The fitness cost of mis-splicing is the main determinant of alternative splicing patterns

Background Most eukaryotic genes are subject to alternative splicing (AS), which may contribute to the production of protein variants or to the regulation of gene expression via nonsense-mediated messenger RNA (mRNA) decay (NMD). However, a fraction of splice variants might correspond to spurious transcripts and the question of the relative proportion of splicing errors to functional splice variants remains highly debated. Results We propose a test to quantify the fraction of AS events corresponding to errors. This test is based on the fact that the fitness cost of splicing errors increases with the number of introns in a gene and with expression level. We analyzed the transcriptome of the intron-rich eukaryote Paramecium tetraurelia. We show that in both normal and in NMD-deficient cells, AS rates strongly decrease with increasing expression level and with increasing number of introns. This relationship is observed for AS events that are detectable by NMD as well as for those that are not, which invalidates the hypothesis of a link with the regulation of gene expression. Our results show that in genes with a median expression level, 92–98% of observed splice variants correspond to errors. We observed the same patterns in human transcriptomes and we further show that AS rates correlate with the fitness cost of splicing errors. Conclusions These observations indicate that genes under weaker selective pressure accumulate more maladaptive substitutions and are more prone to splicing errors. Thus, to a large extent, patterns of gene expression variants simply reflect the balance between selection, mutation, and drift

Cold spells in the Nordic Seas during the early Eocene Greenhouse

Abstract The early Eocene (c. 56 - 48 million years ago) experienced some of the highest global temperatures in Earth’s history since the Mesozoic, with no polar ice. Reports of contradictory ice-rafted erratics and cold water glendonites in the higher latitudes have been largely dismissed due to ambiguity of the significance of these purported cold-climate indicators. Here we apply clumped isotope paleothermometry to a traditionally qualitative abiotic proxy, glendonite calcite, to generate quantitative temperature estimates for northern mid-latitude bottom waters. Our data show that the glendonites of the Danish Basin formed in waters below 5 °C, at water depths of &lt;300 m. Such near-freezing temperatures have not previously been reconstructed from proxy data for anywhere on the early Eocene Earth, and these data therefore suggest that regionalised cool episodes punctuated the background warmth of the early Eocene, likely linked to eruptive phases of the North Atlantic Igneous Province.</jats:p

How expectations became governable: institutional change and the performative power of central banks

Central banks have accumulated unparalleled power over the conduct of macroeconomic policy. Key for this development was the articulation and differentiation of monetary policy as a distinct policy domain. While political economists emphasize the foundational institutional changes that enabled this development, recent performativity-studies focus on central bankers’ invention of expectation management techniques. In line with a few other works, this article aims to bring these two aspects together. The key argument is that, over the last few decades, central banks have identified different strategies to assume authority over “expectational politics” and reinforced dominant institutional forces within them. I introduce a comparative scheme to distinguish two different expectational governance regimes. My own empirical investigation focuses on a monetarist regime that emerged from corporatist contexts, where central banks enjoyed “embedded autonomy” and where commercial banks maintained conservative reserve management routines. I further argue that innovations towards inflation targeting took place in countries with non-existent or disintegrating corporatist structures and where central banks turned to finance to establish a different version of expectation coordination. A widespread adoption of this “financialized” expectational governance has been made possible by broader processes of institutional convergence that were supported by central bankers themselves

A review of soil carbon change in New Zealand’s grazed grasslands

Soil organic matter is a potential sink of atmospheric carbon (C) and critical for maintaining soil quality. We reviewed New Zealand studies of soil C changes after conversion from woody vegetation to pasture, and under long-term pasture. Soil C increased by about 13.7 t C ha⁻¹ to a new steady state when forests were initially converted to pasture. In the last 3–4 decades, resampling of soil profiles demonstrated that under long-term pasture on flat land, soil C had subsequently declined for allophanic, gley and organic soils by 0.54, 0.32 and 2.9 t C ha⁻¹ y⁻¹ , respectively, and soil C had not changed in the remainder of sampled soil orders. For the same time period, pasture soils on stable midslopes of hill country gained 0.6 t C ha⁻¹ y⁻¹ . Whether these changes are ongoing is not known, except for the organic soils where losses will continue so long as they are drained. Phosphorus fertiliser application did not change C stocks. Irrigation decreased carbon by 7 t C ha⁻¹ . Carbon losses during pasture renewal ranged between 0.8 and 4.1 t C ha⁻¹ . Some evidence suggests tussock grasslands can gain C when fertilised and not overgrazed. When combined to the national scale, different data sets suggest either no change or a gain of C, but with large uncertainties. We highlight key land-use practices and soil orders that require further information of soil C stock changes and advocate for a better understanding of underpinning reasons for changes in soil C

Analyse du lancement du tadalafil (cialis) dans le traitement de la dysfonction érectile sur le marché français

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF