bluuebunny/crossref_metadata_2025 huggingface dataset:
Quinone propionic acid‐based redox‐triggered polymer nanoparticles for drug delivery: Computational analysis and in vitro evaluation
Authors: Bae Jungeun , Nael Manal A. , Jiang Lingzhou , Hwang Patrick TaeJoon , Mahdi Fakhri , Jun Ho‐Wook , Elshamy Wael M. , Zhou Yu‐Dong , Murthy S. Narasimha , Doerksen Robert J. , Jo Seongbong
Published: February 2014

Redox‐responsive polymers with pendant quinone propionic acid groups as a redox trigger were optimized by computational modeling to prepare efficient redox‐triggered polymer nanoparticles (NPs) for drug delivery. Lipophilicities at complete reduction of redox‐responsive polymers (<5000 Da) constructed with adipic acid and glutaric acid were remarkably reduced to range from −6.29 to −0.39 compared with nonreduced state (18.87–32.46), suggesting substantial polymer solubility reversal in water. Based on this hypothesis, redox‐responsive NPs were prepared from the synthesized polymers with paclitaxel as model cancer drug. The average size of paclitaxel‐loaded NPs was 249.8 nm and their reconstitutions were stable over eight weeks. In vitro drug release profiles demonstrated the NPs to release >80% of paclitaxel over 24 h at a simulated redox‐state compared with 26.5 to 41.2% release from the control. Cell viability studies revealed that the polymer was nontoxic and the NPs could release paclitaxel to suppress breast cancer cell growth. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40461.
Preparation technique and property evaluation of flame‐retarding/thermal‐insulating/puncture‐resisting PU foam composites
Authors: Li Ting‐Ting , Lou Ching‐Wen , Hsu Ying‐Hsuan , Lin Jia‐Horng
Published: February 2014

In this study, flame‐retarding property of PU foam was realized by compounding with flame‐retarding nonwovens in order to stop flame burning and spread. Followed with global warming, thermal‐insulating materials are also used inside of building for energy conservation. This article presents preparation technique and property evaluation of PU composite board composed of composite nonwovens and PU foam by integrating foaming process. By optimization of composite nonwoven, effects of foam density and nonwoven composition on flame‐retarding and thermal‐insulating properties were discussed. Puncture resistance property of composite board was also investigated for resisting against sharp‐object impacts. The resultant composite board would be applied as partition materials in future building decoration. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40463.
Damping mechanism and different modes of molecular motion through the glass transition of chlorinated butyl rubber and petroleum resin blends
Authors: Zhang Fengshun , He Guansong , Xu Kangming , Wu Hong , Guo Shaoyun , Zhang Chaoliang
Published: February 2014

To further investigate the effect of petroleum resin on damping mechanism and different modes of motion of chlorinated butyl rubber (CIIR), two kinds of petroleum resins with different molecular structures, aliphatic C5 resin and aromatic C9 resin, were incorporated into CIIR. The experimental results showed that the aliphatic C5 resin exhibited a better miscibility with CIIR, compared with aromatic C9 resin. With increase in the content of the C5 resin, the α process and the α′ process of CIIR moved to the higher temperature but to different extents, and the effective damping temperature range was broadened remarkably. The CIIR/C9 resin blends showed two loss peaks, which corresponded to the CIIR matrix and the C9 resin dispersed phase, respectively. The C9 resin neither moved different relaxation modes of CIIR to room temperature nor enhanced the value of the loss damping peak. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40464.
Stabilization of pluronic gels in the presence of different polysaccharides
Authors: Kjøniksen Anna‐Lena , Calejo Maria Teresa , Zhu Kaizheng , Nyström Bo , Sande Sverre Arne
Published: February 2014

Several different polysaccharides have been added to pluronic F127 (poloxamer 407) gels to test their ability to stabilize the gels against dissolution in aqueous media over time. The studied polysaccharides include κ‐carrageenan, chitosan, hyaluronic acid, pectin, alginate, hydroxyethylcellulose, and ethyl(hydroxyethyl)cellulose. Although all the considered polysaccharides slowed down the dissolution time of the pluronic gels, unmodified polysaccharides only had a modest stabilization effect. However, hydrophobic modification of polysaccharides with a sufficiently long hydrocarbon chain (C16) was found to partly prevent the gels from dissolving for more than 6 months. Shorter hydrocarbon chains did not have the same effect, even at high degrees of hydrophobicity. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40465.
TRANSCRIPTION PROFILING OF 12 ASIAN GYPSY MOTH (Lymantria dispar) CYTOCHROME P450 GENES IN RESPONSE TO INSECTICIDES
Authors: Sun Lili , Wang Zhiying , Zou Chuanshan , Cao Chuanwang
Published: February 2014

As the main group of detoxification enzymes, cytochrome P450 monoxygenases (P450s) catalyse an extremely diverse range of reactions that play an important role in the detoxification of foreign compounds. Transcription profiling of 12 Lymantria dispar P450 genes from the CYP6 subfamily believed to be involved in insecticide metabolism was performed in this study. Life‐stage transcription profiling of CYP6 genes revealed significant variations between eggs, larvae, pupae, and adult males and females. Exposure of larvae to sublethal doses of deltamethrin, omethoate, and carbaryl enhanced the transcription of most of the CYP6 P450 genes, with induction peaking between 24 and 72 h after exposure. Transcription profiles were dependent on the levels of insecticide exposure and the various developmental stages.
Oriented covalent immobilization of esterase BioH on hydrophilic‐modified Fe3O4 nanoparticles
Authors: Li Rongrong , Jiang Ling , Ye Lidan , Lu Jie , Yu Hongwei
Published: February 2014

