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Human development I: twenty fundamental problems of biology, medicine, and neuro-psychology related to biological information.

In a new series of papers, we address a number of unsolved problems in biology today. First of all, the unsolved enigma concerning how the differentiation from a single zygote to an adult individual happens has been object for severe research for decades. By uncovering a new holistic biological paradigm that introduces an energetic-informational interpretation of reality as a new way to experience biology, these papers will try to solve the problems connected with the events of biological ontogenesis involving a fractal hierarchy, from a single cell to the function of the human brain. The problems discussed are interpreted within the frames of a universe of roomy fractal structures containing energetic patterns that are able to deliver biological information. We think biological organization is guided by energetic changes on the level of quantum mechanics, interacting with the intention that again guides the energetic conformation of the fractal structures to gain disorders or healthiness. Furthermore, we introduce two new concepts: "metamorphous top down" evolution and "adult human metamorphosis". The first is a new evolutionary theory involving metamorphosis as a main concept of evolution. The last is tightly linked to the evolutionary principle and explains how human self-recovery is governed. Other subjects of special interest that we shall look deeper into are the immunological self-nonself discrimination, the structure and function of the human brain, the etiology and salutogenesis of mental and somatic diseases, and the structure of the consciousness of a human being. We shall criticize Szentagothai's model for the modulated structure of the human cerebral cortex and Jerne's theory of the immunological regulatory anti-idiotypic network.

Biology↗

Human development V: biochemistry unable to explain the emergence of biological form (morphogenesis) and therefore a new principle as source of biological information is needed.

Today's biomedicine builds on the conviction that biochemistry can explain the creation of the body, its anatomy and physiology. Unfortunately there are still deep mysteries strangely "fighting back" when we try to define and understand the organism and its creation in the ontogenesis as emerging from biochemistry. In analysing this from a theoretical perspective using a mathematical model focusing on the noise in complex chemical systems we argue that evolving biological structure cannot in principle be a product of chemistry. In this paper we go through the chemical gradient model and argue that this is not able to explain the ontogenesis. We discuss the used gradients as information carriers in chemical self-organizing systems and argue that by use of the "Turing structures" we are only able to modelling the mostly simple biological systems. The bio-chemical model is only able to model simple organization but not to explain the complexity of biological phenomena. We conclude that we seemingly have presented a formal proof (a NO-GO theorem) that the self-organizing chemical systems that are using chemical gradients are not able to explain complex biological matters as the ontogenesis. We need a fundamentally new, information-carrying principle to understand biological information and biological order.

Biochemical Phenomena↗

Twisting and bending of biological beams: distribution of biological beams in a stiffness mechanospace.

Most biological beams bend and twist relatively easily compared to human-made structures. This paper investigates flexibility in 57 diverse biological beams in an effort to identify common patterns in the relationship between flexural stiffness and torsional stiffness. The patterns are investigated by mapping both ideal and biological beams into a mechanospace defined by flexural and torsional stiffness. The distribution of biological beams is not random, but is generally limited to particular regions of the mechanospace. Biological beams that are stiff in bending are stiff in torsion, while those that bend easily also twist easily. Unoccupied regions of the mechanospace represent rare combinations of mechanical properties, without proving that they are impossible. The mechanical properties of biological beams closely resemble theoretical expectations for ideal beams. Both distributions are potentially being driven by the interdependence of the material and structural properties determining stiffness. The mechanospace can be used as a broadly comparative tool to highlight systems that fall outside the general pattern observed in this study. These outlying beams may be of particular interest to both biologists and engineers due to either material or structural innovations.

Animal Structures↗

Conditions for a theoretical biology: is biology truly an autonomous science?

In a line of a previous paper, the conditions for a theoretical biology were discussed and it was pointed out that the primary condition is that biology is an autonomous science. This statement is connected to the problem of reductionism. A discussion of the autonomy of biology shows that reductionism cannot be maintained, although particularly in physiology often physics and mathematics are used. Development, organization and evolution of biological systems are typical areas of autonomous biological researches and of autonomous theoretical developments. A sort of reduction to history seems today a nonsensical attempt to reduce the area of free theoretical biological activity.

Biology↗

[Knowledge of selected occupational groups about biological agents in the environment and ways of health protection against occupational exposure to biological hazards].

BACKGROUND: Occupational, biological factors of microbial, plant and animal origin may become a health hazard to the exposed workers. The aim of the study was to assess the knowledge of biological agents present in the work environment, related health risks, and health protection against biological exposure at work among workers of certain occupational categories. MATERIALS AND METHODS: A population of 150 workers, employed in the health, forestry and municipal services, was interviewed using a specially developed questionnaire. Each occupational category comprised 50 workers. RESULTS AND CONCLUSIONS: The level of workers' knowledge of occupational, biological agents, their effect on human body, symptoms and diseases induced by occupational exposure to biological hazards is rather limited in the study groups. Personal protective measures, prophylactic vaccination and compliance with principles of personal hygiene are considered to be the most effective ways of health protection against occupational exposure to biological hazards.

Adult↗

Biologicals and biological response modifiers: fourth modality of cancer treatment.

