bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of the mTOR/ Akt pathway in thymic epithelial cells derived from thymomas
Authors: Maury Jean-Michel , du Vignaux Claire Merveilleux , Drevet Gabrielle , Zarza Virginie , Chalabreysse Lara , Tronc François , Girard Nicolas , Leroux Caroline 
Published: May 2018

AbstractThe pathogenesis of thymic epithelial tumors remains poorly elucidated. The PI3K/Akt/mTOR pathway plays a key role in various cancers; interestingly, several phase I/II study reported a positive effect of mTOR inhibitors in disease control in thymoma patients. A major limit for deciphering cellular and molecular events leading to the transformation of thymic epithelial cells or for testing drug candidates is the lack of reliable in vitro cell systemWe analyzed protein expression and activation of key players of the Akt/mTOR pathway namely Akt, mTOR, and P70S6K in thirteen A, B and AB thymomas as well as in normal thymuses. While only Akt and the phospho-Akt were expressed in normal thymuses, both Akt and mTOR were activated, with B2 thymomas expressing higher level of activated phospho-Akt than A or AB subtypes. Phospho-P70S6K was expressed in all thymic tumors whatever their subtypes, and absent in normal thymus. Interestingly, in primary thymic epithelial cells maintained for short period of time after their derivation from seven AB and B thymomas, we report the activation of Akt; mTOR and P70S6. Finally, we analyzed the effect of mTOR inhibitor on thymoma derived epithelial cells and showed that rapamycin (100 nM/ ml) significantly reduced cell proliferation.Our results suggest that the activation of the Akt/ mTOR pathway might participate to the cell proliferation associated with tumor growth. Ultimately, our data enhance the potential role of thymic epithelial cells derived from tissue specimens forin vitroexploration of molecular abnormalities specific to rare thymic tumors.
PLK1 plays dual roles in centralspindlin regulation during cytokinesis
Authors: Adriaans Ingrid E. , Basant Angika , Ponsioen Bas , Glotzer Michael , Lens Susanne M. A. 
Published: May 2018

AbstractCytokinesis starts in anaphase with the formation of an actomyosin-based contractile ring at the equatorial cortex, which is governed by the local activation of the small GTPase RhoA. Here we delineated the contributions of PLK1 and Aurora B to RhoA activation and cytokinesis initiation in human cells. Knock-down of PRC1, which disrupts the spindle midzone, revealed the existence of two pathways that can initiate cleavage furrow ingression. One pathway depends on a well-organized spindle midzone and PLK1, while the other depends on Aurora B activity and centralspindlin oligomerization at the equatorial cortex and can operate independently of PLK1. We further show that PLK1 inhibition sequesters centralspindlin onto the spindle midzone making it unavailable for Aurora B-dependent oligomerization at the equatorial cortex. We propose that PLK1 activity promotes the release of centralspindlin from the spindle midzone through inhibition of PRC1, allowing centralspindlin to function as a regulator of spindle midzone formation and as an activator of RhoA at the equatorial cortex.
Regional integration and entrepreneurship: evidence from European Union
Authors: Tarabar Danko 
Published: May 2018

PurposeThe purpose of this paper is to empirically uncover the relationship between economic integration and levels of entrepreneurial activity across 24 EU countries between 2004 and 2012. The deepening of EU integration corresponds to increases in the size and competitiveness of domestic markets as member states reorient economic activity toward the larger, competitive single market. Spillovers of both economic and political dimensions of integration in the common market on micro firm and self-employment are considered. The paper contributes to the understanding of the hypothesized relationship between globalization and the rise of entrepreneurial economy.Design/methodology/approachThe paper uses fixed effects linear regression models to estimate the marginal effects of economic integration on entrepreneurial activity. Several dependent variables and controls for social, economics, and institutional context are used to confirm the robustness of the results.FindingsThe paper finds that increased economic activity of member countries within the EU common market, as well as institutional compliance and integration in the European Monetary Union and Schengen Agreement are positively and significantly associated with the rise of entrepreneurship. Notably, it is found that a standard deviation increase in economic and political integration is associated with, respectively, 16 and 7.2 percent increase in micro firm density. Some preliminary evidence on the quality of the arising entrepreneurial activity are also given.Originality/valueThe paper takes stock of existing descriptive and theoretical literature on global economic integration and entrepreneurship to uncover, for the first time, the empirical relationship between entrepreneurship and levels of economic and political integration within the EU bloc.
Effect of distance to edge and edge interaction on seedling regeneration and biotic damage in tropical rainforest fragments: A long‐term experiment
Authors: Benítez‐Malvido Julieta , Lázaro Amparo , Ferraz Isolde D. K. 
Published: May 2018

