Achieving high sensitivity in solid-state gas sensors can allow the precise detection of chemical agents. In particular, detection of volatile organic compounds (VOCs) at the parts per billion (ppb) level is critical for the early diagnosis of diseases. To obtain high sensitivity, two requirements need to be simultaneously satisfied: (i) low electrical noise and (ii) strong signal, which existing sensor materials cannot meet. Here, we demonstrate that 2D metal carbide MXenes, which possess high metallic conductivity for low noise and a fully functionalized surface for a strong signal, greatly outperform the sensitivity of conventional semiconductor channel materials. TiCT MXene gas sensors exhibited a very low limit of detection of 50-100 ppb for VOC gases at room temperature. Also, the extremely low noise led to a signal-to-noise ratio 2 orders of magnitude higher than that of other 2D materials, surpassing the best sensors known. Our results provide insight in utilizing highly functionalized metallic sensing channels for developing highly sensitive sensors.

AMP-activated protein kinase (AMPK, also known as SNF1A) has been primarily studied as a metabolic regulator that is activated in response to energy deprivation. Although there is relatively ample information on the biochemical characteristics of AMPK, not enough data exist on the in vivo function of the kinase. Here, using the Drosophila model system, we generated the first animal model with no AMPK activity and discovered physiological functions of the kinase. Surprisingly, AMPK-null mutants were lethal with severe abnormalities in cell polarity and mitosis, similar to those of lkb1-null mutants. Constitutive activation of AMPK restored many of the phenotypes of lkb1-null mutants, suggesting that AMPK mediates the polarity- and mitosis-controlling functions of the LKB1 serine/threonine kinase. Interestingly, the regulatory site of non-muscle myosin regulatory light chain (MRLC; also known as MLC2) was directly phosphorylated by AMPK. Moreover, the phosphomimetic mutant of MRLC rescued the AMPK-null defects in cell polarity and mitosis, suggesting MRLC is a critical downstream target of AMPK. Furthermore, the activation of AMPK by energy deprivation was sufficient to cause dramatic changes in cell shape, inducing complete polarization and brush border formation in the human LS174T cell line, through the phosphorylation of MRLC. Taken together, our results demonstrate that AMPK has highly conserved roles across metazoan species not only in the control of metabolism, but also in the regulation of cellular structures.

The Akt/protein kinase B (PKB) serine/threonine kinase is well known as an important mediator of many cell survival signaling pathways. Here, we demonstrate for the first time a major role of Akt/PKB in the cell invasion properties of the highly metastatic cell line HT1080. Using confocal microscopic analyses of live samples, we found Akt/PKB to be localized in the leading edge membrane area of migrating HT1080 cells. This localization was dependent on phosphoinositide 3-kinase and required the lipid binding ability of the phosphoinositide binding pleckstrin homology domain of Akt/PKB. We examined the possible function of Akt/PKB in HT1080 invasion. Surprisingly, Akt/PKB potently promoted HT1080 invasion, by increasing cell motility and matrix metalloproteinase-9 (MMP-9) production, in a manner highly dependent on its kinase activity and membrane-translocating ability. The increase in MMP-9 production was mediated by activation of nuclear factor-kappaB transcriptional activity by Akt/PKB. However, Akt/PKB did not affect the cell-cell or cell-matrix adhesion properties of HT1080. Our findings thus establish Akt/PKB as a major factor in the invasive abilities of cancer cells.

Superior chemical sensing performance of black phosphorus (BP) is demonstrated by comparison with MoS2 and graphene. Dynamic sensing measurements of multichannel detection show that BP displays highly sensitive, selective, and fast-responsive NO2 sensing performance compared to the other representative 2D sensing materials.

Akt is a protein serine/threonine kinase that plays an important role in the mitogenic responses of cells to variable stimuli. Akt contains a pleckstrin homology (PH) domain and is activated by phosphorylation at threonine 308 and serine 473. Binding of 3-OH phosphorylated phosphoinositides to the PH domain results in the translocation of Akt to the plasma membrane where it is activated by upstream kinases such as (phosphoinositide-dependent kinase-1 (PDK1). Over-expression of constitutively active forms of Akt promotes cell proliferation and survival, and also stimulates p70 S6 kinase (p70S6K). In many cells, an increase in levels of intracellular cyclic AMP (cAMP) diminishes cell growth and promotes differentiation, and in certain conditions cAMP is even antagonistic to the effect of growth factors. Here, we show that cAMP has inhibitory effects on the phosphatidylinositol 3-kinase/PDK/Akt signaling pathway. cAMP potently inhibits phosphorylation at threonine 308 and serine 473 of Akt, which is required for the protein kinase activities of Akt. cAMP also negatively regulates PDK1 by inhibiting its translocation to the plasma membrane, despite not affecting its protein kinase activities. Furthermore, when we co-expressed myristoylated Akt and PDK1 mutants which constitutively co-localize in the plasma membrane, Akt activity was no longer sensitive to raised intracellular cAMP concentrations. Finally, cAMP was also found to inhibit the lipid kinase activity of PI3K and to decrease the levels of phosphatidylinositol 3,4,5-triphosphate in vivo, which are required for the membrane localization of PDK1. Collectively, these data strongly support the theory that the cAMP-dependent signaling pathway inhibits Akt activity by blocking the coupling between Akt and its upstream regulators, PDK, in the plasma membrane.The phosphatidylinositol 3-kinase (PI3K) 1 -dependent cell signaling pathway has emerged as a key regulatory pathway involved in a number of cellular events (1). Upon activation of growth factor tyrosine kinase receptors, the p85 regulatory subunit of PI3K recruits the p110 catalytic subunit to the plasma membrane (2). The p110 catalytic subunit increases the level of PtdIns-3,4,5-P 3 and phosphatidylinositol 3,4-bisphosphate (PtdIns-3,4-P 2 ), which induce the membrane translocation of PDK1 and Akt (also called PKB or RAC-PK) by binding to the pleckstrin homology domain (3). In the membrane, PDK1 phosphorylates and activates Akt in a PtdIns-3,4,5-P 3 -or PtdIns-3,4-P 2 -dependent manner (4, 5). By a mechanism that involves phospholipase C (6), activated Akt is released from the membrane and phosphorylates various targets.This complex and unique signaling pathway has been implicated in a variety of cellular events such as cell proliferation and survival (1, 7). Previously, it has been shown that various survival factors, such as nerve growth factor, require the activation of PI3K to prevent various cell types from undergoing apoptosis (8, 9). The mechanism by which the PI3K pathway protects cells from programm...