bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Coenzyme Q10 Supplementation on Pro-Inflammatory Factors and Adiponectin in Mildly Hypertensive Patients: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Bagheri Nesami Nasim , Mozaffari-Khosravi Hassan , Najarzadeh Azadeh , Salehifar Ebrahim
Published: January 2016

Abstract. Introduction: There is considerable evidence that hypertension may increase the levels of cytokines via endothelial stimulation and may stimulate inflammatory reactions. The purpose of this study was to evaluate the effect of oral coenzyme Q10 supplementation on pro-inflammatory factors and adiponectin in mildly hypertensive patients. Methods: This 12-week randomized, double-blind, placebo-controlled clinical trial was carried out during 2012 - 2013 in Yazd. Sixty mildly hypertensive patients were randomly divided into two groups: placebo (PG, n = 30) and coenzyme Q10 (QG, n = 30). The QG was given 1 capsule containing 100 mg Q10 per day. The PG was given 1 capsule of the same size and color as the Q10 capsules, but it contained 100 mg of lactose. Plasma pro-inflammatory factors (IL6, IL2, and TNF-α), adiponectin, and hs-CRP were determined before and after the intervention. Results: The mean enhancement in adiponectin of QG was significantly higher than PG (from 21.1 ± 14.5 to 24.2 ± 15.5 ng/ml, P = 0.04). Significant declines in the median of IL6 (from 23 to 16 pg/ml, P = 0.001) and in the mean of hs-CRP were also observed in QG after intervention (from 3.53 ± 3.36 to 2.62 ± 2.51 mg/L, P = 0.03). In the two groups, no significant statistical changes were seen in the median of TNF-α and IL2. Conclusion: Daily supplementation of 100 mg coenzyme Q10 can be effective in decreasing some pro-inflammatory factors, such as IL6 and hs-CRP, and in increasing adiponectin.
Oral Zinc Supplementation Restores Superoxide Radical Scavengers to Normal Levels in Spermatozoa of Iraqi Asthenospermic Patients
Authors: Hadwan Mahmoud Hussein , Almashhedy Lamia A. , Alsalman Abdul Razzaq S.
Published: January 2016

Abstract. Background: Oxidative stress and decreased antioxidant levels have been projected as potential factors involved in the pathophysiology of diverse male infertility types, including asthenospermia. The present study was conducted to examine the effect of zinc supplementation on the quantitative and qualitative characteristics of semen along with oxido-sensitive index level (superoxide dismutase/xanthine oxidase ratio) in the seminal plasma of asthenospermic patients. Methods: Semen samples were obtained from 60 fertile (age 31.6 ± 3.3 years) and 60 asthenospermic men (age 32.5 ± 3.23 years) from July 2011 to July 2012, from couples who had consulted the infertility clinic of the Babil hospital of maternity (Hillah, Iraq). The subfertile group was treated with zinc sulfate, every participant took 2 capsules (220 mg each) of zinc sulfate per day for 3 months. Semen samples were obtained (before and after zinc sulfate supplementation). Oxido-sensitive index level, catalase-like activity and various sperm parameters were measured. Results: The value of the oxido-sensitive index of fertile controls (1.28 + 0.31 in seminal plasma and 1.57 + 0.62 in spermatozoa) was significantly higher than that of the infertile patient group (0.56 + 0.48 in seminal plasma and 0.65 + 0.57 spermatozoa) (p = 0.0001). Oxido-sensitive index levels were significantly higher in the infertile group treated with zinc sulfate (1.13 + 0.22 in seminal plasma and 1.15 + 0.16 in spermatozoa) (p = 0.001). Catalase-like activity was increased significantly in spermatozoa and seminal plasma of patients compared to that of healthy controls. Volume of semen, progressive sperm motility and total normal sperm count were increased after zinc supplementation. Conclusion: Zinc supplementation restores oxido-sensitive index and catalase-like activity in semen of asthenozoospermic subjects to normal ranges.
Combined 1,25-Dihydroxy-vitamin D and Resveratrol: A Novel Therapeutic Approach to Ameliorate Ischemia Reperfusion-Induced Myocardial Injury
Authors: Safari Fatemeh , Zarei Farideh , Shekarforoush Shahnaz , Fekri Asefeh , Klishadi Mohsen Sharifi , Hekmatimoghaddam Seyedhossein
Published: January 2016

Abstract. The aim of this study was to assess the effect of combined 1,25-dihydroxyvitamin D (1,25 D) and resveratrol on cardiac arrhythmias, infarct size, and transcription of catalase, thioredoxin-1 and B-cell lymphoma 2 (Bcl-2), following myocardial ischemia-reperfusion (IR) in male rats. Ligation of coronary artery was performed in rats (n = 6 per group) without any treatment (IR group), pretreated with 0.1 μg/kg/day of 1,25 D (1,25 D + IR), 1 mg/kg/day of resveratrol (Res + IR) or a combination (1,25 D + Res + IR) for 14 days. Arrhythmias were analyzed according to the Lambeth conventions, and infarct size was measured by 2,3,5-triphenyl-2H-tetrazolium chloride staining. Expression of prosurvival genes was evaluated by real-time polymerase chain reaction. In the 1,25 D + Res + IR group the mean infarct size was 17.6 ± 3.5 %, which was significantly less than that in the IR, 1,25 D + IR, and Res + IR groups (p < 0.001). Although the single therapy of either 1,25 D or resveratrol did not change the incidence of arrhythmias significantly, a reduction in the number of ventricular ectopic beats was noted in group 1,25 D + Res + IR (179.19 ± 58.87, p < 0.001 vs IR; p < 0.05 vs Res + IR; p < 0.01 vs Vit D + IR). Combination of 1,25 D and resveratrol increased transcription of catalase by 119 ± 37 % (p < 0.001 vs IR, p < 0.01 vs Res + IR, p < 0.001 vs 1,25 D + IR). Our study showed that combination of a non-hypotensive dose of 1,25 D and resveratrol can be a novel and effective strategy for protecting against ischemia.
HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell death
Authors: Jacobsen A V , Lowes K N , Tanzer M C , Lucet I S , Hildebrand J M , Petrie E J , van Delft M F , Liu Z , Conos S A , Zhang J-G , Huang D C S , Silke J , Lessene G , Murphy J M
Published: January 2016

