The Human SLC25A33 and SLC25A36 Genes of Solute Carrier Family 25 Encode Two Mitochondrial Pyrimidine Nucleotide Transporters

The human genome encodes 53 members of the solute carrier family 25 (SLC25), also called the mitochondrial carrier family, many of which have been shown to transport inorganic anions, amino acids, carboxylates, nucleotides, and coenzymes across the inner mitochondrial membrane, thereby connecting cytosolic and matrix functions. Here two members of this family, SLC25A33 and SLC25A36, have been thoroughly characterized biochemically. These proteins were overexpressed in bacteria and reconstituted in phospholipid vesicles. Their transport properties and kinetic parameters demonstrate that SLC25A33 transports uracil, thymine, and cytosine (deoxy)nucleoside di- and triphosphates by an antiport mechanism and SLC25A36 cytosine and uracil (deoxy)nucleoside mono-, di-, and triphosphates by uniport and antiport. Both carriers also transported guanine but not adenine (deoxy)nucleotides. Transport catalyzed by both carriers was saturable and inhibited by mercurial compounds and other inhibitors of mitochondrial carriers to various degrees. In confirmation of their identity (i) SLC25A33 and SLC25A36 were found to be targeted to mitochondria and (ii) the phenotypes of Saccharomyces cerevisiae cells lacking RIM2, the gene encoding the well characterized yeast mitochondrial pyrimidine nucleotide carrier, were overcome by expressing SLC25A33 or SLC25A36 in these cells. The main physiological role of SLC25A33 and SLC25A36 is to import/export pyrimidine nucleotides into and from mitochondria, i.e. to accomplish transport steps essential for mitochondrial DNA and RNA synthesis and breakdown

Emovo Corpus: an Italian Emotional Speech Database

This article describes the first emotional corpus, named EMOVO, applicable to Italian language,. It is a database built from the voices of up to 6 actors who played 14 sentences simulating 6 emotional states (disgust, fear, anger, joy, surprise, sadness) plus the neutral state. These emotions are the well-known Big Six found in most of the literature related to emotional speech. The recordings were made with professional equipment in the Fondazione Ugo Bordoni laboratories. The paper also describes a subjective validation test of the corpus, based on emotion-discrimination of two sentences carried out by two different groups of 24 listeners. The test was successful because it yielded an overall recognition accuracy of 80%. It is observed that emotions less easy to recognize are joy and disgust, whereas the most easy to detect are anger, sadness and the neutral state

Backbone-free duplex-stacked monomer nucleic acids exhibiting Watson-Crick selectivity.

We demonstrate that nucleic acid (NA) mononucleotide triphosphates (dNTPs and rNTPs), at sufficiently high concentration and low temperature in aqueous solution, can exhibit a phase transition in which chromonic columnar liquid crystal ordering spontaneously appears. Remarkably, this polymer-free state exhibits, in a self-assembly of NA monomers, the key structural elements of biological nucleic acids, including: long-ranged duplex stacking of base pairs, complementarity-dependent partitioning of molecules, and Watson-Crick selectivity, such that, among all solutions of adenosine, cytosine, guanine, and thymine NTPs and their binary mixtures, duplex columnar ordering is most stable in the A-T and C-G combinations

Cancer cell metabolism in hypoxia: Role of HIF-1 as key regulator and therapeutic target

In order to meet the high energy demand, a metabolic reprogramming occurs in cancer cells. Its role is crucial in promoting tumor survival. Among the substrates in demand, oxygen is fundamental for bioenergetics. Nevertheless, tumor microenvironment is frequently characterized by low-oxygen conditions. Hypoxia-inducible factor 1 (HIF-1) is a pivotal modulator of the metabolic reprogramming which takes place in hypoxic cancer cells. In the hub of cellular bioenergetics, mitochondria are key players in regulating cellular energy. Therefore, a close crosstalk between mitochondria and HIF-1 underlies the metabolic and functional changes of cancer cells. Noteworthy, HIF-1 represents a promising target for novel cancer therapeutics. In this review, we summarize the molecular mechanisms underlying the interplay between HIF-1 and energetic metabolism, with a focus on mitochondria, of hypoxic cancer cells

Analysis of Co-Channel Coexistence Mitigation Methods Applied to IEEE 802.11p and 5G NR-V2X Sidelink

