Application of machine-learning methods to recognize mitoBK channels from different cell types based on the experimental patch-clamp results

(1) Background: In this work, we focus on the activity of large-conductance voltage- and Ca2+-activated potassium channels (BK) from the inner mitochondrial membrane (mitoBK). The characteristic electrophysiological features of the mitoBK channels are relatively high single-channel conductance (ca. 300 pS) and types of activating and deactivating stimuli. Nevertheless, depending on the isoformal composition of mitoBK channels in a given membrane patch and the type of auxiliary regulatory subunits (which can be co-assembled to the mitoBK channel protein) the characteristics of conformational dynamics of the channel protein can be altered. Consequently, the individual features of experimental series describing single-channel activity obtained by patch-clamp method can also vary. (2) Methods: Artificial intelligence approaches (deep learning) were used to classify the patch-clamp outputs of mitoBK activity from different cell types. (3) Results: Application of the K-nearest neighbors algorithm (KNN) and the autoencoder neural network allowed to perform the classification of the electrophysiological signals with a very good accuracy, which indicates that the conformational dynamics of the analyzed mitoBK channels from different cell types significantly differs. (4) Conclusion: We displayed the utility of machine-learning methodology in the research of ion channel gating, even in cases when the behavior of very similar microbiosystems is analyzed. A short excerpt from the patch-clamp recording can serve as a “fingerprint” used to recognize the mitoBK gating dynamics in the patches of membrane from different cell types

Associations between the dopamine D4 receptor gene polymorphisms and personality traits in elite athletes

Personality traits and temperament may affect sports performance. Previous studies suggest that dopamine may play an important role in behavior regulation and physical exercise performance. The aim of this study is to determine associations between dopamine D4 receptor gene (DRD4 Ex3) polymorphisms and personality traits (such as neuroticism, extraversion, openness, agreeability and conscientiousness) in elite combat athletes. A total of 302 physically active, unrelated, self-reported Caucasian participants were recruited for this study. The participants consisted of 200 elite male combat athletes and 102 healthy male participants (control group). For personality trait measurements, the NEO Five-Factor Personality Inventory (NEO-FFI) and the State-Trait Anxiety Inventory questionnaires were used. For the genetic assays, blood was collected and all samples were genotyped using the real-time PCR method. A 2 x 3 factorial ANOVA revealed statistically significant differences on the Openness NEO Five Factor Inventory scale for both examined factors, i.e. sport status and genetics DTD4 Ex3. Combat athletes achieved higher scores on the Conscientiousness NEO-FFI scale when compared to controls (7.18 vs 5.98). On the other hand, combat athletes scored lower on the Openness scale in comparison with control group (4.42 vs. 4.63). Subjects with the DRD4 Ex3 s/s genotype had lower results on the openness scale in comparison with participants with the DRD4 Ex3 s/1 genotype (4.01 vs. 4.57) and higher DRD4 Ex3 1/1 genotype (4,01 vs. 3,50). In conclusion, we found an association between the dopamine D4 receptor gene in variable number tandem repeat (VNTR) polymorphisms and athletic status for two NEO-FFI factors: Openness and Conscientiousness. The DRD4 exon 3 polymorphism may be associated with the selected personality traits in combat athletes, thereby modulating athletes’ predisposition to participate in high risk sports

Choice of the first job in high school students under their proffesional predispositions

