Showing papers by "Jagiellonian University published in 2011"

Design concepts for the Cherenkov Telescope Array CTA: An advanced facility for ground-based high-energy gamma-ray astronomy

Abstract: Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.

Chronic rhinosinusitis in Europe : an underestimated disease. A GA²LEN study

Abstract: Background: Chronic rhinosinusitis (CRS) is a common health problem, with significant medical costs and impact on general health. Even so, prevalence figures for Europe are unavailable. In this st ...

VPS35 Mutations in Parkinson Disease

Abstract: The identification of genetic causes for Mendelian disorders has been based on the collection of multi-incident families, linkage analysis, and sequencing of genes in candidate intervals. This study describes the application of next-generation sequencing technologies to a Swiss kindred presenting with autosomal-dominant, late-onset Parkinson disease (PD). The family has tremor-predominant dopa-responsive parkinsonism with a mean onset of 50.6 ± 7.3 years. Exome analysis suggests that an aspartic-acid-to-asparagine mutation within vacuolar protein sorting 35 (VPS35 c.1858G>A; p.Asp620Asn) is the genetic determinant of disease. VPS35 is a central component of the retromer cargo-recognition complex, is critical for endosome-trans-golgi trafficking and membrane-protein recycling, and is evolutionarily highly conserved. VPS35 c.1858G>A was found in all affected members of the Swiss kindred and in three more families and one patient with sporadic PD, but it was not observed in 3,309 controls. Further sequencing of familial affected probands revealed only one other missense variant, VPS35 c.946C>T; (p.Pro316Ser), in a pedigree with one unaffected and two affected carriers, and thus the pathogenicity of this mutation remains uncertain. Retromer-mediated sorting and transport is best characterized for acid hydrolase receptors. However, the complex has many types of cargo and is involved in a diverse array of biologic pathways from developmental Wnt signaling to lysosome biogenesis. Our study implicates disruption of VPS35 and retromer-mediated trans-membrane protein sorting, rescue, and recycling in the neurodegenerative process leading to PD.

Inflammation, Immunity, and Hypertension

Abstract: Aprominent pathology textbook used in the United States includes an image illustrating the renal histopathology caused by malignant hypertension. The legend describes striking “onion skin” changes of a renal arteriole. Curiously, a sea of mononuclear inflammatory cells surrounding this arteriole is overlooked both in the legend and in the related text. Moreover, nothing regarding inflammation or immune reactions is discussed. This lack of attention to inflammatory cells is, however, not surprising. Although many experimental studies have implicated inflammation in hypertension, these have largely been performed in experimental animals; there is no proof that inflammation contributes to human hypertension. In fact, some anti-inflammatory or immune-suppressing drugs (eg, nonsteroidal anti-inflammatory drugs and cyclosporine) paradoxically cause hypertension in humans, likely via off-target effects. Often the term “inflammation” is used in the context of cardiovascular disease as a catchall referring to nonspecific phenomena, such as elevation of C-reactive protein or the presence of macrophages in a tissue. Most clinicians and investigators find this vague and difficult to understand. Even more puzzling is that many studies now implicate the adaptive immune response, and in particular, lymphocytes, in hypertension and vascular disease. Traditionally, bacterial, viral, or tumor antigens activate this arm of immune defense. As such, it has been hard to imagine how adaptive immunity could be involved in a disease such as hypertension. In this article, we will attempt to address some of these puzzling questions. We will briefly review components of the innate and adaptive immune response, discuss data from many groups, including our own, that suggest that common forms of hypertension are immune mediated, and provide a working hypothesis of how signals from the central nervous system trigger an immune response that causes hypertension. ### General Concepts Regarding Inflammation and Immunity #### Innate Immunity The first line of defense against pathogens is the innate immune response. Important components of this system include epithelial …

Stability of pollination services decreases with isolation from natural areas despite honey bee visits

