Aims
Negative and positive urgency are emotion‐related impulsivity traits that are thought to be transdiagnostic factors in psychopathology. However, it has recently been claimed that these two ...traits are closely related to each other and that considering them separately might have limited conceptual and methodological value. The present study aimed to examine whether positive and negative urgency constructs constitute separate impulsivity traits.
Methods
In contrast to previous studies that have used latent variable approaches, this study employed an item‐based network analysis conducted in two different samples: a large sample of non‐clinical participants (N = 18,568) and a sample of clinical participants with psychiatric disorders (N = 385).
Results
The network analysis demonstrated that items denoting both positive and negative urgency cohere as a single cluster of items termed “general urgency” in both clinical and non‐clinical samples, thereby suggesting that differentiating positive and negative urgency as separate constructs is not necessary.
Conclusion
These findings have important implications for the conceptualization and assessment of urgency and, more broadly, for future research on impulsivity, personality, and psychopathology.
The peptide KLA (acetyl-(KLAKLAK)2-NH2), which is rather non toxic for eukaryotic cell lines, becomes active when coupled to the cell penetrating peptide, penetratin (Pen), by a disulfide bridge. ...Remarkably, the conjugate KLA–Pen is cytotoxic, at low micromolar concentrations, against a panel of seven human tumor cell lines of various tissue origins, including cells resistant to conventional chemotherapy agents but not to normal human cell lines. Live microscopy on cells possessing fluorescent labeled mitochondria shows that in tumor cells, KLA–Pen had a strong impact on mitochondria tubular organization instantly resulting in their aggregation, while the unconjugated KLA and pen peptides had no effect. But, mitochondria in various normal cells were not affected by KLA–Pen. The interaction with membrane models of KLA–Pen, KLA and penetratin were studied using dynamic light scattering, calorimetry, plasmon resonance, circular dichroism and ATR-FTIR to unveil the mode of action of the conjugate. To understand the selectivity of the conjugate towards tumor cell lines and its action on mitochondria, lipid model systems composed of zwitterionic lipids were used as mimics of normal cell membranes and anionic lipids as mimics of tumor cell and mitochondria membrane. A very distinct mode of interaction with the two model systems was observed. KLA–Pen may exert its deleterious and selective action on cancer cells by the formation of pores with an oblique membrane orientation and establishment of important hydrophobic interactions. These results suggest that KLA–Pen could be a lead compound for the design of cancer therapeutics.
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•KLA–Penetratin selectively inhibits tumor cell growth.•KLA–Penetratin disrupts mitochondria tubular organization.•KLA–penetratin selectively interacts with anionic lipid membranes.•KLA–penetratin strongly perturbs anionic membrane organization.•KLA–penetratin forms pores in anionic membranes.
The diversity of mating and sexual systems in angiosperms is spectacular, but the factors driving their evolution remain poorly understood. In plants of the Oleaceae family, an unusual ...self-incompatibility (SI) system has been discovered recently, whereby only two distinct homomorphic SI specificities segregate stably. To understand the role of this peculiar SI system in preventing or promoting the diversity of sexual phenotypes observed across the family, an essential first step is to characterize the genetic architecture of these two traits. Here, we developed a high-density genetic map of the androdioecious shrub P. angustifolia based on a F1 cross between a hermaphrodite and a male parent with distinct SI genotypes. Using a double restriction-site associated digestion (ddRAD) sequencing approach, we obtained reliable genotypes for 196 offspring and their two parents at 10,388 markers. The resulting map comprises 23 linkage groups totaling 1,855.13 cM on the sexaveraged map. We found strong signals of association for the sex and SI phenotypes, that were each associated with a unique set of markers on linkage group 12 and 18 respectively, demonstrating inheritance of these traits as single, independent, mendelian factors. The P. angustifolia linkage map shows robust synteny to the olive tree genome overall. Two of the six markers strictly associated with SI in P. angustifolia have strong similarity with a recently identified 741kb chromosomal region fully linked to the SI phenotype on chromosome 18 of the olive tree genome, providing strong cross-validation support. The SI locus stands out as being markedly rearranged, while the sex locus has remained relatively more collinear between the two species. This P. angustifolia linkage map will be a useful resource to investigate the various ways by which the sex and SI determination systems have co-evolved in the broader phylogenetic context of the Oleaceae family.
La diversité des systèmes de reproduction et des types sexuels chez les angiospermes est spectaculaire, mais les facteurs de leur évolution restent mal compris. Chez les plantes de la famille des Oleacées, un système d'auto-incompatibilité (SI) inhabituel a été découvert récemment, dans lequel seules deux spécificités SI distinctes mais parfaitement homomorphes ségrégent de manière stable. Pour comprendre le rôle de ce système SI particulier dans la prévention ou la promotion de la diversité des phénotypes sexuels observés dans la famille des Oléacées, une première étape essentielle est de caractériser l'architecture génétique de ces deux traits. Ici, nous avons développé une carte génétique à haute densité de l'arbuste androdioïque P. angustifolia basée sur un croisement F1 entre un hermaphrodite et un parent mâle avec des génotypes SI distincts. En utilisant une approche de séquençage par double digestion associée à un site de restriction (ddRAD), nous avons obtenu des génotypes fiables pour 196 descendants et leurs deux parents sur 10 388 marqueurs. La carte résultante comprend 23 groupes de liaison totalisant 1 855,13 cM sur la carte moyenne par sexe. Nous avons trouvé de forts signaux d'association pour les phénotypes sexe et SI, qui étaient chacun associés à un ensemble unique de marqueurs sur les groupes de liaison 12 et 18 respectivement, démontrant l'héritage de ces traits comme facteurs mendéliens uniques et indépendants. La carte de liaison de P. angustifolia montre une synténie robuste avec le génome de l'olivier dans son ensemble. Deux des six marqueurs strictement associés au SI chez P. angustifolia présentent une forte similitude avec une région chromosomique de 741 kb récemment identifiée et entièrement liée au phénotype SI sur le chromosome 18 du génome de l'olivier, ce qui fournit une forte validation croisée. Le locus SI se distingue par un réarrangement marqué, tandis que le locus sexuel est resté relativement colinéaire entre les deux espèces. Cette carte de liaison de P. angustifolia sera une ressource utile pour étudier les différentes façons dont les systèmes de détermination du sexe et du SI ont co-évolué dans le contexte phylogénétique plus large de la famille des Oléacées.
