bluuebunny/crossref_metadata_2025 huggingface dataset:
Age and sun exposure-related widespread genomic blocks of hypomethylation in nonmalignant skin
Authors: Vandiver Amy R , Irizarry Rafael A , Hansen Kasper D , Garza Luis A , Runarsson Arni , Li Xin , Chien Anna L , Wang Timothy S , Leung Sherry G , Kang Sewon , Feinberg Andrew P
Published: April 2015

Background

Aging and sun exposure are the leading causes of skin cancer. It has been shown that epigenetic changes, such as DNA methylation, are well established mechanisms for cancer, and also have emerging roles in aging and common disease. Here, we directly ask whether DNA methylation is altered following skin aging and/or chronic sun exposure in humans.

Results

We compare epidermis and dermis of both sun-protected and sun-exposed skin derived from younger subjects (under 35 years old) and older subjects (over 60 years old), using the Infinium HumanMethylation450 array and whole genome bisulfite sequencing. We observe large blocks of the genome that are hypomethylated in older, sun-exposed epidermal samples, with the degree of hypomethylation associated with clinical measures of photo-aging. We replicate these findings using whole genome bisulfite sequencing, comparing epidermis from an additional set of younger and older subjects. These blocks largely overlap known hypomethylated blocks in colon cancer and we observe that these same regions are similarly hypomethylated in squamous cell carcinoma samples.

Conclusions

These data implicate large scale epigenomic change in mediating the effects of environmental damage with photo-aging.
Enhanced activation of dendritic cells by autologous apoptotic microvesicles in MRL/lpr mice
Authors: Dieker Jürgen , Hilbrands Luuk , Thielen Astrid , Dijkman Henry , Berden Jo H , van der Vlag Johan
Published: April 2015

Introduction

Systemic lupus erythematosus is associated with a persistent circulation of modified autoantigen-containing apoptotic debris that might be capable of breaking tolerance. We aimed to evaluate apoptotic microvesicles obtained from lupus or control mice for the presence of apoptosis-associated chromatin modifications and for their capacity to stimulate dendritic cells (DC) from lupus and control mice.

Method

Apoptotic microvesicles were in vitro generated from splenocytes, and ex vivo isolated from plasma of both MRL/lpr lupus mice and normal BALB/c mice. Microvesicles were analyzed using flow cytometry. Bone marrow-derived (BM)-DC cultured from MRL/lpr or BALB/c mice were incubated with microvesicles and CD40 expression and cytokine production were determined as measure of activation.

Results

Microvesicles derived from apoptotic splenocytes or plasma of MRL/lpr mice contained more modified chromatin compared to microvesicles of BALB/c mice, and showed enhanced activation of DC, either from MRL/lpr or BALB/c mice, and consecutively an enhanced DC-mediated activation of splenocytes. The content of apoptosis-modified chromatin in microvesicles of apoptotic splenocytes correlated with their potency to induce interleukin-6 (IL-6) production by DC. Microvesicle-activated MRL/lpr DC showed a significant higher production of IL-6 and tumor growth factor-β (TGF-β) compared to BALB/c DC, and were more potent in the activation of splenocytes.

Conclusion

Apoptotic microvesicles from MRL/lpr mice are more potent activators of DC, and DC from MRL/lpr mice appear relatively more sensitive to activation by apoptotic microvesicles. Our findings indicate that aberrations at the level of apoptotic microvesicles and possibly DC contribute to the autoimmune response against chromatin in MRL/lpr mice.
Systematic implantation of dedifferentiated fat cells ameliorated monoclonal antibody 1-22-3-induced glomerulonephritis by immunosuppression with increases in TNF-stimulated gene 6
Authors: Maruyama Takashi , Fukuda Noboru , Matsumoto Taro , Kano Koichiro , Endo Morito , Kazama Minako , Kazama Tomohiko , Ikeda Jin , Matsuda Hiroyuki , Ueno Takahiro , Abe Masanori , Okada Kazuyoshi , Soma Masayoshi , Matsumoto Koichi , Kawachi Hiroshi
Published: April 2015

Introduction

Implantation of mesenchymal stem cells (MSCs) has recently been reported to repair tissue injuries through anti-inflammatory and immunosuppressive effects. We established dedifferentiated fat (DFAT) cells that show identical characteristics to MSCs.

Methods

We examined the effects of 106 of DFAT cells infused through renal artery or tail vein on monoclonal antibody (mAb) 1-22-3-induced glomerulonephritis (as an immunological type of renal injury) and adriamycin-induced nephropathy (as a non-immunological type of renal injury) in rats. The mAb 1-22-3-injected rats were also implanted with 106 of DFAT cells transfected with TSG-6 siRNA through tail vein.

Results

Although DFAT cells transfused into blood circulation through the tail vein were trapped mainly in lungs without reaching the kidneys, implantation of DFAT cells reduced proteinuria and improved glomerulosclerosis and interstitial fibrosis. Implantation of DFAT cells through the tail vein significantly decreased expression of kidney injury molecule-1, collagen IV and fibronectin mRNAs, whereas nephrin mRNA expression was increased. Implantation of DFAT cells did not improve adriamycin-induced nephropathy, but significantly decreased the glomerular influx of macrophages, common leukocytes and pan T cells. However, the glomerular influx of helper T cells, was increased. Implantation of DFAT cells decreased expression of interleukin (IL)-6 and IL-12β mRNAs and increased expression of TNF-stimulated gene (TSG)-6 mRNA in renal cortex from mAb 1-22-3-injected rats. The basal level of TSG-6 protein was significantly higher in DFAT cells than in fibroblasts. Expression of TSG-6 mRNA in MCs cocultured with DFAT cells was significantly higher than in mesangial cells or DFAT cells alone. Systematic implantation of DFAT cells with TSG-6 siRNA through tail vein did not improve proteinuria, renal dysfunction and renal degeneration in the mAb 1-22-3-injected rats.