Abstract: Sustainable agricultural landscapes by definition provide high magnitude and stability of ecosystem services, biodiversity and crop productivity However, few studies have considered landscape effects on the stability of ecosystem services We tested whether isolation from florally diverse natural and semi-natural areas reduces the spatial and temporal stability of flower-visitor richness and pollination services in crop fields We synthesised data from 29 studies with contrasting biomes, crop species and pollinator communities Stability of flower-visitor richness, visitation rate (all insects except honey bees) and fruit set all decreased with distance from natural areas At 1 km from adjacent natural areas, spatial stability decreased by 25, 16 and 9% for richness, visitation and fruit set, respectively, while temporal stability decreased by 39% for richness and 13% for visitation Mean richness, visitation and fruit set also decreased with isolation, by 34, 27 and 16% at 1 km respectively In contrast, honey bee visitation did not change with isolation and represented > 25% of crop visits in 21 studies Therefore, wild pollinators are relevant for crop productivity and stability even when honey bees are abundant Policies to preserve and restore natural areas in agricultural landscapes should enhance levels and reliability of pollination services

Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging

Abstract: Dysregulated signaling through the Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways is often the result of genetic alterations in critical components in these pathways or upstream activators. Unrestricted cellular proliferation and decreased sensitivity to apoptotic-inducing agents are typically associated with activation of these pro-survival pathways. This review discusses the functions these pathways have in normal and neoplastic tissue growth and how they contribute to resistance to apoptotic stimuli. Crosstalk and commonly identified mutations that occur within these pathways that contribute to abnormal activation and cancer growth will also be addressed. Finally the recently described roles of these pathways in cancer stem cells, cellular senescence and aging will be evaluated. Controlling the expression of these pathways could ameliorate human health.

Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Inhibitors: Rationale and Importance to Inhibiting These Pathways in Human Health

Abstract: William H. Chappell 1 , Linda S. Steelman 1,2 , Jacquelyn M. Long 2 , Ruth C. Kempf 2 , Stephen L. Abrams 1 , Richard A. Franklin 1 , Jorg Basecke 3 , Franca Stivala 4 , Marco Donia 4 , Paolo Fagone 4 , Graziella Malaponte 4 , Maria C. Mazzarino 4 , Ferdinando Nicoletti 4 , Massimo Libra 4 , Danijela Maksimovic-Ivanic 5 , Sanja Mijatovic 5 , Giuseppe Montalto 6 , Melchiorre Cervello 7 , Piotr Laidler 8 , Michele Milella 9 , Agostino Tafuri 10 , Antonio Bonati 11 , Camilla Evangelisti 12 , Lucio Cocco 12 , Alberto M. Martelli 12,13 , and James A. McCubrey 1 1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University 2 Department of Physics, Greenville, NC 27858 USA 3 Department of Medicine University of Gottingen, Gottingen, Germany 4 Department of Biomedical Sciences, University of Catania, Catania, Italy 5 Department of Immunology, Institute for Biological Research “Sinisa Stankovic”, University of Belgrade, Belgrade, Serbia 6 Department of Internal Medicine and Specialties, University of Palermo, Palermo, Italy 7 Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunologia Molecolare “Alberto Monroy”, Palermo, Italy 8 Department of Medical Biochemistry Jagiellonian University Medical College, Krakow, Poland 9 Regina Elena Cancer Center, Via Elio Chianesi n.53, Rome 00144, Italy 10 University of Rome, La Sapienza, Department of Hematology-Oncology, Via Benevento 6, Rome 99161, Italy 11 University Hospital of Parma, Unit of Hematology and Bone-Marrow Transplantation, Via Gramsi n.14, Parma 43100, Italy 12 Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell’Apparato Locomotore, Universita di Bologna, Bologna, Italy 13 IGM-CNR, Sezione di Bologna, C/o IOR, Bologna, Italy Keywords: Targeted Therapy, Combination Therapy, Drug Resistance, Cancer Stem Cells, Aging, Senescence, Raf, Akt, PI3K, mTOR Received: February 25, 2011; Accepted: March 10, 2011; Published: March 11, 2011; Correspondence: James A. McCubrey, e-mail: // // Abstract The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Integral components of these pathways, Ras, B-Raf, PI3K, and PTEN are also activated/inactivated by mutations. These pathways have profound effects on proliferative, apoptotic and differentiation pathways. Dysregulation of these pathways can contribute to chemotherapeutic drug resistance, proliferation of cancer initiating cells (CICs) and premature aging. This review will evaluate more recently described potential uses of MEK, PI3K, Akt and mTOR inhibitors in the proliferation of malignant cells, suppression of CICs, cellular senescence and prevention of aging. Ras/Raf/MEK/ERK and Ras/PI3K/PTEN/Akt/mTOR pathways play key roles in the regulation of normal and malignant cell growth. Inhibitors targeting these pathways have many potential uses from suppression of cancer, proliferative diseases as well as aging.

