Decreased myocardial injury and improved contractility after administration of a peptide derived against the alpha-interacting domain of the L-type calcium channel.

BackgroundMyocardial infarction remains the leading cause of morbidity and mortality associated with coronary artery disease. The L-type calcium channel (IC a-L) is critical to excitation and contraction. Activation of the channel also alters mitochondrial function. Here, we investigated whether application of a alpha-interacting domain/transactivator of transcription (AID-TAT) peptide, which immobilizes the auxiliary β2 subunit of the channel and decreases metabolic demand, could alter mitochondrial function and myocardial injury.Methods and resultsTreatment with AID-TAT peptide decreased ischemia-reperfusion injury in guinea-pig hearts ex vivo (n=11) and in rats in vivo (n=9) assessed with uptake of nitroblue tetrazolium, release of creatine kinase, and lactate dehydrogenase. Contractility (assessed with catheterization of the left ventricle) was improved after application of AID-TAT peptide in hearts ex vivo (n=6) and in vivo (n=8) up to 12 weeks before sacrifice. In search of the mechanism for the effect, we found that intracellular calcium ([Ca(2+)]i, Fura-2), superoxide production (dihydroethidium fluorescence), mitochondrial membrane potential (Ψm, JC-1 fluorescence), reduced nicotinamide adenine dinucleotide production, and flavoprotein oxidation (autofluorescence) are decreased after application of AID-TAT peptide.ConclusionsApplication of AID-TAT peptide significantly decreased infarct size and supported contractility up to 12 weeks postcoronary artery occlusion as a result of a decrease in metabolic demand during reperfusion

