bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast cancer cell adhesome and degradome interact to drive metastasis
Authors: Rizwan Asif , Cheng Menglin , Bhujwalla Zaver M , Krishnamachary Balaji , Jiang Lu , Glunde Kristine 
Published: October 2015

Abstract
Background:
Although primary breast tumors are detected early in most cases, it is inevitable that many patients remain at risk for future recurrence and death due to micrometastases. We investigated interactions between the degradome and the adhesome that drive metastasis, and have focused on matrix metalloproteases (MMPs) within the degradome and integrins and E-cadherin within the adhesome.

Aims:
The aim of this study is to identify interaction networks between adhesion molecules and degradative enzymes in breast cancer metastasis.

Methods:
We compared non-metastatic (BT-474, T47D, MCF7) and metastatic (MDA-MB-231, SUM149, SUM159) human breast cancer cell lines and xenografts, in which we measured growth rate, migration, invasion, colony formation, protein expression, and enzyme activity in vitro and in vivo.

Results:
The metastatic breast cancer lines and xenografts displayed higher expression and activity levels of MMPs, which was also confirmed by noninvasive imaging in vivo. These metastatic breast cancer models also displayed elevated heterophilic cell-extracellular matrix (ECM) and lower homophilic cell–cell adhesion compared with those of non-metastatic models. This was conferred by an increased expression of the heterophilic cell adhesion molecule integrin β1 (ITGB1) and a decreased expression of the homophilic cell adhesion molecule E-cadherin. Inhibition of MMPs in metastatic cells led to a reduced expression of ITGB1, and stimulation of ITGB1 resulted in higher MMP activities in metastatic cancer cells, demonstrating reciprocal dependencies between degradome and adhesome. Re-expression of E-cadherin (CDH1) led to an increased expression of the precursor form of ITGB1.

Conclusions:
Our results point toward a concerted interdependence of MMPs, ITGB1, and CDH1 that is critical for breast cancer metastasis.
Activation of the Small G Protein Arf6 by Dynamin2 through Guanine Nucleotide Exchange Factors in Endocytosis
Authors: Okada Risa , Yamauchi Yohei , Hongu Tsunaki , Funakoshi Yuji , Ohbayashi Norihiko , Hasegawa Hiroshi , Kanaho Yasunori 
Published: October 2015

AbstractThe small G protein Arf6 and the GTPase dynamin2 (Dyn2) play key roles in clathrin-mediated endocytosis (CME). However, their functional relationship remains obscure. Here, we show that Arf6 functions as a downstream molecule of Dyn2 in CME. Wild type of Dyn2 overexpressed in HeLa cells markedly activates Arf6, while a GTPase-lacking Dyn2 mutant does not. Of the Arf6-specific guanine nucleotide exchange factors, EFA6A, EFA6B and EFA6D specifically interact with Dyn2. Furthermore, overexpression of dominant negative mutants or knockdown of EFA6B and EFA6D significantly inhibit Dyn2-induced Arf6 activation. Finally, overexpression of the binding region peptide of EFA6B for Dyn2 or knockdown of EFA6B and EFA6D significantly suppresses clathrin-mediated transferrin uptake. These results provide evidence for a novel Arf6 activation mechanism by Dyn2 through EFA6B and EFA6D in CME in a manner dependent upon the GTPase activity of Dyn2.
Three-Dimensional Blood-Brain Barrier Model for in vitro Studies of Neurovascular Pathology
Authors: Cho Hansang , Seo Ji Hae , Wong Keith H. K. , Terasaki Yasukazu , Park Joseph , Bong Kiwan , Arai Ken , Lo Eng H. , Irimia Daniel 
Published: October 2015

AbstractBlood–brain barrier (BBB) pathology leads to neurovascular disorders and is an important target for therapies. However, the study of BBB pathology is difficult in the absence of models that are simple and relevant.In vivoanimal models are highly relevant, however they are hampered by complex, multi-cellular interactions that are difficult to decouple.In vitromodels of BBB are simpler, however they have limited functionality and relevance to disease processes. To address these limitations, we developed a 3-dimensional (3D) model of BBB on a microfluidic platform. We verified the tightness of the BBB by showing its ability to reduce the leakage of dyes and to block the transmigration of immune cells towards chemoattractants. Moreover, we verified the localization at endothelial cell boundaries of ZO-1 and VE-Cadherin, two components of tight and adherens junctions. To validate the functionality of the BBB model, we probed its disruption by neuro-inflammation mediators and ischemic conditions and measured the protective function of antioxidant and ROCK-inhibitor treatments. Overall, our 3D BBB model provides a robust platform, adequate for detailed functional studies of BBB and for the screening of BBB-targeting drugs in neurological diseases.
Dense Helical Electron Bunch Generation in Near-Critical Density Plasmas with Ultrarelativistic Laser Intensities
Authors: Hu Ronghao , Liu Bin , Lu Haiyang , Zhou Meilin , Lin Chen , Sheng Zhengming , Chen Chia-erh , He Xiantu , Yan Xueqing 
Published: October 2015

