Posttranslational modification of the AU-rich element binding protein HuR by protein kinase Cdelta elicits angiotensin II-induced stabilization and nuclear export of cyclooxygenase 2 mRNA

The mRNA stabilizing factor HuR is involved in the posttranscriptional regulation of many genes, including that coding for cyclooxygenase 2 (COX-2). Employing RNA interference technology and actinomycin D experiments, we demonstrate that in human mesangial cells (hMC) the amplification of cytokine-induced COX-2 by angiotensin II (AngII) occurs via a HuR-mediated increase of mRNA stability. Using COX-2 promoter constructs with different portions of the 3' untranslated region of COX-2, we found that the increase in COX-2 mRNA stability is attributable to a distal class III type of AU-rich element (ARE). Likewise, the RNA immunoprecipitation assay showed AngII-induced binding of HuR to this ARE. Using the RNA pulldown assay, we demonstrate that the AngII-caused HuR assembly with COX-2 mRNA is found in free and cytoskeleton-bound polysomes indicative of an active RNP complex. Mechanistically, the increased HuR binding to COX-2-ARE by AngII is accompanied by increased nucleocytoplasmic HuR shuttling and depends on protein kinase Cdelta (PKCdelta), which physically interacts with nuclear HuR, thereby promoting its phosphorylation. Mapping of phosphorylation sites identified serines 221 and 318 as critical target sites for PKCdelta-triggered HuR phosphorylation and AngII-induced HuR export to the cytoplasm. Posttranslational modification of HuR by PKCdelta represents an important novel mode of HuR activation implied in renal COX-2 regulation.

Disruption of glucocorticoid action by environmental chemicals: potential mechanisms and relevance

Glucocorticoids play an essential role in the regulation of key physiological processes, including immunomodulation, brain function, energy metabolism, electrolyte balance and blood pressure. Exposure to naturally occurring compounds or industrial chemicals that impair glucocorticoid action may contribute to the increasing incidence of cognitive deficits, immune disorders and metabolic diseases. Potentially, "glucocorticoid disruptors" can interfere with various steps of hormone action, e.g. hormone synthesis, binding to plasma proteins, delivery to target cells, pre-receptor regulation of the ratio of active versus inactive hormones, glucocorticoid receptor (GR) function, or export and degradation of glucocorticoids. Several recent studies indicate that such chemicals exist and that some of them can cause multiple toxic effects by interfering with different steps of hormone action. For example, increasing evidence suggests that organotins disturb glucocorticoid action by altering the function of factors that regulate the expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) pre-receptor enzymes, by direct inhibition of 11beta-HSD2-dependent inactivation of glucocorticoids, and by blocking GR activation. These observations emphasize on the complexity of the toxic effects caused by such compounds and on the need of suitable test systems to assess their effects on each relevant step.

Mammalian pre-mRNA 3' end processing factor CF I m 68 functions in mRNA export

Export of mRNA from the nucleus is linked to proper processing and packaging into ribonucleoprotein complexes. Although several observations indicate a coupling between mRNA 3' end formation and export, it is not known how these two processes are mechanistically connected. Here, we show that a subunit of the mammalian pre-mRNA 3' end processing complex, CF I(m)68, stimulates mRNA export. CF I(m)68 shuttles between the nucleus and the cytoplasm in a transcription-dependent manner and interacts with the mRNA export receptor NXF1/TAP. Consistent with the idea that CF I(m)68 may act as a novel adaptor for NXF1/TAP, we show that CF I(m)68 promotes the export of a reporter mRNA as well as of endogenous mRNAs, whereas silencing by RNAi results in the accumulation of mRNAs in the nucleus. Moreover, CF I(m)68 associates with 80S ribosomes but not polysomes, suggesting that it is part of the mRNP that is remodeled in the cytoplasm during the initial stages of translation. These results reveal a novel function for the pre-mRNA 3' end processing factor CF I(m)68 in mRNA export.

Climate-induced interannual variability of marine primary and export production in three global coupled climate carbon cycle models

Fully coupled climate carbon cycle models are sophisticated tools that are used to predict future climate change and its impact on the land and ocean carbon cycles. These models should be able to adequately represent natural variability, requiring model validation by observations. The present study focuses on the ocean carbon cycle component, in particular the spatial and temporal variability in net primary productivity (PP) and export production (EP) of particulate organic carbon (POC). Results from three coupled climate carbon cycle models (IPSL, MPIM, NCAR) are compared with observation-based estimates derived from satellite measurements of ocean colour and results from inverse modelling (data assimilation). Satellite observations of ocean colour have shown that temporal variability of PP on the global scale is largely dominated by the permanently stratified, low-latitude ocean (Behrenfeld et al., 2006) with stronger stratification (higher sea surface temperature; SST) being associated with negative PP anomalies. Results from all three coupled models confirm the role of the low-latitude, permanently stratified ocean for anomalies in globally integrated PP, but only one model (IPSL) also reproduces the inverse relationship between stratification (SST) and PP. An adequate representation of iron and macronutrient co-limitation of phytoplankton growth in the tropical ocean has shown to be the crucial mechanism determining the capability of the models to reproduce observed interactions between climate and PP.

The nuclear mRNA export receptor Mex67-Mtr2 of Trypanosoma brucei contains a unique and essential zinc finger motif.

Trypanosoma brucei is the causative agent of Human African Trypanosomiasis. Trypanosomes are early diverged protozoan parasites and show significant differences in their gene expression compared with higher eukaryotes. Due to a lack of individual gene promoters, large polycistronic transcripts are produced and individual mRNAs mature by trans-splicing and polyadenylation. In the absence of transcriptional control, regulation of gene expression occurs post-transcriptionally mainly by control of transcript stability and translation. Regulation of mRNA export from the nucleus to the cytoplasm might be an additional post-transcriptional event involved in gene regulation. However, our knowledge about mRNA export in trypanosomes is very limited. Although export factors of higher eukaryotes are reported to be conserved, only a few orthologues can be readily identified in the genome of T. brucei. Hence, biochemical approaches are needed to identify the export machinery of trypanosomes. Here, we report the functional characterization of the essential mRNA export factor TbMex67. TbMex67 contains a unique and essential N-terminal zinc finger motif. Furthermore, we could identify two interacting export factors namely TbMtr2 and the karyopherin TbIMP1. Our data show that the general heterodimeric export receptor Mex67-Mtr2 is conserved throughout the eukaryotic kingdom albeit exhibiting parasite-specific features.

Legal Implications of the Use of Export Taxes in Addressing Carbon Leakage: Competing Border Adjustment Measures

The prevailing uncertainties about the future of the post-Kyoto international legal framework for climate mitigation and adaptation increase the likelihood of unilateral trade interventions that aim to address climate policy concerns, as exemplified by the controversial European Union initiative to include the aviation industry in its emissions trading system. The emerging literature suggests that border carbon adjustment (BCA) measures imposed by importing countries would lead to substantial legal complications in relation to World Trade Organization law and hence to possible trade disputes. Lack of legal clarity on BCAs is exacerbated by potential counter or pre-emptive export restrictions that exporting countries might impose on carbon-intensive products. In this context, this paper investigates the interface between legal and welfare implications of competing unilateral BCA measures. It argues that carbon export taxes will be an inevitable part of the future climate change regime in the absence of a multilateral agreement. It also describes the channels through which competing BCAs may lead to trade conflicts and political complications as a result of their distributional and welfare impacts at the domestic and global levels.

Past and future carbon fluxes from land use change, shifting cultivation and wood harvest

Carbon emissions from anthropogenic land use (LU) and land use change (LUC) are quantified with a Dynamic Global Vegetation Model for the past and the 21st century following Representative Concentration Pathways (RCPs). Wood harvesting and parallel abandonment and expansion of agricultural land in areas of shifting cultivation are explicitly simulated (gross LUC) based on the Land Use Harmonization (LUH) dataset and a proposed alternative method that relies on minimum input data and generically accounts for gross LUC. Cumulative global LUC emissions are 72 GtC by 1850 and 243 GtC by 2004 and 27–151 GtC for the next 95 yr following the different RCP scenarios. The alternative method reproduces results based on LUH data with full transition information within <0.1 GtC/yr over the last decades and bears potential for applications in combination with other LU scenarios. In the last decade, shifting cultivation and wood harvest within remaining forests including slash each contributed 19% to the mean annual emissions of 1.2 GtC/yr. These factors, in combination with amplification effects under elevated CO2, contribute substantially to future emissions from LUC in all RCPs.

Three Shades of Embeddedness, State Capitalism as the Informal Economy, Emic Notions of the Anti-Market, and Counterfeit Garments in the Mauritian Export Processing Zone

Purpose This paper furthers the analysis of patterns regulating capitalist accumulation based on a historical anthropology of economic activities revolving around and within the Mauritian Export Processing Zone (EPZ). Design/methodology/approach This paper uses fieldwork in Mauritius to interrogate and critique two important concepts in contemporary social theory – “embeddedness” and “the informal economy.” These are viewed in the wider frame of social anthropology’s engagement with (neoliberal) capitalism. Findings A process-oriented revision of Polanyi’s work on embeddedness and the “double movement” is proposed to help us situate EPZs within ongoing power struggles found throughout the history of capitalism. This helps us to challenge the notion of economic informality as supplied by Hart and others. Social implications Scholars and policymakers have tended to see economic informality as a force from below, able to disrupt the legal-rational nature of capitalism as practiced from on high. Similarly, there is a view that a precapitalist embeddedness, a “human economy,” has many good things to offer. However, this paper shows that the practices of the state and multinational capitalism, in EPZs and elsewhere, exactly match the practices that are envisioned as the cure to the pitfalls of capitalism. Value of the paper Setting aside the formal-informal distinction in favor of a process-oriented analysis of embeddedness allows us better to understand the shifting struggles among the state, capital, and labor.

