Functional modulation of the transient outward current Ito by KCNE beta-subunits and regional distribution in human non-failing and failing hearts

Objectives: The function of Kv4.3 (KCND3) channels, which underlie the transient outward current I,, in human heart, can be modulated by several accessory subunits such as KChIP2 and KCNE1-KCNE5. Here we aimed to determine the regional expression of Kv4.3, KChIP2, and KCNE mRNAs in non-failing and failing human hearts and to investigate the functional consequences of subunit coexpression in heterologous expression systems. Methods: We quantified mRNA levels for two Kv4.3 isoforms, Kv4.3-S and Kv4.3-L, and for KChIP2 as well as KCNE1-KCNE5 with real-time RT-PCR. We also studied the effects of KCNEs on Kv4.3 + KChIP2 current characteristics in CHO cells with the whole-cell voltage-clamp method. Results: In non-failing hearts, low expression was found for KCNE1, KCNE3, and KCNE5, three times higher expression for KCNE2, and 60 times higher for KCNE4. Transmural gradients were detected only for KChIP2 in left and right ventricles. Compared to non-failing tissue, failing hearts showed higher expression of Kv4.3-L and KCNE1 and lower of Kv4.3-S, KChIP2, KCNE4, and KCNE5. In CHO cells, Kv4.3 + KChIP2 currents were differentially modified by co-expressed KCNEs: time constants of inactivation were shorter with KCNE1 and KCNE3-5 while time-to-peak was decreased, and V-0.5 of steady-state inactivation was shifted to more negative potentials by all KCNE subunits. Importantly, KCNE2 induced a unique and prominent 'overshoot' of peak current during recovery from inactivation similar to that described for human I-to while other KCNE subunits induced little (KCNE4,5) or no overshoot. Conclusions: All KCNEs are expressed in the human heart at the transcript level. Compared to It. in native human myocytes, none of the combination of KChIP2 and KCNE produced an ideal congruency in current characteristics, suggesting that additional factors contribute to the regulation of the native I-to channel

The impacts of EU accession on the agriculture of the Visegrad Countries

The Visegrad Countries (VC)2 joined the European Union in 2004, which has offered several possibilities and challenges for their agriculture. The aim of the paper is to evaluate the status of the sector in the light of latest available data as well as to identify the factors lying behind different country performances. Results suggest that EU accession has had a diverse impact on the Visegrad Countries’ agriculture and member states capitalised their possibilities in a different manner, due to initial conditions and pre- and post-accession policies

Deep U band and R imaging of GOODS-South: Observations,data reduction and first results

We present deep imaging in the {\em U} band covering an area of 630 arcmin$^{2}$ centered on the southern field of the Great Observatories Origins Deep Survey (GOODS). The data were obtained with the VIMOS instrument at the ESO Very Large Telescope. The final images reach a magnitude limit $U_{lim} \approx 29.8$ (AB, 1$\sigma$, in a 1\arcsec radius aperture), and have good image quality, with full width at half maximum \approx 0.8\arcsec. They are significantly deeper than previous U--band images available for the GOODS fields, and better match the sensitivity of other multi--wavelength GOODS photometry. The deeper U--band data yield significantly improved photometric redshifts, especially in key redshift ranges such as $2<z<4$, and deeper color--selected galaxy samples, e.g., Lyman--break galaxies at $z\approx 3$. We also present the coaddition of archival ESO VIMOS R band data, with $R_{lim} \approx 29$ (AB, 1$\sigma$, 1\arcsec radius aperture), and image quality \approx 0.75 \arcsec. We discuss the strategies for the observations and data reduction, and present the first results from the analysis of the coadded images.Comment: Accepted for publication ApJS, 54 pages, 27 figures. Released data and full-quality paper version available at http://archive.eso.org/cms/eso-data/data-packages/goods-vimos-imaging-data-release-version-1.

Mapping trabecular disconnection "hotspots" in aged human spine and hip

Trabecular bone disconnection is an independent factor in age-related skeletal failure where real termini (ReTm; rare in youth) may cause weakness disproportionate to tissue loss, yet their structural contribution at vulnerable locations remains uncertain. ReTm (previously recorded at the iliac crest) were mapped in "normal" aged vertebral bodies (T11-L5 autopsy; 20 females, 10 males) and corresponding proximal femora (autopsy; 10 females). Results were compared with biomechanically failed femora from orthopaedic subjects aged >. 58. yr (osteoporosis OP, 10 females; osteoarthritis OA, 10 females). A novel direct 2D/3D histological method was applied to large, thick (300. μm) slices superficially silver-stained to separate ReTm (unstained) from apparent termini (planar artefacts, brown). Light microscope field co-ordinates enabled ReTm mapping and statistical testing relative to i) sex, ii) tissue sector and iii) slicing plane. In men ReTm populations were small and random while in women they were large and sector-specific. In vertebrae they clustered anterior/superior being rare posterior/inferior; in the femoral head they concentrated distal/superior and also near the fovea, being fewer distal/inferior. A distribution polarity was evident with 100% more ReTm observed transversely (i.e., on tensile-related cross struts) than longitudinally (i.e., on compression-related vertical struts). Their numbers rose in OP (BV/TV. . 14%), remaining polarised and sector-specific in OP only. Comparative experimentation by marrow elution of an OP animal model demonstrated "floating segments" as a possible outcome. Conclusions were supported statistically that trabecular disconnection "hotspots" at vulnerable locations are sex- and sector-specific, mainly transaxial, and subject to disease modulation

Development of Agricultural Market and Trade Policies in the CEE Candidate Countries.

