Angiopoietins Modulate Survival, Migration, and the Components of the Ang-Tie2 Pathway of Chronic Lymphocytic Leukaemia (CLL) Cells In Vitro

In actuality, chronic lymphocytic leukaemia (CLL) remains an incurable haematopoietic malignancy of high prevalence amongst elderly populations in the West. Malignant CLL cells characteristically accumulate in the peripheral blood, bone marrow, lymph nodes, and spleen of CLL patients. There is evidence that CLL cells express Ang2 and Tie1, two central components of the Ang-Tie2 pro-angiogenic pathway. Central to blood vessel development and maintenance, at present it remains unclear how the Ang-Tie2 pathway modulates CLL pathophysiology. Here we evaluate the status of the Ang-Tie2 pathway in CLL cells and assess Ang1 levels in plasma/cell medium from CLL samples. To understand how angiopoietins in the microenvironment regulate the components of Ang-Tie2 pathway, survival, migration, and metabolic fitness of CLL cells, we exposed CLL cells to recombinant angiopoietins. CLL plasma and CLL cells in culture present significant lower levels of Ang1. CLL cells simultaneously express Ang1, Ang2, and Tie1 mRNA, but lack that of Tie2 and its regulator, VE-PTP. Exposure to Ang1 confers survival advantage in the long-term, whereas Ang2 and trebananib, an angiopoietin blocker, proved detrimental. Angiopoietins differentially modulate expression of Ang1, Ang2, and Tie1 transcripts. Ang2, but not Ang1, induces the concomitant and transient expression of Tie2 and VE-PTP mRNA. Both angiopoietins, particularly Ang2, increase CLL-Tie1 expression and Ang1 clearly induces chemotaxis and transendothelial-like migration of CLL cells. Besides, changes in caspase and ATP content corroborate the sensitivity of CLL cells to angiopoietin exposure. Altogether, this work shows that angiopoietins regulate the fate of CLL cells in a Tie2-independent manner and highlights the potential of the Ang-Tie2 pathway as a therapeutic target in CLL research

Childhood maltreatment as risk factor for lifetime depression: The role of different types of experiences and sensitive periods

Gerke J, Koenig AM, Conrad D, et al. Childhood maltreatment as risk factor for lifetime depression: The role of different types of experiences and sensitive periods. Mental Health & Prevention. 2018;10:56-65

Interdisciplinary Geo-ecological Research across Time Scales in the Northeast German Lowland Observatory (TERENO-NE)

The Northeast German Lowland Observatory (TERENO-NE) was established to investigate the regional impact of climate and land use change. TERENO-NE focuses on the Northeast German lowlands, for which a high vulnerability has been determined due to increasing temperatures and decreasing amounts of precipitation projected for the coming decades. To facilitate in-depth evaluations of the effects of climate and land use changes and to separate the effects of natural and anthropogenic drivers in the region, six sites were chosen for comprehensive monitoring. In addition, at selected sites, geoarchives were used to substantially extend the instrumental records back in time. It is this combination of diverse disciplines working across different time scales that makes the observatory TERENO-NE a unique observation platform. We provide information about the general characteristics of the observatory and its six monitoring sites and present examples of interdisciplinary research activities at some of these sites. We also illustrate how monitoring improves process understanding, how remote sensing techniques are fine-tuned by the most comprehensive ground-truthing site DEMMIN, how soil erosion dynamics have evolved, how greenhouse gas monitoring of rewetted peatlands can reveal unexpected mechanisms, and how proxy data provides a long-term perspective of current ongoing changes