Direct communication between vehicles and surrounding objects, called vehicle-to-everything (V2X), is ready for the market and promises to raise the level of safety and comfort while driving. To this aim, specific bands have been reserved in some countries worldwide and different wireless technologies have been developed; however, these are not interoperable. Recently, the issue of co-channel coexistence has been raised, leading the European Telecommunications Standards Institute (ETSI) to propose a number of solutions, called mitigation methods, for the coexistence of the IEEE 802.11p based ITS-G5 and the 3GPP fourth generation (4G) long term evolution (LTE)-V2X sidelink. In this work, several of the envisioned alternatives are investigated when adapted to the coexistence of the IEEE 802.11p with its enhancement IEEE 802.11bd and the latest 3GPP standards, i.e., the fifth generation (5G) new radio (NR)-V2X. The results, obtained through an open-source simulator that is shared with the research community for the evaluation of additional proposals, show that the methods called A and C, which require modifications to the standards, improve the transmission range of one or both systems without affecting the other, at least in low-density scenarios

Stimulated single-fiber electromyography (sSFEMG) in Lambert-Eaton syndrome

Objective: To report the clinical features and the neurophysiological approach of a patient with Lambert-Eaton myasthenic syndrome (LEMS), highlighting the diagnostic role of the stimulated single fiber electromyography (sSFEMG). Case report: A 60-year-old woman presenting with the LEMS triad (proximal and axial weakness, autonomic dysfunction and areflexia) was evaluated by neurophysiological tests (electroneuromyography, repetitive stimulation test (TSR), voluntary and stimulated SFEMG). We reported: 1) increase of compound muscle action potential (CMAP) amplitude (>60%) following brief isometric exercise compared to the rest (baseline); 2) decremental/incremental response of CMAP amplitude at low- (3 Hz) and high-frequency (30 Hz) repetitive stimulation test (RST), respectively; 3) increased neuromuscular jitter and blocking at voluntary single-fiber electromyography (vSFEMG); 4) stimulation rate-dependent reduction of the neuromuscular jitter and blocking at sSFEMG. Diagnosis was confirmed by serological demonstration of circulating voltage gated calcium channels (VGCC) antibodies. Significance: The present case highlights the role of the sSFEMG in the diagnosis of LEMS, underling the stimulation rate-dependency of both neuromuscular jitter and blocks

Performance Analysis of Sidelink 5G-V2X Mode 2 through an Open-Source Simulator

The Third Generation Partnership Project (3GPP) has recently published a new set of specifications to enable advanced driving applications in fifth generation (5G) vehicle-to-everything (V2X) scenarios, with particular effort dedicated to the sidelink resource allocation in the autonomous mode, named Mode 2. In this paper, we conduct a comprehensive analysis of Mode 2 performance via an open-source system-level simulator, which implements the 5G New Radio (NR) flexible numerology and physical layer aspects together with the newly specified sidelink resource allocation modes for V2X communications and different data traffic patterns. Results collected through extensive simulation campaigns, under a wide variety of vehicle density, data transmission settings and traffic patterns, showcase the effects of the new 5G-V2X features on the sidelink resource allocation performance and provide some insights into possible ways to further improve Mode 2 performance

The Saccharomyces cerevisiae gene YPR011c encodes a mitochondrial transporter of adenosine 5'-phosphosulfate and 3'-phospho-adenosine 5'-phosphosulfate

The genome of Saccharomyces cerevisiae contains 35 members of the mitochondrial carrier family, nearly all of which have been functionally characterized. In this study, the identification of the mitochondrial carrier for adenosine 5'-phosphosulfate (APS) is described. The corresponding gene (YPR011c) was overexpressed in bacteria. The purified protein was reconstituted into phospholipid vesicles and its transport properties and kinetic parameters were characterized. It transported APS, 3'-phospho-adenosine 5'-phosphosulfate, sulfate and phosphate almost exclusively by a counter-exchange mechanism. Transport was saturable and inhibited by bongkrekic acid and other inhibitors. To investigate the physiological significance of this carrier in S. cerevisiae, mutants were subjected to thermal shock at 45°C in the presence of sulfate and in the absence of methionine. At 45°C cells lacking YPR011c, engineered cells (in which APS is produced only in mitochondria) and more so the latter cells, in which the exit of mitochondrial APS is prevented by the absence of YPR011cp, were less thermotolerant. Moreover, at the same temperature all these cells contained less methionine and total glutathione than wild-type cells. Our results show that S. cerevisiae mitochondria are equipped with a transporter for APS and that YPR011cp-mediated mitochondrial transport of APS occurs in S. cerevisiae under thermal stress condition