Niniejsza praca podkreśla potrzebę rozwijania doradztwa zawodowego dla młodzieży. Jej celem jest ukazanie wyboru pierwszej pracy uczniów szkół średnich, w świetle ich predyspozycji zawodowych. W części teoretycznej przedstawiono zainteresowania i zdolności w literaturze. Na początku podano terminologię pojęcia zainteresowanie i kategorii z nim związanych, przedstawiono definicje opisowe zainteresowań, ich zróżnicowane klasyfikacje, omówiono jak się rozwijają w ciągu życia, oraz jak istotną rolę odgrywają dla każdego człowieka. Następnie zobrazowano zależności pomiędzy zainteresowaniami a zdolnościami i scharakteryzowano w skrócie kilka wybranych koncepcji zainteresowań i preferencji zawodowych. Oparte było na nich narzędzie badawcze jakie zastosowano w tej pracy tj. Kwestionariusz Predyspozycji, oraz krótkie dodatkowe pytania dotyczące wizji maturzystów odnośnie ich pierwszej pracy. Kolejnym krokiem było omówienie w skrócie genezy i badań nad zdolnościami, przedstawienie definicji zdolności i uzdolnień, wyszczególnienie ich istoty i charakteru, oraz charakterystyka ucznia zdolnego i jego cech osobowości. Później przedstawiono typologie zdolności i opisano skrótowo koncepcje wybitnych zdolności w rozumieniu różnych autorów. W części metodologicznej zaprezentowano uzasadnienie wyboru tematu, cel i przedmiot badań, określono problemy oraz hipotezy badawcze. Następnie wymieniono zmienne i wskaźniki, scharakteryzowano metody, techniki i narzędzia badawcze, a także opisano teren badań, ich organizację i przebieg. W części empirycznej określono wyniki przeprowadzonych badań, które dotyczyły wyboru edukacyjno-zawodowego młodzieży.The thesis emphasizes the need to develop vocational guidance for young people. Its aim is to show the first choice of job in the high school students, in the light of their professional aptitudes. The theoretical part presents the foundation of interests and abilities based on the current literature. At the beginning the terminology of interest and categories associated with it are described. It follows the descriptive definitions of interests, and their different classifications. Then, there is discussed how they are developing in the lifespan, as well as how important role they play for every person. The relationship between interests and abilities is illustrated, and some selected concepts of professional interests and preferences are briefly characterized. It was based on an empirical survey. The research tools were The Questionnaire of Predispositions and short questionnaire directed to the recognition of the first job choices by lyceum students.. The next step was to discuss briefly the genesis and studies on skills, also the definition of abilities and aptitudes, description of their nature and character, and the characteristics of a talented pupil and his personality traits. There are presented capability typologies and briefly described the concepts of outstanding ability in terms of various authors. The methodological part presents the reasons for the choice of the thesis’ topic. The purpose and objectives of the study are also presented as well as specific issues and research hypotheses. Next, there are listed the variables and indicators, which characterize methods, techniques and research tools, and it is described the area of research, its organization and the course. In the empirical part of the thesis there are described the results of the studies that focus on young people choices concerning further education and occupation

Genetic Factors of Teeth Impaction: Polymorphic and Haplotype Variants of <i>PAX9</i>, <i>MSX1</i>, <i>AXIN2</i>, and <i>IRF6</i> Genes

In recent research, there has been a growing awareness of the role of genetic factors in the positioning and eruption of teeth in the maxilla and mandible. This study aimed to evaluate the potential of specific polymorphic markers of single nucleotide polymorphisms (SNPs) located within the PAX9, MSX1, AXIN2, and IRF6 genes to determine the predisposition to tooth impaction. The study participants were divided into two groups: the first group consisted of individuals with at least one impacted secondary tooth. In contrast, the second group (control group) had no impacted teeth in their jaws. To analyze the genes, real-time PCR (polymerase chain reaction) and TaqMan probes were utilized to detect the selected polymorphisms. The findings suggest that disruptions in the structure and function of the mentioned genetic factors such as polymorphic and haplotype variants of PAX9, MSX1, AXIN2, and IRF6 genes, which play a direct role in tooth and periodontal tissue development, might be significant factors in tooth impaction in individuals with genetic variations. Therefore, it is reasonable to hypothesize that tooth impaction may be influenced, at least in part, by the presence of specific genetic markers, including different allelic variants of the PAX9, AXIN2, and IRF6 genes, and especially MSX1

Flavonoids as Modulators of Potassium Channels

Potassium channels are widely distributed integral proteins responsible for the effective and selective transport of K+ ions through the biological membranes. According to the existing structural and mechanistic differences, they are divided into several groups. All of them are considered important molecular drug targets due to their physiological roles, including the regulation of membrane potential or cell signaling. One of the recent trends in molecular pharmacology is the evaluation of the therapeutic potential of natural compounds and their derivatives, which can exhibit high specificity and effectiveness. Among the pharmaceuticals of plant origin, which are potassium channel modulators, flavonoids appear as a powerful group of biologically active substances. It is caused by their well-documented anti-oxidative, anti-inflammatory, anti-mutagenic, anti-carcinogenic, and antidiabetic effects on human health. Here, we focus on presenting the current state of knowledge about the possibilities of modulation of particular types of potassium channels by different flavonoids. Additionally, the biological meaning of the flavonoid-mediated changes in the activity of K+ channels will be outlined. Finally, novel promising directions for further research in this area will be proposed

A New Method of Identifying Characteristic Points in the Impedance Cardiography Signal Based on Empirical Mode Decomposition

The accurate detection of fiducial points in the impedance cardiography signal (ICG) has a decisive impact on the proper estimation of diagnostic parameters such as stroke volume or cardiac output. It is, therefore, necessary to find an algorithm that is able to assess their positions with great precision. The solution to this problem is, however, quite challenging with regard to the high sensitivity of the ICG technique to the noise and varying morphology of the acquired signals. The aim of this study is to propose a novel method that allows us to overcome these limitations. The developed algorithm is based on Empirical Mode Decomposition (EMD)—an effective technique for processing and analyzing various types of non-stationary signals. We find high correlations between the results obtained from the algorithm and annotated by an expert. This, in turn, implies that the difference in estimation of the diagnostic-relevant parameters is small, which suggests that the method can automatically provide precise clinical information

