bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue vascularization through 3D printing: Will technology bring us flow?
Authors: Paulsen S.J. , Miller J.S.
Published: January 2015

Background: Though in vivo models provide the most physiologically relevant environment for studying tissue function, in vitro studies provide researchers with explicit control over experimental conditions and the potential to develop high throughput testing methods. In recent years, advancements in developmental biology research and imaging techniques have significantly improved our understanding of the processes involved in vascular development. However, the task of recreating the complex, multi‐scale vasculature seen in in vivo systems remains elusive.

Results: 3D bioprinting offers a potential method to generate controlled vascular networks with hierarchical structure approaching that of in vivo networks. Bioprinting is an interdisciplinary field that relies on advances in 3D printing technology along with advances in imaging and computational modeling, which allow researchers to monitor cellular function and to better understand cellular environment within the printed tissue.

Conclusions: As bioprinting technologies improve with regards to resolution, printing speed, available materials, and automation, 3D printing could be used to generate highly controlled vascularized tissues in a high throughput manner for use in regenerative medicine and the development of in vitro tissue models for research in developmental biology and vascular diseases. Developmental Dynamics 244:629–640, 2015. © 2015 Wiley Periodicals, Inc.
Facile Preparation of Mn+‐Doped (M = Cu, Co, Ni, Mn) Hierarchically Mesoporous CeO2 Nanoparticles with Enhanced Catalytic Activity for CO Oxidation
Authors: Zhang Jingcai , Guo Jinxin , Liu Wei , Wang Shuping , Xie Anran , Liu Xiufang , Wang Jun , Yang Yanzhao
Published: January 2015

A series of transition‐metal‐doped (Cu, Co, Ni, Mn) hierarchically mesoporous CeO2 nanoparticles have been fabricated through a simple solvothermal strategy. The effect of these doping metals on the morphology and the phase transformation of the Ce(HCOO)3 precursor was investigated. The specific order in which the doping metal cations (except Cu2+) are added during the synthesis process has a remarkable influence on the precursor morphology. By introducing these different metal cations, the doping composition can be adjusted freely. The XRD, Raman spectroscopy, and X‐ray photoelectron spectroscopy (XPS) results show the high homogeneity of the doped ceria and demonstrate that the transition metal cations have been incorporated into the CeO2 lattice. All of the doped ceria nanoparticles, especially the Cu2+‐doped ceria product, exhibit improved reduction behavior and enhanced CO conversion performance.
Chinese yak and yellow cattle exhibit considerable differences in tissue content of squalene, tocopherol, and fatty acids
Authors: Liu Chunyou , Jin Guofeng , Luo Zhang , Li Shugang , Sun Shuguo , Li Yonggang , Ma Meihu
Published: January 2015

Bioactive components in five tisues (longissimus muscle (LSM), biceps femoris muscle (BFM), liver (LV), subcutaneous adipose tissue (SAT), and abdominal adipose tissue (AAT)) of yak in Tibet and yellow cattle in Hubei were investigated. Yak was significantly higher (p<0.01) than yellow cattle in the squalene content of lipids of BFM (59.82/19.07 mg/100g), LSM (20.99/7.81 mg/100g) and LV (6.94/2.67 mg/100g), respectively, but not in SAT and AAT (p>0.05). Yak was also significantly higher (p<0.05) than yellow cattle in the total tocopherol content. Additionally, yak hepatic lipids showed the highest content of saturated fatty acids (58.11%) and polyunsaturated fatty acids (PUFA, 25.81%) and the lowest content of monounsaturated fatty acids (MUFA, 16.08%), while yellow cattle AAT had the highest content of MUFA (47.54%) and the lowest content of PUFA (2.36%). The considerable differences between the two in composition suggest that the five tissues of yak are potential sources of bioactive components and essential fatty acids for humans.

Practical applications: The results from the analysis of the contents of squalene, tocopherols, total lipids，moisture, ash, and pH and fatty acid profile in the studied tissues of Tibet yak and Hubei yellow cattle provide useful information for developing functional foods using yak meat or other tissues as materials.

Comparison of squalene and total tocopherol contents in different tissues of yak and yellow cattle.
Elaboration of Furopyridine Scaffolds
Authors: Jasselin‐Hinschberger Adeline , Comoy Corinne , Chartoire Anthony , Fort Yves
Published: January 2015

Over the past few decades, furopyridines have emerged as key structural subunits prevalent in a number of natural products and structural analogues associated with interesting biological activities. Consequently, considerable efforts have been devoted to the synthesis of these fused heterocyclic scaffolds. This review covers the main methodologies reported in the literature for the preparation of furopyridines.
Electrochemical Sensor Based on Gold Nanoparticles Stabilized in Poly(Allylamine hydrochloride) for Determination of Vanillin
Authors: Silva Tânia Regina , Brondani Daniela , Zapp Eduardo , Cruz Vieira Iolanda
Published: January 2015

Gold nanoparticles stabilized in poly(allylamine hydrochloride) (AuNP‐PAH) were synthesized, characterized and applied in the development of a new sensor for the determination of vanillin by square‐wave voltammetry. Under optimized conditions, the calibration curve showed a linear range for vanillin of 0.90 to 15.0 µmol L−1, with a limit of detection of 55 nmol L−1. The sensor demonstrated acceptable selectivity and stability, as well as good intra‐day and inter‐day repeatability and electrode‐to‐electrode repeatability (with relative standard deviations of 3.5, 4.5 and 3.9 %, respectively). The sensor was successfully applied in the determination of vanillin in different commercial samples.
Selective and Simultaneous Determination of Dihydroxybenzene Isomers Based on Green Synthesized Gold Nanoparticles Decorated Reduced Graphene Oxide
Authors: Palanisamy Selvakumar , Karuppiah Chelladurai , Chen Shen‐Ming , Muthupandi K. , Emmanuel R. , Prakash P. , Elshikh Mohamed S. , Ajmal Ali M. , Al‐Hemaid Fahad M. A.
Published: January 2015

