bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of novel markers of senescence and their prognostic potential in cancer
Authors: Althubiti M , Lezina L , Carrera S , Jukes-Jones R , Giblett S M , Antonov A , Barlev N , Saldanha G S , Pritchard C A , Cain K , Macip S 
Published: November 2014

AbstractCellular senescence is a terminal differentiation state that has been proposed to have a role in both tumour suppression and ageing. This view is supported by the fact that accumulation of senescent cells can be observed in response to oncogenic stress as well as a result of normal organismal ageing. Thus, identifying senescent cells in in vivo and in vitro has an important diagnostic and therapeutic potential. The molecular pathways involved in triggering and/or maintaining the senescent phenotype are not fully understood. As a consequence, the markers currently utilized to detect senescent cells are limited and lack specificity. In order to address this issue, we screened for plasma membrane-associated proteins that are preferentially expressed in senescent cells. We identified 107 proteins that could be potential markers of senescence and validated 10 of them (DEP1, NTAL, EBP50, STX4, VAMP3, ARMX3, B2MG, LANCL1, VPS26A and PLD3). We demonstrated that a combination of these proteins can be used to specifically recognize senescent cells in culture and in tissue samples and we developed a straightforward fluorescence-activated cell sorting-based detection approach using two of them (DEP1 and B2MG). Of note, we found that expression of several of these markers correlated with increased survival in different tumours, especially in breast cancer. Thus, our results could facilitate the study of senescence, define potential new effectors and modulators of this cellular mechanism and provide potential diagnostic and prognostic tools to be used clinically.
Combination simvastatin and metformin induces G1-phase cell cycle arrest and Ripk1- and Ripk3-dependent necrosis in C4-2B osseous metastatic castration-resistant prostate cancer cells
Authors: Babcook M A , Sramkoski R M , Fujioka H , Daneshgari F , Almasan A , Shukla S , Nanavaty R R , Gupta S 
Published: November 2014

AbstractCastration-resistant prostate cancer (CRPC) cells acquire resistance to chemotherapy and apoptosis, in part, due to enhanced aerobic glycolysis and biomass production, known as the Warburg effect. We previously demonstrated that combination simvastatin (SIM) and metformin (MET) ameliorates critical Warburg effect-related metabolic aberrations of C4-2B cells, synergistically and significantly decreases CRPC cell viability and metastatic properties, with minimal effect on normal prostate epithelial cells, and inhibits primary prostate tumor growth, metastasis, and biochemical failure in an orthotopic model of metastatic CRPC, more effectively than docetaxel chemotherapy. Several modes of cell death activated by individual treatment of SIM or MET have been reported; however, the cell death process induced by combination SIM and MET treatment in metastatic CRPC cells remains unknown. This must be determined prior to advancing combination SIM and MET to clinical trial for metastatic CRPC. Treatment of C4-2B cells with combination 4 μM SIM and 2 mM MET (SIM+MET) led to significant G1-phase cell cycle arrest and decrease in the percentage of DNA-replicating cells in the S-phase by 24 h; arrest was sustained throughout the 96-h treatment. SIM+MET treatment led to enhanced autophagic flux in C4-2B cells by 72–96 h, ascertained by increased LC3B-II (further enhanced with lysosomal inhibitor chloroquine) and reduced Sequestosome-1 protein expression, significantly increased percentage of acidic vesicular organelle-positive cells, and increased autophagic structure accumulation assessed by transmission electron microscopy. Chloroquine, however, could not rescue CRPC cell viability, eliminating autophagic cell death; rather, autophagy was upregulated by C4-2B cells in attempt to withstand chemotherapy. Instead, SIM+MET treatment led to Ripk1- and Ripk3-dependent necrosis by 48–96 h, determined by propidium iodide-Annexin V flow cytometry, increase in Ripk1 and Ripk3 protein expression, necrosome formation, HMGB-1 extracellular release, and necrotic induction and viability rescue with necrostatin-1 and Ripk3-targeting siRNA. The necrosis-inducing capacity of SIM+MET may make these drugs a highly-effective treatment for apoptosis- and chemotherapy-resistant metastatic CRPC cells.
BIS targeting induces cellular senescence through the regulation of 14-3-3 zeta/STAT3/SKP2/p27 in glioblastoma cells
Authors: Lee J-J , Lee J-S , Cui M N , Yun H H , Kim H Y , Lee S H , Lee J-H 
Published: November 2014