The esterase BioH from Escherichia coli was covalently immobilized onto the surface of the functional magnetic nanosupport in an oriented manner. The surface of the Fe3O4 nanosupport was modified with acyl azide groups or both acyl azide groups and hydroxyl groups. The protein loading of the support was increased from 55 to 99 mg/g by an improvement in hydrophilicity, and the activity retention of the immobilized esterase on the nanosupport was improved by 40% after hydrophilic modification (30% and 70% of the free BioH, respectively). For the BioH immobilized on the hydrophilic‐modified nanosupport, the recovery activity remained 80% of the original activity after 10 times of recycling. The catalytic kinetics and thermo‐/pH‐stability of the immobilized esterase BioH were also determined and compared with those of the free enzyme. The comparatively high activity retention, improved thermo‐/pH‐stability, and good reusability of the immobilized enzyme indicate that oriented covalent immobilization is an efficient method for immobilizing esterase BioH.
Conformation and EPR characterization of rigid, 310‐helical peptides with TOAC spin labels: Models for short distances
Authors: Hashemi Shabestari Maryam , van Son Martin , Moretto Alessandro , Crisma Marco , Toniolo Claudio , Huber Martina
Published: February 2014

For 3D‐structure determination in biophysical systems EPR is rapidly gaining ground. Proteins labeled specifically with two nitroxide spin labels can be prepared, and several EPR methods are available for distance determination, which makes it possible to determine distance constraints. However, such methods require frozen solutions, potentially causing non‐physiological states of the sample. Here, we target spin– spin interaction in liquid solution at room temperature using rigid model compounds. A series of 310‐helical peptides, based on α‐aminoisobutyric acid (Aib), is synthesized with pairs of spin labels separated by three, four, and five amino acids. To avoid flexibility, the noncoded nitroxyl‐containing α‐amino acid TOAC that is rigidly connected with the peptide backbone, is used. The EPR spectra of the peptides show a decreasing amount of coupling between the two spin labels within this series. We suggest through‐bond interaction as the dominating mechanism for exchange interaction (J) and find a stronger J‐coupling than in the corresponding Ala‐based TOAC‐peptides investigated previously (Hanson, et al., J Am Chem Soc 1996, 118, 7618–7625). We speculate that stronger coupling in Aib‐ vs Ala‐ peptides is due to intrinsically stronger through‐bond interaction in the Aib‐based peptides. © 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 244–251, 2014.
Hydrothermal treatment and iodine binding provide insights into the organization of glucan chains within the semi‐crystalline lamellae of corn starch granules
Authors: Vamadevan Varatharajan , Hoover Ratnajothi , Bertoft Eric , Seetharaman Koushik
Published: February 2014

The importance of glucan chains that pass through both the amorphous and crystalline lamellae (tie chains) in the organization of corn starch granules was studied using heat‐moisture treatment (HMT), annealing (ANN), and iodine binding. Molecular structural analysis showed that hylon starches (HV, HVII, and HVIII) contained higher proportion of intermediate glucan chains (HVIII > HVII > HV) than normal corn (CN) starch. Wide angle X‐ray scattering revealed that on HMT, the extent of polymorphic transition in hylon starches decreased with increasing proportion of intermediate and long chains. Iodine treated hylon starches exhibited increased order in the V‐type polymorphism as evidenced by the intense peak at 20° 2θ and the strong reflection intensity at 7.5° 2θ and the extent of the change depended on the type of hylon starch. DSC results showed that the gelatinization enthalpy of CN and waxy corn starch (CW) remained unchanged after ANN. However, hylon starches showed a significant increase in enthalpy with more distinct endotherms after ANN. It can be concluded that tie chains influence the organization of crystalline lamellae in amylose extender mutant starches. © 2014 Wiley Periodicals, Inc. Biopolymers 101: 871–885, 2014.
Contributions of Electrokinetics and Bioremediation in the Treatment of Different Petroleum Components
Authors: Fan Ruijuan , Guo Shuhai , Li Tingting , Li Fengmei , Yang Xuelian , Wu Bo
Published: February 2014

The present study investigated the contributions of electrokinetics (EK) and bioremediation (BIO) in the treatment of different petroleum components by using bio‐electrokinetics (BIO‐EK) technology with a 2‐dimensional (2‐D) electric field. The spatiotemporal changes of the contents of total petroleum hydrocarbons (TPH) and its components, as well as microbial activity, were determined during remediation. The results demonstrated that the contribution rate of EK showed a significant positive correlation with electric intensity, while that of BIO was the opposite. The efficiency of BIO was stimulated by the electric field in the coupled BIO‐EK technology, signifying a synergistic effect between EK and BIO. According to the components analysis, alkanes decreased most intensively compared with other components, indicating that alkanes are more susceptible to both EK and BIO. For n‐alkanes, the degradation efficiency was inversely proportional to hydrocarbon chain length. The contribution of EK was higher than that of BIO in the treatment of alkanes, and the contribution of BIO was higher than that of EK in the degradation of aromatics. The use of a 2‐D electric field led to enhanced microbial activity compared to BIO alone. The dehydrogenase activity increased significantly during the first 70 days, correlating with extent of TPH degradation.
Performance Comparison of Raw and Thermal Modified Rice Husk for Decontamination of Oil Polluted Water
Authors: Razavi Zahra , Mirghaffari Nourollah , Rezaei Behzad
Published: February 2014