In the present study, we report the simultaneous electrochemical determination of hydroquinone (HQ), catechol (CC) and resorcinol (RC) at gold nanoparticles (Au‐NPs) decorated reduced graphene oxide (RGO) modified electrode. An enhanced and well defined peak current response with a better peak separation of HQ, CC and RC is observed at RGO/Au‐NPs composite than that of RGO and Au‐NPs modified electrodes. The fabricated modified electrode shows a wide linear response in the concentration range of 3–90 µM, 3–300 µM and 15–150 µM for HQ, CC and RC, respectively. The detection limit of HQ, CC and RC is found as 0.15 µM, 0.12 µM and 0.78 µM, respectively.
Interaction Association Analysis of Imputed SNPs in Case‐Control and Follow‐Up Studies
Authors: Subirana Isaac , González Juan R.
Published: January 2015

A new method is described to assess the interactions of imputed SNPs (single nucleotide polymorphisms) in case‐control and follow‐up studies, properly incorporating SNP imputation uncertainty in the likelihood model. Using simulation studies and analysis of real data obtained from the Framingham study cohort, we compare the performance of this new method to DOSAGE and NAIVE (also known as Best‐Guess) methods, developed and commonly used in the context of single SNP and extended to SNP‐by‐SNP interaction. The results show that only our new method is unbiased under all examined scenarios regarding allele frequencies, imputation uncertainty degree, and interaction effect size. In addition, our method achieves at least as much power as the other two, and exceeds their statistical power in certain follow‐up analysis situations. This method is fast enough to perform Genome Wide Interaction Studies (GWIS) with hundreds of thousands of interactions. By performing an exhaustive simulation study let us to provide recommendations for selecting the most appropriated method depending on MAF, interaction effect size, and uncertainty degree. In general, DOSAGE and our proposed method are recommended in most situations being our method more powerful and accurate when uncertainty and effect increase.
Activation of aryl hydrocarbon receptor dissociates fatty liver from insulin resistance by inducing fibroblast growth factor 21
Authors: Lu Peipei , Yan Jiong , Liu Ke , Garbacz Wojciech G. , Wang Pengcheng , Xu Meishu , Ma Xiaochao , Xie Wen
Published: January 2015

The aryl hydrocarbon receptor (AHR), also known as the dioxin receptor, was originally characterized as a xenobiotic receptor that senses xenotoxicants. We investigated the endobiotic and hepatic role of AHR in fatty liver and energy metabolism and identified the endocrine factor that mediates the metabolic function of AHR. Wild‐type and liver‐specific constitutively activated human AHR transgenic mice were used to investigate the role of AHR in fatty liver and energy homeostasis. Adenovirus expressing short hairpin RNA targeting fibroblast growth factor 21 (FGF21) were used to determine the involvement of FGF21 in the metabolic effect of AHR. We showed that, despite their severe fatty liver, the transgenic mice were protected from diet‐induced obesity and type 2 diabetes. We identified the endocrine hormone FGF21 as a mediator for the metabolic benefit of AHR and established FGF21 as a direct transcriptional target of AHR. Interestingly, the transactivation of FGF21 by AHR contributed to both hepatic steatosis and systemic insulin hypersensitivity, both of which were largely abolished upon FGF21 knockdown. Conclusions: The AHR‐FGF21 endocrine signaling pathway establishes AHR as a pivotal environmental modifier that integrates signals from chemical exposure in the regulation of lipid and energy metabolism. (Hepatology 2015;61:1908–1919)
Cytotoxicity of luteolin in primary rat hepatocytes: the role of CYP3A‐mediated ortho‐benzoquinone metabolite formation and glutathione depletion
Authors: Shi Fuguo , Zhao Peng , Li Xiaobing , Pan Hong , Ma Shiping , Ding Li
Published: January 2015

Luteolin (LUT), an active ingredient in traditional Chinese medicines and an integral part of the human diet, has shown promising pharmacological activities with a great potential for clinical use. The purpose of this study was to evaluate the role of cytochrome P450 (CYP450)‐mediated reactive ortho‐benzoquinone metabolites formation and glutathione (GSH) depletion in LUT‐induced cytotoxicity in primary rat hepatocytes. A reactive ortho‐benzoquinone metabolite was identified by liquid chromatography coupled with tandem mass spectrometry (LC‐MS/MS) in rat liver microsomes (RLMs) and rat hepatocytes. Using a specific chemical inhibitor method, the CYP3A subfamily was found to be responsible for the reactive metabolite formation in RLMs. Induction of CYP3A by dexamethasone enhanced LUT‐induced cytotoxicity, whereas inhibition of CYP3A by ketoconazole (Keto) decreased the cytotoxicity. The cytotoxicity and cell apoptosis induced by LUT were related to the amount of reactive metabolite formation. Furthermore, Keto inhibited the LUT‐induced GSH exhaustion. The cytotoxicity was significantly enhanced by pretreatment with L‐buthionine sulfoximine to deplete the intracellular GSH. A time course experiment showed that GSH depletion by LUT was not via oxidation of GSH and occurred prior to the increase in 2', 7'‐dichlorofluorescein in hepatocytes. Collectively, these data suggest that CYP3A‐mediated reactive metabolite formation plays a critical role in LUT‐induced hepatotoxicity, and the direct GSH depletion is an initiating event in LUT‐mediated cytotoxicity in primary rat hepatocytes. Copyright © 2015 John Wiley & Sons, Ltd.
High adipose LPL activity and adipocyte hypertrophy reduce visceral fat and metabolic risk in obese, older women
Authors: Serra Monica C. , Ryan Alice S. , Sorkin John D. , Favor Knachelle H. , Goldberg Andrew P.
Published: January 2015

Objective

To determine whether higher subcutaneous adipose tissue lipoprotein lipase activity (AT‐LPLA) is associated with greater triglyceride (TG) storage in subcutaneous adipose tissue (SAT), thereby reducing visceral adipose tissue (VAT) accumulation and metabolic dysfunction.

