Search

Conventional implantable electrocardiogram monitors are impenetrable to electromagnetic radiation, posing challenges in imaging (i.e. X-rays). In this study, we demonstrate a radiolucent implantable electrocardiogram (ECG) device using graphene sheets and Parylene substrate which allows bypassing of electromagnetic radiation through the implanted device. Evaluated on a canine model, the graphene electrodes detect signals comparable to those recorded using surface electrodes, presenting a valuable and novel modality for medium and long-term monitoring of cardiac rhythm. When compared with current technology, the new system has the distinct advantages of being flexible and radiolucent, thereby improving patient comfort, and avoiding device artifact and shadowing on clinical radiographic imaging.

A mixture of equivalent amounts of amidine, alcohol, and carbon dioxide forms alklycarbonate amidinium salts. Here we studied the effect of the composition of solutions consisting of ethylene glycol (EG) as the alcohol and one of various amidines on their ability to absorb and desorb carbon dioxide. Compounds containing single or multiple formamidine groups were synthesized and dissolved in EG. The ability of these solutions to absorb carbon dioxide was studied for various ratios of EG to amidine and at various temperatures. An excess of at least ten equivalents of EG relative to the amidine was required for rapid and complete reaction of the base with carbon dioxide. Excess EG also reduced the viscosity of the solution, and in this way increased the absorption rate. However, the excess EG appeared to have stabilized the formed alkyl carbonate salts via hydrogen bonding, resulting in a relatively low degree of decarbonation of the solution at elevated temperatures. This effect would cause the working capacity to be decreased were this type of material be used for carbon dioxide capture applications. Our results suggest that, in general, the compositions of the alcoholic solutions of superbases need to be optimized to achieve high-efficiency absorption and desorption of carbon dioxide.

Wireless communicated sensors currently play a major role in due to the importance of data for internet-of-things (IoT) devices. Specifically, chipless radio frequency identification (RFID) technology is a widely used technique for communication of data due to its printability, simplicity, and low cost. Here, stretchable and chipless RFID strain sensors were fabricated by direct printing of aerosolized nanocomposites using an aerodynamically focused nanomaterial printing system, which is a direct printing process for conductive and stretchable pattern printing onto flexible substrate. In particular, microscale porous conductive patterns composed of silver nanoparticle and multi-walled carbon nanotube composites were printed onto polydimethylsiloxane. The fabricated sensor exhibited motion with a high degree of freedom, including the ability to be stretched, twisted, or folded. Moreover, it demonstrate a gauge factor >0.5 and maximum strain limit >20 %, with resonance frequency controllability due to regulation of the geometrical properties of LC resonance circuits. Because the original sensor characteristics allowed independent sensing in a single direction, we fabricated an RFID strain sensor that could measure normal strain, as well as shear strain in all directions. Finally, we directly printed the sensor onto air tubes and verified its performance.

The trigeminal nerve (cranial nerve V), along with other cranial nerves, has in recent years become a popular target for bioelectric medicine due to its direct access to neuromodulatory centers. Trigeminal nerve stimulation is currently being evaluated as an adjunctive treatment for various neurodegenerative and neuropsychiatric diseases despite the mechanism of action being in question. In this work, we describe the development and validation of a novel neural interface for the infraorbital branch of the trigeminal nerve utilizing a thin film (TF) nerve cuff containing multiple electrode sites allowing for more selective stimulation of the nerve. We characterized the properties of the device using electrochemical impedance spectroscopy, cyclic voltammetry, voltage excursions, and in vivo testing. Electrochemical measurements demonstrate that the platinum-based electrodes possess a capacitive charge carrying mechanism suitable for stimulation of biological tissue with a safe charge injection limit of 73.13 μC/cm2. In vivo stimulation experiments show that the TF cuff can reliably stimulate nerve targets eliciting cortical responses similar to a silicone cuff electrode. Furthermore, selecting different pairs of stimulation electrodes on the TF cuff modulated the magnitude and/or spatial pattern of cortical responses suggesting that the device may be able to selectively stimulate different parts of the nerve. These results suggest that the TF cuff is a viable neural interface for stimulation of the infraorbital branch of the trigeminal nerve that enables future research examining the therapeutic mechanisms of trigeminal nerve stimulation.

Using the Poisson point process we model how the SiPM works and derive the non-linear response formula of the SiPM. Using this non-linear response formula we are able to capture the mean and variance saturation phenomena near the infinity and the linear behavior of the mean and variance near 0. We also introduce a different model of the SiPM. Under this different model we show the mean and variance saturation phenomena near the infinity and the linear behavior of the mean and variance near 0. We provide some open problems on this different model.

