bluuebunny/crossref_metadata_2025_split huggingface dataset:
Warning signals are under positive frequency-dependent selection in nature
Authors: Chouteau Mathieu , Arias Mónica , Joron Mathieu 
Published: February 2016

Significance
Warning coloration and defensive mimicry are textbook examples of antipredator strategies under frequency-dependent selection (FDS), where predators avoid defended prey that are common but attack rarer ones. Whether the efficiency of mimicry truly derives from positive FDS remains unverified, yet assessing FDS is essential for understanding the diversity of warning signals observed. Using wing patterns found in natural communities of toxic butterflies, we demonstrate that warning signals are under strong, nonlinear, positive FDS. Predator knowledge is saturated and protection is optimal only for a few superabundant prey types. Most warning signals fall below optimal protection, limited by their local abundance. This potential for improved protection may explain the extraordinary efficiency of selection to drive convergence in morphology and life history in mimetic prey.
Adaptive methylation regulation ofp53pathway in sympatric speciation of blind mole rats,Spalax
Authors: Zhao Yang , Tang Jia-Wei , Yang Zhi , Cao Yi-Bin , Ren Ji-Long , Ben-Abu Yuval , Li Kexin , Chen Xue-Qun , Du Ji-Zeng , Nevo Eviatar 
Published: February 2016

Significancep53has been shown to play important roles in environmental adaptive evolution. Here we show that p53 and its target genes express differentially between two abutting populations of the blind mole ratSpalax galiliduring its sympatric speciation caused by sharply divergent abutting ecologies of chalk and basalt. Remarkably, the differential expression ofp53is due to differing methylation on sites –1446, –1204, and –1086 of thep53promoter, which plays a key role in regulating the binding of several transcription factors including Cut-Like Homeobox 1, paired box 4 (Pax 4), Pax 6, and activator protein 1. Different expressions ofS. galili p53selectively changed adaptive cell-cycle arrest. This article provides evidence supporting the sympatric speciation ofS. galili, demonstrating the importance of epigenetic modifications in adaptive evolution.
Time-coded neurotransmitter release at excitatory and inhibitory synapses
Authors: Rodrigues Serafim , Desroches Mathieu , Krupa Martin , Cortes Jesus M. , Sejnowski Terrence J. , Ali Afia B. 
Published: February 2016

Significance
Neurotransmitter exocytosis and short-term synaptic plasticity (STSP) regulate large-scale brain electrical activity. This study is the first, to our knowledge, proposing a multiple-time-scale model that bridges between the microscopic and mesoscopic scales. It is parsimonious, yet with enough descriptive power to express, on the one hand, the interactions between the SNARE and Sec1/Munc18 (SM) protein complexes mediating all forms of neurotransmitter release and STSP and, on the other hand, the electrical activity required for neuronal communication. A key finding is the discovery of a mathematical structure, termed activity-induced transcritical canard, which quantifies and explains delayed and irregular exocytosis. This structure also provides a previously unidentified way to understand delayed and irregular processes sensitive to initial conditions across various biology processes.
Self-targeting of TNF-releasing cancer cells in preclinical models of primary and metastatic tumors
Authors: Dondossola Eleonora , Dobroff Andrey S. , Marchiò Serena , Cardó-Vila Marina , Hosoya Hitomi , Libutti Steven K. , Corti Angelo , Sidman Richard L. , Arap Wadih , Pasqualini Renata 
Published: February 2016

Significance
A recent paradigm shift has established “tumor cell seeding” as an intriguing biological phenomenon in cancer biology. However, the clinical implications of a bidirectional flow of cancer cells remains largely unexplored. We show that systemic administration of TNF-expressing cancer cells reduces growth of both primary tumors and metastatic colonies defined here as “tumor self-targeting.” Our findings support a provocative concept in which circulating tumor cells genetically manipulated ex vivo and readministered into the circulating bloodstream may indeed serve as tumor-targeted cellular vectors in preclinical settings and could potentially open a field of translational investigation.
Anti-myostatin antibody increases muscle mass and strength and improves insulin sensitivity in old mice
Authors: Camporez João-Paulo G. , Petersen Max C. , Abudukadier Abulizi , Moreira Gabriela V. , Jurczak Michael J. , Friedman Glenn , Haqq Christopher M. , Petersen Kitt Falk , Shulman Gerald I. 
Published: February 2016