Weakly turbulent instability of anti-de Sitter spacetime.

Abstract: We study the nonlinear evolution of a weakly perturbed anti-de Sitter (AdS) space by solving numerically the four-dimensional spherically symmetric Einstein-massless-scalar field equations with negative cosmological constant. Our results suggest that AdS space is unstable under arbitrarily small generic perturbations. We conjecture that this instability is triggered by a resonant mode mixing which gives rise to diffusion of energy from low to high frequencies.

Hydrodynamics from charged black branes

Abstract: We extend the recent work on fluid-gravity correspondence to charged black-branes by determining the metric duals to arbitrary charged fluid configuration up to second order in the boundary derivative expansion. We also derive the energy-momentum tensor and the charge current for these configurations up to second order in the boundary derivative expansion. We find a new term in the charge current when there is a bulk Chern-Simons interaction thus resolving an earlier discrepancy between thermodynamics of charged rotating black holes and boundary hydrodynamics. We have also confirmed that all our expressions are covariant under boundary Weyl-transformations as expected.

Fibrin Clot Structure and Function A Role in the Pathophysiology of Arterial and Venous Thromboembolic Diseases

Abstract: The formation of fibrin clots that are relatively resistant to lysis represents the final step in blood coagulation. We discuss the genetic and environmental regulators of fibrin structure in relation to thrombotic disease. In addition, we discuss the implications of fibrin structure for treatment of thrombosis. Fibrin clots composed of compact, highly branched networks with thin fibers are resistant to lysis. Altered fibrin structure has consistently been reported in patients with several diseases complicated by thromboembolic events, including patients with acute or prior myocardial infarction, ischemic stroke, and venous thromboembolism. Relatives of patients with myocardial infarction or venous thromboembolism display similar fibrin abnormalities. Low-dose aspirin, statins, lowering of homocysteine, better diabetes control, smoking cessation, and suppression of inflammatory response increase clot permeability and susceptibility to lysis. Growing evidence indicates that abnormal fibrin properties represent a novel risk factor for arterial and venous thrombotic events, particularly of unknown etiology in young and middle-aged patients.

Charged-particle multiplicities in pp interactions measured with the ATLAS detector at the LHC

Abstract: Measurements are presented from proton-proton collisions at centre-of-mass energies of root s = 0.9, 2.36 and 7 TeV recorded with the ATLAS detector at the LHC. Events were collected using a single-arm minimum-bias trigger. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity and the relationship between the mean transverse momentum and charged-particle multiplicity are measured. Measurements in different regions of phase space are shown, providing diffraction-reduced measurements as well as more inclusive ones. The observed distributions are corrected to well-defined phase-space regions, using model-independent corrections. The results are compared to each other and to various Monte Carlo (MC) models, including a new AMBT1 pythia6 tune. In all the kinematic regions considered, the particle multiplicities are higher than predicted by the MC models. The central charged-particle multiplicity per event and unit of pseudorapidity, for tracks with p(T) > 100 MeV, is measured to be 3.483 +/- 0.009 (stat) +/- 0.106 (syst) at root s = 0.9 TeV and 5.630 +/- 0.003 (stat) +/- 0.169 (syst) at root s = 7 TeV.

Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, diagnosis and management: review of the EAACI/ENDA(#) and GA2LEN/HANNA*.

Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are responsible for 21-25% of reported adverse drug events which include immunological and nonimmunological hypersensitivity reactions. This study presents up-to-date information on pathomechanisms, clinical spectrum, diagnostic tools and management of hypersensitivity reactions to NSAIDs. Clinically, NSAID hypersensitivity is particularly manifested by bronchial asthma, rhinosinusitis, anaphylaxis or urticaria and variety of late cutaneous and organ-specific reactions. Diagnosis of hypersensitivity to a NSAID includes understanding of the underlying mechanism and is necessary for prevention and management. A stepwise approach to the diagnosis of hypersensitivity to NSAIDs is proposed, including clinical history, in vitro testing and/or provocation test with a culprit or alternative drug depending on the type of the reaction. The diagnostic process should result in providing the patient with written information both on forbidden and on alternative drugs.

Fermi Large Area Telescope Observations of Markarian 421: The Missing Piece of its Spectral Energy Distribution

Abstract: We report on the gamma-ray activity of the high-synchrotron-peaked BL Lacertae object Markarian 421 (Mrk 421) during the first 1.5 years of Fermi operation, from 2008 August 5 to 2010 March 12. We find that the Large Area Telescope (LAT) gamma-ray spectrum above 0.3 GeV can be well described by a power-law function with photon index Gamma = 1.78 +/- 0.02 and average photon flux F(>0.3 GeV) = (7.23 +/- 0.16) x 10(-8) ph cm(-2) s(-1). Over this time period, the Fermi-LAT spectrum above 0.3 GeV was evaluated on seven-day-long time intervals, showing significant variations in the photon flux (up to a factor similar to 3 from the minimum to the maximum flux) but mild spectral variations. The variability amplitude at X-ray frequencies measured by RXTE/ASM and Swift/BAT is substantially larger than that in gamma-rays measured by Fermi-LAT, and these two energy ranges are not significantly correlated. We also present the first results from the 4.5 month long multifrequency campaign on Mrk 421, which included the VLBA, Swift, RXTE, MAGIC, the F-GAMMA, GASP-WEBT, and other collaborations and instruments that provided excellent temporal and energy coverage of the source throughout the entire campaign (2009 January 19 to 2009 June 1). During this campaign, Mrk 421 showed a low activity at all wavebands. The extensive multi-instrument (radio to TeV) data set provides an unprecedented, complete look at the quiescent spectral energy distribution (SED) for this source. The broadband SED was reproduced with a leptonic (one-zone synchrotron self-Compton) and a hadronic model (synchrotron proton blazar). Both frameworks are able to describe the average SED reasonably well, implying comparable jet powers but very different characteristics for the blazar emission site.

The persistent exclusion of older patients from ongoing clinical trials regarding heart failure.

Abstract: Methods: In the context of the Increasing the PaRticipation of the ElDerly in Clinical Trials (PREDICT) study, data from ongoing clinical trials regarding heart failure were extracted from the World Health Organization Clinical Trials Registry Platform on December 1, 2008. Main outcome measures were the proportion of trials excluding patients by an arbitrary upper age limit or by other exclusion criteria that might indirectly cause limited recruitment of older individuals. We classified exclusion criteria into 2 categories: justified or poorly justified. Results: Among 251 trials investigating treatments for heart failure, 64 (25.5%) excluded patients by an arbitrary upper age limit. Such exclusion was significantly more common in trials conducted in the European Union than in the United States (31/96 [32.3%] vs 17/105 [16.2%];P=.007) and in drug trials sponsored by public institutions vs those by private entities (21/59 [35.6%] vs 5/36 [13.9%];P=.02). Overall, 109 trials (43.4%) on heart failure had 1 or more poorly justified exclusion criteria that could limit the inclusion of older individuals. A similar proportion of clinical trials with poorly justified exclusion criteria was found in pharmacologic and nonpharmacologic trials. Conclusion: Despite the recommendations of national and international regulatory agencies, exclusion of older individuals from ongoing trials regarding heart failure continues to be widespread.