AbstractCellular senescence is an important mechanism for preventing tumor progression. The elevated expression of Bcl-2-interacting cell death suppressor (BIS), an anti-apoptotic and anti-stress protein, often correlates with poor prognosis in several cancers including glioblastoma; however, the role of BIS in the regulation of senescence has not been well defined. Here, we describe for the first time that the depletion of BIS induces G1 arrest and cellular senescence through the accumulation of p27 that is independent of p53, p21 or p16. The increase in p27 expression in BIS-depleted cells was attributable to an impairment of the ubiquitin-mediated degradation of p27, which was caused by a decrease in S-phase kinase-associated protein 2 (SKP2) at the transcriptional level. As an underlying molecular mechanism, we demonstrate that the loss of activity of signal transducer and activator of transcription 3 (STAT3) was specifically linked to the suppression of SKP2 expression. Despite a reduction in phospho-STAT3 levels, total STAT3 levels were unexpectedly increased by BIS depletion, specifically in the insoluble fraction. Our results show that 14-3-3ζ expression is decreased by BIS knockdown and that 14-3-3ζ depletion per se significantly induced senescence phenotypes. In addition, the ectopic expression of 14-3-3ζ blocked senescence caused by BIS depletion, which was paralleled with a decrease in insoluble STAT3 in A172 glioblastoma cells. These findings indicate that the impairment of the protein quality control conferred by BIS and/or 14-3-3ζ is critical for BIS depletion-induced senescence. Moreover, BIS knockdown also induced senescence along with an accumulation of total STAT3 and p27 in several different cell types as well as embryonic fibroblasts derived from Bis-knock out mice with/without variations in 14-3-3ζ levels. Therefore, our findings suggest that a downregulation of BIS expression could serve as a potential strategy for restricting tumor progression via an induction of senescence through the regulation of STAT3/SKP2/p27 pathway.
Field-induced assembly of colloidal ellipsoids into well-defined microtubules
Authors: Crassous Jérôme J. , Mihut Adriana M. , Wernersson Erik , Pfleiderer Patrick , Vermant Jan , Linse Per , Schurtenberger Peter 
Published: November 2014

AbstractCurrent theoretical attempts to understand the reversible formation of stable microtubules and virus shells are generally based on shape-specific building blocks or monomers, where the local curvature of the resulting structure is explicitly built-in via the monomer geometry. Here we demonstrate that even simple ellipsoidal colloids can reversibly self-assemble into regular tubular structures when subjected to an alternating electric field. Supported by model calculations, we discuss the combined effects of anisotropic shape and field-induced dipolar interactions on the reversible formation of self-assembled structures. Our observations show that the formation of tubular structures through self-assembly requires much less geometrical and interaction specificity than previously thought, and advance our current understanding of the minimal requirements for self-assembly into regular virus-like structures.
DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer's disease
Authors: Yuki Dai , Sugiura Yuki , Zaima Nobuhiro , Akatsu Hiroyasu , Takei Shiro , Yao Ikuko , Maesako Masato , Kinoshita Ayae , Yamamoto Takayuki , Kon Ryo , Sugiyama Keikichi , Setou Mitsutoshi 
Published: November 2014

AbstractAlzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by senile plaques, neurofibrillary tangles, synaptic disruption and neuronal loss. Several studies have demonstrated decreases of docosahexaenoic acid-containing phosphatidylcholines (DHA-PCs) in the AD brain. In this study, we used matrix-assisted laser desorption/ionization imaging mass spectrometry in postmortem AD brain to show that PC molecular species containing stearate and DHA, namely PC(18:0/22:6), was selectively depleted in the gray matter of patients with AD. Moreover, in the brain regions with marked amyloid β (Aβ) deposition, the magnitude of the PC(18:0/22:6) reduction significantly correlated with disease duration. Furthermore, at the molecular level, this depletion was associated with reduced levels of the postsynaptic protein PSD-95 but not the presynaptic protein synaptophysin. Interestingly, this reduction in PC(18:0/22:6) levels did not correlate with the degrees of Aβ deposition and neuronal loss in AD. The analysis of the correlations of key factors and disease duration showed that their effects on the disease time course were arranged in order as Aβ deposition, presynaptic disruption, postsynaptic disruption coupled with PC(18:0/22:6) reduction and neuronal loss.
The Effects of Rate on Single-Word Reading Assessment
Authors: Carter Matthew D. , Walker Marianna M. , O'Brien Kevin 
Published: November 2014

Purpose
The purpose of this study was to examine the effects of introducing rapid stimulus presentation durations while limiting response durations on the decoding profiles of college students with reading disorders.

