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PARV4 is a recently discovered human parvovirus widely distributed in injecting drug users in the USA and Europe, particularly in those co-infected with human immunodeficiency virus (HIV). Like parvovirus B19, PARV4 persists in previously exposed individuals. In bone marrow and lymphoid tissue, PARV4 sequences were detected in two sub-Saharan African study subjects with AIDS but without a reported history of parenteral exposure and who were uninfected with hepatitis C virus. PARV4 variants infecting these subjects were phylogenetically distinct from genotypes 1 and 2 (formerly PARV5) that were reported previously. Analysis of near-complete genome sequences demonstrated that they should be classified as a third (equidistant) PARV4 genotype. The availability of a further near-complete genome sequence of this novel genotype facilitated identification of conserved novel open reading frames embedded in the ORF2 coding sequence; one encoded a putative protein with identifiable homology to SAT proteins of members of the genus Parvovirus.

Citation information in Europe Pubmed Central

The genome of hepatitis C virus (HCV) contains cis-acting replication elements (CREs) comprised of RNA stem-loop structures located in both the 5' and 3' noncoding regions (5' and 3' NCRs) and in the NS5B coding sequence. Through the application of several algorithmically independent bioinformatic methods to detect phylogenetically conserved, thermodynamically favored RNA secondary structures, we demonstrate a long-range interaction between sequences in the previously described CRE (5BSL3.2, now SL9266) with a previously predicted unpaired sequence located 3' to SL9033, approximately 200 nucleotides upstream. Extensive reverse genetic analysis both supports this prediction and demonstrates a functional requirement in genome replication. By mutagenesis of the Con-1 replicon, we show that disruption of this alternative pairing inhibited replication, a phenotype that could be restored to wild-type levels through the introduction of compensating mutations in the upstream region. Substitution of the CRE with the analogous region of different genotypes of HCV produced replicons with phenotypes consistent with the hypothesis that both local and long-range interactions are critical for a fundamental aspect of genome replication. This report further extends the known interactions of the SL9266 CRE, which has also been shown to form a "kissing loop" interaction with the 3' NCR (P. Friebe, J. Boudet, J. P. Simorre, and R. Bartenschlager, J. Virol. 79:380-392, 2005), and suggests that cooperative long-range binding with both 5' and 3' sequences stabilizes the CRE at the core of a complex pseudoknot. Alternatively, if the long-range interactions were mutually exclusive, the SL9266 CRE may function as a molecular switch controlling a critical aspect of HCV genome replication.

In his later essay ‘Reason and Belief in God’, [5] Plantinga further developed his notion of the ‘basicality’ of belief in God, i.e. the legitimacy of holding theist beliefs without those beliefs being evidentially ‘based’ on other (non-theistic) beliefs. Arguing against both ‘evidentialism’ (the view that it is wrong to hold any belief without sufficient evidence) and ‘classical foundationalism’ (the view that beliefs are only rational if self-evident, incorrigible, evident to the senses, or held on the basis of other rational beliefs), Plantinga defended the ‘Reformed’ view that belief in God can be ‘properly basic’ — that is, like memory beliefs and perceptual beliefs, it can be perfectly rational without being held on the basis of other beliefs.

Ten years later, Plantinga turned his analytical skills to an analysis of knowledge in general in the first two volumes of his Warrant trilogy. [6] Defining ‘warrant’ as that which (in sufficient measure) distinguishes knowledge from mere true belief , he argued that none of the extant contemporary theories of knowledge — varieties of classical deontologism, internalism, coherentism, and reliabilism — offered a satisfactory analysis of warrant. On the basis of various imaginative counterexamples, [7] Plantinga maintained that in each case the conception of ‘justification’ or ‘warrant’ propounded was either not necessary for knowledge, or not sufficient for knowledge, or both. Plantinga proceeded to argue that these counterexamples (as well as the classic ‘Gettier’ cases) teach us that what is lacking in current analyses of knowledge is the notion of proper function , i.e. of beliefs being formed by noetic processes functioning in the manner in which they were ‘designed’ (whether by God or by evolution) to function. In Warrant and Proper Function , Plantinga fleshed out in more detail his basic contention that “a belief has warrant if and only if it is produced by cognitive faculties functionally properly in a congenial epistemic environment according to a design plan successfully aimed at the production of true belief” [8] by addressing various objections, making some important refinements, and suggesting how his analysis of warrant might cash out in terms of the various types of knowledge we possess ( a priori , perceptual, inductive, etc.). [9]

Warranted Christian Belief first and foremost represents Plantinga’s application of the conclusions of his previous Warrant volumes in a more rigorous defence of the claim in ‘Reason and Belief in God’ that theistic belief can be not only rational, but rational even in the absence of supporting beliefs or arguments. In essence, WCB is Plantinga’s thorough answer to the question, “Is Christian belief intellectually acceptable?” — but in sharp contrast to the received view in secular philosophical circles, Plantinga’s answer is a resounding affirmative (albeit with one crucial qualification, discussed shortly). Plantinga thus characterises his book as a response to the de jure objection to Christian belief (i.e. “Christian belief is unjustified, or irrational, or unwarranted, or otherwise epistemically under par, regardless of whether it turns out to be true or false”) rather than the related but logically distinct de facto objection (i.e. “Christian belief is false or probably false”).

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