Impact of Gravity on Thyroid Cells

Physical and mental health requires a correct functioning of the thyroid gland, which controls cardiovascular, musculoskeletal, nervous, and immune systems, and affects behavior and cognitive functions. Microgravity, as occurs during space missions, induces morphological and functional changes within the thyroid gland. Here, we review relevant experiments exposing cell cultures (normal and cancer thyroid cells) to simulated and real microgravity, as well as wild-type and transgenic mice to hypergravity and spaceflight conditions. Well-known mechanisms of damage are presented and new ones, such as changes of gene expression for extracellular matrix and cytoskeleton proteins, thyrocyte phenotype, sensitivity of thyrocytes to thyrotropin due to thyrotropin receptor modification, parafollicular cells and calcitonin production, sphingomyelin metabolism, and the expression and movement of cancer molecules from thyrocytes to colloids are highlighted. The identification of new mechanisms of thyroid injury is essential for the development of countermeasures, both on the ground and in space, against thyroid cancer. We also address the question whether normal and cancer cells show a different sensitivity concerning changes of environmental conditions

D. Marcus Elieser Bloch\u27s, aus\ufcbenden Arztes zu Berlin ... Naturgeschichte der ausl\ue4ndischen Fische

pt.2:[Atlas 2] (1785-1795) [Lacks:Taf.139

D. Marcus Elieser Bloch\u27s, aus\ufcbenden Arztes zu Berlin ... 6konomische Naturgeschichte der Fische Deutschlands : mit sieben und dreyssig Kupfertafeln nach Originalen

T.2 (1784

D. Marcus Elieser Bloch\u27s, aus\ufcbenden Arztes zu Berlin ... Oeconomische Naturgeschichte der Fische Deutschlands

pt.2:[Atlas 4] (1785-1795

D. Marcus Elieser Bloch\u27s, aus\ufcbenden Arztes zu Berlin ... Oeconomische Naturgeschichte der Fische Deutschlands

pt.2:v.4:Th.7-9 (1793-1795) [Text

D. Marcus Elieser Bloch\u27s, aus\ufcbenden Arztes zu Berlin ... Oeconomische Naturgeschichte der Fische Deutschlands

pt.1:v.1:Th.1-3 (1782-1784) [Text

D. Marcus Elieser Bloch\u27s, aus\ufcbenden Arztes zu Berlin ... Oeconomische Naturgeschichte der Fische Deutschlands

pt.2:v.3:Th.4-6 (1790-1792) [Text

Ichtyologie, ou, Histoire naturelle, générale et particulière des poissons : avec des figures enluminées, dessinées d\u27après nature

ptie.3-4 (1786-1787

-Active AKT signaling triggers CLL towards Richter's transformation via over-activation of Notch1

Richter's transformation (RT) is an aggressive lymphoma which occurs upon progression from chronic lymphocytic leukemia (CLL). Transformation has been associated with genetic aberrations in the CLL-phase involving TP53, CDKN2A, MYC, and NOTCH1, however a significant proportion of RT cases lack CLL-phase associated events. Here, we report that high levels of AKT phosphorylation occurs both in high-risk CLL patients harboring TP53 and NOTCH1 mutations as well as in RT patients. Genetic over-activation of Akt in the murine E-TCL1 CLL mouse model resulted in CLL to RT with significantly reduced survival and an aggressive lymphoma phenotype. In the absence of recurrent mutations, we identified a profile of genomic aberrations intermediate between CLL and DLBCL. Multi-omics assessment by phosphoproteomic/proteomic and single-cell transcriptomic profiles of this Akt-induced murine RT revealed a S100-protein-defined subcluster of highly aggressive lymphoma cells, which developed from CLL cells, through activation of Notch via Notch ligand expressed by T cells. Constitutively active Notch1 similarly induced RT of murine CLL. We identify Akt activation as an initiator of CLL transformation towards aggressive lymphoma by inducing Notch signaling between RT cells and microenvironmental T cells

Guidelines for the use and interpretation of assays for monitoring autophagy

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field