AbstractIn forest fragments, edge effects can influence forest regeneration, but little is known about how edge effects influence seedling performance and the interaction between seedlings and their natural enemies over time.In central Amazonia, we recorded survival and growth (in height and leaf number) and damage by insect herbivores and leaf‐fungal pathogens ofChrysophyllum pomiferum(Sapotaceae) seedlings that were exposed to different numbers of edges and to different distances from the forest edge. Grown seedlings were transplanted into one‐square‐metre plots within 1‐ha blocks located in the centre (no edge), the edge (one edge), and the corner (two edges), and at different distances from the edge towards the interior (i.e., 20, 40, 60, 80, and 100 m) of two rectangular fragments (10‐ and 100‐ha in size). Plots were visited once every 2 months for 1 year (1992–1993) and thereafter every 2 years for almost 8 years (1993–2001).Overall, results showed that seedling survival, height, leaf number, and biotic damage varied over time with the presence of nearby edges and with the distance from the edge. Survival was lower in fragment edges and corners than in centres. Increase in height was similar for all positions within the 100‐ha fragment, whereas in the 10‐ha fragment seedling height had a greater increase at the edge and corner than in the centre. Furthermore, survival increased with distance from the edge as did leaf number, whereas height showed a lower increase closer to the edge than farther away.Regarding biotic damage, for both fragments herbivory was greater at the centres and decreased with edge proximity over time, whereas leaf‐fungal damage was greater at the corners than in the edges and increased significantly over time. Biotic damage was correlated with seedling size. Small seedlings were more susceptible to fungal attack, whereas larger seedlings were so to herbivores.Synthesis. This study demonstrated that despite stochastic environmental factors seedling survival, growth, and biotic damage by herbivores and fungal pathogens varied with the level of edge exposure and proximity, which may threaten forest regeneration in the long term.
The effect of traditional production methods on microbial, physico‐chemical and sensory properties of ‘Slovenská bryndza’ Protected Geographical Indication cheese
Authors: Semjon Boris , Reitznerová Anna , Poláková Zuzana , Výrostková Jana , Maľová Jana , Koréneková Beáta , Dudriková Eva , Lovayová Viera 
Published: May 2018

Bryndza is a natural, white, mature and spreadable kind of cheese, and since 2008, it has been manufactured in specified mountainous areas of the Slovak Republic with Protected Geographical Indication. The aim of this work was to provide useful information about the microbial, physico‐chemical and sensory characteristics of bryndza, taking into consideration the variabilities related to the traditional methods of production technology of three bryndza cheese varieties. Statistically significant differences were observed in bryndza cheese production methods in chemical parameters of NaCl and malondialdehyde content (P < 0.05) and in the microbial presence of Enterococcus spp. (P < 0.001) and Staphylococcus spp. (P < 0.01).
Antidiabetic medication de‐escalation following bariatric surgery
Authors: Vouri Scott M. , Chen Jiajing , Sparkman Jayme , Salles Arghavan , Micek Scott T. 
Published: May 2018

Highlights

There is a de‐escalation of antidiabetes medications prescribed following bariatric surgery.
Antidiabetes medication utilization following bariatric surgery does not appear to be consistent with clinical practice guidelines.
Immune‐related Adverse Events in Cancer Patients
Authors: Pallin Daniel J. , Baugh Christopher W. , Postow Michael A. , Caterino Jeffrey M. , Erickson Timothy B. , Lyman Gary H. 
Published: May 2018

