In the philosophy of science, we can consider debates about the nature of non-causal explanations in general (e.g. Reutlinger, Saatsi 2018; Lange 2017) and then especially those in the life sciences (e.g. Huneman, 2018; Kostić 2020). These debates are accompanied by the development of a new mechanism that is becoming the major response to the nature of scientific explanation in the life sciences (e.g. Craver, Darden 2013; Craver 2006); and also by the development of a design explanation (e.g. Eck, Mennes 2016) that represents a modern variant of a functional explanation. In this paper, we will methodically: 1. evaluate the plurality of explanatory strategies in contemporary science (chapter 2). 2. describe the mechanical philosophy and mechanistic explanation (Glennan 2016; Craver, Darden 2013, etc.) (chapter 3). 3. explicate the role of mechanisms in code biology (Barbieri 2015, 2002, etc.) and its relation to the new mechanism (chapter 4). 4. fulfill the main goal of the paper - to apply mechanistic explanations in code biology (Barbieri 2019, etc.) and to apply their suitability for this scientific domain (chapter 5).

• Klíčová slova
• Biological sciences, Causal and non-causal explanation, Code biology, Mechanistic and design explanation, ‘Why’-questions,
• MeSH
• biologická evoluce MeSH
• biologické modely * MeSH
• biologické vědy metody   MeSH
• biologie metody   MeSH
• filozofie * MeSH
• kauzalita * MeSH
• lidé MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Conscious experience represents one of the most elusive problems of empirical science, namely neuroscience. The main objective of empirical studies of consciousness has been to describe the minimal sets of neural events necessary for a specific neuronal state to become consciously experienced. The current state of the art still does not meet this objective but rather consists of highly speculative theories based on correlates of consciousness and an ever-growing list of knowledge gaps. The current state of the art is defined by the limitations of past stimulation techniques and the emphasis on the observational approach. However, looking at the current stimulation technologies that are becoming more accurate, it is time to consider an alternative approach to studying consciousness, which builds on the methodology of causal explanations via causal alterations. The aim of this methodology is to move beyond the correlates of consciousness and focus directly on the mechanisms of consciousness with the help of the currently focused brain stimulation techniques, such as geodesic transcranial electric neuromodulation. This approach not only overcomes the limitations of the correlational methodology but will also become another firm step in the following science of consciousness.

• Klíčová slova
• brain stimulation, causal explanation, consciousness, excitation, geodesic transcranial electric neuromodulation, inhibition, mechanisms of consciousness, neural correlates of consciousness, transcranial electric stimulation,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: The inverse association between education and obesity was previously found in numerous studies. This study aims to assess several possible mediators in the educational disparities in adiposity. We hypothesize the potential mediating role of lifestyle, socioeconomic, and mental health factors in the association between education and adiposity. METHODS: Cross-sectional population-based sample from Czechia included 2,154 25-64 years old subjects (54.6% women). Education was classified as high, middle, and low. Adiposity was assessed as a latent variable based on body fat percentage, BMI, waist circumference, and visceral fat. The mediation potential of unhealthy dietary behavior, alcohol intake, smoking, sedentary behaviors, income, stress, depression, and quality of life was assessed in age-adjusted sex-specific multiple mediation models. RESULTS: The negative direct effect of education on adiposity was statistically significant at 5% level of significance in both sexes. For men, the indirect effect was statistically significant via sedentary behavior (β = 0.041; 95% CI [0.025-0.062]) with a mediation ratio of 23.7%. In women, the indirect effect was statistically significant via dietary risk (β = -0.023, 95% CI [-0.037, -0.013]), alcohol intake (β = -0.006; 95% CI [-0.014, -0.001]), sedentary behavior (β = 0.012, 95% CI [0.004,0.023]), income (β = -0.022; 95% CI [-0.041, -0.004]), and mental health (β = -0.007; 95% CI [-0.019, -0.001]). The total mediation ratio in women was 30.5%. CONCLUSIONS: Sedentary behaviors had mediating role in the association between education and adiposity in both sexes, with more important role in men. In addition, unhealthy diet and lower income partially mediated the educational gradient in adiposity in women.