Translation initiator EIF4G1 mutations in familial Parkinson disease

Abstract: Genome-wide analysis of a multi-incident family with autosomal-dominant parkinsonism has implicated a locus on chromosomal region 3q26-q28. Linkage and disease segregation is explained by a missense mutation c.3614G>A (p.Arg1205His) in eukaryotic translation initiation factor 4-gamma (EIF4G1). Subsequent sequence and genotype analysis identified EIF4G1 c.1505C>T (p.Ala502Val), c.2056G>T (p.Gly686Cys), c.3490A>C (p.Ser1164Arg), c.3589C>T (p.Arg1197Trp) and c.3614G>A (p.Arg1205His) substitutions in affected subjects with familial parkinsonism and idiopathic Lewy body disease but not in control subjects. Despite different countries of origin, persons with EIF4G1 c.1505C>T (p.Ala502Val) or c.3614G>A (p.Arg1205His) mutations appear to share haplotypes consistent with ancestral founders. eIF4G1 p.Ala502Val and p.Arg1205His disrupt eIF4E or eIF3e binding, although the wild-type protein does not, and render mutant cells more vulnerable to reactive oxidative species. EIF4G1 mutations implicate mRNA translation initiation in familial parkinsonism and highlight a convergent pathway for monogenic, toxin and perhaps virally-induced Parkinson disease.

Insights into the high-energy γ-ray emission of Markarian 501 from extensive multifrequency observations in the Fermi era

Abstract: We report on the gamma-ray activity of the blazar Mrk 501 during the first 480 days of Fermi operation. We find that the average LAT gamma-ray spectrum of Mrk 501 can be well described by a single power-law function with a photon index of 1.78 +/- 0.03. While we observe relatively mild flux variations with the Fermi-LAT (within less than a factor of 2), we detect remarkable spectral variability where the hardest observed spectral index within the LAT energy range is 1.52 +/- 0.14, and the softest one is 2.51 +/- 0.20. These unexpected spectral changes do not correlate with the measured flux variations above 0.3GeV. In this paper, we also present the first results from the 4.5-month-long multifrequency campaign (2009 March 15 - August 1) on Mrk 501, which included the VLBA, Swift, RXTE, MAGIC and VERITAS, the F-GAMMA, GASP-WEBT, and other collaborations and instruments which provided excellent temporal and energy coverage of the source throughout the entire campaign. The average spectral energy distribution of Mrk 501 is well described by the standard one-zone synchrotron self-Compton model. In the framework of this model, we find that the dominant emission region is characterized by a size <~ 0.1 pc (comparable within a factor of few to the size of the partially-resolved VLBA core at 15-43 GHz), and that the total jet power (~10^{44} erg s^{-1}) constitutes only a small fraction (~10^{-3}) of the Eddington luminosity. The energy distribution of the freshly-accelerated radiating electrons required to fit the time-averaged data has a broken power-law form in the energy range 0.3GeV-10TeV, with spectral indices 2.2 and 2.7 below and above the break energy of 20GeV. We argue that such a form is consistent with a scenario in which the bulk of the energy dissipation within the dominant emission zone of Mrk 501 is due to relativistic, proton-mediated shocks.