AbstractThe U.S. Food and Drug Administration has approved immune checkpoint inhibitors and chimeric antigen receptor T cells (CAR‐T cells) as immunotherapy strategies for cancer. These therapies cause a wide variety of adverse events, which mimic other disease states and may emerge months after completion of treatment. This is important because ascertaining a past medical history of cancer treatment within the past year becomes necessary for many presentations. This narrative review summarizes the biology, pathophysiology, and adverse events associated with checkpoint inhibitors and CAR‐T cells and provides a rational approach to management. Proper treatment begins with heightened awareness, rapid diagnosis, and discussion with the patient's oncologist. Treatment of these adverse effects requires only corticosteroids, infliximab, tocilizumab, or fluids or vasopressors when clinically indicated.
Distress intolerance moderation of motivated attention to cannabis and negative stimuli after induced stress among cannabis users: an ERP study
Authors: Macatee Richard J. , Okey Sarah A. , Albanese Brian J. , Schmidt Norman B. , Cougle Jesse R. 
Published: May 2018

AbstractPrevalence of cannabis use is increasing, but many regular users do not develop cannabis use disorder (CUD); thus, CUD risk identification among current users is vital for targeted intervention development. Existing data suggest that high distress intolerance (DI), an individual difference reflective of the ability to tolerate negative affect, may be linked to CUD, but no studies have tested possible neurophysiological mechanisms. Increased motivated attentional processing of cannabis and negative emotional stimuli as indexed by neurophysiology [i.e. the late positive potential (LPP)], particularly during acute stress, may contribute to CUD among high DI users. Frequent cannabis users with high (n = 61) and low DI (n = 44) viewed cannabis, negative, and matched neutral images during electroencephalography (EEG) recording before and after a laboratory stressor. Cannabis cue‐elicited modulation of the 1000‐ to 3000‐milliseconds LPP was larger in high DI users at post‐stressor only, although the effect was only robust in the 1000‐ to 2000‐milliseconds window. Further, modulation magnitude in the high DI group covaried with stress‐relief craving and some CUD indices in the 400‐ to 1000‐milliseconds and 1000‐ to 3000‐milliseconds windows, respectively. No significant effects of DI on negative stimuli‐elicited LPP modulation were found, although inverse associations with some CUD indices were observed. Finally, exploratory analyses revealed some evidence for DI moderation of the relation between subjective stressor reactivity and negative stimuli‐elicited LPP modulation such that greater stressor reactivity was associated with blunted versus enhanced modulation in the high and low DI groups, respectively. Negative and cannabis stimuli‐elicited LPP modulation appear to index distinct, CUD‐relevant neural processes in high DI cannabis users.
Preventing morphine reinforcement with high‐frequency deep brain stimulation of the lateral hypothalamic area
Authors: Fattahi Mojdeh , Ashabi Ghorbangol , Karimian Seyed Morteza , Riahi Esmail 
Published: May 2018

AbstractDeep brain stimulation (DBS) has been proposed as a promising intervention for patients with treatment‐refractory substance use disorder. Here, we investigated if high‐frequency DBS in the lateral hypothalamic area (LHA) could affect drug‐induced reinforcement. Rats were bilaterally implanted with bipolar stimulation electrodes in the LHA and trained to the morphine conditioned place preference. DBS (monophasic square pulses, 130 Hz, 100‐microsecond pulse duration and 150 μA) was applied during the morphine‐pairing trials (30 minutes daily for 4 days) or drug‐free postconditioning test (15 minutes) to determine its effect on the acquisition or expression of morphine reward, respectively. LHA DBS during morphine‐conditioning trials blocked subsequent preference for the drug‐associated context. In contrast, DBS in the postconditioning phase failed to inhibit expression of morphine‐induced conditioned place preference. These results were further controlled by ruling out significant changes by DBS in physical performance and anxiety‐like behavior as measured by an open field test and by precluding anhedonia‐like behavior as measured by sucrose consumption test. Our results suggest that LHA DBS can prevent development of morphine reward without diminishing the motivation for naturally rewarding stimuli. Therefore, the LHA could be a potential target for research in the field of DBS‐based treatment of intractable substance use disorder. Further studies will be necessary to assess the translatability of these findings to the clinic.
Is there more than meets the eye? Seed bank analysis of a typical novel ecosystem, the extensive green roof
Authors: Vanstockem Jan , Ceusters Christiaan , Van Dyck Karen , Somers Ben , Hermy Martin 
Published: May 2018