Methods

Obese postmenopausal women (60 ± 1 years, mean ± SEM; N = 101) had body composition measured by DXA and CT and had fat aspirations to measure fat cell weight (FCW) and AT‐LPLA. Women were ranked by visceral to total abdominal fat ratio (VAT/TAF), and the lowest and highest groups (n = 24) matched for % fat and age.

Results

The prevalence of metabolic dysfunction was 7‐ to 10‐fold higher in women with high VAT/TAF (Ps < 0.01). Women with low VAT/TAF had 11% and 6% lower abdominal and gluteal FCW but 28% and 54% higher AT‐LPLA/106 cells in abdominal and gluteal fat, respectively. Abdominal FCW correlated with AT‐LPLA in women with low (r = 0.63, P < 0.01) but not high (r = 0.14, P = 0.52) VAT/TAF, and these lines differed in slope (P < 0.05) and intercept (P < 0.01), suggesting greater capacity for TG storage with low VAT/TAF. There were no relationships between gluteal FCW and AT‐LPLA. The relationship between SAT and abdominal AT‐LPLA (r = 0.39, P < 0.01) suggests that higher AT‐LPLA promotes TG storage.

Conclusions

These results suggest that higher AT‐LPLA is associated with SAT adipocyte hypertrophy, which reduces visceral adiposity and metabolic risk in obese, older women.
Timing of detection of anencephaly in The Netherlands
Authors: Fleurke‐Rozema J. H. , van Leijden L. , van de Kamp K. , Pajkrt E. , Bilardo C. M. , Snijders R. J. M.
Published: January 2015

Objective

The objective of this study is to assess the gestational age at detection and prevalence of anencephaly in the North of The Netherlands over a 5‐year period.

Methods

A case list of all cases of anencephaly from two fetal medicine units was compiled. Cases were included if the estimated due date was between 1 August 2008 and 31 July 2013.

Results

Overall prevalence of anencephaly was 5.4 per 10.000 pregnancies (n = 110). The majority of cases (69%) was detected before 18 weeks' gestation. Factors determining successful early diagnosis were competence level of the sonographers, with a significantly higher detection rate when scans were performed by a sonographer licensed by the Fetal Medicine Foundation (FMF) for nuchal translucency measurement (p = 0.001), and gestational age at or beyond 11 weeks of gestation (p = 0.024).

Conclusion

Improving detection of anencephaly in the first trimester requires ultrasound screening at or after 11 weeks of gestation, performed by experienced sonographers trained in recognizing fetal anomalies. Sonographers should be instructed that the goal of the first trimester scan is not only to measure nuchal translucency thickness but also to exclude major anomalies. © 2015 John Wiley & Sons, Ltd.
Bent π‐Conjugated Systems Composed of Three‐Dimensional Benzoannulenes
Authors: Nishiuchi Tomohiko , Iyoda Masahiko
Published: January 2015

This article describes bent π‐conjugated systems composed of alternating o‐phenylene and Z‐vinylene units. all‐Z‐[n]Benzo[4n]annulenes are higher homologues of dibenzocyclooctatetraene (DBCOT) with a concave π system, and attempts were made to convert [20]‐ and [24]annulenes having partial belt structures of fullerenes and carbon nanotubes into [10]‐ and [12]phenacenes. A bent π‐conjugated system composed of two DBCOT units showed dynamic syn–anti equilibrium in solution and behaved as dynamic molecular tweezers (DMTs). The syn isomers of the DMTs formed blue charge‐transfer complexes with DDQ in solution, and this complexation and color change were applied to thermochromism. Furthermore, DMTs having two CN groups on each COT ring exhibited crystalline‐state emission in the presence of solvent molecules, although almost no emission was observed in solution or the solid state. Based on this crystalline‐state emission, a vapochromic system was established. The multifunctional properties of DMTs caused by the flexibility of the nonplanar π system are summarized.
Hydrothermal Synthesis of Two Cuprous Bromide Compounds Using Zinc Metal as Reductant
Authors: Gautier Romain , Paul Camille
Published: January 2015

Two new cuprous bromide phases Cu2(ImH)Br3 (Im = imidazole) (1) and Cu3(Trz)2Br3 (Trz = 1,2,4‐triazole) (2) were synthesized by hydrothermal method and characterized by single‐crystal X‐ray diffraction. The compounds exhibit similar triclinic one‐dimensional crystal structures (space group P$\bar{1}$) but they are built from two different copper bromide chains. The influence of the azole ligands on the coordination of the transition metals is discussed. Zinc metal has been shown to be an effective reductant in hydrothermal conditions for stabilizing CuI phases from CuII reactants. UV/Vis spectroscopy and thermal analyses were performed on both materials.
Direct numerical simulation of low-Reynolds-number flow past arrays of rotating spheres
Authors: Zhou Qiang , Fan Liang-Shih
Published: January 2015