Influence of DAT1 Promotor Methylation on Sports Performance

In the mammalian genome, DNA methylation is an epigenetic mechanism involving the transfer of a methyl group onto the C5 position of the cytosine to form 5-methylcytosine. DNA methylation regulates gene expression by recruiting proteins involved in gene repression or by inhibiting the binding of transcription factors (TFs) to DNA. As there are still many questions concerning the role of methylation in creating personality, we concentrated on searching for such associations. The research group was 100 sports male subjects (mean age = 22.88, SD = 6.35), whereas the control group included 239 healthy male volunteers matched for age (mean age = 21.69, SD = 3.39), both of European origin. The methods used in our research were as follows: DNA isolation, methylation-specific PCR, sequencing chromatophores, all conducted according to the manufacturer’s procedure. To evaluate personality traits, the NEO Five-Factor Personality Inventory (NEO-FFI) and STAI Inventory were used. We observed the existence of a statistically significant correlation for all the aspects of personality covered and CpG islands’ methylation. Nonetheless, we think that the tested group and the number of tested promotor islands in the DAT1 gene are still too small to make explicit conclusions, so it needs further profound analysis

Dopamine Receptor DRD2 Gene rs1076560, Personality Traits and Anxiety in the Polysubstance Use Disorder

Development of an addiction is conditioned by many factors. The dopaminergic system has been shown to be the key element in this process. In this paper, we analyzed the influence of dopamine receptor 2 polymorphism rs1076560 in two groups&mdash;polysubstance-dependent male patients (n = 299) and the controls matched for age (n = 301). In both groups, we applied the same questionnaires for testing&mdash;Mini-international neuropsychiatric interview, the NEO Five-Factor Inventory, and the State&ndash;Trait Anxiety Inventory. The real-time PCR method was used for genotyping. When we compared the controls with the case group subjects, we observed significantly higher scores in the second group on both the state and trait scales of anxiety, as well as on the Neuroticism and Openness scales of the NEO-FFI; and lower scores on the scales of Extraversion and Agreeability of the NEO-FFI. The model 2 &times; 3 factorial ANOVA of the addicted subjects and controls was performed, and the DRD2 rs1076560 variant interaction was found for the anxiety state and trait scales, and for the NEO-FFI Neuroticism scale. The observed associations allow noticing that analysis of psychological factors in combination with genetic data opens new possibilities in addiction research

Potassium Channels, Glucose Metabolism and Glycosylation in Cancer Cells

Potassium channels emerge as one of the crucial groups of proteins that shape the biology of cancer cells. Their involvement in processes like cell growth, migration, or electric signaling, seems obvious. However, the relationship between the function of K+ channels, glucose metabolism, and cancer glycome appears much more intriguing. Among the typical hallmarks of cancer, one can mention the switch to aerobic glycolysis as the most favorable mechanism for glucose metabolism and glycome alterations. This review outlines the interconnections between the expression and activity of potassium channels, carbohydrate metabolism, and altered glycosylation in cancer cells, which have not been broadly discussed in the literature hitherto. Moreover, we propose the potential mediators for the described relations (e.g., enzymes, microRNAs) and the novel promising directions (e.g., glycans-orinented drugs) for further research

Analysis of DRD2 Gene Polymorphism in the Context of Personality Traits in a Group of Athletes

The presented study showed the relationship between dopamine receptor gene polymorphism and personality traits in athletes training in martial arts. Behavioral modulation resulting from a balance of the neurotransmitters dopamine and norepinephrine to inactivation of the dorsolateral prefrontal cortex and dysregulation of various pathways involved in attention and impulse control processes; Methods: The study was conducted among martial arts athletes. The study group included 258 volunteers and 284 controls. The genetic test was performed using the real-time PCR method; psychological tests were performed using standardized TCI questionnaires. All analyses were performed using STATISTICA 13. Results: Interaction between martial arts and DRD2 rs1799732 (manual) G/-(VIC/FAM)-ins/del and RD- Harm avoidance and Reward Dependence scale were demonstrated. In athletes, a lower Reward Dependence scale score was associated with the DRD2 rs1799732 (manual)-/-polymorphism compared to the control group. Conclusions: It seems justified to study not only genetic aspects related to brain transmission dopamine in martial arts athletes. In the studied athletes, the features related to reward addiction and harm avoidance are particularly important in connection with the dopaminergic reward system in the brain