Unequal allelic expression of wild-type and mutated β-myosin in familial hypertrophic cardiomyopathy

Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease, which in about 30% of the patients is caused by missense mutations in one allele of the β-myosin heavy chain (β-MHC) gene (MYH7). To address potential molecular mechanisms underlying the family-specific prognosis, we determined the relative expression of mutant versus wild-type MYH7-mRNA. We found a hitherto unknown mutation-dependent unequal expression of mutant to wild-type MYH7-mRNA, which is paralleled by similar unequal expression of β-MHC at the protein level. Relative abundance of mutated versus wild-type MYH7-mRNA was determined by a specific restriction digest approach and by real-time PCR (RT-qPCR). Fourteen samples from M. soleus and myocardium of 12 genotyped and clinically well-characterized FHC patients were analyzed. The fraction of mutated MYH7-mRNA in five patients with mutation R723G averaged to 66 and 68% of total MYH7-mRNA in soleus and myocardium, respectively. For mutations I736T, R719W and V606M, fractions of mutated MYH7-mRNA in M. soleus were 39, 57 and 29%, respectively. For all mutations, unequal abundance was similar at the protein level. Importantly, fractions of mutated transcripts were comparable among siblings, in younger relatives and unrelated carriers of the same mutation. Hence, the extent of unequal expression of mutated versus wild-type transcript and protein is characteristic for each mutation, implying cis-acting regulatory mechanisms. Bioinformatics suggest mRNA stability or splicing effectors to be affected by certain mutations. Intriguingly, we observed a correlation between disease expression and fraction of mutated mRNA and protein. This strongly suggests that mutation-specific allelic imbalance represents a new pathogenic factor for FHC

Disruption of exonic splicing enhancer elements is the principal cause of exon skipping associated with seven nonsense or missense alleles of NF1

Nonsense, missense, and even silent mutation-associated exon skipping is recognized in an increasing number of genes as a novel form of splicing mutation. The analysis of individual mutations of this kind can shed light on basic pre-mRNA splicing mechanisms. Using cDNA,based mutation detection analysis, we have identified one missense and six nonsense mutations that lead to different extents of exon-lacking transcripts in neurofibromatosis type 1 (NF1) patients. We confirmed mutation-associated exon skipping in a heterologous hybrid minigene context. There is evidence that the disruption of functional exonic splicing enhancer (ESE) sequences is frequently the mechanism underlying mutation-associated exon skipping. Therefore, we examined the wild,type and mutant NF1 sequences with two available ESE-prediction programs. Either or both programs predicted the disruption of ESE motifs in six out of the seven analyzed mutations. To ascertain the function of the predicted ESEs, we quantitatively measured their ability to rescue splicing of an enhancer dependent exon, and found that all seven mutant ESEs had reduced splicing enhancement activity compared to the wild,type sequences. Our results suggest that the wild,type sequences function as ESE elements, whose disruption is responsible for the mutation-associated exon skipping observed in the NF1 patients. Further, this study illustrates the utility of ESE-prediction programs for delineating candidate sequences that may serve as ESE elements. However, until more refined prediction algorithms have been developed, experimental data, preferably from patient tissues, remain indispensable to assess the clinical significance, particularly of missense,and silent mutations, and to understand the structure-function relationship in the corresponding protein. (C) 2004 Wiley-Liss, Inc

Coping, schemas, and cardiovascular risks – study protocol

Milos Slepecky,1 Antonia Kotianova,1 Jan Prasko,2 Ivan Majercak,3 Erika Gyorgyova,4 Michal Kotian,1,5 Marta Zatkova,1 Ingrid Tonhajzerova,6,7 Michaela Chupacova,1,5 Marta Popelkova1 1Department of Psychology Sciences, Faculty of Social Science and Health Care, Constantine the Philosopher University in Nitra, Nitra, Slovak Republic; 2Department of Psychiatry, Faculty of Medicine and Dentistry, University Palacky Olomouc, University Hospital Olomouc, Olomouc, Czech Republic; 31st Department of Internal Medicine, Faculty of Medicine, Pavol Josef Safarik University in Košice, 4Internal Medicine and Cardiology Private Practice MUDr Ivan Majercak, Košice, 5Psychagogia, Liptovsky Mikulas, 6Department of Physiology, 7Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic Abstract: The aim of this article is to describe the protocol of a trial focusing on the psychological, anthropometric, cardiac, and psychophysiological factors contributing to increased risk of cardiovascular diseases (CVDs). As background, the article provides a short overview of research literature linking personal traits, maladaptive schemas, and coping styles with CVDs through reactivity of the autonomic nervous system. Keywords: early maladaptive schemas, coping styles, personality traits, dissociation, heart rate variabilit

Which psychological, psychophysiological, and anthropometric factors are connected with life events, depression, and quality of life in patients with cardiovascular disease