Immersed boundary-lattice Boltzmann simulations are used to examine the effects of particle rotation, at low particle Reynolds numbers, on flows in ordered and random arrays of mono-disperse spheres. The drag force, the Magnus lift force and the torque on the spheres, are determined at solid volume fractions up to the close-packed limits of the arrays. The rotational Reynolds number based on the angular velocity and the diameter of the spheres is used to characterize the rotational movement of spheres. The results show that the normalized Magnus lift force produced by particle rotation is approximately in direct proportion to the rotational Reynolds number, while the normalized drag force and torque acting on spheres are barely affected by this number. The Magnus lift force is negligible relative to the magnitude of the drag force when the rotational Reynolds number is low. However, it can be very significant, and even larger than the drag force, as the rotational Reynolds number increases up to $O(10^{2})$, especially for low solid volume fractions. Based on the simulation results, relations for the Magnus lift force and the torque for both ordered arrays and random arrays of rotating spheres at solid volume fractions from zero to close-packed limits are formulated. Further, the drag force relations in the literature are revised based on existing theories and the present simulation results for both arrays of spheres.
ON THE ADAN–WEISS LOSS MODEL HAVING SKILL-BASED SERVERS AND LONGEST IDLE ASSIGNMENT RULE
Authors: Haji Babak
Published: January 2015

We consider a queueing loss system with heterogeneous skill based servers with arbitrary distributions. We assume Poisson arrivals, with each arrival having a vector indicating which of the servers are eligible to serve it. Arrivals can only be assigned to a server that is both idle and eligible. We assume arrivals are assigned to the idle eligible server that has been idle the longest and derive, up to a multiplicative constant, the limiting distribution for this system. We show that the limiting probabilities of the ordered list of idle servers depend on the service time distributions only through their means. Moreover, conditional on the ordered list of idle servers, the remaining service times of the busy servers are independent and have their respective equilibrium service distributions. We also provide an algorithm using Gibbs sampler Markov Chain Monte Carlo method for estimating the limiting probabilities and other desired quantities of this system.
Protecting Holy Heritage in Italy—A Critical Assessment through the Prism of International Law
Authors: Chechi Alessandro
Published: January 2015

In Italy, churches, chapels, and monasteries are often rich in precious artifacts. However, these religious buildings cannot be easily protected from theft because either they have no antitheft measures or they are abandoned. This article examines the problematic state of the holy heritage in the Italian territory from a legal perspective. In particular, it looks at Italian legislation and the international instruments entered into by the Italian State. The article argues that this protective legal regime is affected by various shortcomings and loopholes that mostly relate to the implementation of existing legal standards. Notably, it appears that these problems originate from the fact that most of the holy heritage situated in Italy belongs to the Catholic Church, and at the same time, it constitutes the historical and artistic patrimony of the Italian State. The article calls for a more efficient management of such precious vestiges by the stakeholders involved and for a revision of the domestic legislation with a view of properly incorporating the achievements of international cultural heritage law.
Acute gastrointestinal illness following a prolonged community-wide water emergency
Authors: GARGANO J. W. , FREELAND A. L. , MORRISON M. A. , STEVENS K. , ZAJAC L. , WOLKON A. , HIGHTOWER A. , MILLER M. D. , BRUNKARD J. M.
Published: January 2015

The drinking water infrastructure in the United States is ageing; extreme weather events place additional stress on water systems that can lead to interruptions in the delivery of safe drinking water. We investigated the association between household exposures to water service problems and acute gastrointestinal illness (AGI) and acute respiratory illness (ARI) in Alabama communities that experienced a freeze-related community-wide water emergency. Following the water emergency, investigators conducted a household survey. Logistic regression models were used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for self-reported AGI and ARI by water exposures. AGI was higher in households that lost water service for ⩾7 days (aPR 2·4, 95% CI 1·1–5·2) and experienced low water pressure for ⩾7 days (aPR 3·6, 95% CI 1·4–9·0) compared to households that experienced normal service and pressure; prevalence of AGI increased with increasing duration of water service interruptions. Investments in the ageing drinking water infrastructure are needed to prevent future low-pressure events and to maintain uninterrupted access to the fundamental public health protection provided by safe water supplies. Households and communities need to increase their awareness of and preparedness for water emergencies to mitigate adverse health impacts.
POLITICAL TRANSFORMATIONS AND THE EVERYDAY IN POSTCLASSIC OAXACA
Authors: Joyce Arthur A. , Levine Marc N. , King Stacie M. , Hedgepeth Balkin Jessica , Barber Sarah B.
Published: January 2015

We use excavations of low-status houses to explore Postclassic political and economic transformations in the lower Río Verde Valley, Oaxaca. Following the collapse of Classic period political institutions, commoners experienced greater economic and political autonomy. Residential excavations at Río Viejo indicate that commoners took advantage of the absence of regional authority to gain greater control over surplus craft products, especially cotton thread, as well as access to social valuables and long distance trade. By the Late Postclassic period, the region was once again dominated by powerful rulers. Yet household excavations at Tututepec show that Late Postclassic commoners continued to control some surplus craft production and had access to social valuables like copper and polychrome pottery via market exchange. We argue that Late Postclassic political relations were a product of negotiations among elites and commoners that in part reflect the greater economic autonomy and political power that Early Postclassic people had acquired.
SACRED LANDSCAPES AND BUILDING PRACTICES AT UCI, KANCAB, AND UCANHA, YUCATAN, MEXICO
Authors: Hutson Scott R. , Welch Jacob A.
Published: January 2015