This synthesis report focuses on the evolution of agricultural market and trade policies in the Central and Eastern European (CEE) candidate countries in the period 1997 to 2001. The developments were crucially influenced by (OECD, 2000a): ⢠the situation in world agricultural markets; ⢠the overall macroeconomic development in the countries considered; ⢠the prospective EU accession; ⢠bringing domestic agricultural policy in line with the Uruguay Agreement on Agriculture (URAA). High 1997 agricultural prices on world commodity markets were followed by a marked depression in 1998. With the exemption of milk products this trend continued in 1999. Likewise the economic and financial crisis in Russia had a considerable impact on agricultural policies. It hit the regions´ exports resulting in a decline in industrial as well as agricultural output1. Thus, compared to the previous years most of the CEE candidate countries experienced a slow down or even negative rates of growth in their Gross Domestic Product (GDP) in 1998 and 1999. In addition those countries felt increased budgetary pressures. Agricultural market and trade policies largely reacted to these developments. Border protection was increased in many countries in 1998. This was combined in some cases with export subsidies, and ad hoc producer aids to mitigate the adverse effects. The prospect of EU accession also had an influence on the agricultural policy design in the region with many countries implementing EU-type policy instruments. Thus, the importance of per hectare and per head payments increased in the region, quota like measures were implemented in some countries and as part of this development Estonia introduced tariffs for agro-food imports. Finally, many countries also continued to adjust their policies to comply with their commitments agreed to in the World Trade Organisation (WTO). Despite these general tendencies there are also differences in the development of agricultural policies between the various CEE candidates. Chapter 2 therefore provides an overview of the changes of agricultural market and trade policies in each of the 10 accession countries. It addresses the policy issues market access (e.g. tariffs, special safeguard measures), export subsidies (value and quantities) and domestic support (intervention policies, direct payments, input subsidies, production quotas). Chapter 3 provides a brief assessment of recent policy developments in the region in the light of EU accession and WTO commitments. The development of prices and values, e.g. export subsidies, agricultural support expenditure, were presented in the background papers provided by the country experts in current prices in national currencies. In this synthesis report they are in addition converted in Euro. This firstly allows for a better comparison among the CEE candidate countries as well as between those countries and the EU. Some of the accession countries still suffer from high inflation and thus a strong depreciation of their currency. Thus secondly, the conversion to Euros allows the comparisons to be made in real terms.Industrial Organization, International Development, Productivity Analysis,

Recognizing Emotions in a Foreign Language

Expressions of basic emotions (joy, sadness, anger, fear, disgust) can be recognized pan-culturally from the face and it is assumed that these emotions can be recognized from a speaker's voice, regardless of an individual's culture or linguistic ability. Here, we compared how monolingual speakers of Argentine Spanish recognize basic emotions from pseudo-utterances ("nonsense speech") produced in their native language and in three foreign languages (English, German, Arabic). Results indicated that vocal expressions of basic emotions could be decoded in each language condition at accuracy levels exceeding chance, although Spanish listeners performed significantly better overall in their native language ("in-group advantage"). Our findings argue that the ability to understand vocally-expressed emotions in speech is partly independent of linguistic ability and involves universal principles, although this ability is also shaped by linguistic and cultural variables

Prevalence of Diarrhea and Enteropathogens in Racing Sled Dogs

Background: Diarrhea is highly prevalent in racing sled dogs, although the underlying causes are poorly understood. Hypothesis: Clostridium perfringens enterotoxin (CPE) and Clostridium difficile Toxin A and B are associated with diarrhea in racing sled dogs. Animals: One hundred and thirty-five sled dogs. Methods: Freshly voided feces were obtained from 55 dogs before racing and from 80 dogs after 400 miles of racing. Samples were visually scored for diarrhea, mucus, blood, and melena. CPE and C. difficile Toxin A and B were detected by ELISA. Samples were cultured for C. perfringens, C. difficile, Campylobacter, Salmonella, and Escherichia coli 0157; Giardia and Cryptosporidium spp. were detected via immunofluorescence. Results: Diarrhea occurred in 36% of dogs during racing, and hematochezia, fecal mucus or melena, or all 3 occurred in 57.5% of dogs. Salmonella was isolated from 78.2% of dogs before racing, and from 71.3% of dogs during racing. C. perfringens and C. difficile were isolated from 100 and 58.2% of dogs before racing, and from 95 and 36.3% of dogs during racing. Dogs were more likely to test positive for CPE during than before racing (18.8 versus 5.5%, P 5 .021); however, no enteropathogens or their respective toxins were significantly associated with hematochezia or diarrhea. Conclusions and Clinical Importance: Sled dogs participating in long distance racing have a high prevalence of diarrhea and hematochezia that is not associated with common enteropathogens. It is possible that diarrhea and hematochezia represent the effect of prolonged exercise on the gastrointestinal tract