Small RNA Response to Infection of the Insect-Specific Lammi Virus and Hanko Virus in an Aedes albopictus Cell Line

RNA interference (RNAi)-mediated antiviral immunity is believed to be the primary defense against viral infection in mosquitoes. The production of virus-specific small RNA has been demonstrated in mosquitoes and mosquito-derived cell lines for viruses in all of the major arbovirus families. However, many if not all mosquitoes are infected with a group of viruses known as insect-specific viruses (ISVs), and little is known about the mosquito immune response to this group of viruses. Therefore, in this study, we sequenced small RNA from an Aedes albopictus-derived cell line infected with either Lammi virus (LamV) or Hanko virus (HakV). These viruses belong to two distinct phylogenetic groups of insect-specific flaviviruses (ISFVs). The results revealed that both viruses elicited a strong virus-derived small interfering RNA (vsiRNA) response that increased over time and that targeted the whole viral genome, with a few predominant hotspots observed. Furthermore, only the LamV-infected cells produced virus-derived Piwi-like RNAs (vpiRNAs); however, they were mainly derived from the antisense genome and did not show the typical ping-pong signatures. HakV, which is more distantly related to the dual-host flaviviruses than LamV, may lack certain unknown sequence elements or structures required for vpiRNA production. Our findings increase the understanding of mosquito innate immunity and ISFVs' effects on their host

Transcriptome Analysis of an Aedes albopictus Cell Line Single- and Dual-Infected with Lammi Virus and WNV

Understanding the flavivirus infection process in mosquito hosts is important and fundamental in the search for novel control strategies that target the mosquitoes' ability to carry and transmit pathogenic arboviruses. A group of viruses known as insect-specific viruses (ISVs) has been shown to interfere with the infection and replication of a secondary arbovirus infection in mosquitoes and mosquito-derived cell lines. However, the molecular mechanisms behind this interference are unknown. Therefore, in the present study, we infected the Aedes albopictus cell line U4.4 with either the West Nile virus (WNV), the insect-specific Lammi virus (LamV) or an infection scheme whereby cells were pre-infected with LamV 24 h prior to WNV challenge. The qPCR analysis showed that the dual-infected U4.4 cells had a reduced number of WNV RNA copies compared to WNV-only infected cells. The transcriptome profiles of the different infection groups showed a variety of genes with altered expression. WNV-infected cells had an up-regulation of a broad range of immune-related genes, while in LamV-infected cells, many genes related to stress, such as different heat-shock proteins, were up-regulated. The transcriptome profile of the dual-infected cells was a mix of up- and down-regulated genes triggered by both viruses. Furthermore, we observed an up-regulation of signal peptidase complex (SPC) proteins in all infection groups. These SPC proteins have shown importance for flavivirus assembly and secretion and could be potential targets for gene modification in strategies for the interruption of flavivirus transmission by mosquitoes

Early effects of kidney transplantation on the heart - A cardiac magnetic resonance multi-parametric study

Increased native myocardial T1 times in chronic kidney disease (CKD) may be due to diffuse interstitial myocardial fibrosis (DIF) or due to interstitial edema/inflammation. Concerns relating to nephrogenic systemic fibrosis with gadolinium-based contrast agents (GBCA) limit their use in end-stage kidney disease (ESKD) to measure extracellular volume (ECV) and characterise myocardial fibrosis. This study aimed to examine stability of myocardial T1 and T2 times before, and within 2 months after kidney transplantation; a time frame when volume status normalises but myocardial remodelling is unlikely to have occurred, and to compare these with ECV using GBCA after transplantation. Twenty-four patients with ESKD underwent serial cardiovascular magnetic resonance imaging, including T1 and T2 mapping. GBCA was administered on follow-up provided eGFR was N30 ml/min/1.73 m2 . Eighteen age- and sex-matched controls were studied at one timepoint. ECV (ECV 28 ± 2% vs. 24 ± 2%, p = 0.001) and T2 times were higher in ESKD compared to controls. After transplantation, septal T1 times increased (MOLLI 985 ms ± 25 vs. 1002 ms ± 30, p = 0.014; ShMOLLI 974 ms ± 39 vs. 992 ms ± 33, p = 0.113), LV volumes reduced (LVEDvol indexed 79 ± 24 vs. 63 ± 20 ml/m2 , p = 0.005) but LV mass was unchanged (LV mass index 89 g/m2 ± 38 to 83 g/m2 ± 23, p = 0.141). T2 times did not change after transplantation. Both ECV and myocardial T1 times are elevated in ESKD, supporting the theory that elevated T1 times are due to DIF, although a contribution from myocardial edema cannot be fully excluded. The lack of any fall in T1 or T2 times after transplantation suggests that myocardial T1 times are a stable measure of DIF in CKD

Amyloid-like aggregates sequester numerous metastable proteins with essential cellular functions

Protein aggregation is linked with neurodegeneration and numerous other diseases by mechanisms that are not well understood. Here, we have analyzed the gain-of-function toxicity of artificial β sheet proteins that were designed to form amyloid-like fibrils. Using quantitative proteomics, we found that the toxicity of these proteins in human cells correlates with the capacity of their aggregates to promote aberrant protein interactions and to deregulate the cytosolic stress response. The endogenous proteins that are sequestered by the aggregates share distinct physicochemical properties: They are relatively large in size and significantly enriched in predicted unstructured regions, features that are strongly linked with multifunctionality. Many of the interacting proteins occupy essential hub positions in cellular protein networks, with key roles in chromatin organization, transcription, translation, maintenance of cell architecture and protein quality control. We suggest that amyloidogenic aggregation targets a metastable subproteome, thereby causing multifactorial toxicity and, eventually, the collapse of essential cellular functions. PaperFlick: © 2011 Elsevier Inc

Translational switch for long-term maintenance of synaptic plasticity

Memory can last a lifetime, yet synaptic contacts that contribute to the storage of memory are composed of proteins that have much shorter lifetimes. A physiological model of memory formation, long-term potentiation (LTP), has a late protein-synthesis-dependent phase (L-LTP) that can last for many hours in slices or even for days in vivo. Could the activity-dependent synthesis of new proteins account for the persistence of L-LTP and memory? Here, we examine the proposal that a self-sustaining regulation of translation can form a bistable switch that can persistently regulate the on-site synthesis of plasticity-related proteins. We show that an αCaMKII–CPEB1 molecular pair can operate as a bistable switch. Our results imply that L-LTP should produce an increase in the total amount of αCaMKII at potentiated synapses. This study also proposes an explanation for why the application of protein synthesis and αCaMKII inhibitors at the induction and maintenance phases of L-LTP result in very different outcomes

Estimating taxon-specific population dynamics in diverse microbial communities

Understanding how population-level dynamics contribute to ecosystem-level processes is a primary focus of ecological research and has led to important breakthroughs in the ecology of macroscopic organisms. However, the inability to measure population-specific rates, such as growth, for microbial taxa within natural assemblages has limited ecologists’ understanding of how microbial populations interact to regulate ecosystem processes. Here, we use isotope incorporation within DNA molecules to model taxon- specific population growth in the presence of 18O-labeled water. By applying this model to phylogenetic marker sequencing data collected from stable-isotope probing studies, we estimate rates of growth, mortal- ity, and turnover for individual microbial populations within soil assemblages. When summed across the entire bacterial community, our taxon-specific estimates are within the range of other whole-assemblage measurements of bacterial turnover. Because it can be applied to environmental samples, the approach we present is broadly applicable to measuring population growth, mortality, and associated biogeochemical process rates of microbial taxa for a wide range of ecosystems and can help reveal how individual microbial populations drive biogeochemical fluxes