Necroptosis is a caspase-independent form of regulated cell death that has been implicated in the development of a range of inflammatory, autoimmune and neurodegenerative diseases. The pseudokinase, Mixed Lineage Kinase Domain-Like (MLKL), is the most terminal known obligatory effector in the necroptosis pathway, and is activated following phosphorylation by Receptor Interacting Protein Kinase-3 (RIPK3). Activated MLKL translocates to membranes, leading to membrane destabilisation and subsequent cell death. However, the molecular interactions governing the processes downstream of RIPK3 activation remain poorly defined. Using a phenotypic screen, we identified seven heat-shock protein 90 (HSP90) inhibitors that inhibited necroptosis in both wild-type fibroblasts and fibroblasts expressing an activated mutant of MLKL. We observed a modest reduction in MLKL protein levels in human and murine cells following HSP90 inhibition, which was only apparent after 15 h of treatment. The delayed reduction in MLKL protein abundance was unlikely to completely account for defective necroptosis, and, consistent with this, we also found inhibition of HSP90 blocked membrane translocation of activated MLKL. Together, these findings implicate HSP90 as a modulator of necroptosis at the level of MLKL, a function that complements HSP90’s previously demonstrated modulation of the upstream necroptosis effector kinases, RIPK1 and RIPK3.
Leukemia inhibitory factor (LIF) withdrawal activates mTOR signaling pathway in mouse embryonic stem cells through the MEK/ERK/TSC2 pathway
Authors: Cherepkova M Y , Sineva G S , Pospelov V A
Published: January 2016

Leukemia inhibitory factor (LIF) is indispensable to maintain the pluripotent state of mouse embryonic stem cells (ESCs), but the mechanisms underlying the role of LIF/STAT3 pathway are yet poorly understood. Here we first showed that the LIF/STAT3-regulated signaling pathway contributes to the maintenance of self-renewal and pluripotency of mouse ESCs by suppressing mTOR (mammalian target of rapamycin), which is necessary for early differentiation. When LIF is withdrawn from culture medium, the mTOR activity rapidly increases as detected by phosphorylation of its targets – ribosomal protein S6 and translation factor 4EBP1. In turn, suppression of STAT3 phosphorylation on Tyr-705 by a specific small molecule WP1066 also activates phosphorylation of the mTOR target S6 ribosomal protein. LIF removal strongly activates ERK activity indicating that ERK can be involved in either direct phosphorylation of mTOR or phosphorylation of an upstream negative regulator of mTOR – TSC1/TSC2 proteins. According to western blotting data, LIF withdrawal leads to phosphorylation of TSC2 protein thereby relieving its negative effect on mTOR activity. mTOR activation is accompanied by a decrease of pluripotent gene expression Oct-4, Nanog, Sox2 and by an augmentation of fgf5 gene expression – a marker of post-implantation epiblast. Together, these data indicate that LIF-depleted mouse ESCs undergo a transition from the LIF/STAT3-supported pluripotent state to the FGFR/ERK-committed primed-like state with expression of early differentiation markers mediated through activation of mTOR signaling.
Cdk2 phosphorylation of Bcl-xL after stress converts it to a pro-apoptotic protein mimicking Bax/Bak
Authors: Megyesi J , Tarcsafalvi A , Seng NSHL , Hodeify R , Price PM
Published: January 2016

Apoptosis is a regulated form of cell death that proceeds by defined biochemical pathways. Most apoptosis is controlled by interactions between pro-survival and pro-apoptotic Bcl-2 family proteins in which death is often the consequence of permeabilization of the mitochondrial outer membrane. Many drugs affect this equilibrium to favor apoptosis but this process is not completely understood. We show that the chemotherapeutic drug cisplatin initiates an apoptotic pathway by phosphorylation of a pro-survival Bcl-2 family member, Bcl-xL, by cyclin-dependent kinase 2. The phosphorylation occurred at a previously unreported site and its biologic significance was demonstrated by a phosphomimetic modification of Bcl-xL that was able to induce apoptosis without addition of cisplatin. The mechanism of cell death induction was similar to that initiated by pro-apoptotic Bcl-2 family proteins, that is, phosphorylated Bcl-xL translocated to the mitochondrial membrane, and formed pores in the membrane. This initiated cytochrome c release and caspase activation that resulted in cell death.
Termination layer compensated tunnelling magnetoresistance in ferrimagnetic Heusler compounds with high perpendicular magnetic anisotropy
Authors: Jeong Jaewoo , Ferrante Yari , Faleev Sergey V. , Samant Mahesh G. , Felser Claudia , Parkin Stuart S. P.
Published: January 2016