This article analyzes the question of whether central bank capture by the financial sector has increased in the aftermath of the financial crisis beginning in 2007. According to the Public Choice ...theory, this is inevitable: The financial sector has an increased incentive to capture the central bank for interest rates hikes, inter alia, to prevent inflationary pressures from unconventional monetary policies. On the contrary, for the Post-Keynesian democratic school, this is likely but not inevitable because central bank capture is a complex phenomenon depending on a contest between several actors. The relative ability of the financial sector to affect central bank interest rates, and in which direction it desired to do so, can be time varying. Motivated by profitability, the financial sector can be interested in either interest rate hikes or cuts. This article investigates empirically this theoretical debate for the period from January 1999 to December 2016 for the European Central Bank's Governing Council, the Federal Reserve's Board of Governors, and the Monetary Policy Committee of the Bank of England. We participate in this debate first by constructing, as standard in the literature, an F index indicating the ratio of central bankers with financial career background. Secondly, we test empirically the competing hypotheses on the capture of the central bank interest rate by estimating its relationship with our F index. Results are more favorable to the democratic school.
ABSTRACT
Holoprosencephaly (HPE) is the most common congenital cerebral malformation in humans, characterized by impaired forebrain cleavage and midline facial anomalies. It presents a high ...heterogeneity, both in clinics and genetics. We have developed a novel targeted next‐generation sequencing (NGS) assay and screened a cohort of 257 HPE patients. Mutations with high confidence in their deleterious effect were identified in approximately 24% of the cases and were held for diagnosis, whereas variants of uncertain significance were identified in 10% of cases. This study provides a new classification of genes that are involved in HPE. SHH, ZIC2, and SIX3 remain the top genes in term of frequency with GLI2, and are followed by FGF8 and FGFR1. The three minor HPE genes identified by our study are DLL1, DISP1, and SUFU. Here, we demonstrate that fibroblast growth factor signaling must now be considered a major pathway involved in HPE. Interestingly, several cases of double mutations were found and argue for a polygenic inheritance of HPE. Altogether, it supports that the implementation of NGS in HPE diagnosis is required to improve genetic counseling.
–FGF signaling plays a major role in the onset of HPE
–FGFR1 mutations are involved in isolated HPE
–Mutations in GLI2 are often associated with midline abnormalities
–Several cases of double‐mutations argue for digenic inheritance of HPE
Informations about the effects of intense exercise training on diabetes-induced myocardial dysfunctions are lacking. We have examined the effects of intense exercise training on the cardiac function ...of diabetic rats, especially focusing on the Langendorff β-adrenergic responsiveness and on the β-adrenoceptors protein expression.
Control or Streptozotocin induced-diabetic male Wistar rats were randomly assigned to sedentary or trained groups. The training program consisted of 8 weeks running on a treadmill (10° incline, up to 25 m/min, 60 min/day) and was considered to be intense for diabetic rats.
This intense exercise training amplified the in vivo diabetes-induced bradycardia. It had no effect on Langendorff basal cardiac contraction and relaxation performances in control and diabetic rats. In diabetic rats, it accentuated the Langendorff reduced responsiveness to β-adrenergic stimulation. It did not blunt the diabetes-induced decrease of β1-adrenoceptors protein expression, displayed a significant decrease in the β2-adrenoceptors protein expression and normalized the β3-adrenoceptors protein expression.
Intense exercise training accentuated the decrease in the myocardial responsiveness to β-adrenergic stimulation induced by diabetes. This defect stems principally from the β2-adrenoceptors protein expression reduction. Thus, these results demonstrate that intense exercise training induces specific effects on the β-adrenergic system in diabetes.
Metabolic reprogramming is a hallmark of cancer development, mediated by genetic and epigenetic alterations that may be pharmacologically targeted. Among oncogenes, the kinase Akt is commonly ...overexpressed in tumors and favors glycolysis, providing a rationale for using Akt inhibitors. Here, we addressed the question of whether and how inhibiting Akt activity could improve therapy of non-small cell lung cancer (NSCLC) that represents more than 80% of all lung cancer cases. First, we demonstrated that Akt inhibitors interacted synergistically with Microtubule-Targeting Agents (MTAs) and specifically in cancer cell lines, including those resistant to chemotherapy agents and anti-EGFR targeted therapies. In vivo, we further revealed that the chronic administration of low-doses of paclitaxel - i.e. metronomic scheduling - and the anti-Akt perifosine was the most efficient and the best tolerated treatment against NSCLC. Regarding drug mechanism of action, perifosine potentiated the pro-apoptotic effects of paclitaxel, independently of cell cycle arrest, and combining paclitaxel/perifosine resulted in a sustained suppression of glycolytic and mitochondrial metabolism. This study points out that targeting cancer cell bioenergetics may represent a novel therapeutic avenue in NSCLC, and provides a strong foundation for future clinical trials of metronomic MTAs combined with Akt inhibitors.
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