On a mathematical procedure for detecting significant parameters in the classification of a statistical ensemble of phenomena and its applications

Summary The paper is concerned with a procedure for detecting the uncorrelated linear combinations of a given set of random variables. The linear transformation which is used is related to the eigenvectors of the covariance matrix for the original random variables. If the significant non correlated signals are in number less than the original ones (which have often a high degree of redundancy) the possibility arises for an application of this procedure to some branches of communication theory. The most important applications should be to vocoder for a further compression of information, for masking messages and also for building a machine which should be able to classify a statistical ensemble after suitable coding. The procedure has been tested by trying to extract significant parameters from a special coding of spoken Italian vowels in view of an improvement in the efficiency of speech recognition.     

When Action Meets Emotions: How Facial Displays of Emotion Influence Goal-Related Behavior

Many authors have proposed that facial expressions, by conveying emotional states of the person we are interacting with, influence the interaction behavior. We aimed at verifying how specific the effect is of the facial expressions of emotions of an individual (both their valence and relevance/specificity for the purpose of the action) with respect to how the action aimed at the same individual is executed. In addition, we investigated whether and how the effects of emotions on action execution are modulated by participants'' empathic attitudes. We used a kinematic approach to analyze the simulation of feeding others, which consisted of recording the “feeding trajectory” by using a computer mouse. Actors could express different highly arousing emotions, namely happiness, disgust, anger, or a neutral expression. Response time was sensitive to the interaction between valence and relevance/specificity of emotion: disgust caused faster response. In addition, happiness induced slower feeding time and longer time to peak velocity, but only in blocks where it alternated with expressions of disgust. The kinematic profiles described how the effect of the specificity of the emotional context for feeding, namely a modulation of accuracy requirements, occurs. An early acceleration in kinematic relative-to-neutral feeding profiles occurred when actors expressed positive emotions (happiness) in blocks with specific-to-feeding negative emotions (disgust). On the other hand, the end-part of the action was slower when feeding happy with respect to neutral faces, confirming the increase of accuracy requirements and motor control. These kinematic effects were modulated by participants'' empathic attitudes. In conclusion, the social dimension of emotions, that is, their ability to modulate others'' action planning/execution, strictly depends on their relevance and specificity to the purpose of the action. This finding argues against a strict distinction between social and nonsocial emotions.     

Two novel proteins that are linked to insulin-like growth factor (IGF-I) receptors by the Grb10 adapter and modulate IGF-I signaling

Grb10 is a protein that binds to the intracellular domains of activated tyrosine kinase receptors, including insulin-like growth factor (IGF-I) and insulin receptors. This occurs through the interaction of two C-terminal Grb10 motifs (BPS and Src homology domains) with receptor phosphotyrosine residues. Published data from transfection/overexpression studies support both positive and negative regulatory effects of Grb10, thus leaving its physiological role unclear. Because Grb10 has the structure of an adapter protein, the objective of this study was to determine whether Grb10 links other proteins to IGF-I receptors and thus modulates IGF-I signaling. Using yeast two-hybrid screening, the N terminus of Grb10 was shown to interact with two novel proteins, designated GIGYF1 (Grb10 interacting GYF protein 1) and GIGYF2. Mutation analysis indicates that a 17-amino acid sequence in GIGYF1 and GIGYF2, homologous to the GYF domain described previously, binds to tandem proline-rich regions in the N terminus of Grb10. In IGF-I receptor-expressing R+ fibroblasts, there is detectable binding of a Myc-tagged fragment of GIGYF1 to Grb10 in the basal state. Stimulation with IGF-I results in increased binding of GIGYF1 to Grb10 and transient binding of both Grb10 and GIGYF1 to IGF-I receptors, presumably via the adapter function of Grb10. At later time points, GIGYF1 dissociates, but Grb10 remains linked to IGF-I receptors. Overexpression of the Grb10 binding fragment of GIGYF1 in R+ cells results in a significant increase in IGF-I-stimulated receptor tyrosine phosphorylation. In conclusion, we have identified two members of a novel protein family, which become transiently linked to IGF-I receptors by the Grb10 adapter protein following IGF-I stimulation. Grb10 and GIGYFs may act cooperatively to regulate receptor signaling.     