AbstractThe mechanism for emergence of helical electron bunch(HEB) from an ultrarelativistic circularly polarized laser pulse propagating in near-critical density(NCD) plasma is investigated. Self-consistent three-dimensional(3D) Particle-in-Cell(PIC) simulations are performed to model all aspects of the laser plasma interaction including laser pulse evolution, electron and ion motions. At a laser intensity of 1022 W/cm2, the accelerated electrons have a broadband spectrum ranging from 300 MeV to 1.3 GeV, with the charge of 22 nano-Coulombs(nC) within a solid-angle of 0.14 Sr. Based on the simulation results, a phase-space dynamics model is developed to explain the helical density structure and the broadband energy spectrum.
Sequence analysis, expression profiles and function of thioredoxin 2 and thioredoxin reductase 1 in resistance to nucleopolyhedrovirus in Helicoverpa armigera
Authors: Zhang Songdou , Li Zhen , Nian Xiaoge , Wu Fengming , Shen Zhongjian , Zhang Boyu , Zhang Qingwen , Liu Xiaoxia 
Published: October 2015

AbstractThe thioredoxin system, including NADPH, thioredoxin (Trx) and thioredoxin reductase (TrxR), plays significant roles in maintaining intracellular redox homeostasis and protecting organisms against oxidative damage. In this study, the characteristics and functions of H. armigera HaTrx2 and HaTrxR1 were identified. Sequence analysis showed that HaTrx2 and HaTrxR1 were both highly conserved and shared high sequence identity with other insect counterparts. The mRNA of HaTrx2 was expressed the highest in 5th instar 96 h and was mainly detected in heads and epidermis. The expression of HaTrxR1 was highly concentrated in 5th instar 72 h and 96 h and higher in malpighian tube, midgut and hemocyte than other examined tissues. HaTrx2 and HaTrxR1 were markedly induced by various types of stress. HaTrx2- or HaTrxR1-knockdown increased ROS production in hemocytes and also increased the lipid damage in NPV infected H. armigera larvae. Furthermore, interference with expression of HaTrx2 or HaTrxR1 transcripts in H. armigera larvae resulted in increased sensitivity to NPV infection and shortened LT50 values. Our findings indicated that HaTrx2 and HaTrxR1 contribute to the susceptibility of H. armigera to NPV and also provided the theoretical basis for the in-depth study of insect thioredoxin system.
Novel Monte Carlo approach quantifies data assemblage utility and reveals power of integrating molecular and clinical information for cancer prognosis
Authors: Verleyen Wim , Langdon Simon P. , Faratian Dana , Harrison David J. , Smith V. Anne 
Published: October 2015

AbstractCurrent clinical practice in cancer stratifies patients based on tumour histology to determine prognosis. Molecular profiling has been hailed as the path towards personalised care, but molecular data are still typically analysed independently of known clinical information. Conventional clinical and histopathological data, if used, are added only to improve a molecular prediction, placing a high burden upon molecular data to be informative in isolation. Here, we develop a novel Monte Carlo analysis to evaluate the usefulness of data assemblages. We applied our analysis to varying assemblages of clinical data and molecular data in an ovarian cancer dataset, evaluating their ability to discriminate one-year progression-free survival (PFS) and three-year overall survival (OS). We found that Cox proportional hazard regression models based on both data types together provided greater discriminative ability than either alone. In particular, we show that proteomics data assemblages that alone were uninformative (p = 0.245 for PFS, p = 0.526 for OS) became informative when combined with clinical information (p = 0.022 for PFS, p = 0.048 for OS). Thus, concurrent analysis of clinical and molecular data enables exploitation of prognosis-relevant information that may not be accessible from independent analysis of these data types.
Suppression of Shear Banding and Transition to Necking and Homogeneous Flow in Nanoglass Nanopillars
Authors: Adibi Sara , Branicio Paulo S. , Joshi Shailendra P. 
Published: October 2015