Conclusion

Systematic implantation of DFAT cells effectively ameliorated mAb 1-22-3-induced glomerulonephritis through immunosuppressive effects accompanied by the suppression of macrophage infiltration and expression of IL-6, IL-10 and IL-12β, and increased production of serum and renal TSG-6 that improved the mAb 1-22-3-induced renal degeneration by the immunosuppressive effects of TSG-6. Thus DFAT cells will be suitable cell source for the treatment of immunological progressive renal diseases.
The extracellular death factor (EDF) protects Escherichia coli by scavenging hydroxyl radicals induced by bactericidal antibiotics
Authors: Yan Zhongyi , Li Guodong , Gao Yanfeng , Zhai Wenjie , Qi Yuanming , Zhai Mingxia
Published: April 2015

The newly discovered extracellular death factor (EDF) is a pentapeptide with the sequence NNWNN in Escherichia coli. It was reported that it participated in the cell death process mediated by toxin-antitoxin system mazEF. Reactive oxygen species (ROS) are recently considered as common factors for bactericidal antibiotics-mediated cell death. Previous study indicated that EDF could scavenge hydroxyl radicals and might act as a signal molecule with dual effects, “death” and “survival”. But the structure-activity relationship of EDF and the effects of EDF on the activity of antibiotics remain unclear. In the present study, our results indicated that tryptophan could be the key residue to the hydroxyl radicals-scavenging activity of EDF, and EDF could protect Escherichia coli from killing by bactericidal antibiotics, but not by DNA-damaging or bacteriostatic antibiotics. Our results could provide novel evidence to understand the role of EDF in drug-resistance.
Quantitative assessment of the seismic net-pay method: A case study
Authors: Meza Ramses G. , Florez Juan M. , Kuzmin Stanislav , Castagna John P.
Published: April 2015

We applied the seismic net-pay (SNP) method to an oil discovery and predicted thicknesses consistent with the actual thicknesses at the wellbore locations. This was accomplished by applying the method in a self-calibrating mode that did not require the direct use of well information. For net-pay estimation under a self-calibration scenario, the SNP method thickness estimates proved to be more accurate (mean absolute prediction error at well validation locations under [Formula: see text]) than estimates from a reflectivity-based detuning method ([Formula: see text]) or multiple linear regression ([Formula: see text]). Statistical [Formula: see text]-tests indicated that the correspondences of the predicted thickness estimates with actual net-pay values for the SNP and reflectivity methods (F approximately 5.5–6 for both) were statistically significant, whereas the multiple regression results did not prove to be statistically significant.
Sulfuric Acid-Catalyzed Dehydration of Sorbitol: Mechanistic Study on Preferential Formation of 1,4-Sorbitan
Authors: Yabushita Mizuho , Kobayashi Hirokazu , Shrotri Abhijit , Hara Kenji , Ito Shogo , Fukuoka Atsushi
Published: April 2015

1,4-Sorbitan is a precursor to environmentally benign surfactants, which can be produced from biomass via sorbitol. Currently, sulfuric acid-catalyzed dehydration of sorbitol is the most widely used route for industrial synthesis of 1,4-sorbitan. In this work, we have studied the mechanism of the sorbitol dehydration by sulfuric acid. Our results show that both thermodynamic and kinetic parameters play significant roles to determine the yield of 1,4-sorbitan. Sorbitol preferentially forms an adduct with sulfuric acid, thereby inhibiting the subsequent dehydration of 1,4-sorbitan to isosorbide. Furthermore, a reaction mechanism is proposed for the dehydration reaction, which involves an SN2 reaction on primary C1 of sorbitol attacked by OH of secondary C4.
New in Conflict of Laws Regulation of Obligations Arising from Unjust Enrichment
Authors: Shestakova Marina
Published: April 2015

The article considers modern trends in the development of the Russian conflict of laws regulation with regard to the regulation of legally binding relations arising from unjust enrichment. A brief historical background of this institution in the Russian civil law is provided. Special attention is paid to new amendments and alterations to Section VI “Private International Law” of the Civil Code of the Russian Federation as part of the recent reform of the Russian civil legislation. The author notes a significant expansion of the autonomy of the parties’ will in determining the law to be applied to noncontractual obligations. The author explores the interrelation of common and special rules which regulate the parties’ relationships, criteria and principles of choosing proper sources of legal regulation in respect of specific cases. Alongside with the tendency towards unification of the legal regulation of obligations involving parties belonging to different legal systems, the author notes universalization of approaches to their regulation — extension of a number of principles which were previously applied only to contractual obligations, to non-contractual obligations.
Liability for the Migration Legislation Violation: Legal Issues and Ways of their Negotiation
Authors: Plyugina Inna
Published: April 2015

