bluuebunny/crossref_metadata_2025_split huggingface dataset:
Piperlongumine and immune cytokine TRAIL synergize to promote tumor death
Authors: Li Jiahe , Sharkey Charles C. , King Michael R. 
Published: May 2015

AbstractMalignant transformation results in increased levels of reactive oxygen species (ROS). Adaption to this toxic stress allows cancer cells to proliferate. Recently, piperlongumine (PL), a natural alkaloid, was identified to exhibit novel anticancer effects by targeting ROS signaling. PL induces apoptosis specifically in cancer cells by downregulating several anti-apoptotic proteins. Notably, the same anti-apoptotic proteins were previously found to reduce tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in cancer cells. Therefore, we reasoned that PL would synergize with TRAIL to stimulate potent apoptosis in cancer cells. We demonstrate for the first time that PL and TRAIL exhibit a synergistic anti-cancer effect in cancer cell lines of various origins. PL resulted in the upregulation of TRAIL receptor DR5, which potentiated TRAIL-induced apoptosis in cancer cells. Furthermore, such upregulation was found to be dependent on ROS and the activation of JNK and p38 kinases. Treatment with combined PL and TRAIL demonstrated significant anti-proliferative effects in a triple-negative breast cancer MDA-MB-231 xenograft model. This work provides a novel therapeutic approach for inducing cancer cell death. Combination of PL and TRAIL may suggest a novel paradigm for treatment of primary and metastatic tumors.
Basal protein phosphatase 2A activity restrains cytokine expression: role for MAPKs and tristetraprolin
Authors: Rahman Md. Mostafizur , Rumzhum Nowshin N. , Morris Jonathan C. , Clark Andrew R. , Verrills Nicole M. , Ammit Alaina J. 
Published: May 2015

AbstractPP2A is a master controller of multiple inflammatory signaling pathways. It is a target in asthma; however the molecular mechanisms by which PP2A controls inflammation warrant further investigation. In A549 lung epithelial cells in vitro we show that inhibition of basal PP2A activity by okadaic acid (OA) releases restraint on MAPKs and thereby increases MAPK-mediated pro-asthmatic cytokines, including IL-6 and IL-8. Notably, PP2A inhibition also impacts on the anti-inflammatory protein – tristetraprolin (TTP), a destabilizing RNA binding protein regulated at multiple levels by p38 MAPK. Although PP2A inhibition increases TTP mRNA expression, resultant TTP protein builds up in the hyperphosphorylated inactive form. Thus, when PP2A activity is repressed, pro-inflammatory cytokines increase and anti-inflammatory proteins are rendered inactive. Importantly, these effects can be reversed by the PP2A activators FTY720 and AAL(s), or more specifically by overexpression of the PP2A catalytic subunit (PP2A-C). Moreover, PP2A plays an important role in cytokine expression in cells stimulated with TNFα; as inhibition of PP2A with OA or PP2A-C siRNA results in significant increases in cytokine production. Collectively, these data reveal the molecular mechanisms of PP2A regulation and highlight the potential of boosting the power of endogenous phosphatases as novel anti-inflammatory strategies to combat asthmatic inflammation.
Fortnightly atmospheric tides forced by spring and neap tides in coastal waters
Authors: Iwasaki Shinsuke , Isobe Atsuhiko , Miyao Yasuyuki 
Published: May 2015

AbstractThe influence of sea surface temperature (SST) on atmospheric processes over the open ocean has been well documented. However, atmospheric responses to SST in coastal waters are poorly understood. Oceanic stratification (and consequently, SST) in coastal waters largely depends on the fortnightly spring–neap tidal cycle, because of variations in vertical tidal mixing. Here we investigate how changes in SST during the fortnightly tidal cycle affect the lower-level atmosphere over the Seto Inland Sea, Japan. We use a combination of in situ measurements, satellite observations and a regional atmospheric model. We find that the SST in summer shows cool (warm) anomalies over most of the inland sea during spring (neap) tides. Additionally, surface air temperature is positively correlated with the SST as it varies during the fortnightly tidal cycle. Moreover, the fortnightly spring–neap cycle also influences the surface wind speed because the atmospheric boundary layer becomes stabilized or destabilized in response to the difference between air temperature and SST.
Proteomic analysis of three gonad types of swamp eel reveals genes differentially expressed during sex reversal
Authors: Sheng Yue , Zhao Wei , Song Ying , Li Zhigang , Luo Majing , Lei Quan , Cheng Hanhua , Zhou Rongjia 
Published: May 2015