Reformen av CAP 2013

Den senaste reformen av EU:s gemensamma jordbrukspolitik (CAP) sjösattes 2015 med avsikten att göra det europeiska jordbruket mer konkurrenskraftigt och mer hållbart. Syftet med den här rapporten är att analysera vilka effekter reformen kan väntas få på svenskt jordbruk på områdena konkurrenskraft och miljö, för att undersöka om målen med reformen uppfylls eller ej. Analysen bygger på simuleringar i AgriPoliS, en modell av svenskt jordbruk på gårdsnivå i fyra typiska bygder. Vi fokuserar på tre av reformens huvuddelar; nationell utjämning av gårdsstödet, kopplade stöd för nötkreatur och kravet på ekologiska fokusarealer kopplat till förgröningsstödet (EFA). Utjämningen har medfört att jordbrukare i produktiva regioner har fått ett sänkt stöd, medan jordbrukare i mindre produktiva regioner har fått ett förhöjt stöd. Även nötkreatursstödet gynnar särskilt mindre produktiva regioner, där djurhållning är viktig. Bland de mest omdiskuterade reformelementen finns förgröningsstödet, som efter reformen utgör 30 procent av gårdsstödet och är förbundet med villkor. Bland dem finns krav på att fem procent av arealen ställs om till ekologiska fokusarealer. Vid reformen togs tillläggsbeloppen, dvs. extra stöd för historisk produktion, bort, vilka har varit särskilt betydelsefulla i mindre produktiva regioner. På området konkurrenskraft visar analysen att utjämningen av stödrätternas värde påskyndar strukturomvandling i områden där stödbeloppen sjunker, dvs. att antalet gårdar sjunker och kvarvarande gårdar växer. Det ger kvarvarande gårdar möjlighet att expandera, vilket är positivt för deras konkurrensmässighet. I regioner där stödbeloppen stiger är effekten liten, eftersom dessa regioner samtidigt påverkas av att tilläggsbeloppen slopas. Sammantaget kan utjämningen anses vara ett steg i rätt riktning ur ett konkurrenskraftsperspektiv, eftersom den leder till en påskyndad strukturomvandling. Våra resultat visar att takten i omvandlingen ökar ju mer av gårdsstödet som tas bort, vilket reser frågan om hur direktstöden i sin helhet påverkar konkurrenskraften. Vi analyserar därför hur jordbrukets struktur och konkurrenskraft skulle se ut i en situation utan direktstöden. Utan direktstöden är gårdarna både färre och större. I regioner med goda förutsättningar för jordbruksverksamhet stiger inkomsterna. Skälet är att kvarvarande gårdar får möjlighet att expandera och bli mer konkurrenskraftiga när andra gårdar lägger ner sin verksamhet. I de mindre produktiva regionerna minskar inkomsterna på grund av sämre förutsättningar för konkurrensmässigt jordbruk i dessa regioner. Kopplat stöd till nötkreatur utgör en avvikelse från trenden av marknadsanpassning av CAP. Analysen visar att nötkreatursstödet medför att fler företag överlever. Därmed hämmas utvecklingen mot förbättrad konkurrenskraft i regioner som domineras av djurhållning. Stödet har dessutom produktionseffekter; mjölk- och nötköttsproduktionen ökar till nivåer som överstiger produktionen innan reformen, vilket riskerar att leda till fallande priser. Vi ser också att konkurrensmässiga näringar som lamm trängs undan. På området miljö visar resultaten på små eller obefintliga effekter. Kravet på ekologiska fokusarealer (EFA) leder inte till förbättringar i biologisk mångfald eller ökad landskapsdiversitet, eftersom kravet inte resulterar i några väsentliga förändringar i markanvändningen. Vi utvärderar också om ett striktare regelverk, där mer mark måste ställas om till EFA, skulle ge ett bättre utfall, men finner inte att miljöeffekterna förstärks. Det finns flera skäl till frånvaro av effekter, bl.a. att kraven utformats för att passa in i jordbrukarnas befintliga verksamheter och frånvaro av geografiska restriktioner. Störst miljöeffekt får utjämningen av stödrätternas värden. I slättbygdslandskapet tas mark ur produktion och läggs i träda, vilket ökar variationen i landskapet och flödet av ekosystemtjänster. Nötkreatursstödet bevara öppen jordbruksmark och biologisk mångfald i mindre produktiva områden. I skogsdominerade områden kan stöd till öppen jordbruksmark därför vara befogat ur miljösynpunkt. Sammantaget visar analysen att 2013 års reform kan väntas få begränsad inverkan. Jordbrukets konkurrenskraft förbättras något i produktiva regioner, medan effekterna blir små i mindre produktiva regioner. Djurnäringens konkurrenskraft kan till och med försämras något. På miljöområdet drar vi slutsatsen att förgröningsstödet inte ger några märkbara miljöeffekter

Season of birth and puberty in Santa Inês lambs

Neste estudo, investigou-se o efeito da estação de nascimento sobre a puberdade de cordeiros Santa Inês criados no Distrito Federal. Utilizaram-se 33 cordeiros machos, inteiros, distribuídos em quatro lotes de grupos contemporâneos. A diferença de idade de cada grupo foi de 90 dias, abrangendo as quatro estações do ano. Foram realizadas coletas de dados mensalmente e a cada 15 dias, dependendo da presença ou ausência de espermatozóides no ejaculado de cada animal. A puberdade foi definida quando o sêmen do animal apresentou motilidade total de 10% e concentração espermática de 50 x 106 espermatozóides por mililitro (mL) de ejaculado. Após a definição da puberdade, procedeu-se a mais uma coleta e, após 15 dias, realizou-se a castração dos animais. A idade à puberdade dos animais foi de 194,57 ± 41,97 dias. A estação do ano afetou a idade à puberdade entre os grupos, principalmente em razão do fator nutricional, visto que os pesos à puberdade foram semelhantes. O grupo mais precoce (nascido em agosto) apresentou idade à puberdade de 162,56 ± 35,55 dias. Correlações significativas foram encontradas entre peso e circunferência escrotal (CE), comprimento e largura testicular, sugerindo que a CE pode ser utilizada como critério complementar para a seleção feita com base nos parâmetros produtivos.The present study investigated the effect of calving season on puberty of Santa Inês ram lambs raised in the Distrito Federal, Brazil. Thirty-three ram lambs were assigned to four contemporary groups according to birth date, distributed in three months intervals. Data were collected monthly and every 15 days depending on the presence of sperm in each animal ejaculate. Puberty was defined when the animal presented total motility of 10% and sperm concentration of 50 x 106 per mL of ejaculated semen. This procedure was repeated after puberty and after 15 days the animals were castrated. Mean age at puberty was 194.57 ± 41.97 days. The season affected the puberty age, mainly due to the nutritional factor, since the puberty weights were not significantly different between groups. Average age at puberty for the youngest group (born in August) was 162.56 ± 35.55 days. Significant correlations were found between weight and the scrotal circumference (EC), length and width of testis, suggesting the use of EC as a complementary criterion for selection based on productive parameters