The article analyzes legal issues related to the liability for the migration laws’ violation. The study of foreign experience shows a general tendency of penalties’ upgrading for the wrongdoings in the migration sphere. Various instruments are used as part of prevention and interdiction of illegal migration; however the measures of criminal and administrative punishments remain basic. The article considers the issues arising as a result of the application of corpus delicti introduced in the Russian Federation in 2013; studies the issues related to the liability for a fake registration of a Russian Federation citizen at the place of residence, fake registration of a foreign citizen or a stateless person at the place of residence.
Criminal Policy in the Field of Taxation
Authors: Nazarenko Bogdan
Published: April 2015

The article uses statistical data about the number of detected tax crimes, the indemnification amounts based on the results of investigation of criminal cases initiated on tax and fees legislation violations and which contain elements of crimes, as well as analyzes the current legal mechanism for combating tax crimes and identifying its shortcomings. On the basis of the conducted analysis the author suggests measures to improve the criminal policy in the sphere of taxation, the implementation of which will ensure effective combating tax evasion and, thereby, increasing of the budget incomes in the budgetary system of the Russian Federation. The author focuses on the most problematic issues, among which we could highlight: factual impossibility of identifying tax crimes at the moment of their committing by tax control methods; absence of special law enforcement institutions which would fight tax crimes in the sphere of taxation, hindering the performance of operative and investigative actions on the basis of the arbitration court determination on the satisfaction of the plaintiff’s (taxpayer’s) petition on the suspension of the tax authority’s decision on tax prosecution, etc.
Interpretation of the Convention for the Protection of Human Rights and Fundamental Freedoms by the European Court of Human Rights and the Rule of Law
Authors: Lipkina Nadezhda
Published: April 2015

The Rule of law as one of the core principles of the modern international law is the key principle of organization and activity of any international body. The purpose of this article is to consider specific aspects of the Rule of law’s implementation in the practice of the European Court of Human Rights, which are related to the peculiarities in interpretation by the Court of the provisions of the 1950 Convention for the protection of human rights and fundamental freedoms and the Protocols thereto — the application of the «evolutive interpretation» concept and «subsequent practice in the application of the treaty» concept.
Collateral and the Choice Between Bank Debt and Public Debt
Authors: Lin Leming
Published: April 2015

This paper tests how collateral value affects a firm’s choice between bank debt and public debt by considering the exogenous variation in the market value of a firm’s real-estate assets caused by fluctuations in local real-estate prices. Using local land supply elasticities as an instrument for local real-estate prices, I estimate that a one-standard-deviation increase in collateral value causes bank debt as a fraction of total debt to increase by six percentage points.

This paper was accepted by Wei Jiang, finance.
Combating Strategic Counterfeiters in Licit and Illicit Supply Chains
Authors: Cho Soo-Haeng , Fang Xin , Tayur Sridhar
Published: April 2015

Counterfeit goods are becoming more sophisticated, from shoes to infant milk powder to aircraft parts, creating problems for consumers, firms, and governments. By comparing two types of counterfeiters—deceptive, so infiltrating a licit (but complicit) distributor, or nondeceptive in an illicit channel—we provide insights into the impact of anticounterfeiting strategies on a brand-name company, a counterfeiter, and consumers. Our analysis highlights that the effectiveness of these strategies depends critically on whether a brand-name company faces a nondeceptive or deceptive counterfeiter. For example, by improving quality, the brand-name company can improve her expected profit against a nondeceptive counterfeiter when the counterfeiter steals an insignificant amount of brand value. However, the same strategy does not work well against the deceptive counterfeiter unless high quality facilitates the seizure of deceptive counterfeits significantly. Similarly, reducing price works well in combating the nondeceptive counterfeiter, but it could be ineffective against the deceptive counterfeiter. Moreover, the strategies that improve the profit of the brand-name company may benefit the counterfeiter inadvertently and even hurt consumer welfare. Therefore, firms and governments should carefully consider a trade-off among different objectives in implementing an anticounterfeiting strategy.
Managing nappy rash
Authors: Greener Mark
Published: April 2015

Approximately a quarter of infants develop nappy rash, which arises from the interaction between several mutually reinforcing factors. Three possible causes of nappy rash are: poor hygiene and skin care; sensitivity to detergents, fabric softeners and other external products; and infection. Once nappy rash develops, management aims to repair damage and prevent recurrence. The cornerstones of prevention and treatment are good routine skincare, frequent nappy changes, gentle cleansing and applying a barrier formulation at every nappy change. Candida albicans may cause moderate-to-severe nappy rash, for which topical antifungals may be appropriate. Brief courses of low-potency topical corticosteroids are suitable only when very inflamed dermatitis does not respond to other treatments. There is a need for further investigations of the pathogenesis (e.g. clarifying the role of C. albicans) and management of nappy rash, such as the relative efficacy of over-the-counter treatments.
An ordinary complexity of care: moving beyond ‘the family’ in research with children
Authors: Eldén Sara
Published: April 2015

For some time, studies of care in personal relationships have managed to move beyond a taken-for-granted focus on the nuclear family. In addition, studies of children and care have shown children’s active engagement in doing care. In the project presented here, these two factors have been combined by allowing children to talk about and reflect on their everyday life and caring situation, without preconceived assumptions of in what relationships and under what circumstances care is ‘done’. The results reveal that there are significant practices and relationships of care around children outside the nuclear family. I argue that an ‘ordinary complexity of care’ exists in children’s lives, and these caring practices and relationships need to be taken into account in studies and conceptualisations of children and care. To capture this, the researcher must conduct careful methodological and conceptual work to allow the research participants to include ‘others’ in their telling of their everyday life.
Local minimizers of the Willmore functional
Authors: Skorzinski Florian
Published: April 2015

