37 research outputs found

    A Discontinuous RNA Platform Mediates RNA Virus Replication: Building an Integrated Model for RNA–based Regulation of Viral Processes

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    Plus-strand RNA viruses contain RNA elements within their genomes that mediate a variety of fundamental viral processes. The traditional view of these elements is that of local RNA structures. This perspective, however, is changing due to increasing discoveries of functional viral RNA elements that are formed by long-range RNA–RNA interactions, often spanning thousands of nucleotides. The plus-strand RNA genomes of tombusviruses exemplify this concept by possessing different long-range RNA–RNA interactions that regulate both viral translation and transcription. Here we report that a third fundamental tombusvirus process, viral genome replication, requires a long-range RNA–based interaction spanning ∼3000 nts. In vivo and in vitro analyses suggest that the discontinuous RNA platform formed by the interaction facilitates efficient assembly of the viral RNA replicase. This finding has allowed us to build an integrated model for the role of global RNA structure in regulating the reproduction of a eukaryotic RNA virus, and the insights gained have extended our understanding of the multifunctional nature of viral RNA genomes

    The Molecular Epidemiology and Evolution of Murray Valley Encephalitis Virus: Recent Emergence of Distinct Sub-lineages of the Dominant Genotype 1

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    © 2015 Williams et al. Background: Recent increased activity of the mosquito-borne Murray Valley encephalitis virus (MVEV) in Australia has renewed concerns regarding its potential to spread and cause disease. Methodology/Principal Findings: To better understand the genetic relationships between earlier and more recent circulating strains, patterns of virus movement, as well as the molecular basis of MVEV evolution, complete pre-membrane (prM) and Envelope (Env) genes were sequenced from sixty-six MVEV strains from different regions of the Australasian region, isolated over a sixty year period (1951–2011). Phylogenetic analyses indicated that, of the four recognized genotypes, only G1 and G2 are contemporary. G1 viruses were dominant over the sampling period and found across the known geographic range of MVEV. Two distinct sub-lineages of G1 were observed (1A and 1B). Although G1B strains have been isolated from across mainland Australia, Australian G1A strains have not been detected outside northwest Australia. Similarly, G2 is comprised of only Western Australian isolates from mosquitoes, suggesting G1B and G2 viruses have geographic or ecological restrictions. No evidence of recombination was found and a single amino acid substitution in the Env protein (S332G) was found to be under positive selection, while several others were found to be under directional evolution. Evolutionary analyses indicated that extant genotypes of MVEV began to diverge from a common ancestor approximately 200 years ago. G2 was the first genotype to diverge, followed by G3 and G4, and finally G1, from which subtypes G1A and G1B diverged between 1964 and 1994. Conclusions/Significance: The results of this study provides new insights into the genetic diversity and evolution of MVEV. The demonstration of co-circulation of all contemporary genetic lineages of MVEV in northwestern Australia, supports the contention that this region is the enzootic focus for this virus

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    Hippocampal contribution to vector model hypothesis during cue-dependent navigation

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    Learning to navigate toward a goal is an essential skill. Place learning is thought to rely on the ability of animals to associate the location of a goal with surrounding environmental cues. Using the Morris water maze, a task popularly used to examine place learning, we demonstrate that distal cues provide animals with distance and directional information. We show how animals use the cues in a visually dependent guidance manner to find the goal. Further, we demonstrate how hippocampal lesions disrupt this learning mechanism. Our results can be explained through the vector model of navigation built on associative learning principles rather than evoking a cognitive map.Deposited by bulk impor

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    Not AvailableCrop residue is the non-edible plant parts that are left in the field after harvest. Field residues are materials left in an agricultural field or orchard after the crop has been harvested. These residues include stalks and stubble (stems), leaves and seed pods. The residue can be ploughed directly into the ground or burned first. Ministry of New and Renewable Energy, Govt. of India estimated that about 500 Mt of crop residue is generated every year. There is a large variability in crop residues generation and their use depending on the cropping intensity, productivity and crops grown in different states of India. Residue generation is highest in Uttar Pradesh (60 Mt) followed by Punjab (51 Mt) and Maharashtra (46 Mt). Among different crops, cereals generate 352 Mt residue followed by fibres (66 Mt), oilseed (29 Mt), pulses (13 Mt) and sugarcane (12 Mt). However, a large portion of the residues, about 140 Mt is burned in field primarily to clear the field from straw and stubble after the harvest of the preceding crop. The problem is severe in irrigated agriculture, particularly in the mechanized rice-wheat system. Good management of field residues can increase efficiency of irrigation and control of erosion. Hence, the utilization of balers for crop residue management is the need of the hour. Several researchers have designed and developed the different models of balers for residue management. This paper highlights the various parameters affecting the baling process for agricultural residues.Not Availabl