Quantification of seminolipid by LC-ESI-MS/MS-multiple reaction monitoring: compensatory levels in Cgt mice

Seminolipid, also known as sulfogalactosylglycerolipid (SGG), plays important roles in male reproduction. Therefore, an accurate and sensitive method for SGG quantification in testes and sperm is needed. Here we compare SGG quantitation by the traditional colorimetric Azure A assay with LC-ESI-MS/MS using multiple reaction monitoring (MRM). Inclusion of deuterated SGG as the internal standard endowed accuracy to the MRM method. The results showed reasonable agreement between the two procedures for purified samples, but for crude lipid extracts, the colorimetric assay significantly overestimated the SGG content. Using ESI-MS/MS MRM, C16:0-alkyl/C16:0-acyl SGG of Cgt^+/− mice was quantified to be 406.06 ± 23.63 μg/g testis and 0.13 ± 0.02 μg/million sperm, corresponding to 78% and 87% of the wild-type values, respectively. CGT (ceramide galactosyltransferase) is a critical enzyme in the SGG biosynthesis pathway. Cgt^−/− males depleted of SGG are infertile due to spermatogenesis arrest. However, Cgt^+/− males sire offspring. The higher than 50% expression level of SGG in Cgt^+/− animals, compared with the wild-type expression, might be partly due to compensatory translation of the active CGT enzyme. The results also indicated that 78% of SGG levels in Cgt^+/− mice were sufficient for normal spermatogenesis.     

Energetic aspects of locked nucleic acids quadruplex association and dissociation

The design of modified nucleic acid aptamers is improved by considering thermodynamics and kinetics of their association/dissociation processes. Locked Nucleic Acids (LNA) is a promising class of nucleic acid analogs. In this work the thermodynamic and kinetic properties of a LNA quadruplex formed by the TGGGT sequence, containing only conformationally restricted LNA residues, are reported and compared to those of 2'-OMe-RNA (O-RNA) and DNA quadruplexes. The thermodynamic analysis indicates that the sugar-modified quadruplexes (LNA and O-RNA) are stabilized by entropic effects. The kinetic analysis shows that LNA and O-RNA quadruplexes are characterized by a slower dissociation and a faster association with respect to DNA quadruplex. Interestingly, the LNA quadruplex formation process shows a second-order kinetics with respect to single strand concentration and has a negative activation energy. To explain these data, a mechanism for tetramer formation with two intermediate states was proposed.     

Gender Differences in Sleep Deprivation Effects on Risk and Inequality Aversion: Evidence from an Economic Experiment

Excessive working hours—even at night—are becoming increasingly common in our modern 24/7 society. The prefrontal cortex (PFC) is particularly vulnerable to the effects of sleep loss and, consequently, the specific behaviors subserved by the functional integrity of the PFC, such as risk-taking and pro-social behavior, may be affected significantly. This paper seeks to assess the effects of one night of sleep deprivation on subjects’ risk and social preferences, which are probably the most explored behavioral domains in the tradition of Experimental Economics. This novel cross-over study employs thirty-two university students (gender-balanced) participating to 2 counterbalanced laboratory sessions in which they perform standard risk and social preference elicitation protocols. One session was after one night of undisturbed sleep at home, and the other was after one night of sleep deprivation in the laboratory. Sleep deprivation causes increased sleepiness and decreased alertness in all subjects. After sleep loss males make riskier decisions compared to the rested condition, while females do the opposite. Females likewise show decreased inequity aversion after sleep deprivation. As for the relationship between cognitive ability and economic decisions, sleep deprived individuals with higher cognitive reflection show lower risk aversion and more altruistic behavior. These results show that one night of sleep deprivation alters economic behavior in a gender-sensitive way. Females’ reaction to sleep deprivation, characterized by reduced risky choices and increased egoism compared to males, may be related to intrinsic psychological gender differences, such as in the way men and women weigh up probabilities in their decision-making, and/or to the different neurofunctional substrate of their decision-making.     