Since the Willmore functional is invariant with respect to conformal transformations and reparametrizations, the kernel of the second derivative of the functional at a critical point will always contain a subspace generated by these transformations. We prove that the second derivative being positive definite outside this space is a sufficient condition for a critical point to be a local minimizer.
The pseudosymmetric crystal structure of a Dy(III) complex with 3-(3- pyridin-4-yl-[1,2,4]oxadiazol-5-yl)propionic acid, C30H26DyN9O10
Authors: Zhang Fang , Huang Fang , Jin Ying , Chen Qifan , Quan Wenjing , Liu Fei
Published: April 2015

C30H26DyN9O10, triclinic, P1̄ (no. 2), a = 7.706(5) Å, b = 14.965(5) Å, c = 15.859(5) Å, α = 115.358(5)°, β = 93.621(5)°, γ = 101.313(5)°, V = 1598.0 Å3, Z = 2, Rgt(F) = 0.0417, wRref(F2) = 0.1248, T = 293 K.
Positioning selves, doing relational work and constructing identities in interview talk
Authors: Miller Elizabeth R.
Published: April 2015

This article draws on positioning theory and uses Bamberg’s (2005) three-level analytic approach to analyze how identity construction and relational work implicate the other and are co-constitutive processes in local interactions. To that end, it examines a sequence of excerpts taken from an interview involving the author and a Vietnamese woman and analyzes the co-constructed positioning of self and other that developed over the course of the interview conversation. The article focuses on how (non)delicate topics are introduced, responded to, modified and developed as the interviewee reports on past experience and adopts evaluative stances toward topics initiated by the interviewer. The study further highlights how normative ideologies are indexed and reconstituted in such talk, and points to their role in making particular identities relevant and in mobilizing relational work in local interactions.
On form and function of politeness formulae
Authors: Schlund Katrin
Published: April 2015

This paper focuses on the notion of politeness formulae in linguisticpoliteness research. It argues that the formal make-up of politeness formulaeis crucially motivated by their function. The major claim of this paper is thusthat there is a link between form and function of expressions of linguistic politeness.The usefulness of this account will be illustrated by the analysis ofempirical data from Slavic languages and German. Reference to Roman Jakobson’smarkedness theory will show that the choice of linguistic means is notonly dependent on concrete contexts (as is usually claimed in linguistic politenesstheory) but also motivated by the language system itself.
Linguistic politeness and pragmatic variation in request production in Dakar French
Authors: Johns Andrew , Félix-Brasdefer J. César
Published: April 2015

This article examines linguistic politeness and pragmatic variation in the production of requests among Senegalese speakers of French in Dakar. Drawing on a framework of pragmatic variation (Schneider and Barron 2008; Barron and Schneider 2009) and a model of intercultural communication and politeness systems (Scollon and Scollon 2001), we analyze variation of request variants, internal modification, and variation in the selection of the T/V forms in formal and informal contexts, including solidarity politeness (−P, −D), deference politeness (−P, +D), and hierarchical politeness (+P, +D). The Senegalese French requests were compared to requests from French speakers from France in comparable situations. The realization of politeness and request performance in Senegalese French is influenced by the fact that use of French is normally limited to formal contexts, such as schools and government establishments, with Wolof serving as a lingua franca in informal settings for speakers of many national languages. The results are discussed in light of pragmalinguistic variation, including variation of address forms, request variants, and internal modification.
Neural Precursor Lineages Specify Distinct Neocortical Pyramidal Neuron Types
Authors: Tyler William A. , Medalla Maria , Guillamon-Vivancos Teresa , Luebke Jennifer I. , Haydar Tarik F.
Published: April 2015

Several neural precursor populations contemporaneously generate neurons in the developing neocortex. Specifically, radial glial stem cells of the dorsal telencephalon divide asymmetrically to produce excitatory neurons, but also indirectly to produce neurons via three types of intermediate progenitor cells. Why so many precursor types are needed to produce neurons has not been established; whether different intermediate progenitor cells merely expand the output of radial glia or instead generate distinct types of neurons is unknown. Here we use a novel genetic fate mapping technique to simultaneously track multiple precursor streams in the developing mouse brain and show that layer 2 and 3 pyramidal neurons exhibit distinctive electrophysiological and structural properties depending upon their precursor cell type of origin. These data indicate that individual precursor subclasses synchronously produce functionally different neurons, even within the same lamina, and identify a primary mechanism leading to cortical neuronal diversity.
Widespread Vestibular Activation of the Rodent Cortex
Authors: Rancz Ede A. , Moya Javier , Drawitsch Florian , Brichta Alan M. , Canals Santiago , Margrie Troy W.
Published: April 2015

Much of our understanding of the neuronal mechanisms of spatial navigation is derived from chronic recordings in rodents in which head-direction, place, and grid cells have all been described. However, despite the proposed importance of self-reference information to these internal representations of space, their congruence with vestibular signaling remains unclear. Here we have undertaken brain-wide functional mapping using both fMRI and electrophysiological methods to directly determine the spatial extent, strength, and time course of vestibular signaling across the rat forebrain. We find distributed activity throughout thalamic, limbic, and particularly primary sensory cortical areas in addition to known head-direction pathways. We also observe activation of frontal regions, including infralimbic and cingulate cortices, indicating integration of vestibular information throughout functionally diverse cortical regions. These whole-brain activity maps therefore suggest a widespread contribution of vestibular signaling to a self-centered framework for multimodal sensorimotor integration in support of movement planning, execution, spatial navigation, and autonomic responses to gravito-inertial changes.
Loss of F-box Only Protein 2 (Fbxo2) Disrupts Levels and Localization of Select NMDA Receptor Subunits, and Promotes Aberrant Synaptic Connectivity
Authors: Atkin Graham , Moore Shannon , Lu Yuan , Nelson Rick F. , Tipper Nathan , Rajpal Gautam , Hunt Jack , Tennant William , Hell Johannes W. , Murphy Geoffrey G. , Paulson Henry
Published: April 2015

