Activation of GPR15 and its involvement in the biological effects of smoking

Smoking is one of the most significant modifiable environmental risk factors for many diseases. Smoking causes excessive mortality worldwide. Despite decades of long research, there has not been a clear understanding regarding the molecular mechanism that makes smoking harmful to health. Some recent studies have found that smoking influences most significantly the expression and methylation of GPR15. GPR15 is an orphan receptor that is involved in the regulation of the innate immunity and the T-cell trafficking in the intestinal epithelium. Further studies have confirmed that GPR15 is very strongly involved in smoking and smoking-induced molecular changes. Therefore, the altered expression and epigenetic regulation of GPR15 could have a significant role in the health impact of smoking

Smoking-related general and cause-specific mortality in Estonia

Abstract Background Tobacco smoking is known to be the single largest cause of premature death worldwide. The aim of present study was to analyse the effect of smoking on general and cause-specific mortality in the Estonian population. Methods The data from 51,756 adults in the Estonian Genome Center of the University of Tartu was used. Information on dates and causes of death was retrieved from the National Causes of Death Registry. Smoking status, general survival, general mortality and cause-specific mortality were analysed using Kaplan-Meier estimator and Cox proportional hazards models. Results The study found that smoking reduces median survival in men by 11.4 years and in women by 5.8 years. Tobacco smoking produces a very specific pattern in the cause of deaths, significantly increasing the risks for different cancers and cardiovascular diseases as causes of death for men and women. This study also identified that external causes, such as alcohol intoxication and intentional self-harm, are more prevalent causes of death among smokers than non-smokers. Additionally, smoking cessation was found to reverse the increased risks for premature mortality. Conclusions Tobacco smoking remains the major cause for losses of life inducing cancers and cardiovascular diseases. In addition to the common diseases, external causes also reduce substantially the years of life. External causes of death indicate that smoking has a long-term influence on the behaviour of smokers, provoking self-destructive behaviour. Our study supports the idea, that tobacco smoking generates complex harm to our health increasing mortality from both somatic and mental disorders

Tritium beta polarization

The aim of the investigation described in this thesis was to obtain accurate longitudinal beta-polarization results at lowest possible velocities of the beta-particles in order to check whether or not there are real deviations from theory in the low-velocity range. The tritium decay was selected because of its very low end-point energy of 18.6 keV. In addition, the transition is of interest since it occurs between mirror nuclei, so that both Fermi and Gamow-Teller decay modes participate. This implies that a sufficiently precise polarization result can be of significance for obtaining narrower limits for beta-decay-coupling-constant ratios, especially for the case of vector interaction. The degree of longitudinal polarization was measured by means of the Mott scattering method, using an absolutely calibrated polarimeter. Instrumental asymmetries were reduced and corrected for with two detectors at forward scattering angles and in addition with a source of unpolarized electrons. We showed that depolarization in the tritium source is small near the end-point energy. Our final result for the degree of longitudinal polarization of tritium beta-particles with an average energy of 15.2 keV (v = 0.24c) is: P = -(1.005 +/- 0.026) v/c. This result is in good agreement with the theoretical prediction P = - v/c. Here v is the velocity of the beta-particles and c stands for the velocity of light. Because of this good agreement we propose to disregard the previous deviating results for other allowed decays at velocities below 0.6c. From our result we could deduce that the coupling-constant ratio for vector interaction is limited between 0.61 and 1.65. This range is narrower than the range previously deduced from all other relevant parity experiments combined.

At the dawn of the transcriptomic medicine

Impact statement This review describes the impact of transcriptomics on experimental biology and its integration into medical practice. Transcriptomics is an essential part of modern biomedical research based on highly sophisticated and reliable technology. Transcriptomics can aid clinical practice and improve the precision of clinical diagnoses and decision-making by complementing existing clinical best practice. The power of which will be increased when combined with genomic variation from genome wide association studies and next generation sequencing. We are witnessing the implementation of RNA-based technologies in clinical practice that will eventually lead to the establishment of transcriptional medicine as a routine tool in diagnosis. Progress in genomic analytical technologies has improved our possibilities to obtain information regarding DNA, RNA, and their dynamic changes that occur over time or in response to specific challenges. This information describes the blueprint for cells, tissues, and organisms and has fundamental importance for all living organisms. This review focuses on the technological challenges to analyze the transcriptome and what is the impact of transcriptomics on precision medicine. The transcriptome is a term that covers all RNA present in cells and a substantial part of it will never be translated into protein but is nevertheless functional in determining cell phenotype. Recent developments in transcriptomics have challenged the fundamentals of the central dogma of biology by providing evidence of pervasive transcription of the genome. Such massive transcriptional activity is challenging the definition of a gene and especially the term “pseudogene” that has now been demonstrated in many examples to be both transcribed and translated. We also review the common sources of biomaterials for transcriptomics and justify the suitability of whole blood RNA as the current optimal analyte for clinical transcriptomics. At the end of the review, a brief overview of the clinical implications of transcriptomics in clinical trial design and clinical diagnosis is given. Finally, we introduce the transcriptome as a target for modern drug development as a tool for extending our capacity for precision medicine in multiple diseases