The efficiency of raw rice husk (RRH) and the thermally treated one including black rice husk ash (BRHA) and white rice husk ash (WRHA) was examined for the removal of three oil compounds with different viscosities (crude, engine, and spent oils) from aqueous solution. The sorbents were characterized by CHNS analyzer, scanning electron microscopy, Fourier transform infrared, and thermogravimetric analysis. The results showed that the adsorption kinetic was described by pseudo‐second‐order model. The oil adsorption on BRHA was well fitted by the Langmuir model, while the oil adsorption on RRH and WRHA, except for engine oil on RRH, followed the Freundlich model. The efficiency of the sorbents for the removal of oil compounds from water was in the order: BRHA > RRH > WRHA. Maximum adsorption capacity of BRHA for the adsorption of engine, spent, and crude oils was 2000, 1250, and 1000 mg g−1, respectively. The required amount of BRHA for the total removal of engine, spent, and crude oils from aqueous solutions was two, three, and six times of oil concentration, respectively.
Retinal regeneration is facilitated by the presence of surviving neurons
Authors: Sherpa Tshering , Lankford Tyler , McGinn Tim E. , Hunter Samuel S. , Frey Ruth A. , Sun Chi , Ryan Mariel , Robison Barrie D. , Stenkamp Deborah L.
Published: February 2014

Teleost fish regenerate their retinas after damage, in contrast to mammals. In zebrafish subjected to an extensive ouabain‐induced lesion that destroys all neurons and spares Müller glia, functional recovery and restoration of normal optic nerve head (ONH) diameter take place at 100 days postinjury. Subsequently, regenerated retinas overproduce cells in the retinal ganglion cell (RGC) layer, and the ONH becomes enlarged. Here, we test the hypothesis that a selective injury, which spares photoreceptors and Müller glia, results in faster functional recovery and fewer long‐term histological abnormalities. Following this selective retinal damage, recovery of visual function required 60 days, consistent with this hypothesis. In contrast to extensively damaged retinas, selectively damaged retinas showed fewer histological errors and did not overproduce neurons. Extensively damaged retinas had RGC axons that were delayed in pathfinding to the ONH, and showed misrouted axons within the ONH, suggesting that delayed functional recovery following an extensive lesion is related to defects in RGC axons exiting the eye and/or reaching their central targets. The atoh7, fgf8a, Sonic hedgehog (shha), and netrin‐1 genes were differentially expressed, and the distribution of hedgehog protein was disrupted after extensive damage as compared with selective damage. Confirming a role for Shh signaling in supporting rapid regeneration, shhat4+/‐ zebrafish showed delayed functional recovery after selective damage. We suggest that surviving retinal neurons provide structural/molecular information to regenerating neurons, and that this patterning mechanism regulates factors such as Shh. These factors in turn control neuronal number, retinal lamination, and RGC axon pathfinding during retinal regeneration. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 851–876, 2014
The Wnt cries many: Wnt regulation of neurogenesis through tissue patterning, proliferation, and asymmetric cell division
Authors: Bielen Holger , Houart Corinne
Published: February 2014

During early development Wnt signaling has a key role in patterning the prospective nervous system by regulation of cell fate specification, cell polarity, and cell migration. Wnt also coordinates the formation of neural circuits on multiple levels such as transcription, cell cycle, and asymmetric cell division. Here we review the latest findings addressing the role of canonical Wnt/β‐catenin signaling during developmental and adult neurogenesis; exploring the connection of in vivo data to the recently described Wnt‐driven asymmetric stem cell division in vitro. Understanding how Wnt orchestrates these processes in a spatiotemporal manner during corticogenesis will be of crucial importance for the development of new strategies to regenerate neuronal circuits. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 772–780, 2014
Retinal stem/progenitor cells in the ciliary marginal zone complete retinal regeneration: A study of retinal regeneration in a novel animal model
Authors: Miyake Ayumi , Araki Masasuke
Published: February 2014

Our research group has extensively studied retinal regeneration in adultXenopus laevis. However,X. laevisdoes not represent a suitable model for multigenerational genetics and genomic approaches. Instead,Xenopus tropicalisis considered as the ideal model for these studies, although little is known about retinal regeneration inX. tropicalis. In the present study, we showed that a complete retina regenerates at approximately 30 days after whole retinal removal. The regenerating retina was derived from the stem/progenitor cells in the ciliary marginal zone (CMZ), indicating a novel mode of vertebrate retinal regeneration, which has not been previously reported. In a previous study, we showed that inX. laevis, retinal regeneration occurs primarily through the transdifferentiation of retinal pigmented epithelial (RPE) cells. RPE cells migrate to the retinal vascular membrane and reform a new epithelium, which then differentiates into the retina. InX. tropicalis, RPE cells also migrated to the vascular membrane, but transdifferentiation was not evident. Using two tissue culture models of RPE tissues, it was shown that inX. laevisRPE culture neuronal differentiation and reconstruction of the retinal three‐dimensional (3‐D) structure were clearly observed, while inX. tropicalisRPE culture neither ßIII tubulin‐positive cells nor 3‐D retinal structure were seen. These results indicate that the twoXenopusspecies are excellent models to clarify the cellular and molecular mechanisms of retinal regeneration, as these animals have contrasting modes of regeneration; one mode primarily involves RPE cells and the other mode involves stem/progenitor cells in the CMZ. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 739–756, 2014
Review of the CE‐MS platform as a powerful alternative to conventional couplings in bio‐omics and target‐based applications
Authors: Robledo Virginia Rodríguez , Smyth William Franklin
Published: February 2014