NMDA receptors (NMDARs) play an essential role in some forms of synaptic plasticity, learning, and memory. Therefore, these receptors are highly regulated with respect to their localization, activation, and abundance both within and on the surface of mammalian neurons. Fundamental questions remain, however, regarding how this complex regulation is achieved. Using cell-based models andF-box Only Protein 2(Fbxo2) knock-out mice, we found that the ubiquitin ligase substrate adaptor protein Fbxo2, previously reported to facilitate the degradation of the NMDAR subunit GluN1in vitro, also functions to regulate GluN1 and GluN2A subunit levels in the adult mouse brain. In contrast, GluN2B subunit levels are not affected by the loss of Fbxo2. The loss of Fbxo2 results in greater surface localization of GluN1 and GluN2A, together with increases in the synaptic markers PSD-95 and Vglut1. These synaptic changes do not manifest as neurophysiological differences or alterations in dendritic spine density inFbxo2knock-out mice, but result instead in increased axo-dendritic shaft synapses. Together, these findings suggest that Fbxo2 controls the abundance and localization of specific NMDAR subunits in the brain and may influence synapse formation and maintenance.
Control of Autophagosome Axonal Retrograde Flux by Presynaptic Activity Unveiled Using Botulinum Neurotoxin Type A
Authors: Wang Tong , Martin Sally , Papadopulos Andreas , Harper Callista B. , Mavlyutov Timur A. , Niranjan Dhevahi , Glass Nick R. , Cooper-White Justin J. , Sibarita Jean-Baptiste , Choquet Daniel , Davletov Bazbek , Meunier Frédéric A.
Published: April 2015

Botulinum neurotoxin type A (BoNT/A) is a highly potent neurotoxin that elicits flaccid paralysis by enzymatic cleavage of the exocytic machinery component SNAP25 in motor nerve terminals. However, recent evidence suggests that the neurotoxic activity of BoNT/A is not restricted to the periphery, but also reaches the CNS after retrograde axonal transport. Because BoNT/A is internalized in recycling synaptic vesicles, it is unclear which compartment facilitates this transport. Using live-cell confocal and single-molecule imaging of rat hippocampal neurons cultured in microfluidic devices, we show that the activity-dependent uptake of the binding domain of the BoNT/A heavy chain (BoNT/A-Hc) is followed by a delayed increase in retrograde axonal transport of BoNT/A-Hc carriers. Consistent with a role of presynaptic activity in initiating transport of the active toxin, activity-dependent uptake of BoNT/A in the terminal led to a significant increase in SNAP25 cleavage detected in the soma chamber compared with nonstimulated neurons. Surprisingly, most endocytosed BoNT/A-Hc was incorporated into LC3-positive autophagosomes generated in the nerve terminals, which then underwent retrograde transport to the cell soma, where they fused with lysosomes bothin vitroandin vivo. Blocking autophagosome formation or acidification with wortmannin or bafilomycin A1, respectively, inhibited the activity-dependent retrograde trafficking of BoNT/A-Hc. Our data demonstrate that both the presynaptic formation of autophagosomes and the initiation of their retrograde trafficking are tightly regulated by presynaptic activity.
Imperceptible Somatosensory Stimulation Alters Sensorimotor Background Rhythm and Connectivity
Authors: Nierhaus Till , Forschack Norman , Piper Sophie K. , Holtze Susanne , Krause Thomas , Taskin Birol , Long Xiangyu , Stelzer Johannes , Margulies Daniel S. , Steinbrink Jens , Villringer Arno
Published: April 2015

Most sensory input to our body is not consciously perceived. Nevertheless, it may reach the cortex and influence our behavior. In this study, we investigated noninvasive neural signatures of unconscious cortical stimulus processing to understand mechanisms, which (1) prevent low-intensity somatosensory stimuli from getting access to conscious experience and which (2) can explain the associated impediment of conscious perception for additional stimuli. Stimulation of digit 2 in humans far below the detection threshold elicited a cortical evoked potential (P1) at 60 ms, but no further somatosensory evoked potential components. No event-related desynchronization was detected; rather, there was a transient synchronization in the alpha frequency range. Using the same stimulation during fMRI, a reduced centrality of contralateral primary somatosensory cortex (SI) was found, which appeared to be mainly driven by reduced functional connectivity to frontoparietal areas. We conclude that after subthreshold stimulation the (excitatory) feedforward sweep of bottom-up processing terminates in SI preventing access to conscious experience. We speculate that this interruption is due to a predominance of inhibitory processing in SI. The increase in alpha activity and the disconnection of SI from frontoparietal areas are likely correlates of an elevated perception threshold and may thus serve as a gating mechanism for the access to conscious experience.
Engagement of the GABA to KCC2 Signaling Pathway Contributes to the Analgesic Effects of A3AR Agonists in Neuropathic Pain
Authors: Ford Amanda , Castonguay Annie , Cottet Martin , Little Joshua W. , Chen Zhoumou , Symons-Liguori Ashley M. , Doyle Timothy , Egan Terrance M. , Vanderah Todd W. , De Koninck Yves , Tosh Dilip K. , Jacobson Kenneth A. , Salvemini Daniela
Published: April 2015