AbstractIn order to improve the properties of metallic glasses (MG) a new type of MG structure, composed of nanoscale grains, referred to as nanoglass (NG), has been recently proposed. Here, we use large-scale molecular dynamics (MD) simulations of tensile loading to investigate the deformation and failure mechanisms of Cu64Zr36NG nanopillars with large, experimentally accessible, 50 nm diameter. Our results reveal NG ductility and failure by necking below the average glassy grain size of 20 nm, in contrast to brittle failure by shear band propagation in MG nanopillars. Moreover, the results predict substantially larger ductility in NG nanopillars compared with previous predictions of MD simulations of bulk NG models with columnar grains. The results, in excellent agreement with experimental data, highlight the substantial enhancement of plasticity induced in experimentally relevant MG samples by the use of nanoglass architectures and point out to exciting novel applications of these materials.
Concurrence of oral and genital human papillomavirus infection in healthy men: a population-based cross-sectional study in rural China
Authors: Liu Fangfang , Hang Dong , Deng Qiuju , Liu Mengfei , Xi Longfu , He Zhonghu , Zhang Chaoting , Sun Min , Liu Ying , Li Jingjing , Pan Yaqi , Ning Tao , Guo Chuanhai , Liang Yongmei , Xu Ruiping , Zhang Lixin , Cai Hong , Ke Yang 
Published: October 2015

AbstractHuman papillomavirus (HPV) infection, a primary cause of genital cancer, is also related to the increasing incidence of oropharyngeal cancer among young men. Relatively little is known about the concurrence of oral and genital infection among healthy individuals. Oral and genital swab exfoliated cells were collected simultaneously from 2566 men in rural China. Using general primer-mediated (SPF1/GP6+) PCR and sequencing, HPV testing results were obtained from 2228 men with both valid oral and genital specimens (β-globin-positive). The prevalence of HPV infection was 6.7% in the oral cavity and 16.9% for the external genitalia. Among 43 men (1.9%, 43/2228) with oral-genital coinfection, 60.5% (26/43) harbored an identical HPV type at both sites. The risk of oral HPV infection was higher among men with genital infection than among uninfected men (11.4% vs. 5.7%, Adjusted OR = 2.3, 95% CI: 1.6–3.4). In addition, having multiple lifetime sexual partners was a significant risk for oral-genital HPV coinfection (Adjusted OR = 2.6, 95% CI: 1.0–7.0; 2 partners vs. 1 partner). These findings provide a basis for further understanding the natural history and transmission dynamics of oral HPV infection.
The native ant, Tapinoma melanocephalum, improves the survival of an invasive mealybug, Phenacoccus solenopsis, by defending it from parasitoids
Authors: Feng Dong-Dong , Michaud J.P. , Li Pan , Zhou Zhong-Shi , Xu Zai-Fu 
Published: October 2015

AbstractMutualistic ants can protect their partners from natural enemies in nature. Aenasius bambawalei is an important parasitoid of the the invasive mealybug Phenacoccus solenopsis. We hypothesized that mutualism between native ants and mealybugs would favor survival of mealybugs. To test this, we examined effects of tending by the native mutualistic ant Tapinoma melanocephalum on growth of P. solenopsis colonies on Chinese hibiscus, Hibiscus rosa-sinensis, in a field setting. Ant workers with access to honeydew of mealybugs lived much longer than those provisioned only with water in the laboratory and number of ant workers foraging increased significantly with growth of mealybug colonies in the field. In later observations, there were significant differences in densities of mealybugs between ant-tended and -excluded treatments. Survival rate of mealybugs experiencing parasitoid attack was significantly higher on ant-tended plants than on ant-excluded plants. When the parasitoid was excluded, there was no difference in survival rate of mealybugs between ant-tended and -excluded plants. In most cases, ants directly attacked the parasitoid, causing the parasitoid to take evasive action. We conclude that native ants such as T. melanocephalum have the potential to facilitate invasion and spread of P. solenopsis in China by providing them with protection from parasitoids.
Fourier-transform spectroscopy using an Er-doped fiber femtosecond laser by sweeping the pulse repetition rate
Authors: Lee Keunwoo , Lee Joohyung , Jang Yoon-Soo , Han Seongheum , Jang Heesuk , Kim Young-Jin , Kim Seung-Woo 
Published: October 2015