Significance
Sarcopenia, or aging-associated muscle atrophy, increases the risk of falls and fractures and is associated with metabolic disease. Because skeletal muscle is a major contributor to glucose handling after a meal, sarcopenia has significant effects on whole-body glucose metabolism. Despite the high prevalence and potentially devastating consequences of sarcopenia, no effective therapies are available. Here, we show that treatment of mice with an anti-myostatin antibody for just 4 wk increased muscle mass and strength in both young and old mice. In old mice, this increase in muscle mass was accompanied by an improvement in muscle insulin sensitivity. These data provide support for myostatin inhibition as a potential therapeutic strategy for aging-associated sarcopenia and insulin resistance.
Iontophoretic device delivery for the localized treatment of pancreatic ductal adenocarcinoma
Authors: Byrne James D. , Jajja Mohammad R. N. , Schorzman Allison N. , Keeler Amanda W. , Luft J. Christopher , Zamboni William C. , DeSimone Joseph M. , Yeh Jen Jen 
Published: February 2016

Significance
Drug delivery to pancreatic tumors is impaired by a unique desmoplastic response and poor tumor vascularization. A drug delivery device capable of overcoming these barriers could provide substantial benefit for patients with pancreatic cancer. In this study, we show that local iontophoretic delivery of folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) resulted in better tumor response and tolerability compared with i.v. FOLFIRINOX. Given the low systemic exposure of FOLFIRINOX using iontophoretic delivery, it may be possible to use in combination with systemic delivery to treat micrometastatic disease. Local iontophoretic delivery of cytotoxic agents should be considered as a neoadjuvant approach to improve resection rates and outcome in patients with localized and locally advanced pancreatic cancer.
On the optimum processing conditions of Pb(ZrxTi1−x)O3: revealing the mechanisms to increase the piezoelectric coefficients up to 1100 pm V−1
Authors: Zeibekis M , Vertsioti G , Stamopoulos D 
Published: February 2016

Abstract
The ferroelectric compound family Pb(Zr
x
Ti1−x
)O3 (PZT) is one of the most investigated and widely used piezoelectric materials. Optimization of the piezoelectric coefficients is observed for x ~ 0.52 (Pb(Zr0.52Ti0.48)O3) and is further promoted by the increase of grain size (GS). However, in some cases the piezoelectric properties of Pb(Zr0.52Ti0.48)O3 deteriorate upon processing due to the decrease of density, ρ, that is mostly ascribed to the appearance of byproduct phases. In the present study we discuss the influence of the processing conditions on the piezoelectric properties for polycrystalline Pb(Zr0.52Ti0.48)O3, specifically focusing on the sintering temperature, 1100 °C  ⩽  T
sin  ⩽  1250 °C. To this end, we use atomic force microscopy (AFM), Archimedes’ method, x-ray diffraction (XRD) and a newly introduced local technique, based on a conventional optical microscope, which is further developed here to accommodate non-clamped specimens. The data obtained via this technique in the regime of relatively high electric fields evidence that the absolute piezoelectric coefficients, |d

zi
| (i  =  x, y) show a non-monotonic behavior with an unexpectedly high maximum value |d

zi
| ~ 1100 pm V−1 at T
sin  =  1180 °C. These features are accompanied by a progressive increase of coercivity, reaching maximum value E
C,i
~ 4.5–5.0 kV cm−1 (i  =  x, y) at T
sin  =  1250 °C. To explain these findings, the |d
zi
| coefficients are compared with the microstructure and compositional information, coming from AFM, Archimedes’ method and XRD data. We conclude that the significantly high |d

zi
| values observed for samples prepared at T
sin  =  1180 °C are motivated by the increase of mean GS, <GS>, while for T
sin  >  1180 °C the decrease of density, ρ, ascribed to the appearance of byproduct phases, dominates and deteriorates |d

zi
|. These experimental results on |d

zi
|(T
sin) are reliably reproduced by a phenomenological model with reasonable assumptions for  <GS>  (T
sin) and ρ(T
sin). The unexpectedly high piezoelectric coefficients, |d

zi
| ~ 1100 pm V−1, reported here for the first time, are provocative and call for utilization of the introduced approach in the investigation of the respective properties of other compounds.
Spin polarisation using gate voltage through a Rashba barrier in graphene
Authors: Wu Xiuqiang 
Published: February 2016

