New palynology-based astronomical and revised 40Ar/39Ar ages for the Eocene maar lake of Messel (Germany)

The annually laminated oil shale from the Eocene maar lake at Messel (Federal State of Hessen, Germany) provides unique paleoenvironmental data for a time interval of ~640 ka during the Paleogene greenhouse phase. As a consequence of orbitally controlled changes in the vegetation in the vicinity of the lake, the lacustrine laminites can now be astronomically tuned. Dating is based on the short eccentricity amplitude modulations of the regional pollen rain and their correlation to the astronomical La2010a/La2010d solutions in combination with a revised 40Ar/39Ar age of a basalt fragment from a lapilli tuff section below the first lacustrine sediments. Depending on different newly suggested ages for the Fish Canyon sanidine used as monitor for neutron irradiation, the age for the eruption at Messel is between 48.27 ± 0.22 and 48.11 ± 0.22 Ma. This allows for the first time the exact correlation of a Paleogene lacustrine sequence to the marine record in Central Europe. The Messel oil shale becomes now slightly older than previously assumed and includes the Ypresian/Lutetian boundary that moves the base of the European Land Mammal Age Geiseltalian (MP 11) into the Lower Eocene. This opens a window for establishing an independent chronostratigraphic framework for Paleogene terrestrial records and their correlation to the marine realm. Furthermore, the study reveals that higher amounts of pollen from “wet” and thermophilous plants indicate less seasonal and more balanced precipitation and slightly higher temperatures during a well-expressed eccentricity minimum

Harnessing the immune system in glioblastoma.

Glioblastoma is the most common primary malignant brain tumour. Survival is poor and improved treatment options are urgently needed. Although immunotherapies have emerged as effective treatments for a number of cancers, translation of these through to brain tumours is a distinct challenge, particularly due to the blood-brain barrier and the unique immune tumour microenvironment afforded by CNS-specific cells. This review discusses the immune system within the CNS, mechanisms of immune escape employed by glioblastoma, and the immunological effects of conventional glioblastoma treatments. Novel therapies for glioblastoma that harness the immune system and their current clinical progress are outlined, including cancer vaccines, T-cell therapies and immune checkpoint modulators.N.B. is funded by Cancer Research UK. T.C. is funded by the University College London Hospitals Charity. P.M. is supported by the University College Hospital/University College London Biomedical Research Centre and the National Brain Appeal

Multiple Dynamics in Tumor Microenvironment Under Radiotherapy.

The tumor microenvironment (TME) is an evolutionally low-level and embryonically featured tissue comprising heterogenic populations of malignant and stromal cells as well as noncellular components. Under radiotherapy (RT), the major modality for the treatment of malignant diseases [1], TME shows an adaptive response in multiple aspects that affect the efficacy of RT. With the potential clinical benefits, interests in RT combined with immunotherapy (IT) are intensified with a large scale of clinical trials underway for an array of cancer types. A better understanding of the multiple molecular aspects, especially the cross talks of RT-mediated energy reprogramming and immunoregulation in the irradiated TME (ITME), will be necessary for further enhancing the benefit of RT-IT modality. Coming studies should further reveal more mechanistic insights of radiation-induced instant or permanent consequence in tumor and stromal cells. Results from these studies will help to identify critical molecular pathways including cancer stem cell repopulation, metabolic rewiring, and specific communication between radioresistant cancer cells and the infiltrated immune active lymphocytes. In this chapter, we will focus on the following aspects: radiation-repopulated cancer stem cells (CSCs), hypoxia and re-oxygenation, reprogramming metabolism, and radiation-induced immune regulation, in which we summarize the current literature to illustrate an integrated image of the ITME. We hope that the contents in this chapter will be informative for physicians and translational researchers in cancer radiotherapy or immunotherapy