AbstractFemtosecond lasers allow for simultaneous detection of multiple absorption lines of a specimen over a broad spectral range of infrared or visible light with a single spectroscopic measurement. Here, we present an 8-THz bandwidth, 0.5-GHz resolution scheme of Fourier-transform spectroscopy using an Er-doped fiber femtosecond laser. A resolving power of 1.6 × 104 about a 1560-nm center wavelength is achieved by sweeping the pulse repetition rate of the light source on a fiber Mach-Zehnder interferometer configured to capture interferograms with a 0.02-fs temporal sampling accuracy through a well-stabilized 60-m unbalance arm length. A dual-servo mechanism is realized by combining a mechanical linear stage with an electro-optic modulator (EOM) within the fiber laser cavity, enabling stable sweeping control of the pulse repetition rate over a 1.0-MHz scan range with 0.4-Hz steps with reference to the Rb clock. Experimental results demonstrate that the P-branch lines of the H13CN reference cell can be observed with a signal-to-noise ratio reaching 350 for the most intense line.
Acid-induced off-response of PKD2L1 channel in Xenopus oocytes and its regulation by Ca2+
Authors: Hussein Shaimaa , Zheng Wang , Dyte Chris , Wang Qian , Yang JungWoo , Zhang Fan , Tang Jingfeng , Cao Ying , Chen Xing-Zhen 
Published: October 2015

AbstractPolycystic kidney disease (PKD) protein 2 Like 1 (PKD2L1), also called transient receptor potential polycystin-3 (TRPP3), regulates Ca2+-dependent hedgehog signalling in primary cilia, intestinal development and sour tasting but with an unclear mechanism. PKD2L1 is a Ca2+-permeable cation channel that is activated by extracellular Ca2+ (on-response) in Xenopus oocytes. PKD2L1 co-expressed with PKD protein 1 Like 3 (PKD1L3) exhibits extracellular acid-induced activation (off-response, i.e., activation following acid removal) but whether PKD1L3 participates in acid sensing remains unclear. Here we used the two-microelectrode voltage-clamp, site directed mutagenesis, Western blotting, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunofluorescence and showed that PKD2L1 expressed in oocytes exhibits sustained off-response currents in the absence of PKD1L3. PKD1L3 co-expression augmented the PKD2L1 plasma membrane localization but did not alter the observed properties of the off-response. PKD2L1 off-response was inhibited by an increase in intracellular Ca2+. We also identified two intra-membrane residues aspartic acid 349 (D349) and glutamic acid 356 (E356) in the third transmembrane domain that are critical for PKD2L1 channel function. Our study suggests that PKD2L1 may itself sense acids and defines off-response properties in the absence of PKD1L3.
Retinal oxygen extraction in humans
Authors: Werkmeister René M. , Schmidl Doreen , Aschinger Gerold , Doblhoff-Dier Veronika , Palkovits Stefan , Wirth Magdalena , Garhöfer Gerhard , Linsenmeier Robert A. , Leitgeb Rainer A. , Schmetterer Leopold 
Published: October 2015

AbstractAdequate function of the retina is dependent on proper oxygen supply. In humans, the inner retina is oxygenated via the retinal circulation. We present a method to calculate total retinal oxygen extraction based on measurement of total retinal blood flow using dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen saturation by spectrophotometry. These measurements were done on 8 healthy subjects while breathing ambient room air and 100% oxygen. Total retinal blood flow was 44.3 ± 9.0 μl/min during baseline and decreased to 18.7 ± 4.2 μl/min during 100% oxygen breathing (P < 0.001) resulting in a pronounced decrease in retinal oxygen extraction from 2.33 ± 0.51 μl(O2)/min to 0.88 ± 0.14 μl(O2)/min during breathing of 100% oxygen. The method presented in this paper may have significant potential to study oxygen metabolism in hypoxic retinal diseases such as diabetic retinopathy.
Discovery and functional characterization of a neomorphic PTEN mutation
Authors: Costa Helio A. , Leitner Michael G. , Sos Martin L. , Mavrantoni Angeliki , Rychkova Anna , Johnson Jeffrey R. , Newton Billy W. , Yee Muh-Ching , De La Vega Francisco M. , Ford James M. , Krogan Nevan J. , Shokat Kevan M. , Oliver Dominik , Halaszovich Christian R. , Bustamante Carlos D. 
Published: October 2015

Significance
Identification of putative functional genetic mutations involved in cancer has been dramatically accelerated by developments in next generation sequencing technologies. However, analyzing an individual patient genome and interpreting mutation spectra to inform cancer origin and targeted treatment have been challenging. This study presents a framework interpreting a single patient’s genome and identifies a novel causal mutation in the phosphatase and tensin homolog (PTEN) tumor suppressor. Through computational and experimental approaches, we demonstrate that this mutation causes PTEN to retain known tumor suppressor function while gaining protumor activity. This finding suggests a new role for PTEN and other tumor suppressor involvement in cancer formation and reveals the potential wealth of biological information currently underexploited by the lack of systematic approaches for cancer genome interpretation services.
Exploring the influence of ancient and historic megaherbivore extirpations on the global methane budget
Authors: Smith Felisa A. , Hammond John I. , Balk Meghan A. , Elliott Scott M. , Lyons S. Kathleen , Pardi Melissa I. , Tomé Catalina P. , Wagner Peter J. , Westover Marie L. 
Published: October 2015