Method
Eighteen college-aged individuals with typical reading abilities and 12 college-aged adults who exhibited reading difficulties participated. Participants completed a series of 4 experimental word-naming tasks. Two Word Attack subtests and 2 Word Identification subtests were administered while introducing more rapid stimulus presentation durations along with limited response times. Standard scores and response times were collected. Each individual's results were subjected to a subtyping procedure based on relative decoding strengths and weaknesses.

Results
More rapid conditions were associated with higher sight word decoding scores and lower phonological decoding scores. The results indicated that the subtyping patterns differed drastically depending on the presentation conditions.

Conclusions
The authors hypothesize that the experimental conditions potentially yield a more reliable assessment of the 2 independent methods of single-word reading. The ability to subtype or categorize readers on the basis of their relative strengths and weaknesses is highly dependent on the reliability of the measures used to assess those relative strengths and weaknesses.
Static network structure can stabilize human cooperation
Authors: Rand David G. , Nowak Martin A. , Fowler James H. , Christakis Nicholas A. 
Published: November 2014

Significance
Human populations are both extremely cooperative and highly structured. Mathematical models have shown that fixed network interaction structures can lead to cooperation under certain conditions, by allowing cooperators to cluster together. Here, we provide empirical evidence of this phenomenon. We explore how different fixed social network structures can promote cooperation using economic game experiments. We find that people cooperate at high stable levels, as long as the benefits created by cooperation are larger than the number of neighbors in the network. This empirical result is consistent with a rule predicted by mathematical models of evolution. Our findings show the important role social networks can play in human cooperation and provide guidance for promoting cooperative behavior.
Optimal T-cell receptor affinity for inducing autoimmunity
Authors: Koehli Sabrina , Naeher Dieter , Galati-Fournier Virginie , Zehn Dietmar , Palmer Ed 
Published: November 2014

Significance
The adaptive immune system has the potential to generate a self-reactive response, which can eventually lead to an autoimmune disease. To avoid this outcome, T lymphocytes with high-affinity, self-reactive antigen receptors are blocked from entering the mature T-cell pool (negative selection). Given this mechanism for removing dangerous high-affinity T cells, we wondered whether autoimmunity is more likely to be caused by chronic stimulation of low-affinity T cells or by stimulation of a few high-affinity T cells that escaped negative selection. In this paper, we show that T cells with an affinity just above the selection threshold can bypass negative selection and have the highest potential to cause an experimental autoimmune disease.
Instability-induced pattern formation of photoactivated functional polymers
Authors: Galinski Henning , Ambrosio Antonio , Maddalena Pasqualino , Schenker Iwan , Spolenak Ralph , Capasso Federico 
Published: November 2014

Significance
When azobenzene-containing polymer films are exposed to UV or visible light complex Turing patterns form on the polymer's surface. But despite the large number of applications reported, a physical explanation for the pattern formation in this important class of materials and its dependence on both the lights intensity and polarization is still lacking. In this study, we present a general explanation for the pattern formation on these photoactivated azopolymer films. We believe that our findings are an innovative contribution to the field of pattern formation of functional polymers and photoactivated thin film engineering, which have the potential to boost the development of photoresponsive systems, such as molecular electronic devices.
Credit scores, cardiovascular disease risk, and human capital
Authors: Israel Salomon , Caspi Avshalom , Belsky Daniel W. , Harrington HonaLee , Hogan Sean , Houts Renate , Ramrakha Sandhya , Sanders Seth , Poulton Richie , Moffitt Terrie E. 
Published: November 2014

