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This study explores the conceptual history of systems biology and its impact on philosophical and scientific conceptions of reductionism, antireductionism and emergence. Development of systems biology at the beginning of 21st century transformed biological science. Systems biology is a new holistic approach or strategy how to research biological organisms, developed through three phases. The first phase was completed when molecular biology transformed into systems molecular biology. Prior to the second phase, convergence between applied general systems theory and nonlinear dynamics took place, hence allowing the formation of systems mathematical biology. The second phase happened when systems molecular biology and systems mathematical biology, together, were applied for analysis of biological data. Finally, after successful application in science, medicine and biotechnology, the process of the formation of modern systems biology was completed. Systems and molecular reductionist views on organisms were completely opposed to each other. Implications of systems and molecular biology on reductionist-antireductionist debate were quite different. The analysis of reductionism, antireductionism and emergence issues, in the era of systems biology, revealed the hierarchy between methodological, epistemological and ontological antireductionism. Primarily, methodological antireductionism followed from the systems biology. Only after, epistemological and ontological antireductionism could be supported.

The complexity, entropy and other non-linear measures of the electroencephalogram (EEG), such as Higuchi fractal dimension (FD), have been recently proposed as the measures of anesthesia depth and sedation. We hypothesized that during unconciousness in rats induced by the general anesthetics with opposite mechanism of action, behaviorally and poligraphically controlled as appropriately achieved stable anesthesia, we can detect distinct inter-structure brain dynamic using mean FDs. We used the surrogate data test for nonlinearity in order to establish the existence of nonlinear dynamics, and to justify the use of FD as a nonlinear measure in the time series analysis. The surrogate data of predefined probability distribution and autocorrelation properties have been generated using the algorithm of statically transformed autoregressive process (STAP). FD then is applied to quantify EEG signal complexity at the cortical, hippocampal and pontine level during stable general anesthesia (ketamine/xylazine or nembutal anesthesia). Our study showed for the first time that global neuronal inhibition caused by different mechanisms of anesthetic action induced distinct brain inter-structure complexity gradient in Sprague Dawley rats. EEG signal complexities were higher at cortical and hippocampal level in ketamine/xylazine vs. nembutal anesthesia, with the dominance of hippocampal complexity. In nembutal anesthesia the complexity dominance moved to pontine level, and ponto-hippocampo-cortical decreasing complexity gradient was established. This study has proved the Higuchi fractal dimension as a valuable tool for measuring the anesthesia induced inter-structure EEG complexity.

Clinically-related basic studies on the behavioral effects of ribavirin treatment are still lacking despite its wide use as an antiviral medication. This paper considers the effects of low ribavirin doses (10, 20 and 30 mg/kg/day) on psychomotor activity (novelty-induced exploratory behavior, d-amphetamine (AMPH, 1.5 mg/kg, intraperitoneal)-induced motor activity), and body weight gain in socially undisturbed adult male Wistar rats 24 h after the first, seventh and fourteenth once-a-day injection. Low doses of ribavirin were tested in an attempt to avoid the recognized systemic side effects related to high-dose usage. None of the singly applied ribavirin doses affected exploratory/spontaneous and AMPH-induced motor behavior (locomotion, stereotypy-like and vertical activity), however, body weight gain was significantly lower after treatment with 30 mg/kg of ribavirin. The 7-and 14-day treatments with 10 and 30 mg/kg/day of ribavirin significantly suppressed novelty-induced locomotion and body weight gain; the 14-day treatment with ribavirin at a dose of 30 mg/kg/ day decreased AMPH-induced stereotypy. These findings indicate that repeated application (up to 14 days) of low ribavirin doses results in low novelty-induced locomotion along with reduced weight gain, accentuating the existence of a U-shaped dose-response relationship with a prolonged duration of ribavirin treatment.

This paper examines some methodological and epistemological issues underlying the ongoing -artificial‖ divide between pragmatic-systems biology and systems-theoretical biology. The pragmatic systems view of biology has encountered problems and constraints on its explanatory power because pragmatic systems biologists still tend to view systems as mere collections of parts, not as -emergent realities‖ produced by adaptive interactions between the constituting components. As such, they are incapable of characterizing the higher-level biological phenomena adequately. The attempts of systems-theoretical biologists to explain these -emergent realities‖ using mathematics also fail to produce satisfactory results.Given the increasing strategic importance of systems biology, both from theoretical and research perspectives, we suggest that additional epistemological and methodological insights into the possibility of further integration between traditional experimental studies and complex modeling are required. This integration will help to improve the currently underdeveloped pragmatic-systems biology and system-theoretical biology.The -epistemology of complexity,‖ I contend, acts as a glue that connects and integrates different and sometimes opposing viewpoints, perspectives, streams, and practices, thus maintaining intellectual and research coherence of systems research of life. It allows scientists to shift the focus from traditional experimental research to integrated, modelingbased holistic practices capable of providing a comprehensive knowledge of organizing principles of living systems. It also opens the possibility of the development of new practical and theoretical foundations of systems biology to build a better understanding of complex organismic functions.