Publications

The cognitive mechanisms (especially the gender-related ones) underlying optical illusion processing remain elusive. Since the N400 component of event-related potentials (ERPs) is an index of the semantic integration of information processing tasks, the present study focuses on gender-related differences in N400 waveforms elicited during the reasoning process applied to reach a valid conclusion of optical illusions engaging working memory (WM).Fifty-one healthy participants (28 males, age = 34.25 years ± 10.25, years of education = 16.00 years ± 1.78; and 23 females, age = 33.43 ± 7.93, years of education = 15.56 ± 1.82) were measured. The N400 ERP component was evoked by 39 optical illusions adjusted to induce WM. We compared brain activation patterns while participants maintained conclusions of the optical illusions in WM. The N400 of ERPs was recorded during the WM phase, during which participants were required to draw a logical conclusion regarding the correctness of the optical illusions.Analysis revealed that females compared to males exhibited significantly increased N400 amplitudes located at parietal and occipital sites, whereas males exhibited significantly higher N400 amplitudes located at frontal areas. Furthermore, females compared to males demonstrated significantly prolonged latencies of the N400 component located at right frontotemporal abductions.These results suggest that coupling of optical illusions with WM engages distinct gender-related variations of brain semantic processing as reflected by the N400 ERP component. Based on the dual process account, our study gives support to the notion that women tend to employ a more deliberate and slower semantic reasoning than the men who tend to employ an automatic and fast one. Topographically, within the network sub-serving the semantic operation, the posterior brain areas responsible for sensorimotor integration-related processes elicit a greater brain activation among females while the anterior brain areas responsible for control and storage/retrieval operation elicit a greater brain activation among males.

Abstract TANK binding kinase 1 protein (TBK1) is a kinase that belongs to the IκB (IKK) family. TBK1, also known as T2K, FTDALS4, NAK, IIAE8 and NF-κB, is responsible for the phosphorylation of the amino acid residues Serine and Threonine. This enzyme is involved in various key biological processes, including interferon activation and production, homeostasis, cell growth, autophagy, insulin production and the regulation of TNF-α, IFN-β and IL-6. Mutations in the TBK1 gene alter the protein’s normal function and may lead to an array of pathological conditions, including disorders of the Central Nervous System. The present study sought to elucidate the role of the TBK1 protein in Amyotrophic Lateral Sclerosis (ALS), a human neurodegenerative disorder. A broad evolutionary and phylogenetic analysis of TBK1 was performed across numerous organisms to distinguish conserved regions important for the protein’s function. Subsequently, mutations and SNPs were explored and their potential effect on the enzyme’s function was investigated. These analytical steps, in combination with the study of the secondary, tertiary, and quaternary structure of TBK1, enabled the identification of conserved motifs, which can function as novel pharmacological targets and inform therapeutic strategies for Amyotrophic Lateral Sclerosis.

Background The recently discovered myokine irisin has been implicated in several observational studies, suggesting a potential therapeutic target for obesity‐related diseases. However, no information is available as to the heritability of this hormone. This study aims to fill this gap. Methods A total of 120 families (N=254;121 adults and 133 children) were included in this study taken from the Biomarkers Research Program cohort. Information included anthropometrics, glycemic, lipid and adipocytokine profiles. Irisin was measured using ELISA. Results The most significant heritable traits in sons included irisin (p=1.6*10‐5), systolic blood pressure (p=3.6*10‐4), LDL‐ (p=1.2*10‐6) and total cholesterol (p=3.5*10‐7). Heritable traits between mother and daughter again included irisin (p<0.002), as well as waist (p<0.01), hips (p<0.005) and blood pressure (p<0.002); HDL‐cholesterol was the single most significant predictor for irisin in adults, explaining 17% of variance, whilst in children angiotensin II was the most significant predictor of irisin explaining 19% of variance (p=0.003). Conclusion Circulating irisin appears to be maternally inherited and is predicted by HDL‐cholesterol in adults and angiotensin II in children, both factors influenced by energy expenditure and regulation. Taken together, these findings suggest a significant role of irisin in energy‐generating processes.

The incidence of obesity is increasing worldwide and this is obvious even from childhood, reaching indeed epidemic proportions. This phenomenon is strongly associated with the consequent presentati...

