In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

Ex Input:
Bacille Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis currently used as a vaccine against tuberculosis. Global distribution and propagation of BCG has contributed to the in vitro evolution of the vaccine strain and is thought to partially account for the different outcomes of BCG vaccine trials. Previous efforts by several molecular techniques effectively identified large sequence polymorphisms among BCG daughter strains, but lacked the resolution to identify smaller changes. In this study, we have used a NimbleGen tiling array for whole genome comparison of 13 BCG strains. Using this approach, in tandem with DNA resequencing, we have identified six novel large sequence polymorphisms including four deletions and two duplications in specific BCG strains. Moreover, we have uncovered various polymorphisms in the phoP-phoR locus. Importantly, these polymorphisms affect genes encoding established virulence factors including cell wall complex lipids, ESX secretion systems, and the PhoP-PhoR two-component system. Our study demonstrates that major virulence factors are different among BCG strains, which provide molecular mechanisms for important vaccine phenotypes including adverse effect profile, tuberculin reactivity and protective efficacy. These findings have important implications for the development of a new generation of vaccines.

Ex Output:
BMC Genomics Novel genome polymorphisms in BCG vaccine strains and impact on efficacy


Ex Input:
We determined the interferon-␥ (IFN-␥) cDNA sequence from three porcine breeds, Duroc, Landrance/Duroc hybrid, and Landrance breeds. Five single nucleotide polymorphisms (SNPs) of porcine IFN-␥ (PoIFN-␥) were identified, respectively, at positions 269 (A/G), 376 (C/T), 426 (T/C), and 465 (T/C) of the coding sequence in Landrance/Duroc hybrid, and at position 251 (A/G) in Landrance breed. Among them, A269G and A251G polymorphisms resulted in Q67R and K61R replacements in the mature protein. PoIFN-␥ cDNAs of Duroc breed (PoIFN-␥-W) and Landrance/Duroc hybrid (PoIFN-␥-M), which, respectively, encoded Q67 and R67, were introduced into a prokaryotic expression vector pET32 to express recombinant PoIFN-␥-W (rPoIFN-␥-W) and rPoIFN-␥-M protein variants in Escherichia coli. The identity of both protein variants was further confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). We then compared bioactivities of these two recombinant proteins. Although both recombinant protein variants exhibited comparable activities in antiproliferation of PK-15 cells and in nitric oxide (NO) induction of porcine peripheral monocytes, antiviral activity of rPoIFN-␥-W protein was significantly higher (P < 0.001) than that of rPoIFN-␥-M protein in a plaque inhibition assay using pseudorabies virus (PRV). IC50 values of rPoIFN-␥-W and rPoIFN-␥-M protein in anti-PRV assay were determined as 5.3 ± 1.3 and 9.3 ± 4.3 nM, respectively. In conclusion, we have identified five novel SNPs in PoIFN-␥ cDNA, including two missense polymorphisms that result in Q67R and K61R replacements. Our results further demonstrate that Q67R can markedly reduce antiviral activity of the PoIFN-␥ protein. This is the first report that shows the functional SNP in the coding region of IFN-␥. In the future, it is imperative to determine whether Q67R replacement in IFN-␥ may have disease association.

Ex Output:
A missense polymorphism in porcine interferon-␥ cDNA affects antiviral activity of the protein variant


Ex Input:
Many viruses cause disease within an infected host after spread from an initial portal of entry to secondary sites of replication. Viruses can disseminate via the bloodstream or through nerves. Mammalian orthoreoviruses (reoviruses) are neurotropic viruses that use both bloodborne and neural pathways to spread systemically within their hosts to cause disease. Using a robust mouse model and a dynamic reverse genetics system, we have identified a viral receptor and a viral nonstructural protein that are essential for hematogenous reovirus dissemination. Junctional adhesion molecule-A (JAM-A) is a member of the immunoglobulin superfamily expressed in tight junctions and on hematopoietic cells that serves as a receptor for all reovirus serotypes. Expression of JAM-A is required for infection of endothelial cells and development of viremia in mice, suggesting that release of virus into the bloodstream from infected endothelial cells requires JAM-A. Nonstructural protein σ1s is implicated in cell cycle arrest and apoptosis in reovirus-infected cells but is completely dispensable for reovirus replication in cultured cells. Surprisingly, a recombinant σ1s-null reovirus strain fails to spread hematogenously in infected mice, suggesting that σ1s facilitates apoptosis of reovirus-infected intestinal epithelial cells. It is possible that apoptotic bodies formed as a consequence of σ1s expression lead to reovirus uptake by dendritic cells for subsequent delivery to the mesenteric lymph node and the blood. Thus, both host and viral factors are required for efficient hematogenous dissemination of reovirus. Understanding mechanisms of reovirus bloodborne spread may shed light on how microbial pathogens invade the bloodstream to disseminate and cause disease in infected hosts.

Ex Output:

Mechanisms of Reovirus Bloodstream Dissemination