During the emergence of regional hierarchy around the site of Uci in northwest Yucatan, Mexico, ordinary people affected power relations in at least two ways. First, in the Late Preclassic and Early Classic periods, Uci had the largest ceremonial center and the largest population within a 20 km radius. Uci also physically linked itself to smaller settlements, such as Kancab and Ucanha, by means of a broad stone causeway. Yet Kancab and Ucanha's quadripartite placement of causeways and central plaza suggests that its households created a sacred landscape that gave them a degree of ritual autonomy. Ordinary people impacted power relations a second way by participating in the development of the megalithic architectural style, which was used in the region's most authoritative buildings. The use of this style in domestic platforms illustrates the ability of modest households to make their own decisions and to act in ways that constituted society at large.
DAC can restore expression of NALP1 to suppress tumor growth in colon cancer
Authors: Chen C , Wang B , Sun J , Na H , Chen Z , Zhu Z , Yan L , Ren S , Zuo Y
Published: January 2015

Despite recent progress in the identification of genetic and molecular alternations in colorectal carcinoma, the precise molecular pathogenesis remains unclear. NALP1 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 1) is a member of the nucleotide-binding oligomerization domain-like receptor family of proteins that are key organization proteins in the inflammasome. It is reported that NALP1 plays a central role in cell apoptosis, pyroptosis, inflammatory reactions and autoimmune diseases. DAC (5-aza-2-deoxycytidine) is an antitumor drug useful to lung cancer, myelodysplastic disorders, myelodysplasia and acute myeloid leukemia. In this study, we examined the expression of NALP1 in human normal and cancerous colon tissues using tissue microarray, western blot and quantitative real-time PCR and we measured the expression of NALP1 in three kinds of colon cancer cell lines and animal models before and after treatment with DAC. Furthermore, we examined the treatment effects of DAC on colon cancer in our animal model. Our data indicate that NALP1 is expressed low in human colorectal tumoral tissues relative to paratumoral tissues and was associated with the survival and tumor metastasis of patients. The expression of NALP1 increased after treatment with DAC both in vitro and in vivo. Furthermore, DAC suppressed the growth of colon cancer and increased lifespan in mouse model. Therefore, we conclude that NALP1 is expressed low in colon cancer and associated with the survival and tumor metastasis of patients, and treatment with DAC can restore NALP1 levels to suppress the growth of colon cancer.
Celastrol induces apoptosis and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells: an in vitro and in vivo study
Authors: Li H-Y , Zhang J , Sun L-L , Li B-H , Gao H-L , Xie T , Zhang N , Ye Z-M
Published: January 2015

Osteosarcoma is the most common primary malignant tumor of bone, the long-term survival of which has stagnated in the past several decades. Celastrol, a triterpene from traditional Chinese medicine, has been proved to possess potent anti-tumor effect on various cancers. However, the effect of celastrol on human osteosarcoma and the underlying mechanisms remains to be elucidated. We reported here that celastrol could inhibit cell proliferation by causing G2/M phase arrest. Exposure to celastrol resulted in the activation of caspase-3, -8, and -9, indicating that celastrol induced apoptosis through both extrinsic and intrinsic pathways. Autophagy occurred in celastrol-treated cells as evidenced by formation of autophagosome and accumulation of LC3B-II. The celastrol-induced cell death was remarkably restored by the combination of autophagy and apoptosis inhibitors. Furthermore, inhibition of apoptosis enhanced autophagy while suppression of autophagy diminished apoptosis. Celastrol also induced JNK activation and ROS generation. The JNK inhibitor significantly attenuated celastrol-triggered apoptosis and autophagy while ROS scavenger could completely reverse them. The ROS scavenger also prevented G2/M phase arrest and phosphorylation of JNK. Importantly, we found that celastrol had the similar effects on primary osteosarcoma cells. Finally, in vivo, celastrol suppressed tumor growth in the mouse xenograft model. Taken together, our results revealed that celastrol caused G2/M phase arrest, induced apoptosis and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells. Celastrol is therefore a promising candidate for development of antitumor drugs targeting osteosarcoma.
Genome-wide mRNA and miRNA expression profiling reveal multiple regulatory networks in colorectal cancer
Authors: Vishnubalaji R , Hamam R , Abdulla M-H , Mohammed M A V , Kassem M , Al-Obeed O , Aldahmash A , Alajez N M
Published: January 2015

Despite recent advances in cancer management, colorectal cancer (CRC) remains the third most common cancer and a major health-care problem worldwide. MicroRNAs have recently emerged as key regulators of cancer development and progression by targeting multiple cancer-related genes; however, such regulatory networks are not well characterized in CRC. Thus, the aim of this study was to perform global messenger RNA (mRNA) and microRNA expression profiling in the same CRC samples and adjacent normal tissues and to identify potential miRNA-mRNA regulatory networks. Our data revealed 1273 significantly upregulated and 1902 downregulated genes in CRC. Pathway analysis revealed significant enrichment in cell cycle, integrated cancer, Wnt (wingless-type MMTV integration site family member), matrix metalloproteinase, and TGF-β pathways in CRC. Pharmacological inhibition of Wnt (using XAV939 or IWP-2) or TGF-β (using SB-431542) pathways led to dose- and time-dependent inhibition of CRC cell growth. Similarly, our data revealed up- (42) and downregulated (61) microRNAs in the same matched samples. Using target prediction and bioinformatics, ~77% of the upregulated genes were predicted to be targeted by microRNAs found to be downregulated in CRC. We subsequently focused on EZH2 (enhancer of zeste homolog 2 ), which was found to be regulated by hsa-miR-26a-5p and several members of the let-7 (lethal-7) family in CRC. Significant inverse correlation between EZH2 and hsa-miR-26a-5p (R2=0.56, P=0.0001) and hsa-let-7b-5p (R2=0.19, P=0.02) expression was observed in the same samples, corroborating the belief of EZH2 being a bona fide target for these two miRNAs in CRC. Pharmacological inhibition of EZH2 led to significant reduction in trimethylated histone H3 on lysine 27 (H3K27) methylation, marked reduction in cell proliferation, and migration in vitro. Concordantly, small interfering RNA-mediated knockdown of EZH2 led to similar effects on CRC cell growth in vitro. Therefore, our data have revealed several hundred potential miRNA-mRNA regulatory networks in CRC and suggest targeting relevant networks as potential therapeutic strategy for CRC.
BMCC1, which is an interacting partner of BCL2, attenuates AKT activity, accompanied by apoptosis
Authors: Tatsumi Y , Takano R , Islam M S , Yokochi T , Itami M , Nakamura Y , Nakagawara A
Published: January 2015