Abstract
Gate-tunable spin-resolved scattering through a Rashba spin–orbit (SO) coupling graphene barrier is considered theoretically by using a mode-matching method. In this structure, we investigate the dependence of the tunnelling transmission probability on the spin orientation of the incident electron. It is found that the difference of the transmission probability for opposite spin orientations exhibits considerable incident-angle-dependent features when both gate voltage and Rashba SO coupling in the barrier region are present. The difference is adjustable by the gate voltage. More specifically, we find that the sign of spin polarisation of conductance can switch from positive to negative by adjusting the electric potential at any Rashba SO coupling. These results can provide an efficient way to design graphene spintronic devices without the need for ferromagnets.
Observation of the intrinsic rotation in KSTAR Ohmic L-mode plasmas
Authors: Na D.H. , Na Yong-Su , Lee S.G. , Angioni C. , Yang S.M. , Kim H.-S. , Hahm T.S. , Ko W.H. , Jhang H. , Lee W.J. 
Published: February 2016

Abstract
Two types of experiments were carried out to conduct an intrinsic rotation study in KSTAR. The first was a density ramp-up experiment without neutral beam injection, and the second was an experiment with beam blip technique. In these experiments, some characteristics of the intrinsic rotation were observed in the KSTAR Ohmic L-mode plasmas including: (i) a non-monotonic dependence of the core intrinsic rotation, called U-curve behaviour, with respect to the electron density and the collisionality related to the gradient of the toroidal rotation profile; and (ii) the behaviour of the anchor point in the intrinsic rotation profile for which the region exhibits a roughly flat shape and stays at nearly the same value even if the gradient of the toroidal rotation changes significantly in the core region. The location of the anchor point seems to be related to the q profile, and the toroidal rotation at the anchor point changes with the plasma operation parameters. These observations in the KSTAR Ohmic L-mode plasmas seem to be related to the rotation reversal phenomenon. A transport analysis was performed for the beam blip experiments in order to evaluate the intrinsic torque so that the U-curve behaviour can be further understood. The first results of the transport analysis in the KSTAR Ohmic L-mode plasmas show a correlation of the momentum fluxes and the intrinsic torques with the electron density and the collisionality. The rough magnitude and profiles of the intrinsic torque was experimentally obtained, and their possible mechanism is briefly discussed.
New insights into the generalized Rutherford equation for nonlinear neoclassical tearing mode growth from 2D reduced MHD simulations
Authors: Westerhof E. , de Blank H.J. , Pratt J. 
Published: February 2016

Abstract
Two dimensional reduced MHD simulations of neoclassical tearing mode growth and suppression by ECCD are performed. The perturbation of the bootstrap current density and the EC drive current density perturbation are assumed to be functions of the perturbed flux surfaces. In the case of ECCD, this implies that the applied power is flux surface averaged to obtain the EC driven current density distribution. The results are consistent with predictions from the generalized Rutherford equation using common expressions for

and

. These expressions are commonly perceived to describe only the effect on the tearing mode growth of the helical component of the respective current perturbation acting through the modification of Ohm’s law. Our results show that they describe in addition the effect of the poloidally averaged current density perturbation which acts through modification of the tearing mode stability index. Except for modulated ECCD, the largest contribution to the mode growth comes from this poloidally averaged current density perturbation.
From Curious to Pragmatically Curious: Comment on “From Hopeless to Curious? Thoughts on Hausman's ‘Dubious to Hopeless’ Critique of Contingent Valuation”
Authors: Desvousges William , Mathews Kristy , Train Kenneth 
Published: February 2016

AbstractThis article extends the discussion introduced in this journal by Haab et al. (2013), who critique a 2012 article on contingent valuation (CV) by Hausman. We agree with Haab et al. “that the intellectual debate over [CV] is ongoing and that plenty of work remains to be done for the truly curious researcher” (593). However, our paper illuminates the limitations of current approaches to guide future research.
Genetics of autoimmune diseases: perspectives from genome-wide association studies
Authors: Kochi Yuta 
Published: February 2016