AbstractA variety of mechanisms are engaged in sex determination in vertebrates. The teleost fish swamp eel undergoes sex reversal naturally and is an ideal model for vertebrate sexual development. However, the importance of proteome-wide scanning for gonad reversal was not previously determined. We report a 2-D electrophoresis analysis of three gonad types of proteomes during sex reversal. MS/MS analysis revealed a group of differentially expressed proteins during ovary to ovotestis to testis transformation. Cbx3 is up-regulated during gonad reversal and is likely to have a role in spermatogenesis. Rab37 is down-regulated during the reversal and is mainly associated with oogenesis. Both Cbx3 and Rab37 are linked up in a protein network. These datasets in gonadal proteomes provide a new resource for further studies in gonadal development.
Ultra High-Resolution In vivo Computed Tomography Imaging of Mouse Cerebrovasculature Using a Long Circulating Blood Pool Contrast Agent
Authors: Starosolski Zbigniew , Villamizar Carlos A. , Rendon David , Paldino Michael J. , Milewicz Dianna M. , Ghaghada Ketan B. , Annapragada Ananth V. 
Published: May 2015

AbstractAbnormalities in the cerebrovascular system play a central role in many neurologic diseases. The on-going expansion of rodent models of human cerebrovascular diseases and the need to use these models to understand disease progression and treatment has amplified the need for reproducible non-invasive imaging methods for high-resolution visualization of the complete cerebral vasculature. In this study, we present methods for in vivo high-resolution (19 μm isotropic) computed tomography imaging of complete mouse brain vasculature. This technique enabled 3D visualization of large cerebrovascular networks, including the Circle of Willis. Blood vessels as small as 40 μm were clearly delineated. ACTA2 mutations in humans cause cerebrovascular defects, including abnormally straightened arteries and a moyamoya-like arteriopathy characterized by bilateral narrowing of the internal carotid artery and stenosis of many large arteries. In vivo imaging studies performed in a mouse model of Acta2 mutations demonstrated the utility of this method for studying vascular morphometric changes that are practically impossible to identify using current histological methods. Specifically, the technique demonstrated changes in the width of the Circle of Willis, straightening of cerebral arteries and arterial stenoses. We believe the use of imaging methods described here will contribute substantially to the study of rodent cerebrovasculature.
High-Throughput Microfluidic Platform for 3D Cultures of Mesenchymal Stem Cells, Towards Engineering Developmental Processes
Authors: Occhetta Paola , Centola Matteo , Tonnarelli Beatrice , Redaelli Alberto , Martin Ivan , Rasponi Marco 
Published: May 2015

AbstractThe development of in vitro models to screen the effect of different concentrations, combinations and temporal sequences of morpho-regulatory factors on stem/progenitor cells is crucial to investigate and possibly recapitulate developmental processes with adult cells. Here, we designed and validated a microfluidic platform to (i) allow cellular condensation, (ii) culture 3D micromasses of human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) under continuous flow perfusion and (ii) deliver defined concentrations of morphogens to specific culture units. Condensation of hBM-MSCs was obtained within 3 hours, generating micromasses in uniform sizes (56.2 ± 3.9 μm). As compared to traditional macromass pellet cultures, exposure to morphogens involved in the first phases of embryonic limb development (i.e. Wnt and FGF pathways) yielded more uniform cell response throughout the 3D structures of perfused micromasses (PMMs) and a 34-fold higher percentage of proliferating cells at day 7. The use of a logarithmic serial dilution generator allowed to identify an unexpected concentration of TGFβ3 (0.1 ng/ml) permissive to hBM-MSCs proliferation and inductive to chondrogenesis. This proof-of-principle study supports the described microfluidic system as a tool to investigate processes involved in mesenchymal progenitor cells differentiation, towards a ‘developmental engineering’ approach for skeletal tissue regeneration.
A systems-biological study on the identification of safe and effective molecular targets for the reduction of ultraviolet B-induced skin pigmentation
Authors: Lee Ho-Sung , Goh Myeong-Jin , Kim Junil , Choi Tae-Jun , Kwang Lee Hae , Joo Na Yong , Cho Kwang-Hyun 
Published: May 2015