BNIP2 and Cdc42GAP homology (BCH) motif-containing molecule at the carboxyl-terminal region 1 (BMCC1) gene is highly expressed in patients with favorable neuroblastoma (NB). It encodes a 340-kDa protein with a conserved BCH scaffold domain that may regulate signaling networks and multiple cellular functions, including apoptosis. In this study, we determined the mechanism by which BMCC1 promotes apoptosis in human NB and non-NB cells, as BMCC1 is normally expressed in various organs, particularly in neuronal and epithelial tissues. We demonstrated in this report that BMCC1 was induced by DNA damage, one of the triggers of intrinsic apoptosis. Accordingly, we investigated whether BMCC1 expression impacts intracellular signals in the regulation of apoptosis via its C-terminal region containing BCH scaffold domain. BMCC1 decreased phosphorylation of survival signals on AKT and its upstream kinase PDK1. BMCC1 upregulation was correlated with the activation of forkhead box-O3a (FOXO3a) (a downstream inducer of apoptosis, which is suppressed by AKT) and induction of BCL2 inhibitor BIM, suggesting that BMCC1 negatively regulates phosphorylation pathway of AKT, resulted in apoptosis. In addition, we found that BNIP2 homology region of BMCC1 interacts with BCL2. Intrinsic apoptosis induced by DNA damage was enhanced by BMCC1 overexpression, and was diminished by knockdown of BMCC1. Taken together, we conclude that BMCC1 promotes apoptosis at multiple steps in AKT-mediated survival signal pathway. These steps include physical interaction with BCL2 and attenuation of AKT-dependent inhibition of FOXO3a functions, such as transcriptional induction of BIM and phosphorylation of ataxia telangiectasia-mutated (ATM) after DNA damage. We propose that downregulation of BMCC1 expression, which is frequently observed in unfavorable NB and epithelial-derived cancers, may facilitate tumor development by abrogating DNA damage repair and apoptosis.
A G-quadruplex DNA structure resolvase, RHAU, is essential for spermatogonia differentiation
Authors: Gao X , Ma W , Nie J , Zhang C , Zhang J , Yao G , Han J , Xu J , Hu B , Du Y , Shi Q , Yang Z , Huang X , Zhang Y
Published: January 2015

G-quadruplex (G4) DNA and G4 DNA resolvase are involved in a variety of biological processes. To understand the biological function of G4 DNA structures and their resolvases in spermatogenesis, we investigated the distribution of G4 structures in mouse testis and identified their alterations during spermatogenesis. Meanwhile, we studied the function of RNA helicase associated with AU-rich element (RHAU), a G4 DNA resolvase, in spermatogenesis with a germ-cell-specific knockout mouse model. The results showed that the ablation of RHAU in germ cells caused the increase of G4 structures and thus resulted in the decrease of spermatogonial differentiation. c-kit, a spermatogonia differentiation-related gene, contains two G4 DNA motifs on its promoter. We found its expression was significantly downregulated in RHAU conditional knockout testis. A further analysis demonstrated that RHAU directly bound to the G4 structures to activate c-kit expression. We concluded that RHAU regulates spermatogonia differentiation by promoting c-kit expression via directly binding to the G4 DNA motifs c-kit promoter.
ING1b negatively regulates HIF1α protein levels in adipose-derived stromal cells by a SUMOylation-dependent mechanism
Authors: Bigot N , Guérillon C , Loisel S , Bertheuil N , Sensebé L , Tarte K , Pedeux R
Published: January 2015

Hypoxic niches help maintain mesenchymal stromal cell properties, and their amplification under hypoxia sustains their immature state. However, how MSCs maintain their genomic integrity in this context remains elusive, since hypoxia may prevent proper DNA repair by downregulating expression of BRCA1 and RAD51. Here, we find that the ING1b tumor suppressor accumulates in adipose-derived stromal cells (ADSCs) upon genotoxic stress, owing to SUMOylation on K193 that is mediated by the E3 small ubiquitin-like modifier (SUMO) ligase protein inhibitor of activated STAT protein γ (PIAS4). We demonstrate that ING1b finely regulates the hypoxic response by triggering HIF1α proteasomal degradation. On the contrary, when mutated on its SUMOylation site, ING1b failed to efficiently decrease HIF1α levels. Consistently, we observed that the adipocyte differentiation, generally described to be downregulated by hypoxia, was highly dependent on ING1b expression, during the early days of this process. Accordingly, contrary to what was observed with HIF1α, the absence of ING1b impeded the adipogenic induction under hypoxic conditions. These data indicate that ING1b contributes to adipogenic induction in adipose-derived stromal cells, and thus hinders the phenotype maintenance of ADSCs.
MiR-34c suppresses tumor growth and metastasis in nasopharyngeal carcinoma by targeting MET
Authors: Li Y-Q , Ren X-Y , He Q-M , Xu Y-F , Tang X-R , Sun Y , Zeng M-S , Kang T-B , Liu N , Ma J
Published: January 2015