Abstract
Genome-wide association studies (GWASs) for autoimmune diseases (ADs) have identified many risk loci and have provided insights into the etiology of each disease. Some of these loci, such as PTPN22 , IL23R and STAT4 , are shared among different ADs, and the combination of risk loci may determine an individual’s susceptibility for a disease. The majority of GWAS loci are expression quantitative trait loci (eQTLs), where disease-causing variants regulate expression of neighboring (or sometimes distant) genes. Because the eQTL effects are often cell type-specific, the incorporation of epigenetic data from disease-related cell types and tissues is expected to refine the identification of causal variants. The cumulative eQTL effects in multiple genes may influence the activity or fate of immune cells, which in turn may affect the function of the immune system in individuals. In this paper, I review the etiology of ADs by focusing on important immune cells (T h 1 cells, T h 17 cells and regulatory T cells), important pathways (antigen-receptor signaling and type I interferon signaling) and relevant genes identified in GWASs.
Systemic Cytokine Levels Do Not Predict CD4+ T-Cell Recovery After Suppressive Combination Antiretroviral Therapy in Chronic Human Immunodeficiency Virus Infection
Authors: Norris Philip J. , Zhang Jinbing , Worlock Andrew , Nair Sangeetha V. , Anastos Kathryn , Minkoff Howard L. , Villacres Maria C. , Young Mary , Greenblatt Ruth M. , Desai Seema , Landay Alan L. , Gange Stephen J. , Nugent C. Thomas , Golub Elizabeth T. , Keating Sheila M. ,   the Women's Interagency HIV Study, Anastos Kathryn , Minkoff Howard , Gustafson Deborah , Cohen Mardge , French Audrey , Young Mary , Greenblatt Ruth , Aouizerat Bradley , Tien Phyllis , Gange Stephen , Golub Elizabeth , Milam Joel 
Published: February 2016

AbstractBackground.  Subjects on suppressive combination antiretroviral therapy (cART) who do not achieve robust reconstitution of CD4+ T cells face higher risk of complications and death. We studied participants in the Women's Interagency HIV Study with good (immunological responder [IR]) or poor (immunological nonresponder [INR]) CD4+ T-cell recovery after suppressive cART (n = 50 per group) to determine whether cytokine levels or low-level viral load correlated with INR status.Methods.  A baseline sample prior to viral control and 2 subsequent samples 1 and 2 years after viral control were tested. Serum levels of 30 cytokines were measured at each time point, and low-level human immunodeficiency virus (HIV) viral load and anti-HIV antibody levels were measured 2 years after viral suppression.Results.  There were minimal differences in cytokine levels between IR and INR subjects. At baseline, macrophage inflammatory protein-3β levels were higher in IR subjects; after 1 year of suppressive cART, soluble vascular endothelial growth factor-R3 levels were higher in IR subjects; and after 2 years of suppressive cART, interferon gamma-induced protein 10 levels were higher in INR subjects. Very low-level HIV viral load and anti-HIV antibody levels did not differ between IR and INR subjects.Conclusions.  These results imply that targeting residual viral replication might not be the optimum therapeutic approach for INR subjects.
Quaternary Lidocaine Derivative QX-314 Activates and Permeates Human TRPV1 and TRPA1 to Produce Inhibition of Sodium Channels and Cytotoxicity
Authors: Stueber Thomas , Eberhardt Mirjam J. , Hadamitzky Christoph , Jangra Annette , Schenk Stefan , Dick Felicia , Stoetzer Carsten , Kistner Katrin , Reeh Peter W. , Binshtok Alexander M. , Leffler Andreas 
Published: February 2016

AbstractAbstract
In cells expression human TRPV1 and TRPA1 channels, QX-314 activates both channels and enters the cell to inhibit sodium currents. In these cells, QX-314 produces cytotoxicity by a mechanism dependent on TRPV1 channels.

Background
The relatively membrane-impermeable lidocaine derivative QX-314 has been reported to permeate the ion channels transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential cation channel, subfamily A, member 1 (TRPA1) to induce a selective inhibition of sensory neurons. This approach is effective in rodents, but it also seems to be associated with neurotoxicity. The authors examined whether the human isoforms of TRPV1 and TRPA1 allow intracellular entry of QX-314 to mediate sodium channel inhibition and cytotoxicity.

Methods
Human embryonic kidney 293 (HEK-293) cells expressing wild-type or mutant human (h) TRPV1 or TRPA1 constructs as well as the sodium channel Nav1.7 were investigated by means of patch clamp and ratiometric calcium imaging. Cytotoxicity was examined by flow cytometry.