AbstractQuestions(a) Will seed banks develop on extensive green roofs (EGRs) – prime examples of novel ecosystems – as in (semi‐)natural systems? If so, which type of seed bank (transient or persistent) can be expected? (b) Do EGR characteristics, such as roof age and substrate depth, influence seed bank seed density and species richness? (c) Can differences in successional stages be noticed in the seed bank and vegetation on EGRs?LocationFlanders and Brussels regions of Belgium.MethodsWe conducted a field sampling campaign in which the vegetation and seed bank of 109 EGRs were sampled. Information on roof characteristics (e.g. age, substrate depth) was also collected. Seedling emergence was monitored under standardized greenhouse conditions. Species traits were collected from several existing databases. Data analysis consisted of (generalized) linear mixed modelling.ResultsA total of 18,466 seedlings from 139 different species emerged in the seed bank analysis. Average similarity between vegetation and the seed bank was low, and the majority of species could be considered spontaneous colonizers. Most species were classified as having a transient seed bank. Life forms were shown to be significantly different between vegetation and seed bank. Older EGRs had higher seed bank species richness and seed density, both of which were also positively influenced by sampling date and the vegetation species richness. A discrepancy between seed bank and vegetation successional state, characterized by functional signatures, was present for EGRs.ConclusionsEGRs do develop seed banks and show parallels with seed banks in other novel ecosystems. Seed bank species richness and seed density are influenced by temporal and vegetation related factors. We can also confirm EGR seed bank succession and the discrepancy between seed bank and vegetation successional state, as often observed in natural and novel systems. Furthermore, we argue that seed banks can function as biodiversity reservoirs, which can be considered in EGR vegetation restoration if a set of several conditions is fulfilled. Overall, this study explores seed bank analysis on EGR as a novel ecosystem model. It thereby provides multiple insights in processes impacting EGR plant species diversity, both on and in the soil.
Exponential Family Functional Data Analysis via a Low-Rank Model
Authors: Li Gen , Huang Jianhua Z. , Shen Haipeng 
Published: May 2018

Summary
In many applications, non-Gaussian data such as binary or count are observed over a continuous domain and there exists a smooth underlying structure for describing such data. We develop a new functional data method to deal with this kind of data when the data are regularly spaced on the continuous domain. Our method, referred to as Exponential Family Functional Principal Component Analysis (EFPCA), assumes the data are generated from an exponential family distribution, and the matrix of the canonical parameters has a low-rank structure. The proposed method flexibly accommodates not only the standard one-way functional data, but also two-way (or bivariate) functional data. In addition, we introduce a new cross validation method for estimating the latent rank of a generalized data matrix. We demonstrate the efficacy of the proposed methods using a comprehensive simulation study. The proposed method is also applied to a real application of the UK mortality study, where data are binomially distributed and two-way functional across age groups and calendar years. The results offer novel insights into the underlying mortality pattern.
Stroma: the forgotten cells of innate immune memory
Authors: Crowley T , Buckley C D , Clark A R 
Published: May 2018