Luminosity Determination in pp Collisions at sqrt(s)=7 TeV Using the ATLAS Detector at the LHC

Abstract: Measurements of luminosity obtained using the ATLAS detector during early running of the Large Hadron Collider (LHC) at root s = 7 TeV are presented. The luminosity is independently determined using several detectors and multiple algorithms, each having different acceptances, systematic uncertainties and sensitivity to background. The ratios of the luminosities obtained from these methods are monitored as a function of time and of mu, the average number of inelastic interactions per bunch crossing. Residual time- and mu-dependence between the methods is less than 2% for 0 < mu < 2.5. Absolute luminosity calibrations, performed using beam separation scans, have a common systematic uncertainty of +/- 11%, dominated by the measurement of the LHC beam currents. After calibration, the luminosities obtained from the different methods differ by at most +/- 2%. The visible cross sections measured using the beam scans are compared to predictions obtained with the PYTHIA and PHOJET event generators and the ATLAS detector simulation.

The efficiency of attentional networks in early and late bilinguals: the role of age of acquisition.

Abstract: Previous studies have demonstrated a bilingual advantage in the efficiency of executive attention. A question remains, however, about the impact of the age of L2 acquisition and relative balance of the two languages on the enhancement of executive functions in bilinguals, and whether this is modulated by the similarity of the bilingual’s two languages. The present study explores these issues by comparing the efficiency of attentional networks amongst three groups of young adults living in Australia: English monolinguals and early and late Chinese-English bilinguals. We also address the impact of bilingualism on hemispheric lateralization of cognitive functions, which is of interest since a recent study on early bilinguals revealed reduced hemispheric asymmetry in attentional functioning. In the present study, participants performed a modified version of the lateralized attention network test (LANT). Both early and late bilinguals were found to have more efficient executive network than monolinguals. The late bilinguals, who were also reported to be more balanced in the proficiency and usage of their two languages, showed the greatest advantage in conflict resolution, whereas early bilinguals seemed to show enhanced monitoring processes. These group differences were observed when controlling for nonverbal intelligence and socioeconomic status. Such results suggest that specific factors of language experience may differentially influence the mechanisms of cognitive control. Since the bilinguals had distinct language sets, it seems that the influence of bilingualism on executive functions is present regardless of the similarity between the two languages. As for hemispheric lateralization, although the results were not clear-cut, they suggest the reduced lateralization in early bilinguals.

Conservation of farmland birds faces different challenges in Western and Central-Eastern Europe

Abstract: Birds are commonly used as an example of the strongly declining farmland biodiversity in Europe. The populations of many species have been shown to suffer from intensification of management, reduction of landscape heterogeneity, and habitat loss and fragmentation. These conditions particularly dominate farmland in the economically well developed countries of Western Europe. Currently, the farmland environment in Central-Eastern Europe is generally more extensive than in Western Europe and a larger proportion of people still live in rural areas; thus generating different conditions for birds living in agricultural areas. Furthermore, the quasi-subsistence farming in much of Central-Eastern Europe has resulted in agricultural landscapes that are generally more complex than those in Western Europe. To protect declining bird populations living in farmland, detailed knowledge on both species and communities is necessary. However, due to scientific tradition and availability of funding, the majority of studies have been carried out in Western Europe. In consequence this provokes a question: are findings obtained in western conditions useful to identify the fate of farmland bird biodiversity in Central-Eastern Europe? Therefore, the major goal of this paper is to highlight some local and regional differences in biodiversity patterns within EU farmland by comparing intensive agricultural landscapes with more extensive ones. More specifically, we aim to outline differences in agricultural landscapes and land use history in the two regions, use farmland birds to provide examples of the differences in species dynamics and species-habitat interactions between the two regions, and discuss possible social and ecological drivers of the differences in the context of biodiversity conservation. Factors governing spatio-temporal dynamics of farmland bird populations may differ in intensive and extensive landscapes as illustrated here using the Grey Partridge Perdix perdix and the Red-backed Shrike Lanius collurio as examples. The unevenness of farmland bird studies distribution across Europe was also presented. We call for more emphasis on pluralism in furthering both pan-European research on farmland bird ecology and conservation strategies. We also highlight some features specific to Central-Eastern Europe that merit consideration for the more efficient conservation of farmland birds and farmland biodiversity across Europe.

