In and Out of places, states and activities.

This paper is part of Inna Tolskaya's doctoral thesis which is available in Munin at http://hdl.handle.net/10037/6756This paper explains the polysemy of Russian verbal prefixes through their position in the VP. The lexical entry remains constant throughout all the uses of a given prefix, while the structure into which a prefix is inserted varies

Insertion of short hepatitis virus A amino acid sequences into poliovirus antigenic determinants results in viable progeny

AbstractIn an infectious poliovirus cDNA construct, the determinant encoding antigenic epitope N-Agl (in a loop located between two β-strands in polypeptide VP1) was altered by site-directed mutagenesis, to be partially similar with the determinants for presumptive epitopes in polypeptides VP1 or VP3 of hepatitis A virus (HAV). The modified constructs proved to be infectious. However, another construct, in which the same locus encoded a ‘nonsense’ and a relatively hydrophobic amino acid sequence, exhibited no infectivity. These data showed the feasibility of the insertion of foreign sequences in a specific antigenically active locus of the poliovirus icosahedron, and suggest some limitations with respect to the sequences to be ‘transplanted’

Foot-and-mouth disease virus 2C is a hexameric AAA+ protein with a coordinated ATP hydrolysis mechanism.

Foot-and-mouth disease virus (FMDV), a positive sense, single-stranded RNA virus, causes a highly contagious disease in cloven-hoofed livestock. Like other picornaviruses, FMDV has a conserved 2C protein assigned to the superfamily 3 helicases a group of AAA+ ATPases that has a predicted N-terminal membrane-binding amphipathic helix attached to the main ATPase domain. In infected cells, 2C is involved in the formation of membrane vesicles, where it co-localizes with viral RNA replication complexes, but its precise role in virus replication has not been elucidated. We show here that deletion of the predicted N-terminal amphipathic helix enables overexpression in Escherichia coli of a highly soluble truncated protein, 2C(34–318), that has ATPase and RNA binding activity. ATPase activity was abrogated by point mutations in the Walker A (K116A) and B (D160A) motifs and Motif C (N207A) in the active site. Unliganded 2C(34–318) exhibits concentration-dependent self-association to yield oligomeric forms, the largest of which is tetrameric. Strikingly, in the presence of ATP and RNA, FMDV 2C(34–318) containing the N207A mutation, which binds but does not hydrolyze ATP, was found to oligomerize specifically into hexamers. Visualization of FMDV 2C-ATP-RNA complexes by negative stain electron microscopy revealed hexameric ring structures with 6-fold symmetry that are characteristic of AAA+ ATPases. ATPase assays performed by mixing purified active and inactive 2C(34–318) subunits revealed a coordinated mechanism of ATP hydrolysis. Our results provide new insights into the structure and mechanism of picornavirus 2C proteins that will facilitate new investigations of their roles in infection

Genetic Relationship between Cocirculating Human Enteroviruses Species C

Recombination events between human enteroviruses (HEV) are known to occur frequently and to participate in the evolution of these viruses. In a previous study, we reported the isolation of a panel of viruses belonging to the Human enterovirus species C (HEV-C) that had been cocirculating in a small geographic area of Madagascar in 2002. This panel included type 2 vaccine-derived polioviruses (PV) that had caused several cases of acute flaccid paralysis in humans. Previous partial sequencing of the genome of these HEV-C isolates revealed considerable genetic diversity, mostly due to recombination. In the work presented herein, we carried out a more detailed characterization of the genomes of viruses from this collection. First, we determined the full VP1 sequence of 41 of these isolates of different types. These sequences were compared with those of HEV-C isolates obtained from other countries or in other contexts. The sequences of the Madagascan isolates of a given type formed specific clusters clearly differentiated from those formed by other strains of the same type isolated elsewhere. Second, we sequenced the entire genome of 10 viruses representing most of the lineages present in this panel. All but one of the genomes appeared to be mosaic assemblies of different genomic fragments generated by intra- and intertypic recombination. The location of the breakpoints suggested potential preferred genomic regions for recombination. Our results also suggest that recombination between type HEV-99 and other HEV-C may be quite rare. This first exhaustive genomic analysis of a panel of non-PV HEV-C cocirculating in a small human population highlights the high frequency of inter and intra-typic genetic recombination, constituting a widespread mechanism of genetic plasticity and continually shifting the HEV-C biodiversity

Recombination between Polioviruses and Co-Circulating Coxsackie A Viruses: Role in the Emergence of Pathogenic Vaccine-Derived Polioviruses