Many recent papers and reviews have confirmed the powerful coupling between CE and MS due to efficient and selective separation in combination with selective detection allowing detailed characterization of many biomolecules. It is known that CE‐MS is an increasingly used and sought after technique for analysis in different fields such as environmental science, food analysis, biotechnology, pharmaceutical analysis, biomedical science, forensic science, toxicology, and genetic analysis. CE‐MS is particularly used in bio‐omic applications (proteomic, metabolomic, and also genomic applications) for the determination of biomarkers, disease diagnosis, and therapeutic treatment monitoring. Biomarker qualification, clinical proteomics, and its implementation in routine clinical analysis have certain limitations associated with reproducibility and analytical robustness. However, CE‐MS has been successfully used in numerous clinical applications in recent years when compared with other platforms. The main advantage lies in the availability of large comparable datasets that were all obtained by using the same procedure for sample preparation, analysis, and subsequent data evaluation. The scope of this review is to discuss the performance of CE‐MS as a platform for bio‐omics analysis and target‐based applications focusing on quadrupole (Q), IT, and TOF analyzers, and the types of bioapplications that apply to the particular analyzers. Papers and reviews that were published in 2012 and 2013 with relevant CE‐MS applications are considered in this review.
Simultaneous determination of erlotinib and metabolites in human urine using capillary electrophoresis
Authors: Rodríguez Juana , Castañeda Gregorio , Muñoz Lorena , Navarro Diana , Villa Jose C.
Published: February 2014

The purpose of this study was to develop a simple and sensitive CE‐UV method to quantify erlotinib and metabolites in urine. Following liquid–liquid extraction, erlotinib, and metabolites were separated with a BGE whose composition was phosphate buffer (pH 2.5, 65 mM) with 0.5% Tween 20. The applied voltage was 22 kV, capillary temperature 25°C and the sample injection was performed in the hydrodynamic mode. All the analyses were carried out in a fused silica capillary with an internal diameter of 75 μm and a total length of 37 cm. The detection of target compounds was performed at 240 nm. The calibration was linear in the range 0.15–20 mg/L for erlotinib and metabolites. Inter‐and intraday imprecision were less than 4%. This simple, sensitive, accurate, and cost‐effective method can be used in routine clinical practice to monitor erlotinib concentrations in urine from nonsmall cell lung cancer patients.
Best practices for successful implementation of single‐use technology and qualification
Authors: Hess Philipp N. , Dudziak Gregor
Published: February 2014

Single‐use bioprocessing facilities are providing flexible capacity for clinical trials and low‐ to mid‐volume market supply. However, while this production technology reduces manufacturing cost, quantum jumps in healthcare cost efficiency can be expected from new product technology. In the future, new product technology such as virus‐based systems will need smaller bioprocessing capacities which may be provided by single‐use facilities. The single‐use biomanufacturing facility at Rentschler Biotechnologie received the 2012 Facility of the Year Award in the category Equipment Innovation. The award recognizes the project for its flexible, multiproduct manufacturing facility designed to minimize manufacturing costs and product cycle times. This clinical manufacturing facility proves concepts that pave the way toward the factory of the future for commercial biologics manufacturing. From that and more recent projects, we derived the best practices when implementing such a facility during all project phases (when assessing its feasibility, designing, constructing, qualifying, starting up, and operating it). Challenges, potential solutions, and future single‐use bioprocessing facility design objectives are discussed.
Intersex (testicular oocytes) in largemouth bass (Micropterus salmoides) on the Delmarva Peninsula, USA
Authors: Yonkos Lance T. , Friedel Elizabeth A. , Fisher Daniel J.
Published: February 2014

The authors describe the prevalence and severity of intersex in the form of testicular oocytes in largemouth bass (Micropterus salmoides) collected over a 5-yr period from a variety of surface waters on the Delmarva Peninsula, USA, a region dominated by poultry production and agricultural land use. During a survey from 2005 to 2007 of approximately 200 male specimens representing 6 fish and 2 frog species collected from numerous small-order streams on Delmarva, intersex was observed in only largemouth bass (system-wide prevalence 17%). During 2008 and 2009, testicular oocytes were encountered in male largemouth bass from 6 lakes and 1 large river system, with prevalence ranging from 33% to 88% (weighted arithmetic mean, 57%). The prevalence of testicular oocytes in largemouth bass from Delmarva lakes was comparable to the highest levels reported in a national US Geological Survey reconnaissance of this species, which also occurred in regions of the Atlantic coastal plain with intensive row-crop and animal agriculture. To the authors' knowledge, the present study represents the first report in the peer-reviewed scientific literature of testicular oocytes in fish on the Delmarva Peninsula. Environ Toxicol Chem 2014;33:1163–1169. © 2014 SETAC
Expression of stress‐induced phosphoprotein1 (STIP1) is associated with tumor progression and poor prognosis in epithelial ovarian cancer
Authors: Cho Hanbyoul , Kim Sunghoon , Shin Ha‐Yeon , Chung Eun Joo , Kitano Haruhisa , Hyon Park Jae , Park Lucienne , Chung Joon‐Yong , Hewitt Stephen M. , Kim Jae‐Hoon
Published: February 2014