Penetration and Distribution of Thiocolchicoside through Human Skin: Comparison Between a Commercial Foam (Miotens<Superscript>®</Superscript><Emphasis Type="Bold">) and a Drug Solution</Emphasis>

Penetration and distribution of thiocolchicoside from a commercially available foam (Miotens^® 0.25%, w/v) through human excised full-thickness skin were evaluated using two different in vitro apparatus: a Franz diffusion cell and a Saarbruecken penetration model-based cell. In order to evaluate the intrinsic capability of the drug to penetrate into the skin, a simple drug aqueous solution prepared at the same drug concentration as Miotens^® was also tested. Results showed that both apparatus were suitable to study thiocolchicoside penetration into human skin. Penetrated drug amounts were comparable using the two apparatus, probably because skin acts as “sink” for the drug. Miotens^® was found to significantly promote thiocolchicoside accumulation into full human skin thickness in comparison with the simple drug solution. The mixture of propylene glycol and propylene glycol diperlargonate contained into Miotens^® foam has been proven to be effective to promote penetration of thiocolchicoside into human skin.     

Redox reactivity of the heme Fe<Superscript>3+</Superscript>/Fe<Superscript>2+</Superscript> couple in native myoglobins and mutants with peroxidase-like activity

The reaction enthalpy and entropy for the one-electron reduction of the ferric heme in horse heart and sperm whale aquometmyoglobins (Mb) have been determined exploiting a spectroelectrochemical approach. Also investigated were the T67R, T67K, T67R/S92D and T67R/S92D Mb-H variants (the latter containing a protoheme-l-histidine methyl ester) of sperm whale Mb, which feature peroxidase-like activity. The reduction potential (E°′) in all species consists of an enthalpic term which disfavors Fe³⁺ reduction and a larger entropic contribution which instead selectively stabilizes the reduced form. This behavior differs from that of the heme redox enzymes and electron transport proteins investigated so far. The reduction thermodynamics in the series of sperm whale Mb variants show an almost perfect enthalpy–entropy compensation, indicating that the mutation-induced changes in are dominated by reduction-induced solvent reorganization effects. The modest changes in E°′ originate from the enthalpic effects of the electrostatic interactions of the heme with the engineered charged residues. The small influence that the mutations exert on the reduction potential of myoglobin suggests that the increased peroxidase activity of the variants is not related to changes in the redox reactivity of the heme iron, but are likely related to a more favored substrate orientation within the distal heme cavity.     

Bacterium-bacterium inhibitory interactions among psychrotrophic bacteria isolated from Antarctic seawater (Terra Nova Bay, Ross Sea)

One hundred and forty bacteria isolated from Antarctic seawater samples were examined for their ability to inhibit the growth of indigenous isolates and their sensitivity to antibacterial activity expressed by one another. On the basis of 16S rRNA gene sequencing and analysis, bacterial isolates were assigned to five phylogenetically different taxa, Actinobacteria, alpha and gamma subclasses of Proteobacteria, Bacillaceae, and Bacteroidetes. Twenty-one isolates (15%), predominantly Actinobacteria, exhibited antagonistic properties against marine bacteria of Antarctic origin. Members of Bacteroidetes and Firmicutes did not show any inhibitory activity. Differences were observed among inhibition patterns of single isolates, suggesting that their activity was more likely strain-specific rather than dependent on phylogenetic affiliation. A novel analysis based on network theory confirmed these results, showing that the structure of this population is probably robust to perturbations, but also that it depends strongly on the most active strains. The determination of plasmid incidence in the bacterial strains investigated revealed that there was no correlation between their presence and the antagonistic activity. The data presented here provide evidence for the antagonistic interactions within bacterial strains inhabiting Antarctic seawater and suggest the potential exploitation of Antarctic bacteria as a novel source of antibiotics.     

The synthetic purine reversine selectively induces cell death of cancer cells

The synthetic purine reversine has been shown to possess a dual activity as it promotes the de‐differentiation of adult cells, including fibroblasts, into stem‐cell‐like progenitors, but it also induces cell growth arrest and ultimately cell death of cancer cells, suggesting its possible application as an anti‐cancer agent. Aim of this study was to investigate the mechanism underneath reversine selectivity in inducing cell death of cancer cells by a comparative analysis of its effects on several tumor cells and normal dermal fibroblasts. We found that reversine is lethal for all cancer cells studied as it induces cell endoreplication, a process that malignant cells cannot effectively oppose due to aberrations in cell cycle checkpoints. On the other hand, normal cells, like dermal fibroblasts, can control reversine activity by blocking the cell cycle, entering a reversible quiescent state. However, they can be induced to become sensitive to the molecule when key cell cycle proteins, e.g., p53, are silenced. J. Cell. Biochem. 113: 3207–3217, 2012. © 2012 Wiley Periodicals, Inc.