CTIF is involved in mRNA export in human cells

In eukaryotic cells translation initiation of messenger RNA (mRNA) transcripts can be initiated either by the cap-binding complex (CBC) consisting of CBP80 and CBP20, or by the eukaryotic translation initiation factor (eIF) 4E. Together with eIF4G and eIF4A, eIF4E forms the eIF4F-complex, which mediates initiation of the bulk of cellular translation. Analogous to eIF4G, the CBP80/20-dependent translation initiation factor (CTIF) has been reported to be part of the CBC-dependent translation initiation complex. CTIF consists of a N-terminal CBP80-binding domain and a conserved C-terminal MIF4G domain. This MIF4G domain has been shown to mediate the interaction between CTIF and different factors such as eIF3g and the stem-loop binding protein (SLBP). Here we show data indicating that CTIF, besides its function in translation initiation, is involved in mRNA translocation from the nucleus to the cytoplasm, possibly through a direct interaction with the nuclear export factor NFX1/TAP. Taken together our results suggest that CTIF can function as a platform that interacts with proteins involved in different steps of mRNA metabolism.

CTIF is involved in mRNA export in human cells

In eukaryotic cells translation initiation of messenger RNA (mRNA) transcripts can be initiated either by the cap-binding complex (CBC) consisting of CBP80 and CBP20, or by the eukaryotic translation initiation factor (eIF) 4E. Together with eIF4G and eIF4A, eIF4E forms the eIF4F-complex, which mediates translation initiation during the bulk of cellular protein synthesis [1,2]. Functionally analogous to eIF4G, the CBP80/20-dependent translation initiation factor (CTIF) has been reported to be part of the CBC-dependent translation initiation complex [3,4]. CTIF consists of a N-terminal CBP80-binding domain and a conserved C-terminal MIF4G domain [3]. This MIF4G domain has been shown to mediate the interaction between CTIF and different factors such as eIF3g and the stem-loop binding protein (SLBP) [4,5]. Here we show data indicating that CTIF, besides its function in translation initiation, is involved in mRNA translocation from the nucleus to the cytoplasm, possibly through a direct interaction with the nuclear export factor NFX1/TAP. Taken together our results suggest that CTIF can function as a platform that interacts with proteins involved in different steps of the mRNA metabolism. [1] Haghighat A. and Sonenberg N. (1997) JBC 272:21677-21680 [2] Gross J.D. et al. (2003) Cell 115:739-750 [3] Kim K.M. et al. (2009) Genes Dev 23:2033-2045 [4] Choe J. et al. (2012) JBC 287:18500-18509 [5] Choe J. et al. (2013) NAR 41:1307-1318

Spring-summer temperatures reconstructed for northern Switzerland and southwestern Germany from winter rye harvest dates, 1454–1970

This paper presents a unique 517-yr long documentary data-based reconstruction of spring-summer (MAMJJ) temperatures for northern Switzerland and southwestern Germany from 1454 to 1970. It is composed of 25 partial series of winter grain (secale cereale) harvest starting dates (WGHD) that are partly based on harvest related bookkeeping of institutions (hospitals, municipalities), partly on (early) phenological observations. The resulting main Basel WGHD series was homogenised with regard to dating style, data type and altitude. The calibration and verification approach was applied using the homogenous HISTALP temperature series from 1774–1824 for calibration (r = 0.78) and from 1920–1970 for verification (r = 0.75). The latter result even suffers from the weak data base available for 1870– 1950. Temperature reconstructions based on WGHD are more influenced by spring temperatures than those based on grape harvest dates (GHD), because rye in contrast to vines already begins to grow as soon as sunlight brings the plant to above freezing. The earliest and latest harvest dates were checked for consistency with narrative documentary weather reports. Comparisons with other European documentarybased GHD and WGHD temperature reconstructions generally reveal significant correlations decreasing with the distance from Switzerland. The new Basel WGHD series shows better skills in representing highly climate change sensitive variations of Swiss Alpine glaciers than available GHD series.