SignificanceMost large mammals are endangered or vulnerable across the globe. Although the loss of charismatic fauna is of great concern, their role in ecosystem function remains poorly characterized. Here, we quantify one potential effect of the decline of large herbivores: the reduction of the greenhouse gas methane released as a byproduct of plant digestion. We examine three time periods where large-scale losses of megaherbivores occurred—the African rinderpest epizootic of the 1890s, the massive Great Plains bison kill-off in the 1860s, and the terminal Pleistocene extinction of megafauna. We find detectable decreases in the global methane budget related to the extirpation of megaherbivores. Our findings underscore the importance of large mammals in regulating ecosystems and feedbacks on climate.
Tether mutations that restore function and suppress pleiotropic phenotypes of theC. elegans isp-1(qm150)Rieske iron–sulfur protein
Authors: Jafari Gholamali , Wasko Brian M. , Tonge Ashley , Schurman Nathan , Dong Cindy , Li Zhongyu , Peters Rebecca , Kayser Ernst-Bernhard , Pitt Jason N. , Morgan Phil G. , Sedensky Margaret M. , Crofts Antony R. , Kaeberlein Matt 
Published: October 2015

SignificanceMitochondrial function is critical for health and longevity. Mutation of the highly conserved Rieske iron–sulfur subunit (ISP-1) of complex III in the respiratory chain results in pleiotropic phenotypes inCaenorhabditis elegans, including delayed development and increased lifespan. We identified intragenic mutations within a conserved 6-aa tether region of ISP-1. These suppressors are capable of suppressing all of the phenotypes associated with theisp-1(qm150)mutation. We further demonstrated that this mutation/suppressor relationship is conserved in the Rieske iron–sulfur protein (Rip1) of yeast complex III. These findings provide insights into conserved features of the structure and function of this protein, and allow us to propose a unique “spring-loaded” mechanism to account for these effects, supported by empirical physicochemical data.
Anatomy of funded research in science
Authors: Ma Athen , Mondragón Raúl J. , Latora Vito 
Published: October 2015

SignificanceThe study of scientific collaborations has been predominately focused on characterizing publication coauthorships. Here, we study instead collaboration networks by looking at project partnerships funded over the years and show clearly the substantial impact of funding shifts on the pattern of interactions. We find that the leading universities form a cohesive clique among themselves and occupy brokerage positions between otherwise disconnected entities, and as the inequality in the distribution of funding grows over time, so does the degree of brokerage. Specifically, the elites overattract resources but they also reward in variety of research and quality. We are the first to our knowledge to systematically quantify the far-reaching effects of external forces on the complex interactions in team research that underpin the production and evolution of science.
Optimal group size in a highly social mammal
Authors: Markham A. Catherine , Gesquiere Laurence R. , Alberts Susan C. , Altmann Jeanne 
Published: October 2015

SignificanceWhat are the costs and benefits for animals living in groups of different sizes? Balancing the trade-offs between within-group competition (which favors smaller groups) and between-group competition (which favors larger groups) suggests that intermediate-sized groups may be best, yet empirical support for this prediction has largely been lacking. Using long-term data on wild baboons, we provide novel evidence that individuals living in intermediate-sized groups have energetically optimal space-use strategies and lower glucocorticoid (stress hormone) concentrations than individuals in either large or small groups. Our results offer new insight into the costs and benefits of group living.
Why significant variables aren’t automatically good predictors
Authors: Lo Adeline , Chernoff Herman , Zheng Tian , Lo Shaw-Hwa 
Published: October 2015

Significance
A recent puzzle in the big data scientific literature is that an increase in explanatory variables found to be significantly correlated with an outcome variable does not necessarily lead to improvements in prediction. This problem occurs in both simple and complex data. We offer explanations and statistical insights into why higher significance does not automatically imply stronger predictivity and why variables with strong predictivity sometimes fail to be significant. We suggest shifting the research agenda toward searching for a criterion to locate highly predictive variables rather than highly significant variables. We offer an alternative approach, the partition retention method, which was effective in reducing prediction error from 30% to 8% on a long-studied breast cancer data set.