Cardiolipin drives cytochrome c proapoptotic and antiapoptotic actions

""\\"Cytochrome c (cytc) is pivotal in mitochondrial respiration and apoptosis. The heme-Fe-atom of native hexacoordinated horse heart cytc (hhcytc) displays a very low reactivity toward ligands and does not exhibit catalytic properties. However, on interaction with cardiolipin (CL), hhcytc changes its tertiary structure disrupting the heme-Fe-Met80 distal bond. The CL-hhcytc complex displays a very low midpoint potential, out of the range required for its physiological role, binds CO and NO with high affinity, facilitates peroxynitrite isomerization to NO(3)(-), and displays peroxidase activity. As a whole, the CL-hhcytc complex could play either proapoptotic effects, catalyzing lipid peroxidation and the subsequent hhcytc release into the cytoplasm, or antiapoptotic actions, such as scavenging peroxynitrite (i.e., protecting the mitochondrion from reactive nitrogen and oxygen species), and binding of CO and NO (i.e., inhibiting lipid peroxidation and hhcytc traslocation). Here, the CL-driven allosteric modulation of hhcytc properties is reviewed, highlighting proapoptotic and antiapoptotic actions. (C) 2011 IUBMB IUBMB Life, 63(3): 160-165, 2011\\""

Building typological classification in Switzerland using deep learning methods for seismic assessment

Natural disasters, such as earthquakes, have always represented a danger to human life. Seismic risk assessment consists of the evaluation of existing buildings and their expected response in case of an earthquake; the exposure model of buildings plays a key role in risk calculations. With this respect, in recent years, advanced techniques have been developed to speed up and automatize the processes of data acquisition to data interpretation, although it is worth mentioning that the visual survey is essential to train and validate Machine Learning (ML) methods. In the present study, the identification of building types is conducted by exploiting the traditional visual survey to implement a Deep Learning (DL) classification model. As a first step, city mapping schemes are obtained by classifying buildings according to the main features (i.e., construction period and height classes). Then, Random Forest (RF), a supervised learning algorithm, is applied to classify different building types by exploiting all their attributes. The RF model is trained and tested on the cities of Neuchatel and Yverdon-Les-Bains. The decent accuracy of the results encourages the application of the method to different cities, with proper adjustments in datasets, features and algorithms

INTRA-DUODENAL RELEASE OF A BITTER COMPOUND DECREASES CALORIC INTAKE IN HEALTHY VOLUNTEERS

Background and aim: α-gustducin and bitter taste receptors (T2R) are expressed both in the oral cavity and in the gastrointestinal (GI) tract. Experimental data showed that bitter tastants induce the release of gut hormones from enteroendocrine cells in the gut, suggesting a possible role of bitter taste receptors in the control of food intake and GI functions. We aimed to test the effects of a bitter taste receptor agonist on food intake and GI feelings. Material and methods: We enrolled 19 healthy subjects (9 males, age 27±7, BMI 24±6) in a double-blind placebo controlled study. Each subject randomly received an acid-resistant capsule containing placebo or 18 mg of quinine HCl. 60 minutes after capsule administration, the subjects underwent to an ad libitum test, until the maximum satiation. Meal test was composed by white bread, cheese and meat cream (89 kcal/portion: 50% carbohydrate, 31% fat, 19% protein). Caloric intake, meal duration and satiation levels, scored on a Visual Analogue Scale (VAS) were calculated at the end of the meal test. A questionnaire assessing GI sensations (bloating, fullness, nausea, epigastric discomfort and hunger) was administered before and at the end of the test. Data (mean ± SD) were compared by using paired t test. Results: No oral bitter sensation or side effects was observed both with quinine HCland placebo. No significant differences in terms of GI sensations and hunger feelings were observed between the two sessions of the study. The amount of calories ingested was significantly lower when subjects received quinine HCl than placebo (564±262 vs 667±278 kcal; p=0.02). Conversely, quinine HCl did not affect the meal duration (14.4±4.2 vs 16.6±4.6 min; p=NS) and the satiationintensity (82 vs 82 mm; p=NS). Conclusions: The intra-duodenal release of a bitter compound significantly decreases caloric intake in an ad libitum test meal without affecting GI sensations and hunger feeling. As the bitter compound does not influence meal duration, we hypothesize that quinine HCl decreases the caloric intake by affecting the rate of meal portions consumption. Evaluation of gut hormones kinetics and studies with other bitter taste receptor agonist are needed to establish the role of gastrointestinal bitter taste receptor in the control of food intak

Images in Christmas Balls

We describe light-reflection properties of spherically curved mirrors, like balls in the Christmas tree. In particular, we study the position of the image which is formed somewhere beyond the surface of a spherical mirror, when an eye observes the image of a pointlike light source. The considered problem, originally posed by Abu Ali Hasan Ibn al-Haitham -- alias Alhazen -- more than a millennium ago, turned out to have the now well known analytic solution of a biquadratic equation, being still of great relevance, e.g. for the aberration-free construction of telescopes. We do not attempt to perform an exhaustive survey of the rich historical and engineering literature on the subject, but develop a simple pedagogical approach to the issue, which we believe to be of continuing interest in view of its maltreating in many high-school textbooks.Comment: 13 pages, 7 figures plain LaTeX; Also see http://cft.fis.uc.pt/eef/mirrors.htm, revised version has simplified formulas, more transparent for a wider audience, one reference adde

The Met80Ala and Tyr67His/Met80Ala mutants of human cytochrome cshed light on the reciprocal role of Met80 and Tyr67 in regulating ligand access into the heme pocket.