AbstractMelanogenesis is the process of melanin synthesis through keratinocytes-melanocytes interaction, which is triggered by the damaging effect of ultraviolet-B (UVB) rays. It is known that melanogenesis influences diverse cellular responses, including cell survival and apoptosis, via complex mechanisms of feedback and crosstalk. Therefore, an attempt to suppress melanin production by modulating the melanogenesis pathway may induce perturbations in the apoptotic balance of the cells in response to UVB irradiation, which results in various skin diseases such as melasma, vitiligo and skin cancer. To identify such appropriate target strategies for the reduction of UVB-induced melanin synthesis, we reconstructed the melanogenesis signaling network and developed a Boolean network model. Mathematical simulations of the melanogenesis network model revealed that the inhibition of beta-catenin in the melanocytes effectively reduce melanin production while having minimal influence on the apoptotic balance of the cells. Exposing cells to a beta-catenin inhibitor decreased pigmentation but did not significantly change the B-cell Chronic lymphocytic leukemia/lymphoma 2 expression, a potent regulator of apoptotic balance. Thus, our systems analysis suggests that the inhibition of beta-catenin may be the most appropriate target strategy for the reduction of UVB-induced skin pigmentation.
Integrated Genomics Identifies Convergence of Ankylosing Spondylitis with Global Immune Mediated Disease Pathways
Authors: Uddin Mohammed , Codner Dianne , Mahmud Hasan S M , Scherer Stephen W , O’Rielly Darren D , Rahman Proton 
Published: May 2015

AbstractAnkylosing spondylitis(AS), a highly heritable complex inflammatory arthritis. Although, a handful of non-HLA risk loci have been identified, capturing the unexplained genetic contribution to AS pathogenesis remains a challenge attributed to additive, pleiotropic and epistatic-interactions at the molecular level. Here, we developed multiple integrated genomic approaches to quantify molecular convergence of non-HLA loci with global immune mediated diseases. We show that non-HLA genes are significantly sensitive to deleterious mutation accumulation in the general population compared with tolerant genes. Human developmental proteomics (prenatal to adult) analysis revealed that proteins encoded by non-HLA AS risk loci are 2-fold more expressed in adult hematopoietic cells.Enrichment analysis revealed AS risk genes overlap with a significant number of immune related pathways (p < 0.0001 to 9.8 × 10-12). Protein-protein interaction analysis revealed non-shared AS risk genes are highly clustered seeds that significantly converge (empirical; p < 0.01 to 1.6 × 10-4) into networks of global immune mediated disease risk loci. We have also provided initial evidence for the involvement of STAT2/3 in AS pathogenesis. Collectively, these findings highlight molecular insight on non-HLA AS risk loci that are not exclusively connected with overlapping immune mediated diseases; rather a component of common pathophysiological pathways with other immune mediated diseases. This information will be pivotal to fully explain AS pathogenesis and identify new therapeutic targets.
MicroRNA expression profiles predict clinical phenotypes and prognosis in chromophobe renal cell carcinoma
Authors: Ge Yu-Zheng , Xin Hui , Lu Tian-Ze , Xu Zheng , Yu Peng , Zhao You-Cai , Li Ming-Hao , Zhao Yan , Zhong Bing , Xu Xiao , Zhou Liu-Hua , Wu Ran , Xu Lu-Wei , Wu Jian-Ping , Li Wen-Cheng , Zhu Jia-Geng , Jia Rui-Peng 
Published: May 2015

AbstractChromophobe renal cell carcinoma (chRCC) is the third most common subtype of kidney cancers. In the present study, we identified 58 treatment-naïve primary chRCC patients from The Cancer Genome Atlas dataset and analyzed the genome-wide microRNA (miRNA) expression profiles, with the aim to assess the relationship of miRNA expression with the progression and prognosis of chRCC. Overall, a total of 105 miRNAs were found to be differentially expressed between tumor and the adjacent normal tissues from 22 chRCC patients. In the unpaired condition (58 chRCC vs. 22 normal tissues), 77 (96.3%) samples were distinguished correctly by the signatures. In the progression-related profiles, 27 miRNAs were selected for pathologic T and 9 for lymph node involvement. In the survival analyses, the expression levels of mir-191, mir-19a, mir-210 and mir-425 were significantly associated with both recurrence-free survival (RFS) and overall survival, while mir-210 was proven as an independent prognostic factor in terms of RFS. In summary, miRNAs are expressed differentially in chRCC and unique expression of miRNAs is associated with the progression and prognosis of chRCC.
Licochalcone A-induced human gastric cancer BGC-823 cells apoptosis by regulating ROS-mediated MAPKs and PI3K/AKT signaling pathways
Authors: Hao Wenjin , Yuan Xuan , Yu Lina , Gao Caixia , Sun Xiling , Wang Dong , Zheng Qiusheng 
Published: May 2015