Although high-tunnelling spin polarization has been observed in soft, ferromagnetic, and predicted for hard, ferrimagnetic Heusler materials, there has been no experimental observation to date of high-tunnelling magnetoresistance in the latter. Here we report the preparation of highly textured, polycrystalline Mn3Ge films on amorphous substrates, with very high magnetic anisotropy fields exceeding 7 T, making them technologically relevant. However, the small and negative tunnelling magnetoresistance that we find is attributed to predominant tunnelling from the lower moment Mn–Ge termination layers that are oppositely magnetized to the higher moment Mn–Mn layers. The net spin polarization of the current reflects the different proportions of the two distinct termination layers and their associated tunnelling matrix elements that result from inevitable atomic scale roughness. We show that by engineering the spin polarization of the two termination layers to be of the same sign, even though these layers are oppositely magnetized, high-tunnelling magnetoresistance is possible.
Tumour cell-derived Wnt7a recruits and activates fibroblasts to promote tumour aggressiveness
Authors: Avgustinova Alexandra , Iravani Marjan , Robertson David , Fearns Antony , Gao Qiong , Klingbeil Pamela , Hanby Andrew M. , Speirs Valerie , Sahai Erik , Calvo Fernando , Isacke Clare M.
Published: January 2016

Stromal fibroblast recruitment to tumours and activation to a cancer-associated fibroblast (CAF) phenotype has been implicated in promoting primary tumour growth and progression to metastatic disease. However, the mechanisms underlying the tumour:fibroblast crosstalk that drive the intertumoural stromal heterogeneity remain poorly understood. Using in vivo models we identify Wnt7a as a key factor secreted exclusively by aggressive breast tumour cells, which induces CAF conversion. Functionally, this results in extracellular matrix remodelling to create a permissive environment for tumour cell invasion and promotion of distant metastasis. Mechanistically, Wnt7a-mediated fibroblast activation is not dependent on classical Wnt signalling. Instead, we demonstrate that Wnt7a potentiates TGFβ receptor signalling both in 3D in vitro and in vivo models, thus highlighting the interaction between two of the key signalling pathways in development and disease. Importantly, in clinical breast cancer cohorts, tumour cell Wnt7a expression correlates with a desmoplastic, poor-prognosis stroma and poor patient outcome.
Ancient balancing selection at tan underlies female colour dimorphism in Drosophila erecta
Authors: Yassin Amir , Bastide Héloïse , Chung Henry , Veuille Michel , David Jean R. , Pool John E.
Published: January 2016

Dimorphic traits are ubiquitous in nature, but the evolutionary factors leading to dimorphism are largely unclear. We investigate a potential case of sexual mimicry in Drosophila erecta, in which females show contrasting resemblance to males. We map the genetic basis of this sex-limited colour dimorphism to a region containing the gene tan. We find a striking signal of ancient balancing selection at the ‘male-specific enhancer’ of tan, with exceptionally high sequence divergence between light and dark alleles, suggesting that this dimorphism has been adaptively maintained for millions of years. Using transgenic reporter assays, we confirm that these enhancer alleles encode expression differences that are predicted to generate this pigmentation dimorphism. These results are compatible with the theoretical prediction that divergent phenotypes maintained by selection can evolve simple genetic architectures.
Energy disruptors: rising stars in anticancer therapy?
Authors: Bost F , Decoux-Poullot A-G , Tanti J F , Clavel S
Published: January 2016

The metabolic features of tumor cells diverge from those of normal cells. Otto Warburg was the first to observe that cancer cells dramatically increase their glucose consumption to generate ATP. He also claimed that cancer cells do not have functional mitochondria or oxidative phosphorylation (OXPHOS) but simply rely on glycolysis to provide ATP to the cell, even in the presence of oxygen (aerobic glycolysis). Several studies have revisited this observation and demonstrated that most cancer cells contain metabolically efficient mitochondria. Indeed, to sustain high proliferation rates, cancer cells require functional mitochondria to provide ATP and intermediate metabolites, such as citrate and cofactors, for anabolic reactions. This difference in metabolism between normal and tumors cells causes the latter to be more sensitive to agents that can disrupt energy homeostasis. In this review, we focus on energy disruptors, such as biguanides, 2-deoxyglucose and 5-aminoimidazole-4-carboxamide ribonucleotide, that interfere with the main metabolic pathways of the cells, OXPHOS, glycolysis and glutamine metabolism. We discuss the preclinical data and the mechanisms of action of these disruptors at the cellular and molecular levels. Finally, we consider whether these drugs can reasonably contribute to the antitumoral therapeutic arsenal in the future.
Mucin 1-mediated chemo-resistance in lung cancer cells
Authors: Ham S Y , Kwon T , Bak Y , Yu J-H , Hong J , Lee S K , Yu D-Y , Yoon D-Y
Published: January 2016

Paclitaxel (PTX) is a commonly used drug to treat diverse cancer types. However, its treatment can generate resistance and the mechanisms of PTX-resistance in lung cancers are still unclear. We demonstrated that non-small cell lung cancers (NSCLCs) survive PTX treatment. Compared with the progenitor NSCLC A549 cells, the PTX-resistant A549 cells (A549/PTX) displayed enhanced sphere-formation ability. The proportion of the cancer stem cell marker, aldehyde dehydrogenase-positive cells, and epithelial–mesenchymal transition signaling protein levels were also elevated in A549/PTX. Importantly, the levels of oncoproteins phosphoinositide-3 kinase/Akt, mucin 1 cytoplasmic domain (MUC1-C) and β-catenin were also significantly elevated in A549/PTX. Furthermore, nuclear translocation of MUC1-C and β-catenin increased in A549/PTX. The c-SRC protein, an activator of MUC1-C, was also overexpressed in A549/PTX. These observations led to the hypothesis that enhanced expression of MUC1-C is associated with stemness and PTX resistance in NSCLCs. To test this, we knocked down or overexpressed MUC1-C in A549/PTX and found that inhibition of MUC1-C expression coupled with PTX treatment was sufficient to reduce the sphere-forming ability and survival of A549/PTX. In summary, our in vitro and in vivo studies have revealed a potential mechanism of MUC1-C-mediated PTX resistance and provided insights into a novel therapeutic measure for lung cancers.
Bone alterations are associated with ankle osteoarthritis joint pain
Authors: Nakamura Yukio , Uchiyama Shigeharu , Kamimura Mikio , Komatsu Masatoshi , Ikegami Shota , Kato Hiroyuki
Published: January 2016