Phylotastic! Making Tree-of-Life Knowledge Accessible, Reusable and Convenient

Scientists rarely reuse expert knowledge of phylogeny, in spite of years of effort to assemble a great "Tree of Life" (ToL). A notable exception involves the use of Phylomatic, which provides tools to generate custom phylogenies from a large, pre-computed, expert phylogeny of plant taxa. This suggests great potential for a more generalized system that, starting with a query consisting of a list of any known species, would rectify non-standard names, identify expert phylogenies containing the implicated taxa, prune away unneeded parts, and supply branch lengths and annotations, resulting in a custom phylogeny suited to the user's needs. Such a system could become a sustainable community resource if implemented as a distributed system of loosely coupled parts that interact through clearly defined interfaces. Results: With the aim of building such a "phylotastic" system, the NESCent Hackathons, Interoperability, Phylogenies (HIP) working group recruited 2 dozen scientist-programmers to a weeklong programming hackathon in June 2012. During the hackathon (and a three-month follow-up period), 5 teams produced designs, implementations, documentation, presentations, and tests including: (1) a generalized scheme for integrating components; (2) proof-of-concept pruners and controllers; (3) a meta-API for taxonomic name resolution services; (4) a system for storing, finding, and retrieving phylogenies using semantic web technologies for data exchange, storage, and querying; (5) an innovative new service, DateLife.org, which synthesizes pre-computed, time-calibrated phylogenies to assign ages to nodes; and (6) demonstration projects. These outcomes are accessible via a public code repository (GitHub.com), a website (www.phylotastic.org), and a server image. Conclusions: Approximately 9 person-months of effort (centered on a software development hackathon) resulted in the design and implementation of proof-of-concept software for 4 core phylotastic components, 3 controllers, and 3 end-user demonstration tools. While these products have substantial limitations, they suggest considerable potential for a distributed system that makes phylogenetic knowledge readily accessible in computable form. Widespread use of phylotastic systems will create an electronic marketplace for sharing phylogenetic knowledge that will spur innovation in other areas of the ToL enterprise, such as annotation of sources and methods and third-party methods of quality assessment.NESCent (the National Evolutionary Synthesis Center)NSF EF-0905606iPlant Collaborative (NSF) DBI-0735191Biodiversity Synthesis Center (BioSync) of the Encyclopedia of LifeComputer Science

Day care study showed no differences in long-term symptoms in children who were and were not infected during COVID-19 outbreaks

Peer Reviewe

Detection of a Subset of Posttranscriptional Transfer RNA Modifications in Vivo with a Restriction Fragment Length Polymorphism-Based Method

Transfer RNAs (tRNAs) are among the most heavily modified RNA species. Posttranscriptional tRNA modifications (ptRMs) play fundamental roles in modulating tRNA structure and function and are being increasingly linked to human physiology and disease. Detection of ptRMs is often challenging, expensive, and laborious. Restriction fragment length polymorphism (RFLP) analyses study the patterns of DNA cleavage after restriction enzyme treatment and have been used for the qualitative detection of modified bases on mRNAs. It is known that some ptRMs induce specific and reproducible base “mutations” when tRNAs are reverse transcribed. For example, inosine, which derives from the deamination of adenosine, is detected as a guanosine when an inosine-containing tRNA is reverse transcribed, amplified via polymerase chain reaction (PCR), and sequenced. ptRM-dependent base changes on reverse transcription PCR amplicons generated as a consequence of the reverse transcription reaction might create or abolish endonuclease restriction sites. The suitability of RFLP for the detection and/or quantification of ptRMs has not been studied thus far. Here we show that different ptRMs can be detected at specific sites of different tRNA types by RFLP. For the examples studied, we show that this approach can reliably estimate the modification status of the sample, a feature that can be useful in the study of the regulatory role of tRNA modifications in gene expression