Significance
Credit scoring is expanding into domains beyond lending. Today, credit scores are used by employers, utility companies, and automobile insurers to index high-risk behavior. Life insurance companies even incorporate credit scores into actuarial models. This expansion is controversial, as it is unclear what personal attributes credit scores capture. Following 1,000 individuals from birth to midlife, we show that low credit scores predict cardiovascular disease risk. We also show that the reason credit scores are broadly applicable as a risk stratification tool is because they capture enduring histories of human capital, beginning in childhood. These findings call attention to privacy concerns in a surveillance society, the value of financial literacy, and the importance of early childhood intervention to promote healthy aging.
Earthquake and tsunami forecasts: Relation of slow slip events to subsequent earthquake rupture
Authors: Dixon Timothy H. , Jiang Yan , Malservisi Rocco , McCaffrey Robert , Voss Nicholas , Protti Marino , Gonzalez Victor 
Published: November 2014

Significance
Recent destructive megathrust earthquakes and tsunamis in Japan and Sumatra indicate the difficulty of forecasting these events. Geodetic monitoring of the offshore regions of the subduction zones where these events occur has been suggested as a useful tool, but its potential has never been conclusively demonstrated. Here we show that slow slip events, nondestructive events that release energy slowly over weeks or months, are important mechanisms for releasing seismic strain in subduction zones. Better monitoring of these events, especially those offshore, could allow estimates of the size of future earthquakes and their potential for damaging tsunamis. However, the predictive value of slow slip events remains unclear.
Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling
Authors: Baeyens Nicolas , Mulligan-Kehoe Mary Jo , Corti Federico , Simon David D. , Ross Tyler D. , Rhodes John M. , Wang Thomas Z. , Mejean Cecile O. , Simons Michael , Humphrey Jay , Schwartz Martin A. 
Published: November 2014

Significance
Atherosclerosis, the major cause of death and illness in industrialized nations, develops in regions of arteries in which fluid flow patterns are disturbed and endothelial cells fail to align in the direction of flow. In contrast, regions of laminar flow in which cells are aligned are protected. The current work shows that the transmembrane proteoglycan syndecan 4 is required for endothelial cell alignment in the direction of flow and for the protective effect of high laminar flow, yet other flow responses are intact. The data therefore identify a role for syndecan 4 in flow direction sensing, show that sensing flow direction is separable from sensing flow magnitude, and provide new support for the key role of cell alignment in atheroprotection.
Young capillary vessels rejuvenate aged pancreatic islets
Authors: Almaça Joana , Molina Judith , Arrojo e Drigo Rafael , Abdulreda Midhat H. , Jeon Won Bae , Berggren Per-Olof , Caicedo Alejandro , Nam Hong Gil 
Published: November 2014

Significance
The regulation of blood glucose is a homeostatic process that declines with age, but it is unknown whether this disturbance is a consequence of intrinsic dysfunction of the regulatory organ, the pancreatic islet. In marked contrast to the widely held notion that the insulin-producing pancreatic beta cell loses function with wear and tear, and thus causes age-related disturbances in glucose homeostasis, we show that mouse and human beta cells are fully functional at advanced age. The pancreatic islet as an organ, however, is threatened by vascular senescence. Replacing the islet vasculature in aged islet grafts rejuvenates the islet and fully restores glucose homeostasis, indicating that islet blood vessels should be targeted to mitigate frail glucose homeostasis associated with aging.
Fast high-resolution 3D total internal reflection fluorescence microscopy by incidence angle scanning and azimuthal averaging
Authors: Boulanger Jérôme , Gueudry Charles , Münch Daniel , Cinquin Bertrand , Paul-Gilloteaux Perrine , Bardin Sabine , Guérin Christophe , Senger Fabrice , Blanchoin Laurent , Salamero Jean 
Published: November 2014