SummaryAll organisms are exposed constantly to a variety of infectious and injurious stimuli. These induce inflammatory responses tailored to the threat posed. While the innate immune system is the front line of response to each stimulant, it has been considered traditionally to lack memory, acting in a generic fashion until the adaptive immune arm can take over. This outmoded simplification of the roles of innate and acquired arms of the immune system has been challenged by evidence of myeloid cells altering their response to subsequent encounters based on earlier exposure. This concept of ‘innate immune memory’ has been known for nearly a century, and is accepted among myeloid biologists. In recent years other innate immune cells, such as natural killer cells, have been shown to display memory, suggesting that innate immune memory is a trait common to several cell types. During the last 30 years, evidence has slowly accumulated in favour of not only haematopoietic cells, but also stromal cells, being imbued with memory following inflammatory episodes. A recent publication showing this also to be true in epithelial cells suggests innate immune memory to be widespread, if under-appreciated, in non-haematopoietic cells. In this review, we will examine the evidence supporting the existence of innate immune memory in stromal cells. We will also discuss the ramifications of memory in long-lived tissue-resident cells. Finally, we will pose questions we feel to be important in the understanding of these forgotten cells in the field of innate memory.
The novel atypical antipsychotic cariprazine demonstrates dopamine D2 receptor‐dependent partial agonist actions on rat mesencephalic dopamine neuronal activity
Authors: Delcourte Sarah , Ashby Charles R. , Rovera Renaud , Kiss Béla , Adham Nika , Farkas Bence , Haddjeri Nasser 
Published: May 2018

AbstractAimCariprazine, a dopamine D3‐preferring D3/D2 receptor partial agonist, is FDA approved for the treatment of schizophrenia and acute manic or mixed episodes of bipolar disorder. This study used in vivo electrophysiological techniques in anesthetized rats to determine cariprazine's effect on dopaminergic cell activity in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc).MethodsExtracellular recordings of individual dopaminergic neurons were performed after oral or intravenous administration of cariprazine, the D3 receptor antagonist SB 277011A, the D2 receptor antagonist L741,626, and/or the D3 receptor agonist PD 128,907.ResultsAcute oral treatment with cariprazine significantly increased and chronic cariprazine significantly decreased the number of spontaneously firing dopaminergic neurons in the VTA, but not in the SNc. Intravenous administration of cariprazine partially but significantly inhibited dopaminergic neuronal firing in both regions, which was prevented by L741,626 but not SB 277011A. In both VTA and SNc, cariprazine, SB 277011A, and L741,626 significantly antagonized the suppression of dopamine cell firing elicited by PD 128,907.ConclusionsCariprazine significantly modulates the number of spontaneously active VTA dopamine neurons and moderately suppresses midbrain dopamine neuronal activity. The contribution of dopamine D2 receptors to cariprazine's in vivo effects is prevalent and that of D3 receptors is less apparent.
Prioritizing sites for conservation based on similarity to historical baselines and feasibility of protection
Authors: Popejoy Traci , Randklev Charles R. , Neeson Thomas M. , Vaughn Caryn C. 
Published: May 2018

AbstractThe concept of shifting baselines in conservation science implies advocacy for the use of historical knowledge to inform these baselines but does not address the feasibility of restoring sites to those baselines. In many regions, conservation feasibility varies among sites due to differences in resource availability, statutory power, and land‐owner participation. We used zooarchaeological records to identify a historical baseline of the freshwater mussel community's composition before Euro‐American influence at a river‐reach scale (i.e., a kilometer stretch of river that is abiotically similar) in the Leon River of central Texas (U.S.A.). We evaluated how the community reference position and the feasibility of conservation might enable identification of sites where conservation actions would preserve historically representative communities and be likely to succeed. We devised a conceptual model that incorporated community information and landscape factors to link the best conservation areas to potential cost and conservation benefits. Using fuzzy ordination, we identified modern mussel beds that were most like the historical baseline. We then quantified housing density and land use near each river reach identified to estimate feasibility of habitat restoration. Using our conceptual framework, we identified reaches of high conservation value (i.e., contain the best mussel beds) and where restoration actions would be most likely to succeed. Reaches above Lake Belton were most similar in species composition and relative abundance to zooarchaeological sites. A subset of these mussel beds occurred in locations where conservation actions appeared most feasible. Our results show how to use zooarchaeological data (biodiversity data often readily available) and estimates of conservation feasibility to inform conservation priorities at a local spatial scale.