AbstractBoth phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen activated protein kinase (MAPK) signaling cascades play an important role in cell proliferation, survival, angiogenesis and metastasis of tumor cells. In the present report, we investigated the effects of licochalcone A (LA), a flavonoid extracted from licorice root, on the PI3K/AKT/mTOR and MAPK activation pathways in human gastric cancer BGC-823 cells. LA increased reactive oxygen species (ROS) levels, which is associated with the induction of apoptosis as characterized by positive Annexin V binding and activation of caspase-3 and cleavage of poly-ADP-ribose polymerase (PARP). Inhibition of ROS generation by N-acetylcysteine (NAC) significantly prevented LA-induced apoptosis. Interestingly, we also observed that LA caused the activation of ERK, JNK and p38 MAPK in BGC-823 cells. The antitumour activity of LA-treated BGC-823 cells was significantly distinct in KM mice in vivo. All the findings from our study suggest that LA can interfere with MAPK signaling cascades, initiate ROS generation, induce oxidative stress and consequently cause BGC cell apoptosis.
Enhanced optical transmission and Fano resonance through a nanostructured metal thin film
Authors: Xiao Bo , Pradhan Sangram K. , Santiago Kevin C. , Rutherford Gugu N. , Pradhan Aswini K. 
Published: May 2015

AbstractArtificial and engineered nanostructures expand the degrees of freedom with which one can manipulate the intricate interplay of light and matter. Certain nanostructural arrangements in the excited state enable the efficient electromagnetic coupling of propagating light with localized fields. Here, we demonstrate that light transmitted through a nanostructured metal thin film without any apertures can be significantly enhanced. Distinct asymmetric Fano resonances are observed in the zero-order transmission spectra using an incoherent light source. The transmission efficiency surpasses that of a metal thin film with the same area and thickness at the resonance maxima. The transmission minima and the sharp resonance maxima bear a strong resemblance to the extraordinary optical transmission observed in sub-wavelength nanohole array structures The resonance wavelength closely matches the nanostructural periodicity. The sensitivity of the resonances to the surrounding medium and the transmission efficiency demonstrate the potential for use in energy harvesting, imaging, optical processing and sensing applications.
Improving isolation of slot‐coupled directional couplers
Authors: Moradian M. 
Published: May 2015

A suitable method is introduced to improve the isolation of slot‐coupled directional couplers. The proposed coupler consists of two trapezoidal‐shaped patches that are coupled through a trapezoidal‐shaped slot in a common ground plane. The inherent phase velocity differences between the even‐ and odd‐modes of the slot‐coupled directional coupler are compensated around the centre frequency of the coupler by introducing some slots to the trapezoidal‐shaped patches. A design graph is derived by sweeping some dimensions of the coupler. A hatched area is also added to the design graph that indicates the appropriate coupler dimensions which lead to the equal even‐ and odd‐mode phase velocities around the centre frequency. To demonstrate the effectiveness of the proposed coupler, an 8 dB coupler operating from 1 to 3.3 GHz is designed and constructed. The measurement results are in good agreement with the simulation results. The results show that the isolation of the designed coupler has improved significantly in comparison with the other designed coupler with no cut slots in the patches.
Substrate cross‐talk analysis flow for submicron CMOS system‐on‐chip
Authors: Noulis T. , Baumgartner P. 
Published: May 2015

A substrate coupling analysis flow is presented. The proposed method is fully compatible with the industry analogue/radio‐frequency design methodology, seamlessly integrates into the design environment, provides accurate estimation of the coupling effects and can model adequately all the mask design level isolation performance trends. Its accuracy is confirmed by correlating simulation results against on‐wafer silicon measurements in a 28 nm CMOS set of ring oscillators with a carrier frequency of 670 MHz. The mean error of the proposed method is 665 μV, whereas the error sigma is 765 μV.
Monolithic ultra‐low‐power 6 Gbit/s inductorless PRBS generator for silicon HBT‐based carrier‐injection electro‐absorption modulator
Authors: Fu E. , Koomson V.J. 
Published: May 2015