Ten outbreaks of poliomyelitis caused by pathogenic circulating vaccine-derived polioviruses (cVDPVs) have recently been reported in different regions of the world. Two of these outbreaks occurred in Madagascar. Most cVDPVs were recombinants of mutated poliovaccine strains and other unidentified enteroviruses of species C. We previously reported that a type 2 cVDPV isolated during an outbreak in Madagascar was co-circulating with coxsackieviruses A17 (CA17) and that sequences in the 3′ half of the cVDPV and CA17 genomes were related. The goal of this study was to investigate whether these CA17 isolates can act as recombination partners of poliovirus and subsequently to evaluate the major effects of recombination events on the phenotype of the recombinants. We first cloned the infectious cDNA of a Madagascar CA17 isolate. We then generated recombinant constructs combining the genetic material of this CA17 isolate with that of the type 2 vaccine strain and that of the type 2 cVDPV. Our results showed that poliovirus/CA17 recombinants are viable. The recombinant in which the 3′ half of the vaccine strain genome had been replaced by that of the CA17 genome yielded larger plaques and was less temperature sensitive than its parental strains. The virus in which the 3′ portion of the cVDPV genome was replaced by the 3′ half of the CA17 genome was almost as neurovirulent as the cVDPV in transgenic mice expressing the poliovirus cellular receptor gene. The co-circulation in children and genetic recombination of viruses, differing in their pathogenicity for humans and in certain other biological properties such as receptor usage, can lead to the generation of pathogenic recombinants, thus constituting an interesting model of viral evolution and emergence

Unifying Prepositions and Prefixes in Russian: Conceptual structure versus syntax

This paper is an attempt to unify the polysemous verbal prefixes and prepositions in Russian. At first glance, the variety of possible denotations of a given prefix might appear a chaotic set of idiomatic meanings, e.g., the prefix za- may refer to beginning of an action, movement to a position behind an object, a brief deviation from a path, completion of an action, while the corresponding preposition za can mean ‘behind,’ ‘after,’ ‘for,’ ‘in’ (like in ‘in an hour’), ‘at’ (like in ‘at the table’). I will propose a unified analysis, where the differences in meaning are claimed to arise from different syntactic positions, while the lexical entry of a prefix remains the same. The main focus is on the verbs of motion due to the consistent duality displayed by the prefix meanings when added to directional and non-directional motion verbs. It will turn out that many prefixes appear to modify path when added onto a directional motion verb and to refer to movement in time with non-directional motion verbs. This semantic distinction corresponds to distinct sets of syntactic properties, specific for each set of prefixes. These two classes of prefixes correspond to the lexical versus superlexical distinction. However, a tripartite division will emerge in each set, corresponding to source, path, and goal of motion (FROM, VIA and TO) for lexical prefixes and to initiation, process and result for superlexical prefixes. This leads to the suggestion that the syntactic representation of a VP contains at least six distinct nodes for the Russian verbal prefixes, each characterized by predictable semantic and syntactic properties. The same prefix with a consistent meaning, shared with the corresponding preposition, will receive part of its denotation from the syntactic head it attaches to, thus allowing the polysemy to arise from position, rather than from arbitrary homophony. Thus, conceptual structure will be unified with syntax

Verbal Prefixes: Selection and Interpretation

The striking polysemy of Russian verbal prefixes is a well known phenomenon. I show that there is a system to this chaos: prefix meaning is predictable from verbal structure and the prefixation mechanism is similar to that seen in English examples like outdo and overdo. In my analysis, lexico-syntactic structure plays an important role in explaining the selection and interpretation of prefixes. I uncover a central meaning that remains constant across different uses of a prefix, and describe the formal structural criteria for prefix interpretation in a given context. A uniform analysis of prefixation is developed, where a prefix relates an event to a scale measuring path, change or time. Both change of state and the development of an activity in time mirror a path in space with beginning, duration and a goal. E.g. a heating event can be seen as a journey along the temperature scale from a colder state to a warmer one. The choice of scale that a prefix combines with is a function of the syntactic position of the prefix, determined by the verbal structure. This approach is also fruitful for English, where I show that the acceptability of prefixation correlates with a scalarity-based classification of verbs

Unifying prepositions and prefixes in Russian : conceptual structure versus syntax