Association of Lipidome Remodeling in the Adipocyte Membrane with Acquired Obesity in Humans

Abstract: Identification of early mechanisms that may lead from obesity towards complications such as metabolic syndrome is of great interest. Here we performed lipidomic analyses of adipose tissue in twin pairs discordant for obesity but still metabolically compensated. In parallel we studied more evolved states of obesity by investigating a separated set of individuals considered to be morbidly obese. Despite lower dietary polyunsaturated fatty acid intake, the obese twin individuals had increased proportions of palmitoleic and arachidonic acids in their adipose tissue, including increased levels of ethanolamine plasmalogens containing arachidonic acid. Information gathered from these experimental groups was used for molecular dynamics simulations of lipid bilayers combined with dependency network analysis of combined clinical, lipidomics, and gene expression data. The simulations suggested that the observed lipid remodeling maintains the biophysical properties of lipid membranes, at the price, however, of increasing their vulnerability to inflammation. Conversely, in morbidly obese subjects, the proportion of plasmalogens containing arachidonic acid in the adipose tissue was markedly decreased. We also show by in vitro Elovl6 knockdown that the lipid network regulating the observed remodeling may be amenable to genetic modulation. Together, our novel approach suggests a physiological mechanism by which adaptation of adipocyte membranes to adipose tissue expansion associates with positive energy balance, potentially leading to higher vulnerability to inflammation in acquired obesity. Further studies will be needed to determine the cause of this effect.

Effect of quercetin and its metabolites isorhamnetin and quercetin-3-glucuronide on inflammatory gene expression: role of miR-155.

Abstract: In the present study the effect of quercetin and its major metabolites quercetin-3-glucuronide (Q3G) and isorhamnetin on inflammatory gene expression was determined in murine RAW264.7 macrophages stimulated with lipopolysaccharide. Quercetin and isorhamnetin but not Q3G significantly decreased mRNA and protein levels of tumor necrosis factor alpha. Furthermore a significant decrease in mRNA levels of interleukin 1β, interleukin 6, macrophage inflammatory protein 1α and inducible nitric oxide synthase was evident in response to the quercetin treatment. However Q3G did not affect inflammatory gene expression. Anti-inflammatory properties of quercetin and isorhamnetin were accompanied by an increase in heme oxygenase 1 protein levels, a downstream target of the transcription factor Nrf2, known to antagonize chronic inflammation. Furthermore, proinflammatory microRNA-155 was down-regulated by quercetin and isorhamnetin but not by Q3G. Finally, anti-inflammatory properties of quercetin were confirmed in vivo in mice fed quercetin-enriched diets (0.1 mg quercetin/g diet) over 6 weeks.

Post-Soviet farmland abandonment, forest recovery, and carbon sequestration in western Ukraine

Abstract: Land use is a critical factor in the global carbon cycle, but land-use effects on carbon fluxes are poorly understood in many regions. One such region is Eastern Europe and the former Soviet Union, where land-use intensity decreased substantially after the collapse of socialism, and farmland abandonment and forest expansion have been widespread. Our goal was to examine how land-use trends affected net carbon fluxes in western Ukraine (57 000 km 2 ) and to assess the region’s future carbon sequestration potential. Using satellite-based forest disturbance and farmland abandonment rates from 1988 to 2007, historic forest resource statistics, and a carbon bookkeeping model, we reconstructed carbon fluxes from land use in the 20th century and assessed potential future carbon fluxes until 2100 for a range of forest expansion and logging scenarios. Our results suggested that the low-point in forest cover occurred in the 1920s. Forest expansion between 1930 and 1970 turned the region from a carbon source to a sink, despite intensive logging during socialism. The collapse of the Soviet Union created a vast, but currently largely untapped carbon sequestration potential (up to � 150 Tg C in our study region). Future forest expansion will likely maintain or even increase the region’s current sink strength of 1.48 Tg C yr � 1 . This may offer substantial opportunities for offsetting industrial

Poland health system review.