A low‐power pseudo‐random bit sequence (PRBS) generator for testing a high‐speed optical transmitter module has been realised in a 130 nm bipolar CMOS process. The transmitter consists of a monolithic driver circuit architecture and a heterojunction bipolar transistor (HBT)‐based carrier‐injection electro‐absorption modulator. A 10 Gbit/s current mode logic latch with only 0.6 mW power consumption is designed by scaling down the current density without degrading the overall transmitter speed performance. The 27−1 PRBS generator circuit consumes only 42.75 mW at 6 Gbit/s operating speeds with a 1.5 V dc power supply. The core circuit power consumption is 9 mW.
Monolithic integration of four‐colour InGaN‐based nanocolumn LEDs
Authors: Kishino K. , Yanagihara A. , Ikeda K. , Yamano K. 
Published: May 2015

The monolithic integration of four‐colour indium gallium nitride (InGaN)‐based nanocolumn light‐emitting diodes (LEDs) is demonstrated. In the integrated nanocolumn LED unit, blue‐, sky‐blue‐, green‐ and yellow‐emitting micro‐LEDs (LEDs 1–4) with a 65 μm diameter circular indium tin oxide emission window were arrayed in a 2 × 2 square lattice with a lattice constant of 190 μm. LEDs 1–4 consisted of nanocolumn arrays arranged in a triangular lattice with a lattice constant of 300 nm and their nanocolumn diameters at the position of the InGaN/gallium nitride (GaN) multiple quantum wells (MQWs) were 119, 145, 188 and 231 nm, respectively. The increase in nanocolumn diameter from LED 1 to LED 4 resulted in increasing emission peak wavelengths, which were 465, 489, 510 and 570 nm for LEDs 1–4, respectively. On the same substrate, a red‐emitting micro‐LED was prepared, in which the nanocolumn diameter was increased to 260 nm by using a 350 nm‐lattice‐constant nanocolumn array. A combination of different lattice constants in an integrated LED unit is expected to contribute to the achievement of red–green–blue–yellow (RGBY)‐colour‐integrated nanocolumn LEDs.
Perioperative Outcomes and Adverse Events of Minimally Invasive versus Open Posterior Lumbar Fusion: Meta-Analysis
Authors: Goldstein Christina , Macwan Kevin , Sundararajan Kala , Rampersaud Raja 
Published: May 2015

Introduction The perioperative outcomes and adverse events of minimally invasive surgery (MIS) for lumbar fusion remain unclear. The purpose of this systematic review and meta-analysis is to summarize the perioperative outcomes and adverse event rates for MIS transforaminal or posterior lumbar interbody fusion (TLIF/PLIF) compared with traditional open midline techniques. Materials and Methods A systematic review of Medline, EMBASE, PubMed, Web of Science, and Cochrane databases were performed. A hand search of reference lists was performed. Studies were reviewed by two independent assessors to identify randomized controlled trials or comparative cohort studies including ≥ 10 patients undergoing MIS or open TLIF/PLIF for degenerative lumbar spinal disorders and reporting at least one of the following: clinical outcome measure; perioperative surgical performance or outcome measure; radiographic outcome; or adverse events. Study quality was assessed using the GRADE protocol. When appropriate, a meta-analysis of outcomes data was conducted. Results The systematic review and reference list search identified 3,306 articles, with 26 meeting study inclusion criteria. All studies, including one randomized controlled trial, were of low or very low quality. No significant difference regarding age, gender, surgical levels, or diagnosis was identified between the two cohorts ( n = 856 MIS/ n = 806 open). Meta-analysis revealed changes in the perioperative outcomes of mean estimated blood loss, time to ambulation, and length of stay favoring an MIS approach by 260 mL ( p < 0.00001), 3.5 days ( p = 0.0006) and 2.9 days ( p < 0.00001), respectively. Operative time was not significantly different between the surgical techniques ( p = 0.78). There was no significant difference in surgical adverse events ( p = 0.97); however, MIS cases were significantly less likely to experience medical adverse events (RR [95% CI] MIS vs. open = 0.39 [0.23–0.69], p = 0.001). No difference in nonunion ( p = 0.97) or reoperation rates ( p = 0.97) was observed. Mean Oswestry Disability Index scores were slightly better in the patients with MIS at a median follow-up time of 24 months (mean difference MIS [ n = 346] vs. open [ n = 346] = 3.32, p = 0.001). Conclusion The quality of the current comparative evidence is low to very low with significant inherent bias. The result of this quantitative systematic review of clinical comparative effectiveness research examining MIS versus open TLIF/PLIF for degenerative lumbar pathology suggests equipoise in patient reported clinical outcomes. Furthermore, meta-analysis of adverse event data suggests equivalent rates of surgical complications with lower rates of medical complications in patients undergoing MIS TLIF/PLIF compared with open surgery.