Luminescence thermochronometry of feldspar minerals: Optimisation of measurement conditions for the derivation of thermal kinetic parameters using isothermal holding experiments

Luminescence thermochronometry is sensitive to very low temperatures (below ∼120 °C), and enables the resolution of thermal histories over sub-Quaternary timescales. Here we apply a multi-elevated-temperature post-infrared infrared-stimulated luminescence (MET-pIR-IRSL) measurement protocol to feldspar minerals to extract thermal histories. These thermal histories depend on the thermal stability of the MET signal, and are based on the thermal kinetic parameters extracted from isothermal decay experiments. However, the derived thermal kinetic parameters vary with experimental conditions, specifically with the isothermal holding temperatures (ITL) used. We analyse samples with independently known thermal histories, together with synthetic thermal history samples and samples with unknown thermal histories to test the validity of thermal kinetic parameters obtained from different combinations of isothermal holding data. This approach is tested on feldspars of different mineralogies and lithologies. We find that the temperatures inferred from inverting the data change, depending both on the number and on the highest ITL temperature used for thermal kinetic parameter derivation. Analysed samples validate the MET-pIR-IRSL protocol for extracting thermal histories, and we suggest that four isothermal holding temperatures between 190 and 250 °C are used for appropriate thermal kinetic parameter derivation

Vitamin D Receptor Controls Cell Stemness in Acute Myeloid Leukemia and in Normal Bone Marrow.

Vitamin D (VD) is a known differentiating agent, but the role of VD receptor (VDR) is still incompletely described in acute myeloid leukemia (AML), whose treatment is based mostly on antimitotic chemotherapy. Here, we present an unexpected role of VDR in normal hematopoiesis and in leukemogenesis. Limited VDR expression is associated with impaired myeloid progenitor differentiation and is a new prognostic factor in AML. In mice, the lack of Vdr results in increased numbers of hematopoietic and leukemia stem cells and quiescent hematopoietic stem cells. In addition, malignant transformation of Vdr-/- cells results in myeloid differentiation block and increases self-renewal. Vdr promoter is methylated in AML as in CD34+ cells, and demethylating agents induce VDR expression. Association of VDR agonists with hypomethylating agents promotes leukemia stem cell exhaustion and decreases tumor burden in AML mouse models. Thus, Vdr functions as a regulator of stem cell homeostasis and leukemic propagation

Apoptosis-Related Gene Expression Profiling in Hematopoietic Cell Fractions of MDS Patients

Contains fulltext : 168172.pdf (publisher's version ) (Open Access)Although the vast majority of patients with a myelodysplastic syndrome (MDS) suffer from cytopenias, the bone marrow is usually normocellular or hypercellular. Apoptosis of hematopoietic cells in the bone marrow has been implicated in this phenomenon. However, in MDS it remains only partially elucidated which genes are involved in this process and which hematopoietic cells are mainly affected. We employed sensitive real-time PCR technology to study 93 apoptosis-related genes and gene families in sorted immature CD34+ and the differentiating erythroid (CD71+) and monomyeloid (CD13/33+) bone marrow cells. Unsupervised cluster analysis of the expression signature readily distinguished the different cellular bone marrow fractions (CD34+, CD71+ and CD13/33+) from each other, but did not discriminate patients from healthy controls. When individual genes were regarded, several were found to be differentially expressed between patients and controls. Particularly, strong over-expression of BIK (BCL2-interacting killer) was observed in erythroid progenitor cells of low- and high-risk MDS patients (both p = 0.001) and TNFRSF4 (tumor necrosis factor receptor superfamily 4) was down-regulated in immature hematopoietic cells (p = 0.0023) of low-risk MDS patients compared to healthy bone marrow