234 research outputs found

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

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    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

    Phase separations, liquid crystal ordering and molecular partitioning in mixtures of PEG and DNA oligomers

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    Liquid crystals (LCs) ordering of DNA and RNA oligomers relies on the presence of inter-duplex end-to-end attraction, driving the formation of linear aggregates. Such interactions are gauged, at a macroscopic level, by the osmotic pressure at the isotropic-nematic and nematic-columnar phase transitions. We studied aqueous solutions of PEG and DNA duplex-forming oligomers, finding that there is a wide range of concentrations in which these mixtures phase separate into coexisting PEG-rich and DNA-rich phases, the latter being either in the isotropic state or ordered as a nematic or columnar LC. We determined the phase diagram in mixtures of PEG and DNA duplexes with different terminal motifs\u2013blunt ends, sticky overhangs, aggregation-preventing overhangs\u2013and measured the partitioning of the species in the coexisting phases. On this basis, we determined the osmotic pressure as a function of the DNA concentration across the phase diagram. We compared the equation of state obtained in this way with both the Carnahan\u2013Starling equation of state for hard spheres and with the pressure predicted by computer simulations of a system of aggregating cylinders. We obtain a good agreement between experiments and simulations, and end-to-end attraction energies of the order of 6 kcal/mol, a bit larger than expected, but still in agreement with the current models for DNA-DNA interactions

    Risk of heat illness in men and women: a systematic review and meta-analysis

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    Background Heat illness (HI) is a growing global concern; its incidence has risen dramatically across the world in recent years. The individual factors whereby elevated core temperature produces HI are not well-understood. Given known physiological differences between men and women pertaining to temperature regulation, we hypothesized that women would be at increased risk of HI than men. Objectives We aimed to determine the relative risk of HI in women compared with men through an exhaustive literature review and meta-analysis. Methods We search PubMed and Ovid Medline databases from inception to Apr 2017. Search terms included all permutations of sex and heat illness (including heatstroke and exertional heat illness) with no language restrictions. We included adult or adolescent human data reporting comparable male and female HI rates. One reviewer identified and screened titles and abstracts. Two independent reviewers applied eligibility criteria. Disagreements were resolved with a third reviewer. Results Of 5888 articles identified by searches, 36 were included in the systematic review and 22 in the meta-analysis. The mean (standard deviation) quality score was 3.31(1.25)/5. Overall the rate among women was consistently lower than men across the lifespan. The male: female pooled IRR was 2.28 (p<0.001, 95% CI: 1.66-3.16). There was modest heterogeneity (between-studies variance (Ï„2) = 0.02). The rates did not differ significantly when corrected for severity or occupation. Discussion The rate of HI was significantly increased in men compared with women. Risk for HI might be conferred by psychological and behavioral factors rather than physiological ones. Further research is required to delineate which groups are at greatest risk, leading to the development of mitigation strategies against HI

    stream temperature estimated in situ from thermal infrared images best estimate and uncertainty

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    The paper aims to show a technique to estimate in situ the stream temperature from thermal-infrared images deepening its best estimate and uncertainty. Stream temperature is an important indicator of water quality and nowadays its assessment is important particularly for thermal pollution monitoring in water bodies. Stream temperature changes are especially due to the anthropogenic heat input from urban wastewater and from water used as a coolant by power plants and industrial manufacturers. The stream temperatures assessment using ordinary techniques (e.g. appropriate thermometers) is limited by sparse sampling in space due to a spatial discretization necessarily punctual. Latest and most advanced techniques assess the stream temperature using thermal-infrared remote sensing based on thermal imagers placed usually on aircrafts or using satellite images. These techniques assess only the surface water temperature and they are suitable to detect the temperature of vast water bodies but do not allow a detailed and precise surface water temperature assessment in limited areas of the water body. The technique shown in this research is based on the assessment of thermal-infrared images obtained in situ via portable thermal imager. As in all thermographic techniques, also in this technique, it is possible to estimate only the surface water temperature. A stream with the presence of a discharge of urban wastewater is proposed as case study to validate the technique and to show its application limits. Since the technique analyzes limited areas in extension of the water body, it allows a detailed and precise assessment of the water temperature. In general, the punctual and average stream temperatures are respectively uncorrected and corrected. An appropriate statistical method that minimizes the errors in the average stream temperature is proposed. The correct measurement of this temperature through the assessment of thermal- infrared images obtained in situ via portable thermal imager is confirmed by the direct measurement of stream temperature using an ordinary technique based on an appropriate thermometer