More than 1.5 billion people worldwide suffer from chronic pain, yet current treatment strategies often lack efficacy or have deleterious side effects in patients. Adenosine is an inhibitory neuromodulator that was previously thought to mediate antinociception through the A1and A2Areceptor subtypes. We have since demonstrated that A3AR agonists have potent analgesic actions in preclinical rodent models of neuropathic pain and that A3AR analgesia is independent of adenosine A1or A2Aunwanted effects. Herein, we explored the contribution of the GABA inhibitory system to A3AR-mediated analgesia using well-characterized mouse and rat models of chronic constriction injury (CCI)-induced neuropathic pain. The deregulation of GABA signaling in pathophysiological pain states is well established: GABA signaling can be hampered by a reduction in extracellular GABA synthesis by GAD65 and enhanced extracellular GABA reuptake via the GABA transporter, GAT-1. In neuropathic pain, GABAAR-mediated signaling can be further disrupted by the loss of the KCC2 chloride anion gradient. Here, we demonstrate that A3AR agonists (IB-MECA and MRS5698) reverse neuropathic pain via a spinal mechanism of action that modulates GABA activity. Spinal administration of the GABAAantagonist, bicuculline, disrupted A3AR-mediated analgesia. Furthermore, A3AR-mediated analgesia was associated with reductions in CCI-related GAD65 and GAT-1 serine dephosphorylation as well as an enhancement of KCC2 serine phosphorylation and activity. Our results suggest that A3AR-mediated reversal of neuropathic pain increases modulation of GABA inhibitory neurotransmission both directly and indirectly through protection of KCC2 function, underscoring the unique utility of A3AR agonists in chronic pain.
Voluntary Ethanol Intake Predicts κ-Opioid Receptor Supersensitivity and Regionally Distinct Dopaminergic Adaptations in Macaques
Authors: Siciliano Cody A. , Calipari Erin S. , Cuzon Carlson Verginia C. , Helms Christa M. , Lovinger David M. , Grant Kathleen A. , Jones Sara R.
Published: April 2015

The dopaminergic projections from the ventral midbrain to the striatum have long been implicated in mediating motivated behaviors and addiction. Previously it was demonstrated that κ-opioid receptor (KOR) signaling in the striatum plays a critical role in the increased reinforcing efficacy of ethanol following ethanol vapor exposure in rodent models. Although rodents have been used extensively to determine the neurochemical consequences of chronic ethanol exposure, establishing high levels of voluntary drinking in these models has proven difficult. Conversely, nonhuman primates exhibit similar intake and pattern to humans in regard to drinking. Here we examine the effects of chronic voluntary ethanol self-administration on dopamine neurotransmission and the ability of KORs to regulate dopamine release in the dorsolateral caudate (DLC) and nucleus accumbens (NAc) core. Using voltammetry in brain slices from cynomolgus macaques after 6 months ofad libitumethanol drinking, we found increased KOR sensitivity in both the DLC and NAc. The magnitude of ethanol intake predicted increases in KOR sensitivity in the NAc core, but not the DLC. Additionally, ethanol drinking increased dopamine release and uptake in the NAc, but decreased both of these measures in the DLC. These data suggest that chronic daily drinking may result in regionally distinct disruptions of striatal outputs. In concert with previous reports showing increased KOR regulation of drinking behaviors induced by ethanol exposure, the strong relationship between KOR activity and voluntary ethanol intake observed here gives further support to the hypothesis that KORs may provide a promising pharmacotherapeutic target in the treatment of alcoholism.
Effects of Phospholipid-Coated Extracorporeal Circuits on Clinical Outcome Parameters and Systemic Inflammatory Response in Coronary Artery Bypass Graft Patients
Authors: Schulz Christina , Pritisanac Anita , Sch�tz Albert , Kilger Erich , Platzer Helmut , Reichart Bruno , Wildhirt Stephen M.
Published: April 2015

