CSF1R+ Macrophages Sustain Pancreatic Tumor Growth through T Cell Suppression and Maintenance of Key Gene Programs that Define the Squamous Subtype.

Pancreatic ductal adenocarcinoma (PDAC) is resistant to most therapies including single-agent immunotherapy and has a dense desmoplastic stroma, and most patients present with advanced metastatic disease. We reveal that macrophages are the dominant leukocyte population both in human PDAC stroma and autochthonous models, with an important functional contribution to the squamous subtype of human PDAC. We targeted macrophages in a genetic PDAC model using AZD7507, a potent selective inhibitor of CSF1R. AZD7507 caused shrinkage of established tumors and increased mouse survival in this difficult-to-treat model. Malignant cell proliferation diminished, with increased cell death and an enhanced T cell immune response. Loss of macrophages rewired other features of the TME, with global changes in gene expression akin to switching PDAC subtypes. These changes were markedly different to those elicited when neutrophils were targeted via CXCR2. These results suggest targeting the myeloid cell axis may be particularly efficacious in PDAC, especially with CSF1R inhibitors

An oribatid mite (Arachnida: Acari) from the Oxford Clay (Jurassic: Upper Callovian) of South Cave Station Quarry, Yorkshire, UK

A single specimen of a new species of oribatid mite belonging to the genus Jureremus Krivolutsky, in Krivolutsky and Krassilov 1977, previously described from the Upper Jurassic of the Russian Far East, is described as J. phippsi sp. nov. The mite is preserved by iron pyrite replacement, and was recovered by sieving from the Oxford Clay Formation (Jurassic: Upper Callovian) of South Cave, Yorkshire. It is the first record of a pre-Pleistocene mite, and the second species record of the family Cymbaeremaeidae, from the British Isles; also, it is only the third record of Acari from the Jurassic Period. The presence of a terrestrial mite in a sedimentary sequence of open marine origin is noteworthy, and suggestions for its mode of transport to the site of deposition are discussed

Tmetoceratidae (Ammonitina) fauna from the Gerecse Mts (Hungary)

Abstract Taxonomic and stratigraphic problems of the family Tmetoceratidae and the genera Dumortieria, Catulloceras, Cotteswoldia, Pleydellia and Tmetoceras included in it are briefly discussed. Fifteen species of Tmetoceratidae are described and illustrated from the Upper Toarcian-Aalenian ammonite assemblages of the Gerecse Mts (NE Transdanubian Range, Hungary). The fauna described here is closely allied to the Mediterranean Province of the Mediterranean-Caucasian Realm

Negative Regulation of Endogenous Stem Cells in Sensory Neuroepithelia: Implications for Neurotherapeutics

Stem cell therapies to treat central nervous system (CNS) injuries and diseases face many obstacles, one of which is the fact that the adult CNS often presents an environment hostile to the development and differentiation of neural stem and progenitor cells. Close examination of two regions of the nervous system – the olfactory epithelium (OE), which regenerates, and the neural retina, which does not – have helped identify endogenous signals, made by differentiated neurons, which act to inhibit neurogenesis by stem/progenitor cells within these tissues. In this chapter, we provide background information on these systems and their neurogenic signaling systems, with the goal of providing insight into how manipulation of endogenous signaling molecules may enhance the efficacy of stem cell neurotherapeutics

Designation of a type genus for the nominal order "Ammonoidea" Zittel, 1884, and proposed addition of that name to the "Official list of names in the Order/Class group in Zoology."

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