Stress‐induced phosphoprotein1 (STIP1) is a candidate biomarker in epithelial ovarian cancer (EOC). In this study, we investigated in detail the expression of STIP1, as well as its functions, in EOC. STIP1 expression was assessed by immunohistochemistry (IHC) and the results were compared with clinicopathologic factors, including survival data. The effects of STIP1 gene silencing via small interfering RNA (siRNA) were examined in EOC cells and a xenograft model. The expression of STIP1 protein in EOC was significantly higher than in the other study groups (P < 0.001), and this increase of expression was significantly associated with tumor stage (P = 0.005), tumor grade (P = 0.029), and lymph node metastasis (P = 0.020). In multivariate analysis, overall survival in EOC was significantly shorter in cases with high STIP1 expression (HR = 2.78 [1.01–7.63], P = 0.047). STIP1 silencing in EOC cells resulted in inhibition of cell proliferation and invasion. In addition, in vivo experiments using STIP1 siRNA clearly showed a strong inhibition of tumor growth and a modulation of expression of prosurvival and apoptotic genes, further suggesting that STIP1 silencing can prevent cell proliferation and invasion. In conclusion, increased STIP1 expression is associated with poor survival outcome in EOC, and STIP1 may represent a useful therapeutic target in EOC patients. © 2014 Wiley Periodicals, Inc.
Clear cell sarcoma of the kidney demonstrates an embryonic signature indicative of a primitive nephrogenic origin
Authors: Karlsson Jenny , Holmquist Mengelbier Linda , Ciornei Cristina D. , Naranjo Arlene , O'Sullivan Maureen J. , Gisselsson David
Published: February 2014

Clear cell sarcoma of the kidney (CCSK) is a tumor affecting children with a median age of 3 years at diagnosis. The cell of origin of CCSK is unknown and data on the molecular changes giving rise to CCSK is scarce. This has hindered the identification of positive diagnostic markers and development of molecularly targeted treatment protocols for CCSK. We have characterized a panel of CCSK to gain information regarding its molecular profile and possible origin. High‐resolution genomic analysis with single nucleotide polymorphism array of 37 tumors did not reveal any clues to the mechanisms behind tumor development as remarkably few genetic imbalances were found. Gene expression analysis revealed a highly characteristic gene signature, enriched for pathways involved in embryonic development, including kidney formation. The presence of markers for two different developmental lineages in the embryonic kidney was therefore investigated in the tumor cells. FOXD1 which identifies cells giving rise to stromal elements, and CITED1, a marker for cells primed for nephrogenic epithelial differentiation, were both highly expressed in CCSK. In addition, the early embryonic marker OSR1 was expressed at higher levels in CCSK than in Wilms tumor, normal fetal kidney or adult kidney. As this marker discriminates the intermediate mesoderm from other mesodermal structures, our study could suggest that CCSK arises from a mesodermal cell type that retains the capacity to initiate differentiation towards both nephrons and stroma, but remains locked in a primitive state. © 2014 Wiley Periodicals, Inc.
Mesodermal Mesenchymal Cells Give Rise to Myofibroblasts, but Not Epithelial Cells, in Mouse Liver Injury
Authors: Lua Ingrid , James David , Wang Jiaohong , Wang Kasper S. , Asahina Kinji
Published: February 2014

Hepatic stellate cells (HSCs) and portal fibroblasts (PFs) are believed to be the major source of myofibroblasts that participate in fibrogenesis by way of synthesis of proinflammatory cytokines and extracellular matrices. Previous lineage tracing studies using MesP1Cre and Rosa26lacZflox mice demonstrated that MesP1+ mesoderm gives rise to mesothelial cells (MCs), which differentiate into HSCs and PFs during liver development. In contrast, several

in vivo

and

in vitro

studies reported that HSCs can differentiate into other cell types, including hepatocytes, cholangiocytes, and progenitor cell types known as oval cells, thereby acting as stem cells in the liver. To test whether HSCs give rise to epithelial cells in adult liver, we determined the hepatic lineages of HSCs and PFs using MesP1Cre and Rosa26mTmGflox mice. Genetic cell lineage tracing revealed that the MesP1+ mesoderm gives rise to MCs, HSCs, and PFs, but not to hepatocytes or cholangiocytes, in the adult liver. Upon carbon tetrachloride injection or bile duct ligation surgery-mediated liver injury, mesodermal mesenchymal cells, including HSCs and PFs, differentiate into myofibroblasts but not into hepatocytes or cholangiocytes. Furthermore, differentiation of the mesodermal mesenchymal cells into oval cells was not observed. These results indicate that HSCs are not sufficiently multipotent to produce hepatocytes, cholangiocytes, or oval cells by way of mesenchymal-epithelial transition

in vivo

.