The etiology of ankle osteoarthritis (OA) is largely unknown. We analyzed 24 ankle OA of 21 patients diagnosed by plain radiographs using magnetic resonance imaging (MRI). Ankle joint pain disappeared in 22 out of 24 joints by conservative treatment. MRI bone signal changes in and around the ankle joints were observed in 22 of 24 joints. Bone signal changes along the joint line were seen in 10 of 11 joints as a Kellgren-Lawrence (KL) grade of II to IV. Such signal changes were witnessed in only 4 of 13 joints with KL grade 0 or I. In the talocrural joint, bone alterations occurred in both tibia and talus bones through the joint line in cases of KL grade III or IV, while focal bone alterations were present in the talus only in KL grade I or II cases. Sixteen of 24 joints exhibited intraosseous bone signal changes, which tended to correspond to joint pain of any ankle OA stage. Our results suggest that bone alterations around the ankle joint might be one of the etiologies of OA and associated with ankle joint pain.
Graphene/GaSe-Nanosheet Hybrid: Towards High Gain and Fast Photoresponse
Authors: Lu Rongtao , Liu Jianwei , Luo Hongfu , Chikan Viktor , Wu Judy Z.
Published: January 2016

While high photoconductive gain has been recently achieved in graphene-based hybrid phototransistors using semiconductor two-dimensional transition/post-transition metal dichalcogenides or quantum dots sensitizers, obtaining fast photoresponse simutaneously remains a challenge that must be addressed for practical applications. In this paper we report a graphene/GaSe nanosheets hybrid photodetector, in which GaSe nanosheets provide a favorable geometric link to graphene conductive layer through van Der Waals force. After a vacuum annealing process, a high gain in exceeding 107 has been obtained simitaneously with a dynamic response time of around 10 ms for both light on and off. We attribute the high performance to the elimination of possible deep charge traps, most probably at the graphene/GaSe nanosheets interface. This result demonstrates high photoconductive gain and fast photoresponse can be achieved simultaneously and a clean interface is the key to the high performance of these hybrid devices.
Surface–Atmosphere Moisture Interactions in the Frozen Ground Regions of Eurasia
Authors: Ford Trent W. , Frauenfeld Oliver W.
Published: January 2016

Climate models simulate an intensifying Arctic hydrologic cycle in response to climatic warming, however the role of surface-atmosphere interactions from degrading frozen ground is unclear in these projections. Using Modern-Era Retrospective Analysis for Research and Applications (MERRA) data in high-latitude Eurasia, we examine long-term variability in surface-atmosphere coupling as represented by the statistical relationship between surface evaporative fraction (EF) and afternoon precipitation. Changes in EF, precipitation and their statistical association are then related to underlying permafrost type and snow cover. Results indicate significant positive trends in July EF in the Central Siberian Plateau, corresponding to significant increases in afternoon precipitation. The positive trends are only significant over continuous permafrost, with non-significant or negative EF and precipitation trends over isolated, sporadic and discontinuous permafrost areas. Concurrently, increasing EF and subsequent precipitation are found to coincide with significant trends in May and June snowmelt, which potentially provides the moisture source for the observed enhanced latent heating and moisture recycling in the region. As climate change causes continuous permafrost to transition to discontinuous, discontinuous to sporadic, sporadic to isolated and isolated permafrost disappears, this will also alter patterns of atmospheric convection, moisture recycling and hence the hydrologic cycle in high-latitude land areas.
X-ray PIV measurement of blood flow in deep vessels of a rat: An in vivo feasibility study
Authors: Park Hanwook , Yeom Eunseop , Lee Sang Joon
Published: January 2016

X-ray PIV measurement is a noninvasive approach to measure opaque blood flows. However, it is not easy to measure real pulsatile blood flows in the blood vessels located at deep position of the body, because the surrounding tissues significantly attenuate the contrast of X-ray images. This study investigated the effect of surrounding tissues on X-ray beam attenuation by measuring the velocity fields of blood flows in deep vessels of a live rat. The decrease in image contrast was minimized by employing biocompatible CO2microbubbles as tracer particles. The maximum measurable velocity of blood flows in the abdominal aorta of a rat model was found through comparative examination between the PIV measurement accuracy and the level of image contrast according to the input flow rate. Furthermore, the feasibility of using X-ray PIV to accurately measurein vivoblood flows was demonstrated by determining the velocity field of blood flows in the inferior vena cava of a rat. This study may serve as a reference in conductingin vivoX-ray PIV measurements of pulsatile blood flows in animal disease models and investigating hemodynamic characteristics and circulatory vascular diseases.
Enhanced photoelectrochemical aptasensing platform for TXNDC5 gene based on exciton energy transfer between NCQDs and TiO2 nanorods
Authors: Pang Xuehui , Wang Lin , Ma Hongmin , Zhang Yong , Pan Jihong , Chen Yao , Du Bin , Wei Qin
Published: January 2016

