cell growth in a mouse engraft model. Thus, our findings indicate that p48Ebp1 acts as an oncoprotein through selective interaction and/or modification of the N‐terminal domain that does not exist in its short isoform p42. © 2014 Wiley Periodicals, Inc.