• MeSH
• adipozita * MeSH
• analýza mediace MeSH
• disparity zdravotního stavu MeSH
• dospělí MeSH
• duševní zdraví * MeSH
• lidé středního věku MeSH
• lidé MeSH
• obezita epidemiologie   psychologie   MeSH
• průřezové studie MeSH
• sedavý životní styl MeSH
• socioekonomické faktory * MeSH
• stupeň vzdělání * MeSH
• životní styl * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Present-day biological medicine has not reconciled the modern heritage of mechanistic conception of causality, which in many aspects limits the diagnostic and therapeutic potential of contemporary physicians. If such reduced principle of causality is confronted with Aristotelian conception of four types of disease causes and with the possibility to use it in the study of life nature (and therefore also in medicine), non-trivial differences will be revealed, which can at least bring some inspiration to present day physicians. The contemporary psychosomatically thinking physicians are in a similar position from which Aristotle criticized his foregoers for insufficient explanation of the principle of cause and effect. Medical doctors have many common points with Aristotle and that is why it is possible to speak, with certain hyperbole, about renewal of Aristotelian conceptions in some of the new trends of contemporary medicine, where the present-day mechanistic mentality is replaced with ecosystematic thinking.

• MeSH
• dějiny starověku MeSH
• filozofie * MeSH
• kauzalita * MeSH
• lidé MeSH
• nemoc etiologie   MeSH
• psychosomatické lékařství * MeSH
• Check Tag
• dějiny starověku MeSH
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• biografie MeSH
• časopisecké články MeSH
• historické články MeSH
• práce podpořená grantem MeSH

• O autorovi
• Aristotle

The heterogeneous graphical Granger model (HGGM) for causal inference among processes with distributions from an exponential family is efficient in scenarios when the number of time observations is much greater than the number of time series, normally by several orders of magnitude. However, in the case of "short" time series, the inference in HGGM often suffers from overestimation. To remedy this, we use the minimum message length principle (MML) to determinate the causal connections in the HGGM. The minimum message length as a Bayesian information-theoretic method for statistical model selection applies Occam's razor in the following way: even when models are equal in their measure of fit-accuracy to the observed data, the one generating the most concise explanation of data is more likely to be correct. Based on the dispersion coefficient of the target time series and on the initial maximum likelihood estimates of the regression coefficients, we propose a minimum message length criterion to select the subset of causally connected time series with each target time series and derive its form for various exponential distributions. We propose two algorithms-the genetic-type algorithm (HMMLGA) and exHMML to find the subset. We demonstrated the superiority of both algorithms in synthetic experiments with respect to the comparison methods Lingam, HGGM and statistical framework Granger causality (SFGC). In the real data experiments, we used the methods to discriminate between pregnancy and labor phase using electrohysterogram data of Islandic mothers from Physionet databasis. We further analysed the Austrian climatological time measurements and their temporal interactions in rain and sunny days scenarios. In both experiments, the results of HMMLGA had the most realistic interpretation with respect to the comparison methods. We provide our code in Matlab. To our best knowledge, this is the first work using the MML principle for causal inference in HGGM.

• Klíčová slova
• Granger causality, graphical Granger model, information theory, minimum message length, overestimation,
• Publikační typ
• časopisecké články MeSH

Applications of causal techniques to neural time series have increased extensively over last decades, including a wide and diverse family of methods focusing on electroencephalogram (EEG) analysis. Besides connectivity inferred in defined frequency bands, there is a growing interest in the analysis of cross-frequency interactions, in particular phase and amplitude coupling and directionality. Some studies show contradicting results of coupling directionality from high frequency to low frequency signal components, in spite of generally considered modulation of a high-frequency amplitude by a low-frequency phase. We have compared two widely used methods to estimate the directionality in cross frequency coupling: conditional mutual information (CMI) and phase slope index (PSI). The latter, applied to infer cross-frequency phase-amplitude directionality from animal intracranial recordings, gives opposite results when comparing to CMI. Both metrics were tested in a numerically simulated example of unidirectionally coupled Rössler systems, which helped to find the explanation of the contradictory results: PSI correctly estimates the lead/lag relationship which, however, is not generally equivalent to causality in the sense of directionality of coupling in nonlinear systems, correctly inferred by using CMI with surrogate data testing.

• Klíčová slova
• Conditional mutual information, Coupling directionality, Cross-frequency coupling, EEG, Nonlinear systems, Phase slope index,
• MeSH
• elektroencefalografie * metody   MeSH
• lidé MeSH
• modely neurologické MeSH
• mozek fyziologie   MeSH
• nelineární dynamika * MeSH
• počítačová simulace MeSH
• počítačové zpracování signálu MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Recent rise in tick-borne diseases in many parts of Europe is a phenomenon in need of an explanation. We analyzed temporal trends in spatial distribution of a population at risk of Lyme borreliosis, tick-borne encephalitis, and as a control, also of a 'non-tick-borne disease' in the Czech Republic in 1997-2010. Analysis revealed that the population's exposure had been increasingly confined to the nearest surroundings of residences or in totally residential locations and that the incidence of the diseases depended in some causal way on how close to residences people exposed themselves to the risk. The rise in Lyme borreliosis and tick-borne encephalitis was solely due to infections acquired at or near patients' homes (<5 km), while the number of cases acquired further away was decreasing. The detected patterns in the data question some of the hypotheses which may be applicable in explaining the rise in disease incidences in the Czech Republic including the effect of climate change. Potentially causal factors are discussed.

