Role of cAMP-responsive Element-binding Protein (CREB)-regulated Transcription Coactivator 3 (CRTC3) in the Initiation of Mitochondrial Biogenesis and Stress Response in Liver Cells*

Peroxisome proliferator-activated receptor α, coactivator 1α (PGC-1α) is the master regulator of mitochondrial biogenesis. PGC-1α expression is under the control of the transcription factor, cAMP-responsive element-binding protein (CREB). In searching for candidate transcription factors that mediate mitochondrial stress-initiated mitochondria-to-nucleus signaling in the regulation of mitochondrial biogenesis, we assessed the effect of silencing CREB-regulated transcription co-activators (CRTC). CRTC isoforms are co-activators of CREB-regulated transcription by a CREB phosphorylation-independent pathway. Using cultured HepG2 cells and primary mouse hepatocytes, we determined that mitochondrial stress imposed by the complex I inhibitor rotenone elicited mitochondrial biogenesis, which was dependent on an induction of PGC-1α, which was inhibited by silencing PGC-1α. PGC-1α induction in response to rotenone was inhibited by silencing the expression of CRTC3, which blocked downstream mitochondria biogenesis. In contrast, silencing CRTC2 did not affect the induction of this pathway in response to rotenone. Thus, CRTC3 plays a selective role in mitochondrial biogenesis in response to rotenone

Caffeine for apnea of prematurity trial: benefits may vary in subgroups

There is evidence of variable beneficial effects of caffeine. Infants receiving respiratory support appeared to derive more neurodevelopmental benefits from caffeine than infants not receiving support. Earlier initiation of caffeine may be associated with a greater reduction in time on ventilation

Neo-Tethyan magmatism and metallogeny in Myanmar - An Andean analogue?

© 2015 Elsevier Ltd. Plate margin tectonism, magmatic and hydrothermal processes, and the genesis of mineral deposits are intricately linked. In Myanmar two near-parallel magmatic belts, that together contain a significant proportion of that country's mineral wealth, have contrasting metallogenic endowments. The Mogok-Mandalay-Mergui Belt hosts crustal melt S-type granites with significant tin-tungsten mineralization, while the Wuntho-Popa Arc comprises I-type granites and granodiorites with copper-gold mineralization. The spatial juxtaposition of the two belts and their distinct but consistent metallogenic endowment bears strong similarities to the metallogenic belts of the South American Cordillera. Recent U-Pb age dating has shown the potential for the two belts to be near-contemporary from the Late Cretaceous to Eocene. Here we investigate whether an Andean-type setting during subduction of Neo-Tethys could explain the observed magmatism and mineralization within these two belts