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

t-DCF: a Detection Cost Function for the Tandem Assessment of Spoofing Countermeasures and Automatic Speaker Verification

International audienceThe ASVspoof challenge series was born to spearhead research in anti-spoofing for automatic speaker verification (ASV). The two challenge editions in 2015 and 2017 involved the assessment of spoofing countermeasures (CMs) in isolation from ASV using an equal error rate (EER) metric. While a strategic approach to assessment at the time, it has certain shortcomings. First, the CM EER is not necessarily a reliable predic-tor of performance when ASV and CMs are combined. Second, the EER operating point is ill-suited to user authentication applications , e.g. telephone banking, characterised by a high target user prior but a low spoofing attack prior. We aim to migrate from CM-to ASV-centric assessment with the aid of a new tandem detection cost function (t-DCF) metric. It extends the conventional DCF used in ASV research to scenarios involving spoofing attacks. The t-DCF metric has 6 parameters: (i) false alarm and miss costs for both systems, and (ii) prior probabilities of target and spoof trials (with an implied third, nontar-get prior). The study is intended to serve as a self-contained, tutorial-like presentation. We analyse with the t-DCF a selection of top-performing CM submissions to the 2015 and 2017 editions of ASVspoof, with a focus on the spoofing attack prior. Whereas there is little to choose between countermeasure systems for lower priors, system rankings derived with the EER and t-DCF show differences for higher priors. We observe some ranking changes. Findings support the adoption of the DCF-based metric into the roadmap for future ASVspoof challenges, and possibly for other biometric anti-spoofing evaluations

Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.

To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1-/-) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1-/- mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome

Botulinum Toxin Is Effective in the Management of Neurogenic Dysphagia. Clinical-Electrophysiological Findings and Tips on Safety in Different Neurological Disorders

Background and Aims: Neurogenic dysphagia linked to failed relaxation of the upper esophageal sphincter (UES) can be treated by injecting botulinum toxin (BTX) into the cricopharyngeal (CP) muscle. We compared the effects of this treatment in different neurological disorders with dysphagia, to evaluate its efficacy over time including the response to a second injection. Materials and Methods: Sixty-seven patients with neurogenic dysphagia associated with incomplete or absent opening of the UES (24 with brainstem or hemispheric stroke, 21 with parkinsonian syndromes, 12 with multiple sclerosis, and 10 with spastic-dystonic syndromes secondary to post-traumatic encephalopathy) were treated with the injection of IncobotulinumtoxinA (dose 15–20 U) into the CP muscle under electromyographic guidance. The patients were assessed at baseline and after the first and second treatment through clinical evaluation and fiberoptic endoscopy of swallowing, while their dysphagia was quantified using the Dysphagia Outcome and Severity Scale (DOSS). An electrokinesiographic/electromyographic study of swallowing was performed at baseline. Results: Most patients responded to the first BTX treatment: 35 patients (52.2%) were classified as high responders (DOSS score increase >2 levels), while other 19 patients (28.4%) were low responders (DOSS score increase of ≤2 levels). The effect of the first treatment usually lasted longer than 4 months (67%), and in some cases up to a year. The treatment efficacy remained high also after the second injection: 31 patients (46.3%) qualified as high responders and other 22 patients (32.8%) showed a low response. Only in the parkinsonian syndromes group we observed a reduction in the percentage of high responders as compared with the first treatment. Side effects were mostly mild and reported in non-responders following the first injection. A severe side effect, consisting of ingestion pneumonia, was observed following the second BTX injection in two patients who had both been non-responders to the first. Non-responders were characterized electromyographically by higher values of the oropharyngeal interval. Conclusion: These findings confirm the effectiveness of IncobotulinumtoxinA injection in the treatment of neurogenic dysphagia due to hyperactivity and relaxation failure of the UES. Caution should be used as regards, the re-injection in non-responders to the first treatment

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