Abstract
Understanding the complex development the genitourinary system will improve diagnosis and treatment of a vast array of conditions, including congenital defects. The authors of this report have undertaken the monumental task of cataloguing the spectrum of gene expression in the genitourinary tract of mice throughout development and maturation. This effort has led to the creation of the Genitourinary Development Molecular Anatomy Project (GUDMAP), and their data is publicly available at http://www.gudmap.org. This atlas of temporal and spatial gene expression is designed as a comprehensive reference for studies of cell lineage, cell fate and disease processes. Gene expression data is derived from a variety of modalities, including microarrays, RNA in situ hybridization and immunohistochemistry. Anatomic and histologic images are well-annotated and intimately linked to the gene expression information. These tools will be a valuable resource to anyone interested in genitourinary development and pathology.
Little MH, Brennan J, Georgas K, et al. A high-resolution anatomical ontology of the developing murine genitourinary tract. Gene Expression Patterns
In placental mammals, T cell receptors (TCRs) are formed by somatic recombination of the variable (V), diversity (D), and joining (J) segments. The VDJ rearrangements allow TCRs to possess remarkably diverse binding specificities. The four TCR chains α, β, γ, and δ, are expressed as αβ or γδ heterodimers. Parra and colleagues have discovered an additional novel TCR in marsupials, which they have named TCRμ. TCRμ exists in one of two forms – it can have somatic VDJ recombination as seen in placental mammals, or it can be prejoined in the germline DNA. There is no known homolog to TCRμ in eutherian mammals, but it does share some features with the recently described shark TCRδ isoform. Further investigation of the role of the marsupial TCRμ and its possible relationship to TCRs in sharks may uncover similar new TCRs in other vertebrates.
Parra ZE, Baker ML, Schwarz RS. A unique T cell receptor discovered in marsupials. Proceedings of the National Academy of Sciences
Cell membranes are composed of a lipid bilayer that forms a physical barrier between the cytoplasm and the extracellular environment. Exchange of molecules between the intra- and extracellular compartments occur via structural changes in the membrane that facilitate fusion or the formation of pores (channels). Enveloped viruses gain entry into the cell using membrane-anchored glycoproteins; however, the mechanism of entry for non-enveloped viruses is not well understood. The authors of this report investigated how Infectious Bursal Disease Virus (IBDV) is able to disrupt cell membranes to secure its entry into the cell. IBDV, a double-stranded RNA avian birnavirus, uses one of its four structural peptides, pep46, to deform cell membranes and induce pore formation, resulting in pores with a diameter less than 10 nm. The amphiphilic and proline isomerization properties of pep46 were shown to be essential to the viral life cycle. Furthermore, the activity of pep46 is controlled in part by differential calcium concentrations, which appear to contribute to endocytosis (higher concentration) and endosome permeabilization (lower concentration). The authors suggest that this mechanism may also apply to single-stranded RNA viruses and may be helpful in future studies of anti-viral strategies.
Galloux M, Libersou S, Morellet N. Infectious bursal disease virus, a non-enveloped virus, possesses a capsid-associated peptide that deforms and perforates biological membranes. Journal of Biological Chemistry
Angiotensin-convertin enzyme (ACE) is a peptidase best known for the cleavage of angiotensin I, but it also cleaves a variety of other substrates including substance P, AcSDKP, β-endorphins and other peptides, causing effects on diverse physiological processes. Here, investigators put ACE under the control of the macrophage-specific c-fms promoter in mice (ACE 10/10/mice). This resulted in mice with high levels of ACE in macrophages, but they lacked expression in normal tissues such as blood vessels and kidneys. The ACE 10/10 mice were resistant to the formation of melanomas when challenged with the aggressive B16 mouse melanoma cell line. They had increased numbers of tumor epitope-specific CD8+ T cells, and their macrophages produced increased interleukin-12 and nitric oxide. When wild-type mice were engrafted with ACE 10/10 bone marrow, the recipients were also resistant to development of B16 melanomas. This work may lead to other strategies to enhance the immune response in the setting of melanomas.
Shen XZ, LiP, Weiss D. Mice with enhanced macrophage angiotensin-converting enzyme are resistant to melanoma. American Journal of Pathology