The over expression of thioredoxin domain-containing protein 5 (TXNDC5) can promote the growth of castration-resistant prostate cancer (CRPC). A novel highly sensitive photoelectrochemical (PEC) aptsensor was developed for the detection of TXNDC5 by using the nanohybrids (TiO2 NRs/NCQDs) of nitrogen-doped carbon quantum dots (NCQDs) and TiO2 nanorods as the photo-to-electron conversion medium. TiO2 NRs/NCQDs nanohybrids were prepared by controlling the experimental condition. TiO2 NRs were self-assembled to form the nanopores with good photocurrent conversion efficiency. NCQDs possessed carboxyl groups (−COOH) and amino groups (−NH2) in the preparation process. −COOH and −NH2 groups played important roles for anchoring the capture probes (5′ primer and 3′ primer) through covalent binding. The ultrasensitive and stable detection for TXNDC5 was achieved by the specific recognition between the capture probes and the targets. The fabricated aptsensor showed excellent performance with a wide linear range (0.5 fmol/L ∼ 10 nmol/L) and a low detection limit of 0.1 fmol/L. This kind of aptsensor would provide a potential application for TXNDC5.
Interferon-gamma improves impaired dentinogenic and immunosuppressive functions of irreversible pulpitis-derived human dental pulp stem cells
Authors: Sonoda Soichiro , Yamaza Haruyoshi , Ma Lan , Tanaka Yosuke , Tomoda Erika , Aijima Reona , Nonaka Kazuaki , Kukita Toshio , Shi Songtao , Nishimura Fusanori , Yamaza Takayoshi
Published: January 2016

Clinically, irreversible pulpitis is treated by the complete removal of pulp tissue followed by replacement with artificial materials. There is considered to be a high potential for autologous transplantation of human dental pulp stem cells (DPSCs) in endodontic treatment. The usefulness of DPSCs isolated from healthy teeth is limited. However, DPSCs isolated from diseased teeth with irreversible pulpitis (IP-DPSCs) are considered to be suitable for dentin/pulp regeneration. In this study, we examined the stem cell potency of IP-DPSCs. In comparison with healthy DPSCs, IP-DPSCs expressed lower colony-forming capacity, population-doubling rate, cell proliferation, multipotency, in vivo dentin regeneration and immunosuppressive activity, suggesting that intact IP-DPSCs may be inadequate for dentin/pulp regeneration. Therefore, we attempted to improve the impaired in vivo dentin regeneration and in vitro immunosuppressive functions of IP-DPSCs to enable dentin/pulp regeneration. Interferon gamma (IFN-γ) treatment enhanced in vivo dentin regeneration and in vitro T cell suppression of IP-DPSCs, whereas treatment with tumor necrosis factor alpha did not. Therefore, these findings suggest that IFN-γ may be a feasible modulator to improve the functions of impaired IP-DPSCs, suggesting that autologous transplantation of IFN-γ-accelerated IP-DPSCs might be a promising new therapeutic strategy for dentin/pulp tissue engineering in future endodontic treatment.
dbEM: A database of epigenetic modifiers curated from cancerous and normal genomes
Authors: Singh Nanda Jagpreet , Kumar Rahul , Raghava Gajendra P. S.
Published: January 2016

We have developed a database called dbEM (database of Epigenetic Modifiers) to maintain the genomic information of about 167 epigenetic modifiers/proteins, which are considered as potential cancer targets. In dbEM, modifiers are classified on functional basis and comprise of 48 histone methyl transferases, 33 chromatin remodelers and 31 histone demethylases. dbEM maintains the genomic information like mutations, copy number variation and gene expression in thousands of tumor samples, cancer cell lines and healthy samples. This information is obtained from public resources viz. COSMIC, CCLE and 1000-genome project. Gene essentiality data retrieved from COLT database further highlights the importance of various epigenetic proteins for cancer survival. We have also reported the sequence profiles, tertiary structures and post-translational modifications of these epigenetic proteins in cancer. It also contains information of 54 drug molecules against different epigenetic proteins. A wide range of tools have been integrated in dbEM e.g. Search, BLAST, Alignment and Profile based prediction. In our analysis, we found that epigenetic proteins DNMT3A, HDAC2, KDM6A and TET2 are highly mutated in variety of cancers. We are confident that dbEM will be very useful in cancer research particularly in the field of epigenetic proteins based cancer therapeutics. This database is available for public at URL: http://crdd.osdd.net/raghava/dbem.
Development of a luminescent G-quadruplex-selective iridium(III) complex for the label-free detection of adenosine
Authors: Lu Lihua , Zhong Hai-Jing , He Bingyong , Leung Chung-Hang , Ma Dik-Lung
Published: January 2016

A panel of six luminescent iridium(III) complexes were synthesized and evaluated for their ability to act as G-quadruplex-selective probes. The novel iridium(III) complex 1 was found to be highly selective for G-quadruplex DNA and was employed for the construction of a label-free G-quadruplex-based adenosine detection assay in aqueous solution. Two different detection strategies were investigated for adenosine detection and the results showed that initial addition of adenosine to the adenosine aptamer gave superior results. The assay exhibited a linear response for adenosine in the concentration range of 5 to 120 μM (R2 = 0.992) and the limit of detection for adenosine was 5 μM. Moreover, this assay was highly selective for adenosine over other nucleosides and exhibited potential use for biological sample analysis.
Isolation of highly enriched primary human microglia for functional studies
Authors: Rustenhoven Justin , Park Thomas I-H , Schweder Patrick , Scotter John , Correia Jason , Smith Amy M. , Gibbons Hannah M. , Oldfield Robyn L. , Bergin Peter S. , Mee Edward W. , Faull Richard L. M. , Curtis Maurice A. , Scott Graham E. , Dragunow Mike
Published: January 2016