    Childhood outcomes after low-grade Intraventricular Haemorrhage: a systematic review and meta-analysis

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    Aim To undertake a systematic review and meta-analysis exploring school-aged neurodevelopmental outcomes of children after low-grade intraventricular haemorrhage (IVH). Methods The published and grey literature was extensively searched to identify observational comparative studies exploring neurodevelopmental outcomes after IVH grade 1-2. Our primary outcome was neurodevelopmental impairment after 5 years of age, which included cognitive, motor, speech and language, behavioural, hearing or visual impairments. Results This review included 12 studies and over 2,036 preterm infants with low grade IVH. Studies used 30 different neurodevelopmental tools to determine outcomes. There was conflicting evidence of the composite risk of neurodevelopmental impairment after low-grade IVH. There was evidence of an association between low-grade IVH and lower IQ at school age -4.23 95% CI (-7.53, -0.92) I2=0% but impact on school performance was unclear. Studies reported an increased crude risk of cerebral palsy after low-grade IVH OR 2.92 95%CI (1.95, 4.37) I2=41%. No increased risk of speech and language impairment or behavioural impairment was found. Few studies addressed hearing and visual impairment. Interpretation This review presents evidence that low-grade IVH is associated with specific neurodevelopmental impairments at school age, lending support to the theory that low-grade IVH is not a benign condition

    Preterm brain injury and neurodevelopmental outcomes: a meta-analysis

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    Context: Preterm brain injuries are common; neurodevelopmental outcomes following contemporary neonatal care are continually evolving. Objective: To systematically review and meta-analyze neurodevelopmental outcomes among preterm infants after intraventricular hemorrhage (IVH) and white matter injury (WMI). Data Sources: Published and grey literature were searched across 10 databases between 2000-2021 Study Selection: Observational studies reporting 3-year neurodevelopmental outcomes for preterm infants with IVH or WMI compared to preterm infants without injury. Data extraction: Study characteristics, population characteristics, and outcome data were extracted. Results: 38 studies were included. There was an increased adjusted risk of moderate-severe neurodevelopmental impairment after IVH grade 1-2 (aOR 1.35 [95% CI 1.05, 1.75]) and IVH grade 3-4 (aOR 4.26 [3.25, 5.59]). Children with IVH grade 1-2 had higher risks of cerebral palsy (OR 1.76 [1.39, 2.24)], cognitive (OR 1.79 [1.09, 2.95]), hearing (OR 1.83 CI [1.03. 3.24]), and visual impairment (OR 1.77 [1.08, 2.9]). Children with IVH grade 3-4 had markedly higher risks of cerebral palsy (OR 4.98 [4.13, 6.00)], motor (OR 2.7 [1.52, 4.8)], cognitive (OR 2.3 [1.67, 3.15)], hearing (OR 2.44 [1.42, 4.2)), and visual impairment (OR 5.42 [2.77, 10.58)). Children with WMI had much higher risks of cerebral palsy (OR 14.91 [7.3, 30.46), motor (OR 5.3 [3, 9.36)], and cognitive impairment (OR 3.48 [2.18, 5.53)). Limitations: Heterogeneity of outcome data. Conclusions: Mild IVH, severe IVH, and WMI are associated with adverse neurodevelopmental outcomes. Utilization of core outcomes sets and availability of open-access study data would improve our understanding of the nuances of these outcomes

    Genetic characterization of K13965, a strain of Oak Vale virus from Western Australia

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    K13965, an uncharacterized virus, was isolated in 1993 from Anopheles annulipes mosquitoes collectedin the Kimberley region of northern Western Australia. Here, we report its genomic sequence, identifyit as a rhabdovirus, and characterize its phylogenetic relationships. The genome comprises a P (C) and SH protein similar to the recently characterized Tupaia and Durham viruses, and shows overlap between G and L genes. Comparison of K13965 genome sequence to other rhabdoviruses identified K13965 as a strain of the unclassified Australian Oak Vale rhabdovirus, whose complete genome sequence we also determined. Phylogenetic analysis of N and L sequences indicated genetic relationship to a recently proposed Sandjima virus clade, although the Oak Vale virus sequences form a branch separate from the African members of that group
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