Results
Activation of hTRPA1 by carvacrol and hTRPV1 by capsaicin produced a QX-314–independent reduction of sodium current amplitudes. However, permeation of QX-314 through hTRPV1 or hTRPA1 was evident by a concentration-dependent, use-dependent inhibition of Nav1.7 activated at 10 Hz. Five and 30 mM QX-314 activated hTRPV1 via mechanisms involving the intracellular vanilloid-binding domain and hTRPA1 via unknown mechanisms independent of intracellular cysteins. Expression of hTRPV1, but not hTRPA1, was associated with a QX-314–induced cytotoxicity (viable cells 48 ± 5% after 30 mM QX-314) that was ameliorated by the TRPV1 antagonist 4-(3-chloro-2-pyridinyl)-N-[4-(1,1-dimethylethyl)phenyl]-1-piperazinecarboxamide (viable cells 81 ± 5%).

Conclusions
The study data demonstrate that QX-314 directly activates and permeates the human isoforms of TRPV1 and TRPA1 to induce inhibition of sodium channels, but also a TRPV1-dependent cytotoxicity. These results warrant further validation of this approach in more intact preparations and may be valuable for the development of this concept into clinical practice.
Depressive symptoms in midlife: the role of reproductive stage
Authors: Almeida Osvaldo P. , Marsh Kylie , Flicker Leon , Hickey Martha , Sim Moira , Ford Andrew 
Published: February 2016

Abstract

Objective:
The aim of the study was to determine the prevalence of depression among community-dwelling women in the premenopause, menopausal transition (MT), and postmenopause stage. We also sought to clarify the direct and indirect contribution of menopausal status on the risk of depression.

Methods:
Cross-sectional survey of 1,612 women aged 45 to 55 years living in the Perth metropolitan region, who were recruited using a random sample of the electoral roll (voting is compulsory in Australia), was conducted. Women with clinically significant symptoms of depression had Patient Health Questionnaire (PHQ-9) scores of at least 10, and those with major depression, reported symptoms consistent with Diagnostic and Statistical Manual of Mental Disorders, 5th ed (DSM-5), criteria. We used past and current gynecological and reproductive data to classify women as premenopausal, undergoing the MT, and postmenopausal. Other study measures included age, place of birth, education, marital status, drinking habit, number of children, medical illnesses, and history of premenstrual syndrome, postnatal depression, and past depression or anxiety. We investigated the direct and indirect effect of reproductive status with mediation/modulation analysis.

Results:
Among the women included in the survey, 8.2%, 11.5%, and 13.0% of women in premenopause, MT, and postmenopause had PHQ-9 at least 10, whereas major depression was present in 2.2%, 3.4%, and 3.6% of them. Reproductive status did not affect the prevalence of major depression, but more postmenopausal than premenopausal women had PHQ-9 score equal to or greater than 10 (P = 0.013). Compared with premenopausal women, MT was associated with a direct odds ratio (OR) 1.35 (95% confidence interval [CI] = 0.90, 2.01) and indirect OR 1.08 (95% CI = 0.92, 1.26) for PHQ-9 at least 10. Similarly, the direct and indirect effect of the postmenopause on the odds of PHQ-9 at least 10 was OR 1.31 (95% CI = 0.87, 1.98) and OR 1.29 (95% CI = 1.10, 1.52).

Conclusions:
The slight, but not significant, excess of depressive symptoms during MT and early postmenopause cannot be attributed to a direct effect of reproductive status.
Using capital theory to explore problem solving and innovation in small firms
Authors: Glover Jane , Champion Donna , Daniels Kevin , Boocock Grahame 
Published: February 2016

Purpose– The purpose of this paper is to investigate how small firms work at a micro-level, applying Bourdieu’s Capital Theory to give insight into the way individuals use the social and cultural capital at their disposal, to innovate and solve problems.Design/methodology/approach– The authors applied qualitative methods to explore problem solving and innovation activities at the micro-level in small firms, using interviews and thematic analysis.Findings– The findings reveal that, compared to firms with lower levels of social and cultural capital, firms which possess higher levels of social and cultural capital have a higher success rate in problem solving and are more likely to engage in innovative activity. Social and cultural capitals complement and reinforce one another in small firms, for example an enhanced ability to utilise networks (social capital) allows small firms to access a greater diversity of knowledge (cultural capital).Originality/value– Little is known about how different forms of capital are utilised in the day-to-day operations and problem solving of small firms: the application of Bourdieu’s Capital Theory offered an original frame in which to explore these activities.