Abstract: Since the successful transition to a freely elected parliament and a market economy after 1989, Poland is now a stable democracy and is well represented within political and economic organizations in Europe and worldwide. The strongly centralized health system based on the Semashko model was replaced with a decentralized system of mandatory health insurance, complemented with financing from state and territorial self-government budgets. There is a clear separation of health care financing and provision: the National Health Fund (NFZ) the sole payer in the system is in charge of health care financing and contracts with public and non-public health care providers. The Ministry of Health is the key policy-maker and regulator in the system and is supported by a number of advisory bodies, some of them recently established. Health insurance contributions, borne entirely by employees, are collected by intermediary institutions and are pooled by the NFZ and distributed between the 16 regional NFZ branches. In 2009, Poland spent 7.4% of its gross domestic product (GDP) on health. Around 70% of health expenditure came from public sources and over 83.5% of this expenditure can be attributed to the (near) universal health insurance. The relatively high share of private expenditure is mostly represented by out-of-pocket (OOP) payments, mainly in the form of co-payments and informal payments. Voluntary health insurance (VHI) does not play an important role and is largely limited to medical subscription packages offered by employers. Compulsory health insurance covers 98% of the population and guarantees access to a broad range of health services. However, the limited financial resources of the NFZ mean that broad entitlements guaranteed on paper are not always available. Health care financing is overall at most proportional: while financing from health care contributions is proportional and budgetary subsidies to system funding are progressive, high OOP expenditures, particularly in areas such as pharmaceuticals, are highly regressive. The health status of the Polish population has improved substantially, with average life expectancy at birth reaching 80.2 years for women and 71.6 years for men in 2009. However, there is still a vast gap in life expectancy between Poland and the western European Union (EU) countries and between life expectancy overall and the expected number of years without illness or disability. Given its modest financial, human and material health care resources and the corresponding outcomes, the overall financial efficiency of the Polish system is satisfactory. Both allocative and technical efficiency leave room for improvement. Several measures, such as prioritizing primary care and adopting new payment mechanisms such as diagnosis-related groups (DRGs), have been introduced in recent years but need to be expanded to other areas and intensified. Additionally, numerous initiatives to enhance quality control and build the required expertise and evidence base for the system are also in place. These could improve general satisfaction with the system, which is not particularly high. Limited resources, a general aversion to cost-sharing stemming from a long experience with broad public coverage and shortages in health workforce need to be addressed before better outcomes can be achieved by the system. Increased cooperation between various bodies within the health and social care sectors would also contribute in this direction. The HiT profiles are country-based reports that provide a detailed description of a health system and of policy initiatives in progress or under development. HiTs examine different approaches to the organization, financing and delivery of health services, and the role of the main actors in health systems; they describe the institutional framework, process, content and implementation of health and health care policies; and highlight challenges and areas that require more in-depth analysis.

Hsa-miR-34b is a plasma-stable microRNA that is elevated in pre-manifest Huntington's disease

Abstract: Huntington's disease (HD) is a devastating, neurodegenerative condition, which lacks effective treatment Normal Huntingtin (HTT) and mutant Huntingtin (mHTT) are expressed in multiple tissues and can alter transcription of microRNAs (miRs) Importantly, miRs are present in a bio-stable form in human peripheral blood plasma and have recently been shown to be useful biomarkers in other diseases We therefore sought to identify potential miR biomarkers of HD that are present in, and have functional consequences for, neuronal and non-neuronal tissues In a cell line over-expressing mHTT-Exon-1, miR microarray analysis was used to identify candidate miRs We then examined their presence and bio-stability in control and HD plasma We found that miR-34b is significantly elevated in response to mHTT-Exon-1, and its blockade alters the toxicity of mHTT-Exon-1 in vitro We also show that miR-34b is detectable in plasma from small input volumes and is insensitive to freeze-thaw-induced RNA degradation Interestingly, miR-34b is significantly elevated in plasma from HD gene carriers prior to symptom onset This is the first study suggesting that plasma miRs might be used as biomarkers for HD