Conclusion :

Cell lineage tracing demonstrated that mesodermal mesenchymal cells including HSCs are the major source of myofibroblasts but do not differentiate into epithelial cell types such as hepatocytes, cholangiocytes, and oval cells. (Hepatology 2014;60:311–322)
Six1: A critical transcription factor in tumorigenesis
Authors: Wu Wangjun , Ren Zhuqing , Li Pinghua , Yu Debing , Chen Jie , Huang Ruihua , Liu Honglin
Published: February 2014

In the past two decades, many studies have shown that sine oculis homeobox 1 (Six1) is a powerful regulator of organogenesis and disease, with important roles in tumorigenesis; therefore, it is important to review the biology of Six1 gene comprehensively. This review describes the function of Six1 in normal organ development, summarizes its role in several diseases, including cancer. The review will extend our understanding about the functional roles of Six1 and suggests opportunities to target Six1 for diagnostic, prognostic, and therapeutic purposes.
Human miR‐1228 as a stable endogenous control for the quantification of circulating microRNAs in cancer patients
Authors: Hu Jie , Wang Zheng , Liao Bo‐Yi , Yu Lei , Gao Xue , Lu Shaohua , Wang Shuyang , Dai Zhi , Zhang Xin , Chen Qing , Qiu Shuang‐Jian , Wu Ying , Zhu Hongguang , Fan Jia , Zhou Jian , Wang Jiping
Published: February 2014

Circulating microRNAs are promising biomarkers for non‐invasive testing and dynamic monitoring in cancer patients. However, no consensus exists regarding the normalization of circulating microRNAs in the quantification, making the results incomparable. We investigated global circulating microRNA profiles to identify a stable endogenous control for quantifying circulating microRNAs using three cohorts (n = 544), including 168 control individuals (healthy subjects and those with chronic hepatitis B and cirrhosis) and 376 cancer patients (hepatocellular, colorectal, lung, esophageal, gastric, renal, prostate, and breast cancer patients). GeNorm, NormFinder, and coefficient of variability (CV) were used to select the most stable endogenous control, whereas Ingenuity Pathway Analysis (IPA) was adopted to explore its signaling pathways. Seven candidates (miR‐1225‐3p, miR‐1228, miR‐30d, miR‐939, miR‐940, miR‐188‐5p, and miR‐134) from microarray analysis and four commonly used controls (miR‐16, miR‐223, let‐7a, and RNU6B) from literature were subjected to real‐time quantitative reverse transcription‐polymerase chain reaction validation using independent cohorts. MiR‐1228 (CV = 5.4%) with minimum M value and S value presented as the most stable endogenous control across eight cancer types and three controls. IPA showed miR‐1228 to be involved extensively in metabolism‐related signal pathways and organ morphology, implying that miR‐1228 functions as a housekeeping gene. Functional network analysis found that “hematological system development” was on the list of the top networks that associate with miR‐1228, implying that miR‐1228 plays an important role in the hematological system. The results explained the steady expression of miR‐1228 in the blood. In conclusion, miR‐1228 is a promising stable endogenous control for quantifying circulating microRNAs in cancer patients.
Ontogenetic variation in the mandibular ramus of great apes and humans
Authors: Terhune Claire E. , Robinson Chris A. , Ritzman Terrence B.
Published: February 2014

Considerable variation exists in mandibular ramus form among primates, particularly great apes and humans. Recent analyses of adult ramal morphology have suggested that features on the ramus, especially the coronoid process and sigmoid notch, can be treated as phylogenetic characters that can be used to reconstruct relationships among great ape and fossil hominin taxa. Others have contended that ramal morphology is more influenced by function than phylogeny. In addition, it remains unclear how ontogeny of the ramus contributes to adult variation in great apes and humans. Specifically, it is unclear whether differences among adults appear early and are maintained throughout ontogeny, or if these differences appear, or are enhanced, during later development. To address these questions, the present study examined a broad ontogenetic sample of great apes and humans using two‐dimensional geometric morphometric analysis. Variation within and among species was summarized using principal component and thin plate spline analyses, and Procrustes distances and discriminant function analyses were used to statistically compare species and age classes. Results suggest that morphological differences among species in ramal morphology appear early in ontogeny and persist into adulthood. Morphological differences among adults are particularly pronounced in the height and angulation of the coronoid process, the depth and anteroposterior length of the sigmoid notch, and the inclination of the ramus. In all taxa, the ascending ramus of the youngest specimens is more posteriorly inclined in relation to the occlusal plane, shifting to become more upright in adults. These results suggest that, although there are likely functional influences over the form of the coronoid process and ramus, the morphology of this region can be profitably used to differentiate among great apes, modern humans, and fossil hominid taxa. J. Morphol. 275:661–677, 2014. © 2013 Wiley Periodicals, Inc.
Analysis of estrogens and estrogen mimics in edible matrices—A review
Authors: Adamusova Hana , Bosakova Zuzana , Coufal Pavel , Pacakova Vera
Published: February 2014

This review provides a brief survey of the biological effects of selected endocrine‐disrupting compounds that are formed after internal exposure of organisms. Further, the present analytical methods available for the determination of these compounds in foodstuffs are critically evaluated. The attention is primarily devoted to the methods for sample pretreatment, which are the main source of errors and are usually the most time‐consuming step of the whole analysis. This review is focused on selected natural and synthetic estrogens, estrogen conjugates, and chemical additives used in the plastic industry that can act as estrogen mimics.
Retention behavior of a homologous series and positional isomers of aliphatic amino acids in hydrophilic interaction chromatography
Authors: Douša Michal , Srbek Jan , Stránský Zdeněk , Gibala Petr , Nováková Lucie
Published: February 2014

