Autophagy in DNA Damage Response

DNA damage response (DDR) involves DNA repair, cell cycle regulation and apoptosis, but autophagy is also suggested to play a role in DDR. Autophagy can be activated in response to DNA-damaging agents, but the exact mechanism underlying this activation is not fully understood, although it is suggested that it involves the inhibition of mammalian target of rapamycin complex 1 (mTORC1). mTORC1 represses autophagy via phosphorylation of the ULK1/2–Atg13–FIP200 complex thus preventing maturation of pre-autophagosomal structures. When DNA damage occurs, it is recognized by some proteins or their complexes, such as poly(ADP)ribose polymerase 1 (PARP-1), Mre11–Rad50–Nbs1 (MRN) complex or FOXO3, which activate repressors of mTORC1. SQSTM1/p62 is one of the proteins whose levels are regulated via autophagic degradation. Inhibition of autophagy by knockout of FIP200 results in upregulation of SQSTM1/p62, enhanced DNA damage and less efficient damage repair. Mitophagy, one form of autophagy involved in the selective degradation of mitochondria, may also play role in DDR. It degrades abnormal mitochondria and can either repress or activate apoptosis, but the exact mechanism remains unknown. There is a need to clarify the role of autophagy in DDR, as this process may possess several important biomedical applications, involving also cancer therapy

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

Analysis of microsatellite instability and loss of heterozygosity in breast cancer with the use of a well characterized multiplex system.

Analysis of microsatellite instability (MI) and loss of heterozygosity (LOH) is recommended for screening patients with sporadic and hereditary malignancies. This study shows an application of a fluorescent hexaplex PCR system for microsatellite typing on A.L.F. DNA Sequencer (Pharmacia Biotech). This technique detects changes in microsatellites providing a time-efficient, reliable and accurate method for MI and LOH analyses. The Fragment Manager software was used for automated size calculation and quantitation of DNA fragments, enabling rapid and precise measurement of allelic ratios. We examined 70 breast cancer and 70 control DNA specimens, classified all the patterns of microsatellite alterations, and set up MI and LOH assessment criteria for the automated multiplex fluorescent method

Association between Polymorphism rs1799732 of DRD2 Dopamine Receptor Gene and Personality Traits among MMA Athletes

Four factors—namely, harm avoidance, novelty seeking, reward addiction and persistence—represent the nature of temperament that is not genetically determined in itself. It was shown in earlier studies that a strong propensity to look for novelty or a tendency to engage in risky behavior is correlated with genetic variants in the area of the genes encoding dopamine receptors. Therefore, the aim of this study is to determine whether there is a relationship between personality traits and genetic variants in the area of the DRD2 dopamine receptor gene in MMA athletes. The participants consisted of 85 mixed martial arts (MMA) athletes and 284 healthy, non-MMA male participants. Their personality traits were measured using the Revised Temperament and Character Inventory. Blood was collected for genetic assays and all samples were genotyped using the real-time PCR method. We observed a statistically significant effect of a complex factor of the DRD2 rs1799732 genotype on MMA participants’ control and reward dependence. Engaging in high-risk sport may be associated with several personality characteristics. The DRD2 rs1799732 polymorphism may be associated with reduced harm avoidance in martial arts athletes, thereby modulating athletes’ predisposition to participate in high-risk sport

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—polysubstance-dependent male patients (n = 299) and the controls matched for age (n = 301). In both groups, we applied the same questionnaires for testing—Mini-international neuropsychiatric interview, the NEO Five-Factor Inventory, and the State–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 × 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

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

Sosnowsky’s hogweed (Heracleum sosnowskyi) – a plant endangering human health

Sosnowsky’s hogweed (Heracleum sosnowskyi) is considered to be an intrusive plant species in Poland which endangers human health and life. The paper aims at showing the complexity of influence of Sosnowsky’s hogweed on the human organism and its consequences for human health. The paper describes general physical and biochemical characteristics of this species. The authors analyze the influence of the species on human health and present general rules how to deal with possible negative health consequences. The paper draws attention to the necessity of undertaking educational activities related to the health risk in direct and indirect contact with the plant.Barszcz Sosnowskiego uważany jest za inwazyjny gatunek roślinny w Polsce, który stanowi zagrożenie dla zdrowia i życia ludzkiego. Celem pracy jest wykazanie złożoności oddziaływania i skutków zdrowotnych barszczu Sosnowskiego na organizm człowieka. Przedstawiono cechy fizyczne i biochemiczne tego gatunku. Omówiono jego wpływ na zdrowie ludzi oraz przedstawiono ogólne zasady postępowania w przypadku wystąpienia negatywnych skutów zdrowotnych. Zwrócono uwagę na konieczność podjęcia działań edukacyjnych związanych z ryzykiem zdrowotnym w bezpośrednim lub pośrednim kontakcie z tą rośliną