Absence Of B2 Research Articles

Breast magnetic resonance imaging for estimation of the tumour extent in patients with pure ductal carcinoma in situ: Comparison between full diagnostic and abbreviated protocols

PurposeTo evaluate the rate of concordance between pathology and preoperative breast MRI performed with an abbreviated protocol (AP) or a full diagnostic protocol (FDP) for estimation of the tumour extent in patients with pure ductal carcinoma in situ (DCIS). MethodsThis retrospective study included 164 patients with pathologically proven DCIS who underwent preoperative breast MRI. Two radiologists independently evaluated the tumour extent on MRI with (FDP) and without the delayed phase (AP) and compared the readings with the pathological tumour extent. The background parenchymal enhancement (BPE) and morphology were also evaluated. Furthermore, the influence of the degree of BPE, presence or absence of B2 and B3 lesions, and pathological DCIS grade on the accuracy of MRI findings was assessed. Concordance between MRI and pathology was evaluated using correlation analysis. ResultsSpearman’s rank correlation coefficients for the concordance between MRI and pathology were 0.63 (reader 1) and 0.69 (reader 2) with AP and 0.65 and 0.73 (readers 1 and 2, respectively) with FDP. For both readers, the difference in the measured value between FDP and pathology was significantly smaller than that between AP and pathology (p < 0.001). The inter-reader variation in the measured tumour extent was larger with FDP than with AP. The presence of B3 lesions, low-grade DCIS, and moderate/marked BPE lowered the rate of concordance between MRI and pathology. ConclusionsOur findings suggest that preoperative MRI with FDP is more accurate than that with AP alone for estimation of the tumour extent in patients with pure DCIS.

First analysis of ancient mtDNA genetic diversity in Northern coast of Argentinean Patagonia

In the past decades, archaeological research advances in different Patagonian sectors have contributed to the knowledge of lifestyle and evolution of pre-Columbian populations in these regions. The San Matías Gulf archaeological record (Río Negro province, Northern Patagonia, Argentina) shows that humans occupied the area from Middle Holocene to contact period, where palaeodietary and technological changes are evident from around 1700 14C BP. Nevertheless, few studies have been done on biological origin and evolution of these populations. For this reason and in order to investigate mitochondrial genetic variability in comparison with other ancient and contemporary Patagonian populations, we analyzed ancient DNA on human skeletal remains belonging to different chronologies of this area. We found a prevalence of founding lineages C1, D1 (D1g and D1j subclades) and D4h3a, low frequency of A2 and absence of B2. This supports the hypothesis of genetic drift acting on populations of the Southern Cone of South America. Individuals analyzed present similar haplotypes, indicating a possible temporal and regional continuity or a common population origin. Those lineages are also present in Tehuelche and Mapuche contemporary populations. However, B2 is highly represented in these extant groups possibly as a consequence of recent migrations related with Araucanization process.

RNA Distribution During Flock House Virus Infection

The mechanisms involved in the specific packaging of multipartite genomes by (+) RNA viruses remain poorly understood. In order to gain insight into the location of genomic RNA encapsidation, we employed fluorescence in situ hybridization (FISH) to visualize the sub‐cellular distribution of (+) vRNA in cells infected with the model nodavirus, Flock House virus (FHV). During FHV assembly, genomic RNAs 1 and 2 are encapsidated into a T = 3 icosahedral capsid. Previously it has been shown that while vRNA replication and CP synthesis are initially targeted to different cellular locations (mitochondria and ER, respectively), these regions converge into perinuclear clusters late in infection. Our analysis of the cellular distribution of FHV RNA during infection, however, suggests that the vast majority of (+) RNA is trafficked towards the periphery of the cell relatively early during the infectious cycle (within 3 hours post infection) and does not relocate to the perinuclear region during mitochondrial condensation (15 hours post infection). In addition, the (+) RNA fits well within the region occupied by CP at the time points we tested. Our findings show that RNA transport precedes genome packaging and virus assembly. This suggests that genomic RNA is likely released from vRNA replication sites fairly soon after synthesis and trafficked to peripheral sites prior to encapsidation. Our analysis in mammalian cells also revealed that in the absence of B2, a small virus‐encoded protein known to bind dsRNAs, RNA2 is stalled in cytoplasmic aggregates while RNA1 trafficking is largely unaffected.

Cytoplasmic Granule Formation and Translational Inhibition of Nodaviral RNAs in the Absence of the Double-Stranded RNA Binding Protein B2

Flock House virus (FHV) is a positive-sense RNA insect virus with a bipartite genome. RNA1 encodes the RNA-dependent RNA polymerase, and RNA2 encodes the capsid protein. A third protein, B2, is translated from a subgenomic RNA3 derived from the 3' end of RNA1. B2 is a double-stranded RNA (dsRNA) binding protein that inhibits RNA silencing, a major antiviral defense pathway in insects. FHV is conveniently propagated in Drosophila melanogaster cells but can also be grown in mammalian cells. It was previously reported that B2 is dispensable for FHV RNA replication in BHK21 cells; therefore, we chose this cell line to generate a viral mutant that lacked the ability to produce B2. Consistent with published results, we found that RNA replication was indeed vigorous but the yield of progeny virus was negligible. Closer inspection revealed that infected cells contained very small amounts of coat protein despite an abundance of RNA2. B2 mutants that had reduced affinity for dsRNA produced analogous results, suggesting that the dsRNA binding capacity of B2 somehow played a role in coat protein synthesis. Using fluorescence in situ hybridization of FHV RNAs, we discovered that RNA2 is recruited into large cytoplasmic granules in the absence of B2, whereas the distribution of RNA1 remains largely unaffected. We conclude that B2, by binding to double-stranded regions in progeny RNA2, prevents recruitment of RNA2 into cellular structures, where it is translationally silenced. This represents a novel function of B2 that further contributes to successful completion of the nodaviral life cycle.

B cell clones that sustain long-term plasmablast growth in T-independent extrafollicular antibody responses

Some antigens induce Ab responses without T lymphocyte help. Among these, many polysaccharide-based antigens cause marginal zone B cells to proliferate and differentiate into plasma cells. B1 cells also respond to some of these antigens. In this article, we report that antigen-specific B1b cells, in response to the T-independent antigen (4-hydroxy-3-nitrophenyl)-acetyl (NP)-Ficoll, develop into clones that sustain Ab production for months with continued production of plasma cells and the accumulation of antigen-specific B cells in follicles. The persistence of this T-independent plasmablast response contrasts with the short-term plasmablast growth associated with T-dependent extrafollicular responses. The nature of the cells responding to NP-Ficoll was probed by using chimeras that have B1 cells but lack primary B lymphopoietic capacity and have very few B2 cells or T cells. The chimeras were constructed by transferring 10(5) IgM(+) IgD(-) peritoneal exudate cells into mice unable to produce their own T and B cells because of deficiency in recombinase-activating gene 1 (RAG-1). The chimeras mounted sustained IgM and IgG3 anti-NP Ab responses to NP-Ficoll. This finding was associated with continued NP-specific extrafollicular plasmablast growth and the accumulation of NP-specific B cells in follicles. B cells were not found in the marginal zones of chimeras, and they also lacked recirculating IgD(+) cells and CD3(+) cells. The absence of B2 and T cells confirms that hemopoietic cell chimerism leading to primary lymphopoiesis had not been established.