The retention behavior of several series of free α‐ and ω‐amino acids and positional isomers of amino pentanoic acid in the hydrophilic interaction chromatography mode (HILIC) was studied. The study was carried out on three stationary phases followed by post‐column derivatization with fluorescence detection in order to describe the retention mechanism of the tested amino acids. The effect of chromatographic conditions including acetonitrile content in the mobile phase, mobile phase pH (ranging from 3.5 to 6.5) and concentration of buffer in the mobile phase was investigated. The effect of the number of carbon atoms (nC) in aliphatic chains of the individual homologue of α‐ and ω‐amino acids and the logarithm of the partition coefficient (logD) on retention was also a part of the presented study. A good correlation (r > 0.98) between the logk and logD values of amino acids or nC, respectively, was observed. The described linear relationships were subsequently applied to predict the retention behavior of individual members of the homologous series of amino acids and to optimize the mobile phase composition in HILIC. The obtained results confirmed that the retention mechanism of α‐amino acids, ω‐amino acids and positional isomers of amino acids was based on the logD values and the number of carbon atoms in the aliphatic chains of amino acids. The elution order of ω‐amino acids and positional isomers of amino pentanoic acid was strongly dependent on the mobile phase pH in the investigated range whereas the retention factors of all α‐amino acids remained essentially unchanged on all tested stationary phases.
Integral models in unramified mixed characteristic (0, 2) of hermitian orthogonal Shimura varieties of PEL type, Part II
Authors: Vasiu Adrian
Published: February 2014

We construct relative PEL type embeddings in mixed characteristic (0, 2) between hermitian orthogonal Shimura varieties of PEL type. We use this to prove the existence of integral canonical models in unramified mixed characteristic (0, 2) of hermitian orthogonal Shimura varieties of PEL type.
Rough singular integrals and maximal operators with mixed homogeneity along compound curves
Authors: Wu Huoxiong
Published: February 2014

The parabolic singular integrals along certain compound curves as well as the related maximal operators are considered. Under rather weakened size conditions on the integral kernels both on the unit sphere and in the radial direction, the ‐mapping properties for such operators are established. Some previous results are greatly extended and improved.
Hyponormality of bounded‐type Toeplitz operators
Authors: Curto Raúl E. , Hwang In Sung , Lee Woo Young
Published: February 2014

In this paper we deal with the hyponormality of Toeplitz operators with matrix‐valued symbols. The aim of this paper is to provide a tractable criterion for the hyponormality of bounded‐type
Toeplitz operators (i.e., the symbol is a matrix‐valued function such that Φ and are of bounded type). In particular, we get a much simpler criterion for the hyponormality of when the co‐analytic part of the symbol Φ is a left divisor of the analytic part.
Copolymer Composition Deviations from Mayo–Lewis Conventional Free Radical Behavior in Nitroxide Mediated Copolymerization
Authors: Zapata‐González Iván , Hutchinson Robin A. , Matyjaszewski Krzysztof , Saldívar‐Guerra Enrique , Ortiz‐Cisneros José
Published: February 2014

The validity of the Mayo‐Lewis (ML) terminal model for copolymer composition in nitroxide mediated copolymerization is systematically tested by simulation. Significant deviations in copolymer composition from ML behavior occur under various parameter combinations before the nitroxide quasi‐equilibrium condition (QEC) is reached. Maximum deviations are usually below 5 pp, and absent at conversions higher than 3%, but after 10% in some cases. High reactivity ratios lead to larger deviations; low reactivity ratios (faster cross‐propagation) produce near ML behavior. An additional continuous radical source leads to faster attainment of the QEC and reduces the deviations from ML behavior.
Population Balance Modeling of Aggregation and Coalescence in Colloidal Systems
Authors: Kryven Ivan , Lazzari Stefano , Storti Giuseppe
Published: February 2014

A complex interplay between aggregation and coalescence occurs in many colloidal polymeric systems and determines the morphology of the final clusters of primary particles. To describe this process, a 2D population balance equation (PBE) based on cluster mass and fractal dimension is solved, employing a discretization method based on Gaussian basis functions. To prove the general reliability of the model and to show its potential, parametric simulations are performed employing both diffusion‐limited‐cluster aggregation (DLCA) and reaction‐limited‐cluster‐aggregation (RLCA) kernels and different coalescence rates. It turns out that in both DLCA and RLCA regimes, a faster coalescence leads to smaller sized and more compact clusters, whereas a slow coalescence promotes the formation of highly reactive fractals, resulting in larger aggregates.
Tideglusib reduces progression of brain atrophy in progressive supranuclear palsy in a randomized trial
Authors: Höglinger Günter U. , Huppertz Hans‐Jürgen , Wagenpfeil Stefan , Andrés María V , Belloch Vincente , León Teresa , del Ser Teodoro ,   for the TAUROS MRI Investigators
Published: February 2014