Introduction: The use of extracorporeal circulation (ECC) during coronary artery bypass graft (CABG) surgery is associated with a systemic inflammatory response due to the contact of blood with artificial surfaces. The clinical relevance of ECC-related systemic inflammation varies with the patient, and such inflammation may be accompanied by intermittent organ dysfunction and an increased catecholamine requirement. We investigated the effects of a new phospholipid coating system of ECC on systemic inflammatory response and clinical outcome following CABG. Methods: Patients scheduled for CABG surgery were prospectively divided randomly into 2 patient groups: patients using noncoated ECC materials and patients using phospholipid-coated ECC materials. Clinical data measured perioperatively included hemodynamics, aortic clamp time, duration of bypass, time to extubation, catecholamine requirement, length of intensive care unit (ICU) stay, postoperative blood loss, and amount of blood transfused. In addition, blood samples were collected before cannulation and at 2, 24, and 48 hours postoperative. Cytokines (tumor necrosis factor 3 [TNF-3] and interleukin 10 [IL-10]) and P-selectin were measured with an enzyme-linked immunosorbent assay. Plasma nitrate/nitrite levels (NOx) were determined by the Griess reaction. Results: A significant increase of TNF-3 level was noted in the uncoated control group only. In the uncoated group, IL-10 levels significantly increased at 2 hours postoperative, whereas levels remained unchanged in the phospholipid coating group. P-selectin increased 2 hours postoperative in the uncoated group, and no significant changes were noted in the phospholipid coating group. At 24 hours postoperative, total plasma NOx production significantly increased in the phospholipid coating group but remained constant in the control group. No significant differences with respect to postoperative parameters (time to extubation, ICU stay, amount of bleeding, blood transfused, and catecholamine requirement) were observed. Conclusions: Phospholipid coating significantly reduces the systemic increase in proinflammatory and anti-inflammatory cytokines and P-selectin. Despite the comparable clinical outcomes in this study, the observed significant reduction in systemic inflammatory parameter values suggests an improved biocompatibility of ECC materials when they are coated with phospholipids.
Off-Pump Coronary Artery Bypass Surgery Is Associated with Reduced Neutrophil Activation as Measured by the Expression of CD11b: A Prospective Randomized Study
Authors: Al-Ruzzeh Sharif , Hoare Ginette , Marczin Nandor , Asimakopoulos George , George Shane , Taylor Kenneth , Amrani Mohamed
Published: April 2015

Background: Coronary artery bypass grafting (CABG) surgery is associated with systemic inflammation. Activation of neutrophils is a crucial step in inflammation and results in neutrophil sequestration within the tissues. One of the potential advantages of performing off-pump coronary artery bypass (OPCAB) surgery is the attenuation of the systemic inflammatory response. This prospective randomized study compares neutrophil activation in patients undergoing OPCAB versus those undergoing CABG with cardiopulmonary bypass (CPB). Methods: Twenty patients undergoing primary isolated CABG were randomly divided prospectively into 2 groups: 1 group underwent CABG with CPB, and the other group underwent OPCAB. Central venous blood samples were obtained before skin incision and at 15 minutes, 60 minutes, 2 hours, 5 hours, and 24 hours following the initiation of CPB or application of the stabilization device. Differential white cell counts were measured with routine laboratory techniques. CD11b surface expression on neutrophils was measured by flow cytometry. Interleukin 8 levels in the plasma were measured by enzyme-linked immunosorbent assays. Results: The 2 groups were matched with respect to preoperative and operative characteristics. White cell and neutrophil counts rose in both groups following the operation but were significantly higher in the OPCAB group at 5 hours (P < .001 and P = .002, respectively). Interleukin 8 concentrations were significantly higher in the CPB group at 5 hours following the initiation of CPB (P = .034). CD11b levels were significantly higher in the CPB group at 60 minutes (P = .002). Conclusion: This prospective randomized study demonstrates that the activation of circulating neutrophils as measured by CD11b expression is lower following OPCAB than in CPB. Although OPCAB is associated with significantly higher neutrophil counts, these neutrophils exhibit fewer activation markers. The lower postoperative neutrophil counts occurring in the CPB group may be explained by the activation and consequent sequestration of the neutrophils in the CPB circuit and tissues.
A Complex Mitral Valve Reconstruction: A Case Report
Authors: Buklas Dimitrios , Massetti Massimo , Saloux Eric , Neri Eugenio , LePage Olivier , Ivascau Calin , Babatasi Gerard , Khayat Andre
Published: April 2015

Several techniques are currently in use for mitral valve reconstruction. We report a mitral repair case in which the use of a combination of different surgical techniques resulted in the necessary correction. A 47-year-old woman underwent surgical intervention to treat severe mitral valve insufficiency due to A1/A2/A3 and P2 prolapsed valve tissue. A combination of quadrangular resection, sliding leaflet, single chordal transposition, "flip-over" leaflet, and ring annuloplasty techniques were applied, and postsurgical correct valve function was documented by results of a left ventricular saline filling test and transesophageal echocardiography control. Complex mitral valve repairing techniques can be combined to reestablish valvular function.
HEAVY METALS CONTENT IN SHEEP PRODUCTS FROM MIDLE SPIŠ
Authors: Marek SlÃ¡vik , Tomáš TÃ³th , Miriama KopernickÃ¡ , Július Ãrvay , Ľuboš Harangozo
Published: April 2015

In this work, we evaluated the risk of contamination of animal products by heavy metals. Samples of animal raw materials were obtained in 2013 in the municipalities of Porac and Matejovce nad Hornádom. Samples of muscle and internal organs were collected from domestic sheep (Ovis aries) reared in the village of Rudnianska burdened area where mercury along with other heavy metals contamination is above the limit value of agricultural soil. Measuring the concentration of heavy metals in the samples was performed in accordance with the general requirements set out in the tenth chapter of the Food Code of the Slovak Republic. Mercury content in biological materials were assessed by total mercury as on the AMA 254 in fresh samples. The other heavy metal content, was determined after wet mineralization (HNO3: H2O - 1: 1) using the device AAS Varian 240 FS. The contamination of the environment showed increased accumulation of heavy metals in the - studiet sheep tissues intended for consumption. Such as Hg content in the kidneys of domestic sheep exceed the limit value by 1.3 times, whereas, in the case of cadmium 3 times exceeding the limit value in meat was recordered. Exceed limit was recorded in the case of lead and copper in the liver.
PRELIMINARY SIMULATION OF EGG AND LARVAL DISPERSAL OF CORAL REEF FISH IN NHA TRANG MARINE PROTECTED AREA
Authors: Viet Dang Do Hung , Vinh Vu Duy , Chien Pham Van , The Nguyen Duc
Published: April 2015

