Induction of GADD34 Is Necessary for dsRNA-Dependent Interferon-β Production and Participates in the Control of Chikungunya Virus Infection

Nucleic acid sensing by cells is a key feature of antiviral responses, which generally result in type-I Interferon production and tissue protection. However, detection of double-stranded RNAs in virus-infected cells promotes two concomitant and apparently conflicting events. The dsRNA-dependent protein kinase (PKR) phosphorylates translation initiation factor 2-alpha (eIF2α) and inhibits protein synthesis, whereas cytosolic DExD/H box RNA helicases induce expression of type I-IFN and other cytokines. We demonstrate that the phosphatase-1 cofactor, growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a), an important component of the unfolded protein response (UPR), is absolutely required for type I-IFN and IL-6 production by mouse embryonic fibroblasts (MEFs) in response to dsRNA. GADD34 expression in MEFs is dependent on PKR activation, linking cytosolic microbial sensing with the ATF4 branch of the UPR. The importance of this link for anti-viral immunity is underlined by the extreme susceptibility of GADD34-deficient fibroblasts and neonate mice to Chikungunya virus infection

Analysing the Risks Posed by Biological Invasions to South Africa

Studies of the impact of alien species on the environment are increasingly being carried out, and there has been ongoing debate about how to standardise the description of these impacts. This chapter evaluates the state of knowledge on the impacts of alien species on biodiversity in South Africa based on different assessment methods. Despite South Africa being one of the most biologically diverse countries in the world, there have been very few studies that formally document the impacts of alien species on biodiversity. Most of what is known is based on expert opinion, and consequently the level of confidence in the estimates of the magnitude of these impacts is low. However, it is clear that a significant number of alien species cause major negative impacts, and that there is cause for serious concern. There is a growing global effort to assess all alien species with standardised protocols to alleviate the problem of comparing impacts measured using different approaches. Formal assessments have been done for a few alien species in South Africa, but most naturalised and invasive species have not been evaluated, and, we suspect, for most alien species there has been no attempt, as yet, to document their impacts. However, red-listing processes found that alien species were frequently included as a significant extinction risk for several native species of fish, amphibians, and plants. There are very few studies that cover the combined impacts of co-occurring alien species in particular areas, and these studies could provide the rationale for regulation and management, which is often absent. While reductions due to alien species in the value of ecosystem services, the productivity of rangelands, and biodiversity intactness are relatively low at present these impacts are expected to grow rapidly as more invasive species enter a stage of exponential growth

Energy efficiency trade-offs drive nucleotide usage in transcribed regions

Efficient nutrient usage is a trait under universal selection. A substantial part of cellular resources is spent on making nucleotides. We thus expect preferential use of cheaper nucleotides especially in transcribed sequences, which are often amplified thousand-fold compared with genomic sequences. To test this hypothesis, we derive a mutation-selection-drift equilibrium model for nucleotide skews (strand-specific usage of ‘A' versus ‘T' and ‘G' versus ‘C'), which explains nucleotide skews across 1,550 prokaryotic genomes as a consequence of selection on efficient resource usage. Transcription-related selection generally favours the cheaper nucleotides ‘U' and ‘C' at synonymous sites. However, the information encoded in mRNA is further amplified through translation. Due to unexpected trade-offs in the codon table, cheaper nucleotides encode on average energetically more expensive amino acids. These trade-offs apply to both strand-specific nucleotide usage and GC content, causing a universal bias towards the more expensive nucleotides ‘A' and ‘G' at non-synonymous coding sites