It is believed that glycogen synthase kinase‐3 hyperphosphorylates tau protein in progressive supranuclear palsy (PSP). The Tau Restoration on PSP (TAUROS) trial assessed the glycogen synthase kinase‐3 inhibitor tideglusib as potential treatment. For the magnetic resonance imaging (MRI) substudy reported here, we assessed the progression of brain atrophy. TAUROS was a multinational, phase 2, double‐blind, placebo‐controlled trial in patients with mild‐to‐moderate PSP who were treated with oral tideglusib (600 mg or 800 mg daily) or with placebo for 1 year. A subset of patients underwent baseline and 52‐week MRI. Automated, observer‐independent, atlas‐based, and mask‐based volumetry was done on high‐resolution, T1‐weighted, three‐dimensional data. For primary outcomes, progression of atrophy was compared both globally (brain, cerebrum) and regionally (third ventricle, midbrain, pons) between the active and placebo groups (Bonferroni correction). For secondary outcomes, 15 additional brain structures were explored (Benjamini & Yekutieli correction). In total, MRIs from 37 patient were studied (placebo group, N = 9; tideglusib 600 mg group, N = 19; tideglusib 800 mg group, N = 9). The groups compared well in their demographic characteristics. Clinical results showed no effect of tideglusib over placebo. Progression of atrophy was significantly lower in the active group than in the placebo group for the brain (mean ± standard error of the mean: −1.3% ± 1.4% vs. −3.1% ± 2.3%, respectively), cerebrum (−1.3% ± 1.5% vs. −3.2% ± 2.1%, respectively), parietal lobe (−1.6% ± 1.9% vs. −4.1% ± 3.0%, respectively), and occipital lobe (−0.3% ± 1.8% vs. −2.7% ± 3.2%, respectively). A trend toward reduced atrophy also was observed in the frontal lobe, hippocampus, caudate nucleus, midbrain, and brainstem. In patients with PSP, tideglusib reduced the progression of atrophy in the whole brain, particularly in the parietal and occipital lobes. © 2014 International Parkinson and Movement Disorder Society
Neuropathology of prodromal Lewy body disease
Authors: Iranzo Alex , Gelpi Ellen , Tolosa Eduard , Molinuevo José Luis , Serradell Mónica , Gaig Carles , Santamaria Joan
Published: February 2014

Background

Current evidence suggests that there is a prodromal stage in Parkinson disease characterized by a variety of nonmotor symptoms.

Methods and Results

A 69‐year‐old man presented to our sleep center with isolated rapid eye movement sleep behavior disorder. During a 10‐year follow‐up period, longitudinal clinical and laboratory assessments indicated the development of hyposmia, depression, mild cognitive impairment, and constipation. Parkinsonism was absent, but dopamine transporter imaging showed subclinical substantia nigra damage. Postmortem examination demonstrated neuronal loss and Lewy body pathology in the peripheral autonomic nervous system (eg, cardiac and myenteric plexus), olfactory bulb, medulla, pons, substantia nigra pars compacta (estimated cell loss, 20%‐30%), nucleus basalis of Meynert, and amygdala, sparing the neocortex.

Conclusions

Our observations indicate that nonmotor symptoms plus widespread peripheral and central nervous system pathological changes occur before parkinsonism and dementia onset in diseases associated with Lewy pathology. The current diagnostic criteria for Parkinson's disease miss these patients, who present only with nonmotor symptoms. © 2014 International Parkinson and Movement Disorder Society
Pre‐maturation with cAMP modulators in conjunction with EGF‐like peptides during in vitro maturation enhances mouse oocyte developmental competence
Authors: Richani D. , Wang X. , Zeng H.T. , Smitz J. , Thompson J.G. , Gilchrist R.B.
Published: February 2014

Recent studies have independently shown that cyclic adenosine 3′5′‐monophosphate (cAMP) modulation prior to in vitro maturation (IVM) and epidermal growth factor (EGF)‐like peptide supplementation during IVM improve subsequent oocyte developmental outcomes. This study investigated the effects of an IVM system that incorporates these two concepts. Cumulus–oocyte complexes (COCs) were collected from pre‐pubertal mice either 46 hr post‐equine chorionic gonadotropin (eCG) (IVM) or post‐eCG + post‐human chorionic gonadotropin (hCG) stimulation (in vivo maturation; IVV). IVM COCs were treated with the cAMP modulators forskolin and IBMX for 1, 2, or 4 hr (pre‐IVM phase) prior to IVM. COCs then underwent IVM with the EGF‐like peptides amphiregulin or epiregulin, or with the common IVM stimulants follicle‐stimulating hormone (FSH) or EGF. A pre‐IVM phase increased the size of the subsequent blastocysts' inner‐cell‐mass compared to standard IVM, regardless of IVM treatment (P < 0.05). Unlike FSH or EGF, amphiregulin or epiregulin significantly increased blastocyst quality (trophectoderm and total cell numbers) and/or yield (P < 0.01) compared to standard IVM, and were the only treatments that produced blastocysts comparable to IVV‐derived blastocysts. Forskolin acutely up‐regulated EGF‐like peptide mRNA expression after a 2‐hr pre‐IVM phase (P < 0.001), although EGF receptor and ERK1/2 activities were not significantly different than control. IVV‐like levels of EGF‐like peptide mRNA expression during IVM were maintained only by supplementing with EGF‐like peptides and EGF, since expression levels induced by FSH were significantly lower in vitro than during IVV. However, EGF receptor and ERK1/2 phosphorylation levels were not significantly different across treatment groups. In conclusion, a pre‐IVM phase in conjunction with IVM in the presence of EGF‐like peptides endows high oocyte developmental competence, as evidenced by increased embryo yield and/or quality relative to FSH and EGF.Mol. Reprod. Dev. 81: ???–???, 2014. © 2014 Wiley Periodicals, Inc.