A Recombinant Avian Infectious Bronchitis Virus Expressing a Heterologous Spike Gene Belonging to the 4/91 Serotype

We have shown previously that replacement of the spike (S) gene of the apathogenic IBV strain Beau-R with that from the pathogenic strain of the same serotype, M41, resulted in an apathogenic virus, BeauR-M41(S), that conferred protection against challenge with M41 [1]. We have constructed a recombinant IBV, BeauR-4/91(S), with the genetic backbone of Beau-R but expressing the spike protein of the pathogenic IBV strain 4/91(UK), which belongs to a different serogroup as Beaudette or M41. Similar to our previous findings with BeauR-M41(S), clinical signs observations showed that the S gene of the pathogenic 4/91 virus did not confer pathogenicity to the rIBV BeauR-4/91(S). Furthermore, protection studies showed there was homologous protection; BeauR-4/91(S) conferred protection against challenge with wild type 4/91 virus as shown by the absence of clinical signs, IBV RNA assessed by qRT-PCR and the fact that no virus was isolated from tracheas removed from birds primarily infected with BeauR-4/91(S) and challenged with IBV 4/91(UK). A degree of heterologous protection against M41 challenge was observed, albeit at a lower level

The Replicase Gene of Avian Coronavirus Infectious Bronchitis Virus Is a Determinant of Pathogenicity

We have previously demonstrated that the replacement of the S gene from an avirulent strain (Beaudette) of infectious bronchitis virus (IBV) with an S gene from a virulent strain (M41) resulted in a recombinant virus (BeauR-M41(S)) with the in vitro cell tropism of the virulent virus but that was still avirulent. In order to investigate whether any of the other structural or accessory genes played a role in pathogenicity we have now replaced these from the Beaudette strain with those from M41. The recombinant IBV was in effect a chimaeric virus with the replicase gene derived from Beaudette and the rest of the genome from M41. This demonstrated that it is possible to exchange a large region of the IBV genome, approximately 8.4 kb, using our transient dominant selection method. Recovery of a viable recombinant IBV also demonstrated that it is possible to interchange a complete replicase gene as we had in effect replaced the M41 replicase gene with the Beaudette derived gene. Analysis of the chimaeric virus showed that it was avirulent indicating that none of the structural or accessory genes derived from a virulent isolate of IBV were able to restore virulence and that therefore, the loss of virulence associated with the Beaudette strain resides in the replicase gene

Independent large scale duplications in multiple M. tuberculosis lineages overlapping the same genomic region

Mycobacterium tuberculosis, the causative agent of most human tuberculosis, infects one third of the world's population and kills an estimated 1.7 million people a year. With the world-wide emergence of drug resistance, and the finding of more functional genetic diversity than previously expected, there is a renewed interest in understanding the forces driving genome evolution of this important pathogen. Genetic diversity in M. tuberculosis is dominated by single nucleotide polymorphisms and small scale gene deletion, with little or no evidence for large scale genome rearrangements seen in other bacteria. Recently, a single report described a large scale genome duplication that was suggested to be specific to the Beijing lineage. We report here multiple independent large-scale duplications of the same genomic region of M. tuberculosis detected through whole-genome sequencing. The duplications occur in strains belonging to both M. tuberculosis lineage 2 and 4, and are thus not limited to Beijing strains. The duplications occur in both drug-resistant and drug susceptible strains. The duplicated regions also have substantially different boundaries in different strains, indicating different originating duplication events. We further identify a smaller segmental duplication of a different genomic region of a lab strain of H37Rv. The presence of multiple independent duplications of the same genomic region suggests either instability in this region, a selective advantage conferred by the duplication, or both. The identified duplications suggest that large-scale gene duplication may be more common in M. tuberculosis than previously considere

Two-particle decays of B_c meson into charmonium states

The factorization of hard and soft contributions into the hadronic decays of B_c meson at large recoils is explored in order to evaluate the decay rates into the S, P and D-wave charmonia associated with rho and pi. The constraints of approach applicability and uncertainties of numerical estimates are discussed. The mode with the J/psi in the final state is evaluated taking into account the cascade radiative electromagnetic decays of excited P-wave states, that enlarges the branching ratio by 20-25%.Comment: 13 pages, LaTeX axodraw-style, 1 figure, 2 table

Positions in the N‐methyl‐D‐aspartate Receptor GluN2C Subunit M3 and M4 Domains Regulate Alcohol Sensitivity and Receptor Kinetics

Background Alcohol alters synaptic transmission in the brain. The N‐methyl‐D‐aspartate (NMDA) receptor (NMDAR), a subtype of glutamate‐gated ion channel, is an important synaptic target of alcohol in the brain. We and others have previously identified 4 alcohol‐sensitive positions in the third and fourth membrane‐associated (M) domains, designated M31‐2and M41‐2, of the GluN1, GluN2A, and GluN2B NMDAR subunits. In the present study, we tested whether the corresponding positions in the GluN2C subunit also regulate alcohol sensitivity and ion channel gating. Methods We performed alanine‐ and tryptophan‐scanning mutagenesis in the GluN2C subunit followed by expression in HEK 293 cells and electrophysiological patch‐clamp recording. Results Alanine substitution at the M31 (F634) and M41‐2 (M821 and M823) positions did not alter ethanol (EtOH) sensitivity, whereas substitution of alanine at the M32 position (F635) yielded nonfunctional receptors. Tryptophan substitution at the M31‐2 positions did not change EtOH sensitivity, whereas tryptophan substitution at the M41 position increased, and at the M42 position decreased, EtOH sensitivity. The increased EtOH sensitivity of the tryptophan mutant at M41 is in marked contrast to previous results observed in the GluN2A and GluN2B subunits. In addition, this mutant exhibited increased desensitization, but to a much lesser extent compared to the corresponding mutations in GluN2A and GluN2B. A series of mutations at M41 altered EtOH sensitivity, glutamate potency, and desensitization. Seven amino acid substitutions (of 15 tested) at this position yielded nonfunctional receptors. Among the remaining mutants at M41, EtOH sensitivity was not significantly correlated with hydrophobicity, molecular volume, or polarity of the substituent, or with glutamate EC50 values, but was correlated with maximal steady‐state‐to‐peak current ratio, a measure of desensitization. Conclusions The identity and characteristics of alcohol‐sensitive positions in the GluN2C subunit differ from those previously reported for GluN2A and GluN2B subunits, despite the high homology among these subunits

Prepotentials of N=2 SU(2) Yang-Mills theories coupled with massive matter multiplets

We discuss N=2 SU(2) Yang-Mills gauge theories coupled with N_f (=2,3) massive hypermultiplets in the weak coupling limit. We determine the exact massive prepotentials and the monodromy matrices around the weak coupling limit. We also study that the double scaling limit of these massive theories and find that the massive N_f -1 theory can be obtained from the massive N_f theory. New formulae for the massive prepotentials and the monodromy matrices are proposed. In these formulae, N_f dependences are clarified.Comment: A version is published in J. Math. Phys. 38 (1997) 68

Monomial, Gorenstein and Bass Orders

In this article we study a class of orders called {\it monomial orders} in a central simple algebra over a non-Archimedean local field. Monomial orders are easily represented and they may be also viewed as a direct generalization of Eichler orders in quaternion algebras. A criterion for monomial orders to be Gorenstein or to be Bass is given. It is shown that a monomial order is Bass if and only if it is either a hereditary or an Eichler order of period two.Comment: 13 pages; fix typos in the proof of Theorem 3.