• Klíčová slova
• Exposure risk, Lyme borreliosis, Spatial analysis, Tick-borne encephalitis, Time series analysis,
• MeSH
• Borrelia burgdorferi izolace a purifikace   MeSH
• dítě MeSH
• dospělí MeSH
• incidence MeSH
• klíšťová encefalitida epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymeská nemoc epidemiologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoci přenášené klíšťaty epidemiologie   MeSH
• prostorová analýza MeSH
• rizikové faktory MeSH
• roční období MeSH
• sexuální faktory MeSH
• věkové faktory MeSH
• viry klíšťové encefalitidy izolace a purifikace   MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

Despite the wide occurrence of ritual behavior in humans and animals, much of its causal underpinnings, as well as evolutionary functions, remain unknown. A prominent line of research focuses on ritualization as a response to anxiogenic stimuli. By manipulating anxiety levels, and subsequently assessing their motor behavior dynamics, our recent study investigated this causal link in a controlled way. As an extension to our original argument, we here discuss 2 theoretical explanations of rituals-ritualized behavior and automated behavior-and their link to anxiety. We propose that investigating participant's locus of attention can discriminate between these 2 models.

• Klíčová slova
• anxiety, automated behavior, ritual, ritualized behavior, routine,
• Publikační typ
• časopisecké články MeSH

DNA damage tolerance (DDT) and homologous recombination (HR) stabilize replication forks (RFs). RAD18/UBC13/three prime repair exonuclease 2 (TREX2)-mediated proliferating cell nuclear antigen (PCNA) ubiquitination is central to DDT, an error-prone lesion bypass pathway. RAD51 is the recombinase for HR. The RAD51 K133A mutation increased spontaneous mutations and stress-induced RF stalls and nascent strand degradation. Here, we report in RAD51K133A cells that this phenotype is reduced by expressing a TREX2 H188A mutation that deletes its exonuclease activity. In RAD51K133A cells, knocking out RAD18 or overexpressing PCNA reduces spontaneous mutations, while expressing ubiquitination-incompetent PCNAK164R increases mutations, indicating DDT as causal. Deleting TREX2 in cells deficient for the RF maintenance proteins poly(ADP-ribose) polymerase 1 (PARP1) or FANCB increased nascent strand degradation that was rescued by TREX2H188A, implying that TREX2 prohibits degradation independent of catalytic activity. A possible explanation for this occurrence is that TREX2H188A associates with UBC13 and ubiquitinates PCNA, suggesting a dual role for TREX2 in RF maintenance.

• Klíčová slova
• DNA damage tolerance, double-strand break repair, genomic instability, homologous recombination, replication fork maintenance,
• MeSH
• exodeoxyribonukleasy genetika   metabolismus   MeSH
• fosfoproteiny genetika   metabolismus   MeSH
• lidé MeSH
• mutace * MeSH
• myši MeSH
• rekombinasa Rad51 biosyntéza   genetika   metabolismus   MeSH
• replikace DNA * MeSH
• transfekce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• exodeoxyribonukleasy MeSH
• fosfoproteiny MeSH
• RAD51 protein, human MeSH Prohlížeč
• rekombinasa Rad51 MeSH
• TREX2 protein, human MeSH Prohlížeč

A total of 53 subjects with working exposure to styrene (1-29 years) has been investigated. On lipid and lipoproteins examination, only 8 persons (15%) showed normal values. The amount of 26 (49%) persons had the increase in HDL-cholesterol values. Subjects with protracted exposure to styrene (11-29 years) had higher level of cholesterol, absolute HDL-cholesterol values, total VLDLs and atherogenic index as compared to those which have worked at risk of styrene for 1-10 years. However, there was no statistically significant difference. Occupationnaly styrene exposed persons had statistically higher HDL-cholesterol (expressed both absolutely and relatively) in comparison with 21 clinically healthy controls. Changes of total cholesterol, VLDLs and of atherogenic index may partly be explained with factor of age. However, this is no such an explanation for HDL-cholesterol, since in adverse to that it decreases with more age in a normal population. Authors assume the pathologically higher HDL-cholesterol levels may exhibit causal interaction with occupational exposure to styrene, probably through the induction of microsomal liver enzymatic systems.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipidy krev   MeSH
• lipoproteiny krev   účinky léků   MeSH
• mladiství MeSH
• pracovní expozice * MeSH
• senioři MeSH
• styren MeSH
• styreny farmakologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• lipidy MeSH
• lipoproteiny MeSH
• styren MeSH
• styreny MeSH