AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress

Overcoming metabolic stress is a critical step for solid tumour growth. However, the underlying mechanisms of cell death and survival under metabolic stress are not well understood. A key signalling pathway involved in metabolic adaptation is the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. Energy stress conditions that decrease intracellular ATP levels below a certain level promote AMPK activation by LKB1. Previous studies showed that LKB1-deficient or AMPK-deficient cells are resistant to oncogenic transformation and tumorigenesis, possibly because of the function of AMPK in metabolic adaptation. However, the mechanisms by which AMPK promotes metabolic adaptation in tumour cells are not fully understood. Here we show that AMPK activation, during energy stress, prolongs cell survival by redox regulation. Under these conditions, NADPH generation by the pentose phosphate pathway is impaired, but AMPK induces alternative routes to maintain NADPH and inhibit cell death. The inhibition of the acetyl-CoA carboxylases ACC1 and ACC2 by AMPK maintains NADPH levels by decreasing NADPH consumption in fatty-acid synthesis and increasing NADPH generation by means of fatty-acid oxidation. Knockdown of either ACC1 or ACC2 compensates for AMPK activation and facilitates anchorage-independent growth and solid tumour formation in vivo, whereas the activation of ACC1 or ACC2 attenuates these processes. Thus AMPK, in addition to its function in ATP homeostasis, has a key function in NADPH maintenance, which is critical for cancer cell survival under energy stress conditions, such as glucose limitations, anchorage-independent growth and solid tumour formation in vivo.     

Satellite imagery in the study and forecast of malaria

More than 30 years ago, human beings looked back from the Moon to see the magnificent spectacle of Earth-rise. The technology that put us into space has since been used to assess the damage we are doing to our natural environment and is now being harnessed to monitor and predict diseases through space and time. Satellite sensor data promise the development of early-warning systems for diseases such as malaria, which kills between 1 and 2 million people each year.     

The relative effect of 2,3-diphosphoglycerate on the oxygen affinity of fetal and adult hemoglobin in whole blood

Riassunto Experimenti condotti sul sangue intero di individui neonati e adulti hanno dimostrato che l'affinità del sangue per l'ossigeno (P 50) dipende dalla concentrazione intraeritrocitaria di 2,3-difosfoglicerato (DPG) e dalle proporzioni relative di emoglobina adulta (HbA) e fetale (HbF). I risultati ottenuti indicano che nel sangue in toto l'effetto del DPG sulla P50 della HbF è circa il 40% di quello sulla P50 della HbA.