RNA polymerase (RNAP) is the essential enzyme responsible for transcribing the genetic information stored in DNA to RNA. Understanding the structure and function of RNAP is important for those who study basic principles in gene expression, such as the mechanisms of transcription and its regulation, as well as translational sciences such as antibiotic development. With over a half-century of investigations, there is a wealth of information available on the structure and function of Escherichia coli RNAP. This review introduces the structural features of E. coli RNAP, organized by subunit, giving information on the function, location, and conservation of these features to early stage investigators who have just started their research of E. coli RNAP.
Therapeutic studies with cross‐transplant cross‐transfusion were begun in 1966 and have included 56 patients with melanoma, 2 with renal cell carcinoma, 3 with osteogenic sarcoma, 2 with colon cancer, and 1 with synovial sarcoma. Minced fragments of viable tumor were implanted subcutaneously into ABO‐Rh matched pairs with similar tumor on days 1 and 10, followed on the 14th day by 3–10 daily cross‐transfusions of plasma and white blood cells. Subsequently, intradermal implants of viable tumor cells grown in tissue culture have been used, some with added BCG. Complete responses have occurred in 3 patients with melanoma lasting 12, 46, and 51 months; the latter 2 remain alive and well. Partial response occurred in 6 others. Three melanoma patients with a poor prognosis were immunized prophylactically following primary surgical treatment. These 3 developed antibodies (shown by flourescence) against their tumor and remained free of disease—1 for 2 years and 2 for 1 year. Complications have mainly resulted from transfusion incompatibility. Transfer factor is now being used to avoid this problem. Two patients died following the seventh transfusion from complications probably related to treatment.
CD4+ αβ T-cells are key mediators of the immune response to a first Plasmodium infection, undergoing extensive activation and splenic expansion during the acute phase of an infection. However, the clonality and clonal composition of this expansion has not previously been described. Using a comparative infection model, we sequenced the splenic CD4+ T-cell receptor repertoires generated over the time-course of a Plasmodium chabaudi infection. We show through repeat replicate experiments, single-cell RNA-seq, and analyses of independent RNA-seq data, that following a first infection - within a highly polyclonal expansion - T-effector repertoires are consistently dominated by TRBV3 gene usage. Clustering by sequence similarity, we find the same dominant clonal signature is expanded across replicates in the acute phase of an infection, revealing a conserved pathogen-specific T-cell response that is consistently a hallmark of a first infection, but not expanded upon re-challenge. Determining the host or parasite factors driving this conserved response may uncover novel immune targets for malaria therapeutic purposes.
B cells are key pathogenic drivers of chronic inflammation in rheumatoid arthritis (RA). There is limited understanding of the relationship between synovial B cell subsets and pathogenic antibody secreting cells (ASCs). This knowledge is crucial for the development of more targeted B-cell depleting therapies. While CD11c+ double-negative 2 (DN2) B cells have been suggested as an ASC precursor in lupus, to date there is no proven link between the two subsets in RA. We have used both single-cell gene expression and BCR sequencing to study synovial B cells from patients with established RA, in addition to flow cytometry of circulating B cells. To better understand the differentiation patterns within the diseased tissue, a combination of RNA-based trajectory inference and clonal lineage analysis of BCR relationships were used. Both forms of analysis indicated that DN2 B cells serve as a major precursors to synovial ASCs. This study advances our understanding of B cells in RA and reveals the origin of pathogenic ASCs in the RA synovium. Given the significant role of DN2 B cells as a progenitor to pathogenic B cells in RA, it is important to conduct additional research to investigate the origins of DN2 B cells in RA and explore their potential as therapeutic targets in place of the less specific pan-B cells depletion therapies currently in use.
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