To examine whether the hypothalamic corticotropin-releasing hormone (CRH) neuron is regulated by CRH, by products of the proopiomelanocortin (POMC) gene, and/or by glucocorticoids, we used a rat hypothalamic organ culture system in which rat CRH secretion from single explanted hypothalami was evaluated by an RIA (iCRH) specific for rat CRH. The effects of graded concentrations of ovine CRH (oCRH), adrenocorticotropin hormone (ACTH), beta-endorphin (beta-EP), alpha-melanocyte-stimulating hormone (alpha-MSH), corticotropin-like intermediate lobe peptide (CLIP), ovine beta-lipotropin (ovine beta-LPH), and dexamethasone (DEX) upon unstimulated and serotonin- (5HT), acetylcholine- (ACh), and norepinephrine-(NE) stimulated CRH secretion were determined. oCRH and DEX inhibited unstimulated iCRH secretion with ID50 at the 10(-8) M range. ACTH had no detectable suppressive effect at 10(-8) M. oCRH, ACTH, and DEX inhibited 5HT-, ACh-, and NE-stimulated iCRH secretion in a dose-dependent fashion. beta-EP, alpha-MSH, and CLIP also inhibited 5HT-induced iCRH secretion. Of the latter peptides, the strongest inhibitor was beta-EP and the weakest was CLIP. Ovine beta-LPH had only a weak inhibitory effect on 5HT-induced iCRH secretion. Generally, the concentrations required for 50% suppression of neurotransmitter-stimulated iCRH secretion were significantly lower than those required for a similar suppression of unstimulated iCRH secretion. In conclusion, these data suggest the presence of multiple negative feedback loops involved in the regulation of the hypothalamic CRH neuron: an ultrashort CRH-mediated loop, a short, hypothalamic POMC-derived peptide loop, and a long, glucocorticoid-mediated negative feedback loop. The potency of these negative feedback loops may be determined by the state of activation of the CRH neuron.

Abstract Glucocorticoids are widely used in the therapy of inflammatory, autoimmune, and allergic diseases. As the end-effectors of the hypothalamic-pituitary-adrenal axis, endogenous glucocorticoids also play an important role in suppressing innate and cellular immune responses. Previous studies have indicated that glucocorticoids inhibit Th1 and enhance Th2 cytokine secretion. IL-12 promotes Th1 cell-mediated immunity, while IL-4 stimulates Th2 humoral-mediated immunity. Here, we examined the regulatory effect of glucocorticoids on key elements of IL-12 and IL-4 signaling. We first investigated the effect of dexamethasone on IL-12-inducible genes and showed that dexamethasone inhibited IL-12-induced IFN-γ secretion and IFN regulatory factor-1 expression in both NK and T cells. This occurred even though the level of expression of IL-12 receptors and IL-12-induced Janus kinase phosphorylation remained unaltered. However, dexamethasone markedly inhibited IL-12-induced phosphorylation of Stat4 without altering its expression. This was specific, as IL-4-induced Stat6 phosphorylation was not affected, and mediated by the glucocorticoid receptor, as it was antagonized by the glucocorticoid receptor antagonist RU486. Moreover, transfection experiments showed that dexamethasone reduced responsiveness to IL-12 through the inhibition of Stat4-dependent IFN regulatory factor-1 promoter activity. We conclude that blocking IL-12-induced Stat4 phosphorylation, without altering IL-4-induced Stat6 phosphorylation, appears to be a new suppressive action of glucocorticoids on the Th1 cellular immune response and may help explain the glucocorticoid-induced shift toward the Th2 humoral immune response.

Studies on extracellular vesicles have increased in recent years. The multi‑dimensional nature of their roles in cellular homeostasis, cell‑to‑cell and tissue‑to‑tissue communication at the level of the organism, as well as their actions on the holobiome (intra‑/interspecies interaction), have garnered the interest of a large number of researchers. Exosomes are one of the most researched classes of extracellular vesicles because they are carriers of targeted protein and DNA/RNA loads. Their multi‑functional cargo have been indicated to regulate a vast number of biological pathways in target cells. However, the mechanisms governing these interactions have not yet been fully determined. Endocrinology, by definition, focuses on homeostatic, and cell‑to‑cell and tissue‑to‑tissue communication mechanisms. Therefore exosomes should be included in this research topic. Exosomes have previously been associated with a number of endocrine disorders, including obesity, type 2 diabetes mellitus, disorders of the reproductive system and cancer. Furthermore, their biogenesis, composition and function have been associated with viruses, an entirely different domain of life. The profound roles of exosomes in homeostasis, stress and several pathological conditions, in conjunction with their selective and cell‑specific composition/function, allude to their use as promising circulating clinical biomarkers of systemic stress and specific pathologic states, and as biocompatible vehicles of therapeutic cargo. The current review provides information on exosomes and discusses their endocrine implications.