Microglia, the resident macrophages of the central nervous system play vital roles in brain homeostasis through clearance of pathogenic material. Microglia are also implicated in neurological disorders through uncontrolled activation and inflammatory responses. To date, the vast majority of microglial studies have been performed using rodent models. Human microglia differ from rodent counterparts in several aspects including their response to pharmacological substances and their inflammatory secretions. Such differences highlight the need for studies on primary adult human brain microglia and methods to isolate them are therefore required. Our procedure generates microglial cultures of >95% purity from both biopsy and autopsy human brain tissue using a very simple media-based culture procedure that takes advantage of the adherent properties of these cells. Microglia obtained in this manner can be utilised for research within a week. Isolated microglia demonstrate phagocytic ability and respond to inflammatory stimuli and their purity makes them suitable for numerous other forms of in vitro studies, including secretome and transcriptome analysis. Furthermore, this protocol allows for the simultaneous isolation of neural precursor cells during the microglial isolation procedure. As human brain tissue is such a precious and valuable resource the simultaneous isolation of multiple cell types is highly beneficial.
Evidencing the existence of exciting half-metallicity in two-dimensional TiCl3 and VCl3 sheets
Authors: Zhou Yungang , Lu Haifeng , Zu Xiaotao , Gao Fei
Published: January 2016

Half-metallicity combined with wide half-metallic gap, unique ferromagnetic character and high Curie temperature has become a key driving force to develop next-generation spintronic devices. In previous studies, such half-metallicity always occurred under certain manipulation. Here, we, via examining a series of two-dimensional transition-metal trichlorides, evidenced that TiCl3 and VCl3 sheets could display exciting half-metallicity without involving any external modification. Calculated half-metallic band-gaps for TiCl3 and VCl3 sheets are about 0.60 and 1.10 eV, respectively. Magnetic coupled calculation shows that both sheets favor the ferromagnetic order with a substantial collective character. Estimated Curie temperatures can be up to 376 and 425 K for TiCl3 and VCl3 sheets, respectively. All of these results successfully disclose two new promising two-dimensional half-metallic materials toward the application of next-generation paper-like spintronic devices.
Ion-beam assisted laser fabrication of sensing plasmonic nanostructures
Authors: Kuchmizhak Aleksandr , Gurbatov Stanislav , Vitrik Oleg , Kulchin Yuri , Milichko Valentin , Makarov Sergey , Kudryashov Sergey
Published: January 2016

Simple high-performance, two-stage hybrid technique was developed for fabrication of different plasmonic nanostructures, including nanorods, nanorings, as well as more complex structures on glass substrates. In this technique, a thin noble-metal film on a dielectric substrate is irradiated by a single tightly focused nanosecond laser pulse and then the modified region is slowly polished by an accelerated argon ion (Ar+) beam. As a result, each nanosecond laser pulse locally modifies the initial metal film through initiation of fast melting and subsequent hydrodynamic processes, while the following Ar+-ion polishing removes the rest of the film, revealing the hidden topography features and fabricating separate plasmonic structures on the glass substrate. We demonstrate that the shape and lateral size of the resulting functional plasmonic nanostructures depend on the laser pulse energy and metal film thickness, while subsequent Ar+-ion polishing enables to vary height of the resulting nanostructures. Plasmonic properties of the fabricated nanostructures were characterized by dark-field micro-spectroscopy, Raman and photoluminescence measurements performed on single nanofeatures, as well as by supporting numerical calculations of the related electromagnetic near-fields and Purcell factors. The developed simple two-stage technique represents a new step towards direct large-scale laser-induced fabrication of highly ordered arrays of complex plasmonic nanostructures.
Squalene epoxidase is a bona fide oncogene by amplification with clinical relevance in breast cancer
Authors: Brown David N. , Caffa Irene , Cirmena Gabriella , Piras Daniela , Garuti Anna , Gallo Maurizio , Alberti Saverio , Nencioni Alessio , Ballestrero Alberto , Zoppoli Gabriele
Published: January 2016

SQLEencodes squalene epoxidase, a key enzyme in cholesterol synthesis.SQLEhas sporadically been reported among copy-number driven transcripts in multi-omics cancer projects. Yet, its functional relevance has never been subjected to systematic analyses. Here, we assessed the correlation ofSQLEcopy number (CN) and gene expression (GE) across multiple cancer types, focusing on the clinico-pathological associations in breast cancer (BC). We then investigated whether any biological effect of SQLE inhibition could be observed in BC cell line models. Breast, ovarian and colorectal cancers showed the highest CN driven GE among 8,783 cases from 22 cancer types, with BC presenting the strongest one.SQLEoverexpression was more prevalent in aggressive BC and was an independent prognostic factor of unfavorable outcome. Through SQLE pharmacological inhibition and silencing in a panel of BC cell lines portraying the diversity ofSQLECN and GE, we demonstrated that SQLE inhibition resulted in a copy-dosage correlated decrease in cell viability and in a noticeable increase in replication time, only in lines with detectableSQLEtranscript. Altogether, our results pinpointSQLEas abona fidemetabolic oncogene by amplification and as a therapeutic target in BC. These findings could have implications in other cancer types.
Adiponectin-derived active peptide ADP355 exerts anti-inflammatory and anti-fibrotic activities in thioacetamide-induced liver injury
Authors: Wang Huafeng , Zhang Huan , Zhang Zimu , Huang Biao , Cheng Xixi , Wang Dan , la Gahu Zha , Xue Zhenyi , Da Yurong , Li Daiqing , Yao Zhi , Gao Fei , Xu Aimin , Zhang Rongxin
Published: January 2016