Our previous microarray analysis indicated that miR-34c was downregulated in nasopharyngeal carcinoma (NPC). However, little is known about the function and molecular mechanism of miR-34c in NPC. In this study, miR-34c was found to be significantly downregulated in NPC cell lines and clinical tissues. Ectopic expression of miR-34c suppressed NPC cell viability, colony formation, anchorage-independent growth, cell migration and invasion in vitro, and inhibited xenograft tumor growth and lung metastasis in vivo. MET proto-oncogene (MET) was identified as a direct target of miR-34c using luciferase reporter assays, quantitative RT-PCR, western blotting and immunofluorescent staining. Overexpression of miR-34c markedly reduced MET expression at both the mRNA and protein levels. Knockdown of MET suppressed NPC cell proliferation, migration and invasion, whereas the restoration of MET rescued the suppressive effects of miR-34c. The demethylation agent 5-aza-2′-deoxycytidine (DAC) restored the expression of miR-34c in NPC cell lines. The promoter region of miR-34c was hypermethylated in NPC cells. In conclusion, miR-34c suppresses tumor growth and metastasis in NPC by targeting MET. The newly identified miR-34c/MET pathway provides further insights into the development and progression of NPC, and may represent a novel therapeutic target for NPC treatment.
Structural analysis of herpes simplex virus by optical super-resolution imaging
Authors: Laine Romain F. , Albecka Anna , van de Linde Sebastian , Rees Eric J. , Crump Colin M. , Kaminski Clemens F.
Published: January 2015

Herpes simplex virus type-1 (HSV-1) is one of the most widespread pathogens among humans. Although the structure of HSV-1 has been extensively investigated, the precise organization of tegument and envelope proteins remains elusive. Here we use super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM) in combination with a model-based analysis of single-molecule localization data, to determine the position of protein layers within virus particles. We resolve different protein layers within individual HSV-1 particles using multi-colour dSTORM imaging and discriminate envelope-anchored glycoproteins from tegument proteins, both in purified virions and in virions present in infected cells. Precise characterization of HSV-1 structure was achieved by particle averaging of purified viruses and model-based analysis of the radial distribution of the tegument proteins VP16, VP1/2 and pUL37, and envelope protein gD. From this data, we propose a model of the protein organization inside the tegument.
A proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting
Authors: Byron Adam , Askari Janet A. , Humphries Jonathan D. , Jacquemet Guillaume , Koper Ewa J. , Warwood Stacey , Choi Colin K. , Stroud Matthew J. , Chen Christopher S. , Knight David , Humphries Martin J.
Published: January 2015

Integrin activation, which is regulated by allosteric changes in receptor conformation, enables cellular responses to the chemical, mechanical and topological features of the extracellular microenvironment. A global view of how activation state converts the molecular composition of the region proximal to integrins into functional readouts is, however, lacking. Here, using conformation-specific monoclonal antibodies, we report the isolation of integrin activation state-dependent complexes and their characterization by mass spectrometry. Quantitative comparisons, integrating network, clustering, pathway and image analyses, define multiple functional protein modules enriched in a conformation-specific manner. Notably, active integrin complexes are specifically enriched for proteins associated with microtubule-based functions. Visualization of microtubules on micropatterned surfaces and live cell imaging demonstrate that active integrins establish an environment that stabilizes microtubules at the cell periphery. These data provide a resource for the interrogation of the global molecular connections that link integrin activation to adhesion signalling.
Thermal conductivity of skutterudite CoSb3 from first principles: Substitution and nanoengineering effects
Authors: Guo Ruiqiang , Wang Xinjiang , Huang Baoling
Published: January 2015

CoSb3-based skutterudites are promising intermediate-temperature thermoelectric materials and fundamental understanding of the thermal transport in CoSb3 is crucial for further improving its performance. We herein calculate the lattice thermal conductivity κL of CoSb3 with first-principles methods and conduct a comprehensive analysis on phonon mode contribution, relaxation time and mean free path (MFP) distributions. The contribution of optical phonons is found to be significant (28% at 300 K) and important optical modes usually involve two or more pnicogen atoms moving synchronously. The MFP (~135 nm at 300 K) corresponding to 50% κL accumulation in CoSb3 is much larger than that predicted from the kinetic theory (~4 nm), providing an opportunity to reduce κL by nanoengineering. The effects of elemental substitution and nanoengineering on κL are therefore investigated. A 10% substitution of Sb by As results in 57% reduction of κL while the in-plane (cross-plane) κL of a 50-nm CoSb3 thin film is only 56% (33%) of the bulk κL at 300 K. The impurity scattering and boundary scattering mainly suppress phonons in different frequency regimes. By combining these two effects, κL can be reduced by more than 70% at 300 K, potentially leading to much improved ZT near room temperature.
Concomitant spin-canted antiferromagnetic ordering and proton conduction in homometallic and homoleptic coordination polymers
Authors: Goswami Soumyabrata , Biswas Soumava , Konar Sanjit
Published: January 2015