Milos Slepecky,1 Antonia Kotianova,1,2 Jan Prasko,1,3 Ivan Majercak,4,5 Erika Gyorgyova,5 Michal Kotian,1,2 Marta Zatkova,1 Marta Popelkova,1 Marie Ociskova,3 Ingrid Tonhajzerova6 1Department of Psychology Sciences, Faculty of Social Science and Health Care, Constantine the Philosopher University in Nitra, Nitra, 2Psychagogia, Liptovsky Mikulas, Slovak Republic; 3Department of Psychiatry, Faculty of Medicine and Dentistry, University Palacky Olomouc, University Hospital Olomouc, Olomouc, Czech Republic; 4First Department of Internal Medicine, Faculty of Medicine, Pavol Josef Safarik University in Kosice, 5Internal Medicine and Cardiology Private Practice, MUDr Ivan Majercak, Kosice, 6Department of Physiology and Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia Objective: The aim of the study was to determine psychological, psychophysiological, and anthropometric factors connected with life events, level of depression, and quality of life in people at risk for cardiovascular disease and healthy controls.Methods: This is a cross-sectional study involving arterial hypertension patients and healthy controls. There were several measurements including physical, anthropological, cardiovascular, and psychophysiological measurements and administration of questionnaires.Results: A total of 99 participants were recruited for this study, 54 healthy controls (mean age: 35.59±13.39 years) and 45 patients with cardiovascular disease (CVD) (mean age: 46.33±12.39 years). The healthy controls and the patients with CVD significantly differed in the mean total score of life events, level of depression, quality of life score, temperature, blood pressure (BP), pulse transit time, heart rate, high-frequency total power, heart rate variability total power, waist-to-height ratio (WHtR), body fat percentage, fat control, pulse wave velocity, and augmentation index. In healthy subjects, the total score of the life events was not correlated with any cardiovascular or anthropometric factor. A score of depression significantly correlated with the WHtR, augmentation index, body fat percentage, and fat control. The quality of life – visual scale correlated with the body temperature, BP, and percentage of body fat. In the group of the patients with CVD, the score of the life events did not correlate with any measured cardiovascular or anthropometric factor. The level of depression correlated with the augmentation index. The quality of life – visual scale significantly correlated with body temperature, WHtR, and fat control.Conclusion: The patients with CVD reported higher scores of life events, worse quality of life, and a greater level of depressive symptoms than healthy controls. In healthy controls, a higher mean total score of life events significantly negatively correlated with high-frequency total power, and the degree of depression correlated with being overweight. In patients with CVD, a score of depression was linked to being overweight. Keywords: life events, depression, quality of life, heart rate variability, autonomic nervous system, parameters of cardiovascular syste

Sex differences in human mate preferences vary across sex ratios

This material is based on work supported by the National Science Foundation under grant no. 1845586. The work of T.T.K.H. was supported by grant no. 501.01-2016.02 from the Vietnam National Foundation for Science and Technology Development (NAFOSTED). A.O. was supported by the Ministry of Science and Higher Education (grant no. 626/STYP/12/2017). A.S. and P.S. were supported by National Science Center-Poland (grant no. 2014/13/B/HS6/02644). Marina Butovskaya and D.D. were supported by State assignment project No. 01201370995 of the Institute of Ethnology and Anthropology, Moscow, Russia. P.G., A.L. and N.M. were supported by the Hungarian Scientific Research Fund-(OTKA; grant no. K125437). F.J. was supported by the National Nature Science Foundation of China (grant no. 71971225). G.A. was supported by UKRI/GCRF Gender, Justice, Security Grant (grant no. AH/S004025/1).A wide range of literature connects sex ratio and mating behaviours in non-human animals. However, research examining sex ratio and human mating is limited in scope. Prior work has examined the relationship between sex ratio and desire for short-term, uncommitted mating as well as outcomes such as marriage and divorce rates. Less empirical attention has been directed towards the relationship between sex ratio and mate preferences, despite the importance of mate preferences in the human mating literature. To address this gap, we examined sex ratio’s relationship to the variation in preferences for attractiveness, resources, kindness, intelligence and health in a long-term mate across 45 countries (n = 14 487). We predicted that mate preferences would vary according to relative power of choice on the mating market, with increased power derived from having relatively few competitors and numerous potential mates. We found that each sex tended to report more demanding preferences for attractiveness and resources where the opposite sex was abundant, compared to where the opposite sex was scarce. This pattern dovetails with those found for mating strategies in humans and mate preferences across species, highlighting the importance of sex ratio for understanding variation in human mate preferences.National Science Foundation (NSF) 1845586National Foundation for Science & Technology Development (NAFOSTED) 501.01-2016.02Ministry of Science and Higher Education, PolandEuropean Commission 626/STYP/12/2017National Science Centre, Poland 2014/13/B/HS6/02644Institute of Ethnology and Anthropology, Moscow, Russia 01201370995Orszagos Tudomanyos Kutatasi Alapprogramok (OTKA) K125437National Natural Science Foundation of China (NSFC) 71971225UKRI/GCRF Gender, Justice, Security Grant AH/S004025/