    Mentalizing subtypes in eating disorders: A latent profile analysis

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    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

    Room temperature polariton condensation from Whispering gallery modes in CsPbBr3 microplatelets

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    Room temperature (RT) polariton condensate holds exceptional promise for revolutionizing various fields of science and technology, encompassing optoelectronics devices to quantum information processing. Using perovskite materials like all-inorganic CsPbBr3 single crystal provides additional advantages, such as ease of synthesis, cost-effectiveness, and compatibility with existing semiconductor technologies. In this work, we show the formation of whispering gallery modes (WGM) in CsPbBr3 single crystals with controlled geometry, synthesized using a lowcost and efficient capillary bridge method. Through the implementation of microplatelets geometry, we achieve enhanced optical properties and performance thanks to the presence of sharp edges and a uniform surface, effectively avoiding non-radiative scattering losses caused by defects. This allows us not only to observe strong light matter coupling and formation of whispering gallery polaritons, but also to demonstrate the onset of polariton condensation at RT. This investigation not only contributes to the advancement of our knowledge concerning the exceptional optical properties of perovskite-based polariton systems, but also unveils prospects for the exploration of WGM polariton condensation within the framework of a 3D perovskite-based platform, working at RT. The unique characteristics of polariton condensate, including low excitation thresholds and ultrafast dynamics, open up unique opportunities for advancements in photonics and optoelectronics devices

    Backbone-free duplex-stacked monomer nucleic acids exhibiting Watson&#8211;Crick selectivity

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    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\u2013Crick 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

    Testosterone positively regulates vagina NO-induced relaxation: an experimental study in rats

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    PURPOSE: Female sexual response involves a complex interplay between neurophysiological mechanisms and the nitric oxide (NO)-mediated relaxation of clitoris and vagina. The aim of this study was to evaluate sex steroids regulation of the relaxant pathway in vagina, using a validated animal model. METHODS: Subgroups of OVX Sprague–Dawley rats were treated with 17β-estradiol, testosterone, or testosterone and letrozole, and compared with a group of intact animals. Masson’s trichrome staining was performed for morphological evaluation of the distal vaginal wall, in vitro contractility studies investigated the effect of OVX and in vivo treatments on vaginal smooth muscle activity. RNA from vaginal tissue was analyzed by semi-quantitative RT-PCR. RESULTS: Immunohistochemical analysis showed that OVX induced epithelial and smooth muscle structural atrophy, testosterone and testo + letrozole increased the muscle bundles content and organization without affecting the epithelium while 17β-estradiol mediated the opposite effects. In vitro contractility studies were performed on noradrenaline pre-contracted vaginal strips from each experimental group. Acetylcholine (0.001–10 µM) stimulation induced a concentration-dependent relaxation, significantly reduced by NO-synthase inhibitor L-NAME and by guanylate cyclase inhibitor ODQ. OVX resulted in a decreased responsiveness to acetylcholine, restored by testosterone, with or without letrozole, but not by 17β-estradiol. OVX sensitivity to the NO-donor SNP was higher than in the control. Vardenafil, a PDE5 inhibitor, enhanced SNP effect in OVX + testosterone as well as in control, as supported by RNA expression analysis. CONCLUSIONS: Our study demonstrates that testosterone improves the NO-mediated smooth muscle vaginal cells relaxation confirming its role in maintaining the integrity of muscular relaxant machinery
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