Lactic Acidosis Triggers Starvation Response with Paradoxical Induction of TXNIP through MondoA

Although lactic acidosis is a prominent feature of solid tumors, we still have limited understanding of the mechanisms by which lactic acidosis influences metabolic phenotypes of cancer cells. We compared global transcriptional responses of breast cancer cells in response to three distinct tumor microenvironmental stresses: lactic acidosis, glucose deprivation, and hypoxia. We found that lactic acidosis and glucose deprivation trigger highly similar transcriptional responses, each inducing features of starvation response. In contrast to their comparable effects on gene expression, lactic acidosis and glucose deprivation have opposing effects on glucose uptake. This divergence of metabolic responses in the context of highly similar transcriptional responses allows the identification of a small subset of genes that are regulated in opposite directions by these two conditions. Among these selected genes, TXNIP and its paralogue ARRDC4 are both induced under lactic acidosis and repressed with glucose deprivation. This induction of TXNIP under lactic acidosis is caused by the activation of the glucose-sensing helix-loop-helix transcriptional complex MondoA:Mlx, which is usually triggered upon glucose exposure. Therefore, the upregulation of TXNIP significantly contributes to inhibition of tumor glycolytic phenotypes under lactic acidosis. Expression levels of TXNIP and ARRDC4 in human cancers are also highly correlated with predicted lactic acidosis pathway activities and associated with favorable clinical outcomes. Lactic acidosis triggers features of starvation response while activating the glucose-sensing MondoA-TXNIP pathways and contributing to the “anti-Warburg” metabolic effects and anti-tumor properties of cancer cells. These results stem from integrative analysis of transcriptome and metabolic response data under various tumor microenvironmental stresses and open new paths to explore how these stresses influence phenotypic and metabolic adaptations in human cancers

Single port access holographic particle image velocimetry

An optical system, which requires only a single optical window mounted on a test volume, is proposed for holographic particle image velocimetry (HPIV). The optical system is a derivative of the double-exposure, double-reference-beam, off-axis HPIV system, but the innovative idea behind the system is to use back scattered light from the particles as the object wave. A 45{degree} beam splitter inserted in front of the window serves to admit the illuminating beam and extract the back scattered light. This concept can be of great engineering interest because optical access is often limited to one window in practical devices. The preliminary results of the technique appear quite promising, with current studies aimed at defining the optical resolution capabilities

The susceptibility of primary cultured rhesus macaque kidney epithelial cells to rhesus cytomegalovirus strains

Kidney epithelial cells are common targets for human and rhesus cytomegalovirus (HCMV and RhCMV) in vivo, and represent an important reservoir for long-term CMV shedding in urine. To better understand the role of kidney epithelial cells in primate CMV natural history, primary cultures of rhesus macaque kidney epithelial cells (MKE) were established and tested for infectivity by five RhCMV strains, including two wild-type strains (UCD52 and UCD59) and three strains containing different coding contents in UL/b′. The latter strains included 180.92 [containing an intact RhUL128-RhUL130-R hUL131 (RhUL128L) locus but deleted for the UL/b′ RhUL148–rh167-loci], 68-1 (RhUL128L-defective and fibroblast-tropic) and BRh68-1.2 (the RhUL128L-repaired version of 68-1). As demonstrated by RhCMV cytopathic effect, plaque formation, growth kinetics and early virus entry, we showed that MKE were differentially susceptible to RhCMV infection, related to UL/b′ coding contents of the different strains. UCD52 and UCD59 replicated vigorously in MKE, 68-1 replicated poorly, and 180.92 grew with intermediate kinetics. Reconstitution of RhUL128L in 68-1 (BRh68-1.2) restored its replication efficiency in MKE as compared to UCD52 and UCD59, consistent with the essential role of UL128L for HCMV epithelial tropism. Further analysis revealed that the UL/b′ UL148-rh167-loci deletion in 180.92 impaired RhUL132 (rh160) expression. Given that 180.92 retains an intact RhUL128L, but genetically or functionally lacks genes from RhUL132 (rh160) to rh167 in UL/b′, its attenuated infection efficiency indicated that, along with RhUL128L, an additional protein(s) encoded within the UL/b′ RhUL132 (rh160)-rh167 region (potentially, RhUL132 and/or RhUL148) is indispensable for efficient replication in MKE

Emulating Bilingual Synaptic Response Using a Junction-Based Artificial Synaptic Device

Excitatory and inhibitory postsynaptic potentials are the two fundamental categories of synaptic responses underlying the diverse functionalities of the mammalian nervous system. Recent advances in neuroscience have revealed the co-release of both glutamate and GABA neurotransmitters from a single axon terminal in neurons at the ventral tegmental area that can result in the reconfiguration of the postsynaptic potentials between excitatory and inhibitory effects. The ability to mimic such features of the biological synapses in semiconductor devices, which is lacking in the conventional field effect transistor-type and memristor-type artificial synaptic devices, can enhance the functionalities and versatility of neuromorphic electronic systems in performing tasks such as image recognition, learning, and cognition. Here, we demonstrate an artificial synaptic device concept, an ambipolar junction synaptic devices, which utilizes the tunable electronic properties of the heterojunction between two layered semiconductor materials black phosphorus and tin selenide to mimic the different states of the synaptic connection and, hence, realize the dynamic reconfigurability between excitatory and inhibitory postsynaptic effects. The resulting device relies only on the electrical biases at either the presynaptic or the postsynaptic terminal to facilitate such dynamic reconfigurability. It is distinctively different from the conventional heterosynaptic device in terms of both its operational characteristics and biological equivalence. Key properties of the synapses such as potentiation and depression and spike-timing-dependent plasticity are mimicked in the device for both the excitatory and inhibitory response modes. The device offers reconfiguration properties with the potential to enable useful functionalities in hardware-based artificial neural network