Adiponectin is an adipocyte-derived circulating protein with beneficial effects on injured livers. Adiponectin-deficient (adipo(−/−)) mice develop enhanced liver fibrosis, suggesting that adiponectin could be a therapeutic target for liver injury. In the present study, we investigated the protective role of ADP355, an adiponectin-based active short peptide, in thioacetamide (TAA)-induced acute injury and chronic liver fibrosis in mice. ADP355 remarkably reduced TAA-induced necroinflammation and liver fibrosis. ADP355 treatment increased liver glycogen, decreased serum alanine transaminase and alkaline phosphatase activity and promoted body weight gain, hyper-proliferation and hypo-apoptosis. In addition, ADP355 administration suppressed the TAA-induced activation of hepatic stellate cells and macrophages in the liver. These were associated with the inactivation of TGF-β1/SMAD2 signaling and the promotion of AMPK and STAT3 signaling. Sensitivity of adipo(−/−) mice to chronic liver injury was decreased with ADP355. In conclusion, ADP355 could mimic adiponectin’s action and may be suitable for the preclinical or clinical therapy of chronic liver injury.
Identification and developmental expression profiling of putative alkaloid biosynthetic genes in Corydalis yanhusuo bulbs
Authors: Liao Dengqun , Wang Pengfei , Jia Chan , Sun Peng , Qi Jianjun , Zhou Lili , Li Xian’en
Published: January 2016

Alkaloids in bulbs ofCorydalis(C.)yanhusuoare the major pharmacologically active compounds in treatment of blood vessel diseases, tumors and various pains. However, due to the absence of gene sequences inC. yanhusuo, the genes involved in alkaloid biosynthesis and their expression during bulb development remain unknown. We therefore established the first transcriptome database ofC. yanhusuovia Illumina mRNA-Sequencing of a RNA composite sample collected at Bulb initiation (Day 0), early enlargement (Day 10) and maturation (Day 30). 25,013,630 clean 90 bp paired-end reads werede novoassembled into 47,081 unigenes with an average length of 489 bp, among which 30,868 unigenes (65.56%) were annotated in four protein databases. Of 526 putative unigenes involved in biosynthesis o f various alkaloids, 187 were identified as the candidate genes involved in the biosynthesis of benzylisoquinoline alkaloids (BIAs), the only alkaloid type reported inC. yanhusuountill now. BIAs biosynthetic genes were highly upregulated in the overall pathway during bulb development. Identification of alkaloid biosynthetic genes inC. yanhusuoprovide insights on pathways and molecular regulation of alkaloid biosynthesis, to initiate metabolic engineering in order to improve the yield of interesting alkaloids and to identify potentially new alkaloids predicted from the transcriptomic information.
Direct measurement of nonlocal entanglement of two-qubit spin quantum states
Authors: Cheng Liu-Yong , Yang Guo-Hui , Guo Qi , Wang Hong-Fu , Zhang Shou
Published: January 2016

We propose efficient schemes of direct concurrence measurement for two-qubit spin and photon-polarization entangled states via the interaction between single-photon pulses and nitrogen-vacancy (NV) centers in diamond embedded in optical microcavities. For different entangled-state types, diversified quantum devices and operations are designed accordingly. The initial unknown entangled states are possessed by two spatially separated participants and nonlocal spin (polarization) entanglement can be measured with the aid of detection probabilities of photon (NV center) states. This non-demolition entanglement measurement manner makes initial entangled particle-pair avoid complete annihilation but evolve into corresponding maximally entangled states. Moreover, joint inter-qubit operation or global qubit readout is not required for the presented schemes and the final analyses inform favorable performance under the current parameters conditions in laboratory. The unique advantages of spin qubits assure our schemes wide potential applications in spin-based solid quantum information and computation.
Comprehensive Structural Characterization of the Bacterial Homospermidine Synthase–an Essential Enzyme of the Polyamine Metabolism
Authors: Krossa Sebastian , Faust Annette , Ober Dietrich , Scheidig Axel J.
Published: January 2016

The highly conserved bacterial homospermidine synthase (HSS) is a key enzyme of the polyamine metabolism of many proteobacteria including pathogenic strains such as Legionella pneumophila and Pseudomonas aeruginosa; The unique usage of NAD(H) as a prosthetic group is a common feature of bacterial HSS, eukaryotic HSS and deoxyhypusine synthase (DHS). The structure of the bacterial enzyme does not possess a lysine residue in the active center and thus does not form an enzyme-substrate Schiff base intermediate as observed for the DHS. In contrast to the DHS the active site is not formed by the interface of two subunits but resides within one subunit of the bacterial HSS. Crystal structures of Blastochloris viridis HSS (BvHSS) reveal two distinct substrate binding sites, one of which is highly specific for putrescine. BvHSS features a side pocket in the direct vicinity of the active site formed by conserved amino acids and a potential substrate discrimination, guiding and sensing mechanism. The proposed reaction steps for the catalysis of BvHSS emphasize cation-π interaction through a conserved Trp residue as a key stabilizer of high energetic transition states.
Magnetic MoS2 pizzas and sandwiches with Mnn (n = 1–4) cluster toppings and fillings: A first-principles investigation
Authors: Zhang Meng , Huang Zhongjia , Wang Xiao , Zhang Hongyu , Li Taohai , Wu Zhaolong , Luo Youhua , Cao Wei
Published: January 2016

The inorganic layered crystal (ILC) MoS2 in low dimensions is considered as one of the most promising and efficient semiconductors. To enable the magnetism and keep intrinsic crystal structures, we carried out a first-principles study of the magnetic and semiconductive monolayer MoS2 adsorbed with the Mnn (n = 1–4) clusters and bilayer MoS2 intercalated with the same clusters. Geometric optimizations of the Mnn@MoS2 systems show the complexes prefer to have Mnn@MoS2(M) pizza and Mnn@MoS2(B) sandwich forms in the mono- and bi-layered cases, respectively. Introductions of the clusters will enhance complex stabilities, while bonds and charge transfers are found between external Mn clusters and the S atoms in the hosts. The pizzas have medium magnetic moments of 3, 6, 9, 4 μB and sandwiches of 3, 2, 3, 2 μB following the manganese numbers. The pizzas and sandwiches are semiconductors, but with narrower bandgaps compared to their corresponding pristine hosts. Direct bandgaps were found in the Mnn@MoS2(M) (n = 1,4) pizzas and excitingly in the Mn1@MoS2(B) sandwich. Combining functional clusters to the layered hosts, the present work shows a novel material manipulation strategy to boost semiconductive ILCs applications in magnetics.
Auranofin-loaded nanoparticles as a new therapeutic tool to fight streptococcal infections
Authors: Díez-Martínez Roberto , García-Fernández Esther , Manzano Miguel , Martínez Ángel , Domenech Mirian , Vallet-Regí María , García Pedro
Published: January 2016