A case of penile fracture with complete urethral disruption during sexual intercourse: a case report

Penile fracture is a rare condition. Primarily it is a rupture of the corpus cavernosum that occurs when the penis is erect. The rupture can also affect the corpus spongiosum and the urethra. We report a case of a 37 year old man who presented with acute penile pain, penile swelling and the inability to pass urine after a blunt trauma during sexual intercourse. In emergency surgery we found bilateral partial rupture of the corpus cavernosum with complete urethral and corpus spongiosum disruption. In the one year follow up the patient presented with normal erectile and voiding function. Emergency surgical repair in penile fracture can preserve erectile and voiding function

Impacts of direct payments – lessons for CAP post-2020 from a quantitative analysis

In this report we aim to analyse the economic and environmental impacts of Pillar I direct payments, and to demonstrate alternative instruments that are better suited to achieve CAP objectives. The instruments—a targeted payment to land at risk of abandonment and a tax on mineral fertilisers—were selected on the basis of the Polluter Pays and Provider Gets Principles. We do this using two state‐of‐the‐art agricultural economic simulation models. The first model, CAPRI, is used to quantify the large‐scale or aggregate impacts for individual countries, the EU and the world. The other model, AgriPoliS, is used to quantify the fine‐scale or farm and field level impacts in a selection of contrasting agricultural regions, to consider the potential influence of the large spatial variability in agricultural and environmental conditions across the EU. The results show that direct payments are keeping more farms in the sector and more land in agricultural use than would otherwise be the case, and thus avoiding land abandonment, principally in marginal regions. Particularly the area of grassland is substantially higher, because it is generally less productive than arable land and hence more dependent on direct payments for keeping it in agricultural use. The magnitudes of the impacts of direct payments on land use therefore vary strongly across regions due to spatial variability in productivity: marginal regions with large areas of less productive land are heavily influenced by direct payments, while regions with large areas of relatively productive land are hardly affected, because this land would be farmed in any case. By keeping more farmers in the sector longer, direct payments are slowing structural change, which can hamper agricultural development. However the potential benefits of faster structural change vary considerably among our study regions. In relatively productive regions direct payments are hindering development, because too many farmers are staying in the sector and preventing the consolidation of land in larger farms, which would improve their competitiveness and increase farm profits. On the contrary, the mass departure of farms that is currently avoided, will not lead to the same general benefits in marginal regions. Instead of freed land being absorbed by remaining farms, large areas of relatively unproductive land are abandoned without payments. This land is unprofitable to maintain in agricultural land use, even if integrated into larger farms, because current market prices are too low to motivate farming it. Consequently direct payments pose a serious goal conflict: the avoidance of land abandonment on the one hand, which can have negative impacts on public goods, and restricting agricultural development on the other hand. Once again this goal conflict is rooted in the spatial variability of agricultural conditions in the EU. Maintaining extensively managed farmland, particularly semi‐natural pastures, is central for conservation of biodiversity and preservation of the cultural landscape. Therefore direct payments are contributing to the provisioning of these public goods, but principally in marginal areas. Further, abandonment of land can reduce its agricultural productivity due to erosion or afforestation. Thus, direct payments are contributing to food security by preserving the productive potential of land for the future, but only marginal land since relatively productive land is farmed in any case. Production of agricultural commodities is affected to a lesser degree by direct payments than land use per se. Nevertheless, food exports from the EU are higher and imports lower as a consequence of direct payments. However, the additional supply generated by direct payments also lowers output prices, which reduces the profitability of commodity production; thereby partially offsetting the additional revenues from direct payments. The higher agricultural output brought about by direct payments causes higher levels of environmentally damaging greenhouse‐gas emissions, nutrient surpluses and pesticide use. The higher greenhouse‐gas emissions