The spectroscopic and functional properties of the single Met80Ala and double Tyr67His/Met80Ala mutants of human cytochrome c have been investigated in their ferric and ferrous forms, and in the presence of different ligands, in order to clarify the reciprocal effect of these two residues in regulating the access of exogenous molecules into the heme pocket. In the ferric state, both mutants display an aquo high spin and a low spin species. The latter corresponds to an OH- ligand in Met80Ala but to a His in the double mutant. The existence of these two species is also reflected in the functional behavior of the mutants. The observation that (i) a significant peroxidase activity is present in the Met80Ala mutants, (ii) the substitution of the Tyr67 by His leads to only a slight increase of the peroxidase activity in the Tyr67His/Met80Ala double mutant with respect to wild type, while the Tyr67His mutant behaves as wild type, as previously reported, suggests that the peroxidase activity of cytochrome c is linked to an overall conformational change of the heme pocket and not only to the disappearance of the Fe-Met80 bond. Therefore, in human cytochrome c there is an interplay between the two residues at positions 67 and 80 that affects the conformation of the distal side of the heme pocket, and thus the sixth coordination of the hem

The key role played by charge in the interaction of cytochrome c with cardiolipin

Cytochrome c undergoes structural variations upon binding of cardiolipin, one of the phospholipids constituting the mitochondrial membrane. Although several mechanisms governing cytochrome c/cardiolipin (cyt c/CL) recognition have been proposed, the interpretation of the process remains, at least in part, unknown. To better define the steps characterizing the cyt c-CL interaction, the role of Lys72 and Lys73, two residues thought to be important in the protein/lipid binding interaction, were recently investigated by mutagenesis. The substitution of the two (positively charged) Lys residues with Asn revealed that such mutations cancel the CL-dependent peroxidase activity of cyt c; furthermore, CL does not interact with the Lys72Asn mutant. In the present paper, we extend our study to the Lys → Arg mutants to investigate the influence exerted by the charge possessed by the residues located at positions 72 and 73 on the cyt c/CL interaction. On the basis of the present work a number of overall conclusions can be drawn: (i) position 72 must be occupied by a positively charged residue to assure cyt c/CL recognition; (ii) the Arg residues located at positions 72 and 73 permit cyt c to react with CL; (iii) the replacement of Lys72 with Arg weakens the second (low-affinity) binding transition; (iv) the Lys73Arg mutation strongly increases the peroxidase activity of the CL-bound protein

Mediterranean River Buffalo CSN1S1 gene: search for polymorphisms and association studies.

The aim of the present work was to study the variability at CSN1S1 locus of the Italian Mediterranean river buffalo and to investigate possible allele effects on milk yield and its composition. Effects of parity, calving season and month of production were also evaluated. Three SNPs were detected. The first mutation, located at position 89 of 17th exon (c.628C>T), is responsible for the amino acid change (p.Ser178Leu). The other two polymorphisms, detected at the positions 144 (c.882G>A) and 239 (c.977A>G) of 19th exon respectively, are silent (3’ UTR). Associations between the CSN1S1 genotypes and milk production traits were investigated using 4,122 test day records of 503 lactations from 175 buffalo cows. Milk yield, fat and protein percentages were analyzed using a mixed linear model. A significant association between the c.628C>T SNP and the protein percentage was found. In particular, the CC genotype showed an average value of about 0.04% higher than the CT and TT genotypes. The allele substitution effect of the cytosine into the thymine was -0.014, with a quite low (0.3%) protein percentage (PP) contribution on total phenotypic variance. A large dominance effect was detected. Furthermore, a characterization of the CSN1S1 transcripts and a method based on MboI-ACRS-PCR for a rapid genotyping of c.628C>T were provided

Evaluating the Targeting Efficiency of Anti-EGFR Functionalised Nanoparticles to Head and Neck Cancer Cells for Use in NIR-II Optical Window

Gold nanoparticles have been indicated for use in a diagnostic and/or therapeutic role in several cancer types. The use of gold nanorods (AuNRs) with a surface plasmon resonance (SPR) in the second near-infrared II (NIR-II) optical window promises deeper anatomical penetration through increased maximum permissible exposure and lower optical attenuation. In this study, the targeting and therapeutic efficiency of anti-epidermal growth factor receptor (EGFR)-antibody-functionalised AuNRs with an SPR at 1064 nm was evaluated in vitro. Four cell lines, KYSE-30, CAL-27, Hep-G2 and MCF-7, which either over- or under-expressed EGFR, were used once confirmed by flow cytometry and immunofluorescence. Optical microscopy demonstrated a significant difference (p 97%) in head and neck cancer cell line CAL-27 using tAuNRs but not uAuNRs, apoptosis being the major mechanism of cell death. This successful targeting and therapeutic outcome highlight the future use of tAuNRs for molecular photoacoustic imaging or tumour treatment through plasmonic photothermal therapy