At first glance, the variety of possible denotations of a given prefix might appear a chaotic set of idiomatic meanings, e.g. the prefix `za-´ may refer to the beginning of an action, movement to a position behind an object, a brief deviation from a path, or completion of an action. I propose a unified analysis of prefixes, where the differences in meaning are claimed to arise from different syntactic positions, while the lexical entry of a prefix remains the same. The main focus is on the verbs of motion due to the consistent duality displayed by the prefix meanings when added to directional and non-directional motion verbs. It turns out that prefixes modify path when added onto a directional motion verb and refer to movement in time with non-directional motion verbs. This semantic distinction corresponds to distinct sets of syntactic properties, characteristic of the lexical and superlexical prefixes. Furthermore, a tripartite division emerges in each set of prefixes, corresponding to source, path, and goal of motion (FROM, VIA and TO) for lexical prefixes and to beginning, duration and completion for superlexical prefixes. This leads to the suggestion that the same prefix with a consistent conceptual meaning, shared with the corresponding preposition, receives part of its denotation from its position in the syntactic representation. The separation of conceptual meaning from the structural meaning allows the polysemy to arise from position, rather than from arbitrary homophony. Thus, conceptual structure is unified with syntax

Verbal Prefixes in Russian: Conceptual structure versus syntax

At a first glance, the variety of possible denotations of a given prefix might appear a chaotic set of idiomatic meanings, e.g. the prefix za- may refer to the beginning of an action, movement to a position behind an object, a brief deviation from a path, or completion of an action. I propose a unified analysis of prefixes, where the differences in meaning are claimed to arise from different syntactic positions, while the lexical entry of a prefix remains the same. The main focus is on the verbs of motion due to the consistent duality displayed by the prefix meanings when added to directional and non-directional motion verbs. It turns out that prefixes modify path when added onto a directional motion verb and refer to movement in time with non-directional motion verbs. This semantic distinction corresponds to distinct sets of syntactic properties, characteristic of the lexical and superlexical prefixes. Furthermore, a tripartite division emerges in each set of prefixes, corresponding to source, path, and goal of motion (TO, FROM, VIA) for lexical prefixes and to beginning, completion and duration for superlexical prefixes. This leads to the suggestion that the same prefix with a consistent conceptual meaning, shared with the corresponding preposition, receives part of its denotation from its position in the syntactic representation. The separation of conceptual meaning from the structural meaning allows the polysemy to arise from position, rather than from arbitrary homophony. Thus, conceptual structure is unified with syntax

Oroch vowel harmony

In this paper I examine vowel harmony in Oroch, a recently extinct Manchu-Tungusic language. Oroch vowels are subject to the interplay of retracted tongue root (RTR) harmony and rounding harmony. The two kinds of harmony have contrasting effects on neutral vowels. The front vowels /i/ and / æ/ are transparent to RTR harmony, while the vowels /i/, /æ/, /ʊ/ and /u/ are opaque to rounding harmony. Crucially, if the root contains only neutral vowels /i/ and /æ/, the RTR feature of the suffix is unpredictable. There are several works on Manchu-Tungusic Vowel Harmony, though none of them deal directly with Oroch. Kaun (1995) offers an analysis of languages with similar rounding harmonies in terms of phonetically grounded Optimality Theory (OT). Li (1996) offers a combination of feature architecture and OT, while Zhang (1996) uses contrastive feature specification. However, none of these analyses have an explanation for the distribution of RTR features on suffixes attached to neutral roots. This paper puts forth a Stratal OT analysis of Oroch vowel harmony, along the lines of Kiparsky (2000). The neutral vowels are assumed to be subject to RTR harmony at the stem level, where the most harmonic candidate wins, but at the word level there is a constraint against [i] bearing [+RTR] feature and against [æ] bearing [−RTR] feature; thus on the surface the effect of RTR harmony is undone on transparent vowels. Thus, the transparency of the neutral vowels is predicted, as well as the distribution of suffixes with neutral roots, the underlying RTR specification of which spreads onto suffixes at the stem level. This is supported by the fact that in related languages, where both [+RTR] and [−RTR] versions of the front vowels exist, the RTR features of the root coincide with the features of the Oroch suffixes. In addition, the Stratal OT approach allows avoiding unmotivated contrast in the ranking of *GAP constraint for RTR and rounding harmony, required by other analyses to derive the transparency vs. opacity effects of these two harmonies. On the contrary, my Stratal analysis obeys strict locality, i.e. preading is restricted to adjacent segments. Thus, the problems encountered by previous approaches do not arise under the Stratal approach, which allows a more economic account of the Oroch vowel harmony in terms of a small set of necessary and phonetically grounded constraints, with a coherent ranking predicting the transparency with respect to RTR harmony, opacity with respect to rounding harmony, and suffix harmony triggered by the neutral roots