for the EU are, to some extent, moderated by lower emissions in the rest of the world. Nevertheless, the net effect of direct payments is higher global emissions of greenhouse gases. The environmental impacts of higher nutrient surpluses and pesticide inputs are less conclusive, since these depend also on spatial factors, i.e., where the emissions occur. Although EU‐scale and regional emissions are higher due to direct payments, agricultural production is less intensive generally, on account of the lower output prices. Analysing the net effects of these two opposing forces requires additional biophysical modelling at relevant spatial scales, such as watersheds or landscapes, which is beyond the scope of this study. Pillar I direct payments generate a significant transfer of income to farmers and land owners who are not necessarily farmers; 40 billion euro annually. Of this transfer a substantial proportion goes to farmers in relatively productive regions and, further, to a minority of farmers that need them least. In relatively productive regions payments are not needed for continued agricultural production and preservation of farmland, but instead rather fuel higher land and rental prices, which hampers structural change. On the contrary, the need for support is greatest in marginal regions, because some form of payment to marginal land is needed to avoid its abandonment and the loss of associated public goods. Finally, the direct payments even come at the cost of lower market returns for farmers due to slower structural change (smaller and less competitive farms) and lower output prices (due to greater EU output). On the other hand the lower output prices lead to somewhat lower food prices, but at the greater cost of financing the direct payments. Our main conclusion is that Pillar I direct payments are generating serious goal conflicts due to spatial variability in conditions across the EU. On the one hand these payments are contributing to the provisioning of public goods by preserving marginal agricultural land. On the other hand they are hampering agricultural development, primarily in relatively productive regions. Payments to relatively productive land that would be farmed any way not only inflate land values (capitalisation) but also slow structural change, which are both likely to hinder agricultural development and hence the competitiveness of the EU on the global market. The direct payments also increase environmental pressure; by subsidising land use generally and the associated production, they are incapable of controlling environmentally damaging emissions, which is also in conflict with broad CAP objectives. The goal conflict arises because direct payments are universal, a payment principal that does not consider spatial variability in the EU and the associated trade‐offs in regard to development and environmental effectiveness. Our analysis considered two alternative policy instruments that have the potential to curb the identified goal conflicts associated with direct payments, by applying the Polluter Pays and Provider (of public goods) Gets Principles at appropriate spatial scales. Replacing direct payments with a payment targeted on marginal land (and associated public goods) prevents land abandonment at a lower cost, by avoiding payments to relatively productive land that is farmed in any case. This also allows surviving farms in regions with relatively productive land to compensate for lost direct payments through expansion and associated scale economies, as well as higher output prices. This instrument therefore finances the provisioning of public goods without adverse effects on development and the efficiency of agricultural production. The EU‐wide tax on mineral fertiliser demonstrates that this instrument has the potential to reduce nutrient surpluses. Since direct payments cause higher levels of polluting emissions, policy instruments targeting emissions at relevant spatial scales are needed to achieve cost‐effective abatement. Overall we find that Pillar I direct payments are not addressing the diversity of challenges facing European agriculture. In fact our quantitative analysis indicates that the potential for the current system to meet these challenges is seriously impaired by goal conflicts and spatial variability across the EU. A better policy requires that instruments are targeted on desired outcomes and designed according to sound principles, specifically the Polluter Pays and Provider Gets Principles. These principles would ensure that farmers are provided with appropriate incentives to i) generate public goods that otherwise would be underprovided; ii) mitigate environmentally damaging emissions at the lowest possible cost to society; and iii) continually strive to improve environmental performance. Such instruments are also fairer and promote a more competitive or viable agricultural sector by not obstructing structural change and hence agricultural development