NMD3 regulates both mRNA and rRNA nuclear export in African trypanosomes via an XPOI-linked pathway

Trypanosomes mostly regulate gene expression through post-transcriptional mechanisms, particularly mRNA stability. However, much mRNA degradation is cytoplasmic such that mRNA nuclear export must represent an important level of regulation. Ribosomal RNAs must also be exported from the nucleus and the trypanosome orthologue of NMD3 has been confirmed to be involved in rRNA processing and export, matching its function in other organisms. Surprisingly, we found that TbNMD3 depletion also generates mRNA accumulation of procyclin-associated genes (PAGs), these being co-transcribed by RNA polymerase I with the procyclin surface antigen genes expressed on trypanosome insect forms. By whole transcriptome RNA-seq analysis of TbNMD3-depleted cells we confirm the regulation of the PAG transcripts by TbNMD3 and using reporter constructs reveal that PAG1 regulation is mediated by its 5'UTR. Dissection of the mechanism of regulation demonstrates that it is not dependent upon translational inhibition mediated by TbNMD3 depletion nor enhanced transcription. However, depletion of the nuclear export factors XPO1 or MEX67 recapitulates the effects of TbNMD3 depletion on PAG mRNAs and mRNAs accumulated in the nucleus of TbNMD3-depleted cells. These results invoke a novel RNA regulatory mechanism involving the NMD3-dependent nuclear export of mRNA cargos, suggesting a shared platform for mRNA and rRNA export.

Tree Species Composition and Harvest Intensity Affect Herbivore Density and Leaf Damage on Beech, Fagus sylvatica, in Different Landscape Contexts

Most forests are exposed to anthropogenic management activities that affect tree species composition and natural ecosystem processes. Changes in ecosystem processes such as herbivory depend on management intensity, and on regional environmental conditions and species pools. Whereas influences of specific forest management measures have already been addressed for different herbivore taxa on a local scale, studies considering effects of different aspects of forest management across different regions are rare. We assessed the influence of tree species composition and intensity of harvesting activities on arthropod herbivores and herbivore-related damage to beech trees, Fagus sylvatica, in 48 forest plots in three regions of Germany. We found that herbivore abundance and damage to beech trees differed between regions and that – despite the regional differences - density of tree-associated arthropod taxa and herbivore damage were consistently affected by tree species composition and harvest intensity. Specifically, overall herbivore damage to beech trees increased with increasing dominance of beech trees – suggesting the action of associational resistance processes – and decreased with harvest intensity. The density of leaf chewers and mines was positively related to leaf damage, and several arthropod groups responded to beech dominance and harvest intensity. The distribution of damage patterns was consistent with a vertical shift of herbivores to higher crown layers during the season and with higher beech dominance. By linking quantitative data on arthropod herbivore abundance and herbivory with tree species composition and harvesting activity in a wide variety of beech forests, our study helps to better understand the influence of forest management on interactions between a naturally dominant deciduous forest tree and arthropod herbivores.

Modelling and Validation of a Mass Imbalance Oscillation Generator to Harvest Heart Motion Energy

An autonomous energy source within a human body is of key importance in the development of medical implants. This work deals with the modelling and the validation of an energy harvesting device which converts the myocardial contractions into electrical energy. The mechanism consists of a clockwork from a commercially available wrist watch. We developed a physical model which is able to predict the total amount of energy generated when applying an external excitation. For the validation of the model, a custom-made hexapod robot was used to accelerate the harvesting device along a given trajectory. We applied forward kinematics to determine the actual motion experienced by the harvesting device. The motion provides translational as well as rotational motion information for accurate simulations in three-dimensional space. The physical model could be successfully validated.

Amino Acid Export in Developing Arabidopsis Seeds Depends on UmamiT Facilitators

Essential amino acids cannot be synthesized by humans and animals. They often are limiting in plant-derived foods and determine the nutritional value of a given diet [1]. Seeds and fruits often represent the harvestable portion of plants. In order to improve the amino acid composition of these tissues, it is indispensable to understand how these substrates are transported within the plant. Amino acids result from nitrogen assimilation, which often occurs in leaves, the source tissue. They are transported via the vasculature, the xylem, and the phloem into the seeds, the so-called sink tissue, where they are stored or consumed. In seeds, several tissues are symplasmically isolated [2, 3], i.e., not connected by plasmodesmata, channels in the cell walls that enable a cytoplasmic continuum in plants [4]. Consequently, amino acids must be exported from cells into the apoplast and re-imported many times to support seed development. Several amino acid importers are known, but exporters remained elusive [5, 6]. Here, we characterize four members of the plant-specific UmamiT transporter family from Arabidopsis, related to the amino acid facilitator SIAR1 and the vacuolar auxin transporter WAT1 [7, 8]. We show that the proteins transport amino acids along their (electro)chemical potential across the plasma membrane. In seeds, they are found in tissues from which amino acids are exported. Loss-of-function mutants accumulate high levels of free amino acids in fruits and produce smaller seeds. Our results strongly suggest a crucial role for the UmamiTs in amino acid export and possibly a means to improve yield quality.