Drug-loaded nanoparticles (NPs) can improve infection treatment by ensuring drug concentration at the right place within the therapeutic window. Poly(lactic-co-glycolic acid) (PLGA) NPs are able to enhance drug localization in target site and to sustainably release the entrapped molecule, reducing the secondary effects caused by systemic antibiotic administration. We have loaded auranofin, a gold compound traditionally used for treatment of rheumatoid arthritis, into PLGA NPs and their efficiency as antibacterial agent against two Gram-positive pathogens, Streptococcus pneumoniae and Streptococcus pyogenes was evaluated. Auranofin-PLGA NPs showed a strong bactericidal effect as cultures of multiresistant pneumococcal strains were practically sterilized after 6 h of treatment with such auranofin-NPs at 0.25 μM. Moreover, this potent bactericidal effect was also observed in S. pneumoniae and S. pyogenes biofilms, where the same concentration of auranofin-NPs was capable of decreasing the bacterial population about 4 logs more than free auranofin. These results were validated using a zebrafish embryo model demonstrating that treatment with auranofin loaded into NPs achieved a noticeable survival against pneumococcal infections. All these approaches displayed a clear superiority of loaded auranofin PLGA nanocarriers compared to free administration of the drug, which supports their potential application for the treatment of streptococcal infections.
On-chip integratable all-optical quantizer using strong cross-phase modulation in a silicon-organic hybrid slot waveguide
Authors: Kang Zhe , Yuan Jinhui , Zhang Xianting , Sang Xinzhu , Wang Kuiru , Wu Qiang , Yan Binbin , Li Feng , Zhou Xian , Zhong Kangping , Zhou Guiyao , Yu Chongxiu , Farrell Gerald , Lu Chao , Yaw Tam Hwa , Wai P. K. A.
Published: January 2016

High performance all-optical quantizer based on silicon waveguide is believed to have significant applications in photonic integratable optical communication links, optical interconnection networks and real-time signal processing systems. In this paper, we propose an integratable all-optical quantizer for on-chip and low power consumption all-optical analog-to-digital converters. The quantization is realized by the strong cross-phase modulation and interference in a silicon-organic hybrid (SOH) slot waveguide based Mach-Zehnder interferometer. By carefully designing the dimension of the SOH waveguide, large nonlinear coefficients up to 16,000 and 18,069 W−1/m for the pump and probe signals can be obtained respectively, along with a low pulse walk-off parameter of 66.7 fs/mm and all-normal dispersion in the wavelength regime considered. Simulation results show that the phase shift of the probe signal can reach 8π at a low pump pulse peak power of 206 mW and propagation length of 5 mm such that a 4-bit all-optical quantizer can be realized. The corresponding signal-to-noise ratio is 23.42 dB and effective number of bit is 3.89-bit.
Impurity Resonant States p-type Doping in Wide-Band-Gap Nitrides
Authors: Liu Zhiqiang , Yi Xiaoyan , Yu Zhiguo , Yuan Guodong , Liu Yang , Wang Junxi , Li Jinmin , Lu Na , Ferguson Ian , Zhang Yong
Published: January 2016

In this work, a new strategy for achieving efficient p-type doping in high bandgap nitride semiconductors to overcome the fundamental issue of high activation energy has been proposed and investigated theoretically and demonstrated experimentally. Specifically, in an AlxGa1−xN/GaN superlattice structure, by modulation doping of Mg in the AlxGa1−xN barriers, high concentration of holes are generated throughout the material. A hole concentration as high as 1.1 × 1018 cm−3 has been achieved, which is about one order of magnitude higher than that typically achievable by direct doping GaN. Results from first-principle calculations indicate that the coupling and hybridization between Mg 2p impurity and the host N 2p orbitals are main reasons for the generation of resonant states in the GaN wells, which further results in the high hole concentration. We expect this approach to be equally applicable for other high bandgap materials where efficient p-type doing is difficult. Furthermore, a two-carrier-species Hall-effect model is proposed to delineate and discriminate the characteristics of the bulk and 2D hole, which usually coexist in superlattice-like doping systems. The model reported here can also be used to explain the abnormal freeze-in effect observed in many previous reports.
A Novel Equivalent Agglomeration Model for Heat Conduction Enhancement in Nanofluids
Authors: Sui Jize , Zheng Liancun , Zhang Xinxin , Chen Ying , Cheng Zhengdong
Published: January 2016

We propose a multilevel equivalent agglomeration (MEA) model in which all particles in an irregular cluster are treated as a new particle with equivalent volume, the liquid molecules wrapping the cluster and in the gaps are considered to assemble on the surface of new particle as mixing nanolayer (MNL), the thermal conductivity in MNL is assumed to satisfy exponential distribution. Theoretical predictions for thermal conductivity enhancement are highly in agreement with the classical experimental data. Also, we first try to employ TEM information quantitatively to offer probable reference agglomeration ratio (not necessary a very precise value) to just test rational estimations range by present model. The comparison results indicate the satisfactory priori agglomeration ratio estimations range from renovated model.