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

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

Statins, fibrates and retinoic acid upregulate mitochondrial acylcarnitine carrier gene expression

In this study, we investigated the effects of statins, fibrates, 9-cis-retinoic acid and forskolin on the transcription of the mitochondrial carnitine/acylcarnitine carrier (CAC) gene. Statins, fibrates, retinoic acid and forskolin activate luciferase gene reporter activity driven by the -334/+3 bp region of the human CAC promoter containing wild-type (but not mutated) PPRE. These four agents also increase CAC transcript and protein levels. The combinations of statins and fibrates, retinoic acid and fibrates and fibrates and forskolin act synergistically. Mevalonate abolishes the activation of CAC gene expression by statins; the inhibitor of the PKA pathway H89 suppresses the stimulation of CAC gene expression by forskolin. Because CAC is essential for fatty acid beta-oxidation, the above results on the regulation of CAC gene expression provide a novel contribution to the understanding of the hypolipidemic action of statins, fibrates and retinoic acid

The effects of body exposure on self-body image and esthetic appreciation in anorexia nervosa.

Repeated exposures to thin-idealized body shapes may alter women's perceptions of what normal (e.g., accepted) and ideal (e.g., desired) bodies in a cultural environment look like. The aim of the present study was to investigate whether exposure to thin and round body shapes may change the subsequent esthetic appreciation of others' bodies and the perceptual and cognitive-affective dimensions of self-body image in patients suffering from anorexia nervosa (AN). Thirteen AN patients and 13 matched healthy controls were exposed to pictures of either thin or round unfamiliar body models and, before and after exposure, they were required to either express liking judgments about round and slim figures of unfamiliar bodies (esthetic task) or to adjust distorted pictures of their own body to their perceptual (How do you see yourself?), affective (How do you feel yourself?), metacognitive (How do others see you?) and ideal (How would you like to look like?) body image (self-body adjustment task). Brief exposures to round models increased liking judgments of round figures in both groups. However, only in AN patients, exposure to round models induced an increase in thin figures liking, which positively correlated with their preoccupation with dieting. Furthermore, exposure to round bodies in AN patients, but not in controls, increased the distortion for the perceptual body image and decreased the size of the ideal one. No differences between the two groups were obtained after adaptation to thin models. Our results suggest that AN patients' perception of their own and others' body is more easily malleable by exposure to round figures as compared to controls. Crucially, this mechanism may strongly contribute to the development and maintenance of self-body image disturbances

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

Statins, fibrates and retinoic acid upregulate mitochondrial acylcarnitine carrier gene expression

In this study, we investigated the effects of statins, fibrates, 9-cis-retinoic acid and forskolin on the transcription of the mitochondrial carnitine/acylcarnitine carrier (CAC) gene. Statins, fibrates, retinoic acid and forskolin activate luciferase gene reporter activity driven by the -334/+3 bp region of the human CAC promoter containing wild-type (but not mutated) PPRE. These four agents also increase CAC transcript and protein levels. The combinations of statins and fibrates, retinoic acid and fibrates and fibrates and forskolin act synergistically. Mevalonate abolishes the activation of CAC gene expression by statins; the inhibitor of the PKA pathway H89 suppresses the stimulation of CAC gene expression by forskolin. Because CAC is essential for fatty acid beta-oxidation, the above results on the regulation of CAC gene expression provide a novel contribution to the understanding of the hypolipidemic action of statins, fibrates and retinoic acid

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

Mentalizing subtypes in eating disorders: A latent profile analysis

Background: Mentalizing, the mental capacity to understand oneself and others in terms of mental states, has been found to be reduced in several mental disorders. Some studies have suggested that eating disorders (EDs) may also be associated with impairments in mentalizing. The aim of this work is to investigate the possible presence of mentalizing subtypes in a sample of patients with EDs. Method: A sample of patients with eating disorders (N = 157) completed a battery of measures assessing mentalization and related variables, including the Reflective Functioning Questionnaire (RFQ), the Difficulties in Emotion Regulation Strategies (DERS), the Interpersonal Reactivity Index (IRI). Clinicians rated patients in relation to imbalances in different dimensions of mentalization to prementalizing modes and attachment style by using the Mentalization Imbalances Scale, the Modes of Mentalization Scale (MMS), and the Adult Attachment Questionnaire. A latent profile analysis was conducted to test the possible presence of different subgroups. MANOVA was used to test the possible differences between the four mentalizing profiles in relation to emotion dysregulation (DERS), empathy (IRI), and adequate and impairments in mentalizing (MMS and RFQ). Results: The latent profile analysis suggested the presence of four different profiles in relation to impairments in the dimensions of mentalization: (1) affective/self/automatic imbalances, (2) external imbalance, (3) cognitive/self/automatic imbalances, and (4) cognitive/other/automatic imbalances. Patients belonging to profile 1 are characterized by the prevalence of affective mentalization that overwhelms the capacity to reflect on mental states with an imbalance on the self-dimension; profile 2 patients are excessively focused on the external cues of mentalization; profile 3 patients are characterized by an over-involvement on the cognitive and self-facets of mentalization, with an impairment in adopting the other mind perspective; and profile 4 patients have similar impairments compared to profile 3 patients but with an excessive focus on others and deficits in self-reflection. These profiles were heterogeneous in terms of EDs represented in each group and presented significant differences on various variables such as attachment style, emotion dysregulation, empathy, interpersonal reactivity, and reflective function. This study represents, so far, the first work that confirms the presence of different mentalizing patterns in ED patients. Conclusions: ED patients can be classified in relation to impairments in different dimensions of mentalization above and beyond ED diagnosis

The anticipation, perception of affective touch in women with, recovered from Anorexia Nervosa

Disruptions in reward processing and anhedonia have long been observed in Anorexia Nervosa (AN). Interoceptive deficits have also been observed in AN, including reduced tactile pleasure. However, the extent to which this tactile anhedonia is specifically liked to an impairment in a specialized, interoceptive C-tactile system originating at the periphery, or a more top-down mechanism in the processing of tactile pleasantness remains debated. Here, we investigated differences between patients with and recovered from AN and healthy controls in the perception of pleasantness of touch delivered in a CT-optimal versus a CT-non-optimal manner, and in their top-down, anticipatory beliefs about the perceived pleasantness of touch. To this end, we measured the anticipated pleasantness of various materials touching the skin and the perceived pleasantness of light, dynamic touch applied to theforearmof 27 women with AN, 24 women who have recovered and 30 healthy controls using C Tactile (CT) afferents-optimal (slow) and non-optimal (fast) velocities. Our results showed that both clinical groups anticipated tactile experiences and rated delivered tactile stimuli as less pleasant than healthy controls, but the latter difference was not related to the CT optimality of the stimulation. Instead, differences in the perception of CT-optimal touch were predicted by differences in top-down beliefs, alexithymia and interoceptive sensibility. Thus, tactile anhedonia in AN might persist as a trait even after otherwise successful recovery of AN and it is not linked to a bottom-up interoceptive deficit in the CT system, but rather to a learned, defective top-down anticipation of tactile pleasantness