Two oxonate based 1D zig-zag coordination polymers with FeII and CoII are reported. These complexes are the first oxonate based systems to exhibit spin canted antiferromagnetic ordering at low temperatures and good proton conduction ability at elevated temperatures and under high humidity conditions.
Np(v) complexation with propionate in 0.5–4 M NaCl solutions at 20–85 °C
Authors: Vasiliev Aleksandr N. , Banik Nidhu L. , Marsac Rémi , Froehlich Daniel R. , Rothe Jörg , Kalmykov Stepan N. , Marquardt Christian M.
Published: January 2015

The present study shows that the stability constant for the formation of the 1 : 1 NpO2+-propionate complex, with log β0 (25 °C) = 1.26 ± 0.03, increases with both the ionic strength (0.5 < NaCl < 4.37 m) and temperature (20 < T < 85 °C).
Flexible organic field-effect transistors on biodegradable cellulose paper with efficient reusable ion gel dielectrics
Authors: Qian Chuan , Sun Jia , Yang Junliang , Gao Yongli
Published: January 2015

Flexible P3HT FETs on cellulose paper with biopolymer chitosan smoothing layers and efficient reusable ion gel dielectrics are demonstrated. The device performance of the FETs with reused ion gel dielectrics is not degenerated with repeated use.
Enteromorpha based porous carbons activated by zinc chloride for supercapacitors with high capacity retention
Authors: Wu Mingbo , Li Peng , Li Yang , Liu Jun , Wang Yang
Published: January 2015

Porous carbons were prepared from enteromorpha with ZnCl2 as active reagent. The prepared porous carbon with a specific surface area of 1651 m2 g−1 exhibited a specific capacitance of 206 F g−1 and capacity retention of 93% even after 5000 cycles.
Tuning the optical and dielectric properties of calcium copper titanate CaxCu3−xTi4O12 nanopowders
Authors: Turky Ali Omar , Rashad Mohamed Mohamed , Zaki Zaki Ismail , Ibrahim Ibrahim Ahmed , Bechelany Mikhael
Published: January 2015

The present study acts as a simple and effective way in the synthesis and characterization of CCTO with tunable optical and dielectrical properties.
Enhanced thermal, mechanical and fire-retarding properties of polystyrene sulphonate-grafted-nanosilica/polypropylene composites
Authors: Hassan M. M. , Koyama K.
Published: January 2015

The addition of pSS-grafted-nanosilica to PP showed enhanced fire retardancy as assessed by mass loss, cone calorimetry and LOI measurements.
Influence of particle size on performance of a nickel oxide nanoparticle-based supercapacitor
Authors: Pilban Jahromi Siamak , Pandikumar Alagarsamy , Goh Boon Tong , Lim Yee Seng , Basirun Wan Jefrey , Lim Hong Ngee , Huang Nay Ming
Published: January 2015

Particle size effects of Nickel oxide (NiO) as an active material on its supercapacitor performance were investigated.
Formal [4 + 1] cycloaddition of o-quinone methides: facile synthesis of dihydrobenzofurans
Authors: Lei Xiantao , Jiang Chun-Huan , Wen Xiaoan , Xu Qing-Long , Sun Hongbin
Published: January 2015

An efficient and straightforward method for the rapid synthesis of 2-substituted dihydrobenzofurans has been developed via reaction of sulfur ylides with o-quinone methides (o-QMs).
Cellulose composite aerogel for highly efficient electromagnetic interference shielding
Authors: Huang Hua-Dong , Liu Chun-Yan , Zhou Dong , Jiang Xin , Zhong Gan-Ji , Yan Ding-Xiang , Li Zhong-Ming
Published: January 2015

An ultra-light, conductive green composite aerogel with an open and highly porous structure was produced for efficient electromagnetic interference shielding.
Solid-state dye-sensitized solar cells from poly(ethylene oxide)/polyaniline electrolytes with catalytic and hole-transporting characteristics
Authors: Duan Yanyan , Tang Qunwei , Chen Yuran , Zhao Zhiyuan , Lv Yang , Hou Mengjin , Yang Peizhi , He Benlin , Yu Liangmin
Published: January 2015

Iodide/triiodide-incorporated PEO/PANi solid-state electrolyte is realized for dye-sensitized solar cell with the aim of expanding the catalytic event of the triiodide species and shortening the charge diffusion path length, yielding an impressive efficiency of 6.1%.
An ultrasensitive electrochemical immunosensor for CEA using MWCNT-NH2 supported PdPt nanocages as labels for signal amplification
Authors: Li Na , Wang Yaoguang , Cao Wei , Zhang Yunhui , Yan Tao , Du Bin , Wei Qin
Published: January 2015

An ultrasensitive sandwich-type immunosensor was proposed by using MWCNT-NH2 supported PdPt nanocages as labels for signal amplification.
Image stitching using chaos‐inspired dissimilarity measure
Authors: Song Taeyup , Jeon Changwon , Ko Hanseok
Published: January 2015

A novel image‐stitching algorithm is proposed that uses the chaos‐inspired dissimilarity measure. Previous approaches to image stitching generally employed invariant local features and random sample consensus (RANSAC), to verify image matches. In panoramic stitching, however, RANSAC is highly sensitive to illumination difference between the pair of images stemming from two different exposures, which essentially results in mismatched pairs, leading to poor stitching performance. By applying chaos theory, the contextual change of an image becomes chaos‐like, and results in a complex fractal trajectory in phase space. The specific chaos behaviour between a pair of images is exploited, whereby the resulting phase space exhibits strong invariance to illumination changes. Accordingly, the chaos‐inspired dissimilarity between images is measured, thereby the matched pairs are robustly found under the presence of illumination difference. Representative performance experiments demonstrate significant improvements over the conventional method.