Modeling the dispersal of coral reef fish eggs and larvae (FE-FL) in Nha Trang bay MPA simulated two scenarios in 03/2009 and 08/2009. The assumption each time for scenario was 30 days. The dispersal results of FE-FL from the Nha Trang bay to the surrounding areas just concentrated in coastal areas with very small quantities. A small number of FE-FL under the effects of water current were also take to the Northern coastal areas and the Southern coastal areas but no FE-FL spread to open sea. The dispersal range was not much different between the tidal phases and monsoons but significantly affected by the source (fish eggs produced).
Performance of cement-based sensors with CNT for strain sensing
Authors: Camacho-Ballesta Carmen , Zornoza Emilio , Garcés Pedro
Published: April 2015

Strain-sensing functions of Portland cement pastes with different dosages of carbon nanotubes (CNT) are systematically studied. This is one of the relevant functions that multifunctional composites are able to develop when a conductive addition is included in the cement matrix. Strain sensing refers to the ability of a structural material to sense its own condition, such as strain or stress, through the piezoresistive behaviour (change of volume electrical resistivity when it is subjected to a force). CNTs, which possess exceptional electromechanical properties, are considered as a promising addition for practical applications such as structural health and load monitoring. Nevertheless, there is still an important challenge regarding CNT cement composite fabrication: achieving their effective dispersion. This point is addressed by means of a comparison between different physical and chemical dispersion methods. The technique used for that purpose is light-scattering particle size analysis. After selecting the optimal dispersing procedure, the effect on the strain-sensing properties of CNT reinforced cement pastes was studied for the following variables: CNT dosage, curing age, current intensity, loading rate and maximum stress applied. All these parameters are discussed taking gauge factor value as the reference.
Editorial
Authors: Editorial Equipo
Published: April 2015

Editorial
Las voces y el cine invisible
Authors: Cantalozella Joaquim , Negre Marta
Published: April 2015

La excéntrica y provocadora personalidad de João César Monteiro, así como ciertos episodios biográficos relacionados con desequilibrios mentales, quedan reflejados, a menudo, en sus poco convencionales filmes. El presente artículo es una aproximación a la faceta más irracional del autor, y plantea un análisis de los vínculos entre su obra y los trastornos de la razón. También se abordan aspectos relacionados con la psiquiatría y el cine, y se contextualiza la obra del director dentro de la problemática de la representación de la locura en el ámbito cinematográfico. Finalmente se estudia Branca de neve, película clave dentro de su producción, para ver cómo se desarrollan los temas anteriormente abordados, desde una perspectiva que se aleja del cine convencional y que se vincula a propuestas experimentales propias del arte contemporáneo.
Revista completa
Authors: Editorial Equipo
Published: April 2015

Número 2 Revista BRAC completa
Intersecciones Semánticas entre Visión Artificial y Mirada Artística
Authors: Rosado Rodrigo Pilar , Figueras Ferrer Eva , Reverter Comes Ferran
Published: April 2015

En el presente artículo se ha desarrollado un sistema capaz de categorizar de forma automática la base de datos de imágenes que sirven de punto de partida para la ideación y diseño en la producción artística del escultor M. Planas. La metodología utilizada está basada en características locales. Para la construcción de un vocabulario visual se sigue un procedimiento análogo al que se utiliza en el análisis automático de textos (modelo "Bag-of-Words"-BOW) y en el ámbito de las imágenes nos referiremos a representaciones "Bag-of-Visual Terms" (BOV). En este enfoque se analizan las imágenes como un conjunto de regiones, describiendo solamente su apariencia e ignorando su estructura espacial. Para superar los inconvenientes de polisemia y sinonimia que lleva asociados esta metodología, se utiliza el análisis probabilístico de aspectos latentes (PLSA) que detecta aspectos subyacentes en las imágenes, patrones formales. Los resultados obtenidos son prometedores y, además de la utilidad intrínseca de la categorización automática de imágenes, este método puede proporcionar al artista un punto de vista auxiliar muy interesante.
Sentido y responsabilidad: Una perspectiva bioética sobre la creación, mutación e hibridación experimental en el campo interdisciplinar de la tecnociencia y el arte.
Authors: Baigorri Ballarín Laura
Published: April 2015

Sólo los humanos hemos creado una tecnociencia capaz de borrar a nuestra propia especie, y a todas las demás, de la faz de la Tierra y si, como afirma el filósofo Hans Jonas, la responsabilidad es un correlato del poder, la magnitud del poder debe determinar la magnitud de la responsabilidad. En la última década, numerosos artistas han comenzado a trabajar en las zonas fronterizas de la ciencia y la tecnología planteando la necesidad de un análisis crítico en este campo desarrollado a partir de criterios extra-médicos o extra-industriales. Este texto analiza trabajos de artistas, realizados bajo los parámetros del bioarte, que inciden particularmente en el sentido ético de la conducta humana hacia los animales y los seres vivos en general. La mayoría de proyectos han sido desarrollados en laboratorios científicos y tienen que ver con la creación (generación de vida), la mutación e hibridación genética, y con las simbióticas relaciones entre animales e humanos. A través de ellos, los artistas demuestran su sentido de la responsabilidad y su capacidad para asumir las consecuencias de sus creaciones con el objetivo abrir nuevos debates éticos sobre la ciencia.