Defining the mechanisms underlying the control of mitochondrial fusion and fission is critical to understanding cellular adaptation to diverse physiological conditions. Here we demonstrate that hypoxia induces fission of mitochondrial membranes, dependent on availability of the mitochondrial scaffolding protein AKAP121. AKAP121 controls mitochondria dynamics through PKA-dependent inhibitory phosphorylation of Drp1 and PKA-independent inhibition of Drp1-Fis1 interaction. Reduced availability of AKAP121 by the ubiquitin ligase Siah2 relieves Drp1 inhibition by PKA and increases its interaction with Fis1, resulting in mitochondrial fission. High AKAP121 levels, seen in cells lacking Siah2, attenuate fission and reduce apoptosis of cardiomyocytes under simulated ischemia. Infarct size and degree of cell death were reduced in Siah2(-/-) mice subjected to myocardial infarction. Inhibition of Siah2 or Drp1 in hatching C. elegans reduces their life span. Through modulating Fis1/Drp1 complex availability, our studies identify Siah2 as a key regulator of hypoxia-induced mitochondrial fission and its physiological significance in ischemic injury and nematode life span.

Mutations in N-RAS and B-RAF, which commonly occur in melanomas, result in constitutive activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) signaling. Active ERK increases expression and activity of the c-Jun transcription factor, linking ERK and Jun N-terminal kinase (JNK) cascades. Here, we show that c-Jun regulates transcription of phosphoinositide-dependent kinase 1 (PDK1) with a concomitant impact on Akt and protein kinase C (PKC) activity and related substrates. Inhibition of c-Jun reduces PDK1 expression and attenuates Akt and PKC activity, which can be restored by exogenous PDK1. c-Jun regulation of PDK1 in melanoma contributes to growth rate and the ability to form tumors in mice. Correspondingly, increased levels of c-Jun in melanoma cell lines coincide with up-regulation of PDK1 and phosphorylation of PKC and Akt. The identification of c-Jun as a transcriptional regulator of PDK1 expression highlights key mechanisms underlying c-Jun oncogenic activity, and provides new insight into the nature of up-regulated Akt and PKC in melanoma.

Myocyte enhancer factor 2 (MEF2) plays pivotal roles in various biological processes, and its transcriptional activity is regulated by histone acetylation/deacetylation enzymes in a calcium-dependent fashion. A calcineurin-binding protein 1 (Cabin1) has been shown to participate in repression of MEF2 by recruiting mSin3 and its associated histone deacetylases. Here, we report that histone methylation also takes a part in Cabin1-mediated repression of MEF2. Immunoprecipitate of Cabin1 complex can methylate histone H3 by association with SUV39H1. SUV39H1 increased Cabin1-mediated repression of MEF2 transcriptional activity in MEF2-targeting promoters. The SUV39H1 was revealed to bind to the 501-900-amino acid region of Cabin1, which was distinct from its histone deacetylase-recruiting domain. In addition, the Gal4-Cabin1-(501-900) alone repressed a constitutively active Gal4-tk-promoter, indicating that Cabin1 recruits SUV39H1 and represses transcriptional activity. Finally, both SUV39H1 and Cabin1 were shown to bind on the MEF2 target promoter in a calcium-dependent manner. Thus, Cabin1 recruits chromatin-modifying enzymes, both histone deacetylases and a histone methyltransferase, to repress MEF2 transcriptional activity.

Despite the involvement in diverse physiological process and pleiotropic expression profile, the molecular functions of Nur77 are not likely to be fully elucidated. From the effort to find a novel function of Nur77, we detected molecular interaction between Nur77 and PKC. Details of interaction revealed that C-terminal ligand binding domain (LBD) of Nur77 specifically interacted with highly conserved glycine-rich loop of PKC required for catalytic activity. This molecular interaction resulted in inhibition of catalytic activity of PKCtheta by Nur77. C-terminal LBD of Nur77 is sufficient for inhibiting the phosphorylation of substrate by PKCtheta. Ultimately, inhibition of catalytic activity by Nur77 is deeply associated with repression of PKC-mediated activation of AP-1 and NF-kappaB. Therefore, these findings demonstrate a novel function of Nur77 as a PKC inhibitor and give insights into molecular mechanisms of various Nur77-mediated physiological phenomena.

von Hippel-Lindau (VHL) disease is a rare autosomal dominant cancer syndrome. Although hypoxia-inducible factor-alpha (HIFalpha) is a well-documented substrate of von Hippel-Lindau tumor suppressor protein (pVHL), it remains unclear whether the dysregulation of HIF is sufficient to account for de novo tumorigenesis in VHL-deleted cells. Here we found that pVHL directly associates with and stabilizes p53 by suppressing Mdm2-mediated ubiquitination and nuclear export of p53. Moreover, upon genotoxic stress, pVHL invoked an interaction between p53 and p300 and the acetylation of p53, which ultimately led to an increase in p53 transcriptional activity and p53-mediated cell cycle arrest and apoptosis. These results suggest that the tumor suppressor pVHL has an unexpected function to upregulate the tumor suppressor p53.

The HIV1 protease inhibitor nelfinavir is being investigated as a cancer therapeutic. In this issue of Cancer Cell, Smith et al. (2016) report that nelfinavir suppresses MITF expression induced by MAPK pathway inhibition in melanoma cells and sensitizes melanoma cells with NRAS or BRAF plus NRAS mutations to MEK inhibitors.

Melanoma cells acquire multiple genetic and epigenetic alterations that promote their metastasis and resistance to available therapies. In this issue of Cancer Cell, Soengas and colleagues reveal that the induction of endosome-mediated autophagy results in efficient melanoma cell death, thereby offering new potential means for treatment of this devastating cancer.