Significance
Recent progress has pushed forward the resolving capacity of optical microscopy at the expense of a low acquisition rate and use of specific probes. Such limitations make these techniques incompatible with dynamics localization of multiple elements in single cell. We report here a method to recover 3D volumes from images obtained using several total internal reflection fluorescence (TIRF) incidence angles at dense regime of acquisition. This approach allows investigating several dynamical processes occurring in depth of the cell up to 800 nm from the plasma membrane such as actin remodeling. The study of time-correlated molecular behaviors at the very late steps of vesicle docking–fusion during exocytosis of two distinct recycling transport intermediates, in 3D and at high axial resolution, is also accessible.
An engineered affibody molecule with pH-dependent binding to FcRn mediates extended circulatory half-life of a fusion protein
Authors: Seijsing Johan , Lindborg Malin , Höidén-Guthenberg Ingmarie , Bönisch Heiko , Guneriusson Elin , Frejd Fredrik Y. , Abrahmsén Lars , Ekblad Caroline , Löfblom John , Uhlén Mathias , Gräslund Torbjörn 
Published: November 2014

SignificanceOne of the central questions in biopharmaceutical development is how to extend circulation residence times of protein-based drugs to improve efficacy and patient comfort. Immunoglobulin G and serum albumin are rescued from lysosomal degradation by the pH-dependent binding to the neonatal Fc receptor and consequently have naturally long circulation half-lives. Here we describe the development and characterization of small affinity proteins (affibody molecules) that can hitchhike on the neonatal Fc receptor rescue system. We find that addition of the affibody molecules to an already half-life–extended recombinant protein leads to a nearly threefold longer circulation residence time in mice. Such affibody molecules may have a general use as fusion partners with biopharmaceuticals to extend their circulation residence times.
Rethinking natural altruism: Simple reciprocal interactions trigger children’s benevolence
Authors: Cortes Barragan Rodolfo , Dweck Carol S. 
Published: November 2014

Significance
This research showed that a very simple reciprocal activity elicited high degrees of altruism in 1- and 2-y-old children (as well as older children), whereas friendly but nonreciprocal activity did not. By doing so, it calls into question the current, dominant claim that young humans are naturally and spontaneously altruistic and that socialization cannot account for their altruistic actions. Beyond their scientific innovation, the findings can have important implications for adult–child interactions. Caregivers may engage in simple reciprocal activities that foster both the enactment of altruism in children and their expectation of altruism from others.
Essential oils and plant extracts with activity against oral microorganisms: prevention and treatment of oral diseases
Authors: Herman Anna , Młynarczyk Andrzej 
Published: November 2014

The aim of this study was to compare the antimicrobial activity of essential oils and extracts of Salvia officinalis, Thymus vulgaris, Mentha piperita, Juniperus communis and Rosmarinus officinalis with antibiotics against physiological and pathological strains of microorganisms isolated from the oral cavity. The antibacterial and antifungal activities of essential oils, extracts and antibiotics were evaluated using the disc diffusion method. Essential oils exhibited higher inhibitory activity against physiological microflora and all tested pathogenic microorganism strains than those observed for antibiotics and plant extracts. Essential oils and ethanolic extracts of Thymus vulgaris were the most potent growth inhibitor of all microorganisms isolated from the oral cavity. Depending on the bacterial strain tested, Thymus vulgaris oil had 3–8 times higher inhibitory activity compared with all tested antibiotics and exhibited the same strength of antifungal activity as amfotericin and miconazol against Candida albicans. Essential oils and extracts may be useful in the prevention and treatment of oral diseases caused by oral microorganisms.
Both HMG boxes in Hmo1 are essential for DNA binding in vitro and in vivo
Authors: Higashino Ayako , Shiwa Yuh , Yoshikawa Hirofumi , Kokubo Tetsuro , Kasahara Koji 
Published: November 2014

Abstract
Hmo1, a member of the high mobility group B family proteins in Saccharomyces cerevisiae, associates with the promoters of ribosomal protein genes (RPGs) to direct accurate transcriptional initiation. Here, to identify factors involved in the binding of Hmo1 to its targets and the mechanism of Hmo1-dependent transcriptional initiation, we developed a novel reporter system using the promoter of the RPG RPS5. A genetic screen did not identify any factors that influence Hmo1 binding, but did identify a number of mutations in Hmo1 that impair its DNA binding activity in vivo and in vitro. These results suggest that Hmo1 binds to its target promoters autonomously without any aid of additional factors. Furthermore, characterization of Hmo1 mutants showed that the box A domain plays a pivotal role in DNA binding and may be required for the recognition of structural properties of target promoters that occur in native chromatin.