Considerable progress has been made in the last 5 years toward the development of specific biological approaches to the treatment of cancer. The techniques of genetic engineering, mass cell culture, and improved techniques in protein and nucleic acid sequencing and synthesis have made available biologicals as specific, highly purified molecules that can be used in cancer therapy. While extensive clinical trials are needed to demonstrate that biologicals and biological response modifiers can provide a survival advantage for patients with cancer, the preliminary data indicate that these approaches can be useful in inducing responses in patients with clinically apparent disease. Further studies with these approaches in conjunction with surgery, radiotherapy, and chemotherapy should be helpful in definitively establishing biologicals and biological response modifiers as the fourth modality of cancer treatment.

Adjuvants, Immunologic↗

Biological complexity and drug discovery: a practical systems biology approach.

Drugs fail in clinical studies most often from lack of efficacy or unexpected toxicities. These failures result from an inadequate understanding of drug action and follow, in part, from our dependence on drug discovery technologies that do not take into account the complexity of human disease biology. Biological systems exhibit many features of complex engineering systems, including modularity, redundancy, robustness, and emergent properties. Addressing these features has contributed to the successful design of an improved biological assay technology for inflammation drug discovery. This approach, termed Biologically Multiplexed Activity Profiling (BioMAP), involves the statistical analysis of protein datasets generated from novel complex primary human cell-based assay systems. Compound profiling in these systems has revealed that a surprisingly large number of biological mechanisms can be detected and distinguished. Features of these assays relevant to the behaviour of complex systems are described.

Animals↗

A natural 15N approach to determine the biological fixation of atmospheric nitrogen by biological soil crusts of the Negev Desert.

Biological soil crusts are important cryptogamic communities covering the sand dunes of the north-western Negev. The biological crusts contain cyanobacteria and other free-living N(2)-fixing bacteria and are hence able to fix atmospheric nitrogen (N). This is why they are considered to be one of the main N input pathways into the desert ecosystem. However, up to now, in situ determinations of the N(2) fixation in the field are not known to have been carried out. We examined the natural (15)N method to determine the biological N(2) fixation by these soil crusts under field conditions. This novel natural (15)N method uses the lichen Squamarina with symbiotic green algae--which are unable to fix N(2)--as a reference in order to determine N(2) fixation. Depending on the sampling location and year, the relative biological fixation of atmospheric nitrogen was estimated at 84-91% of the total N content of the biological soil crust. The cyanobacteria-containing soil lichen Collema had a fixation rate of about 88%. These fixation rates were used to derive an absolute atmospheric N input of 10-41 kg N ha(-1) year(-1). These values are reasonable results for the fixation of atmospheric N(2) by the biological crusts and cyanolichens and are in agreement with other comparable lab investigations. As far as we are aware, the results presented are the first to have been obtained from in situ field measurements, albeit only one location of the Negev with a small number of samples was investigated.

Atmosphere↗

The mathematical transformation of growth and form--I:Transferring the wave - particle duality from physics to biology and proposing wave interaction as a key determinant of biological structure.

Just as the material units of existence, atoms and basic particles, can be viewed as waves or particles, depending on the observational frame chosen by the physicist, so also can biochemical macro-molecules, the units of biological existence, be viewed as waves or particles by the biologist. It is proposed that the flux of different waveforms which floods biological systems provides an interference pattern, whose energetic distribution forms a scaffold for the construction of biological forms. In this way the biological whole becomes the Fourier transform of the parts and histological pattern becomes the determinant of macroscopic form. Evidence is adduced suggesting that biological forms follow the energy patterns laid down by the environment. It is proposed that the ability of bipolymers to re-radiate coherent waveforms derived from the environment, has given evolved systems the autonomy which has allowed a free and prolific evolution. This coherent illumination can be analysed by Fourier methods and this shows that the results are peculiarly appropriate for biological systems. The Gaussian waveform is all-important and may explain the influence of homogeneous and heterogeneous DNA in cell surface kinetics, hybridisation and carcinogenesis.

Action Potentials↗

Modulation of biological phenotypes for tumor growth and metastasis by target-specific biological inhibitors in gastric cancer.

For tumor progression, a cascade of linked sequential biological events is essential. We tried to test whether biological therapy can modulate specific biological phenotypes and increase the anti-tumor effect when combined with chemotherapy. Five human gastric cancer cell lines (YCC-1, YCC-2, YCC-3, YCC-7, AGS) were used in these studies. Pentosan polysulfate (PPS) as a heparin-binding growth factor inhibitor, Tranexamic acid as a plasmin inhibitor, Lovastatin as an adhesion inhibitor and Adriamycin as a chemotherapeutic agent were selected. The effects of each drug on colony formation and tumor cell proliferation were evaluated by soft agar assay and cell proliferation assay, respectively to test direct anti-tumor effect. The expression of uPA, PAI-1 was determined by ELISA, while MMPs activity was evaluated by zymography. PPS suppressed the colony-forming activity as much as Adriamycin did, but it showed only cytostatic effects in cell proliferation assay. Migration capacity using Boyden chamber assay was more closely correlated with adhesive capacity than uPA or MMP-2 expression. The motility inhibitory effect of Tranexamic acid was observed in the YCC-7 cell line, which expressed all the required biological phenotypes for migration. In AGS, with high cell motility and adhesiveness, the adhesion was inhibited by Lovastatin and most of the inhibitory effect was recovered by Mevalonate. When PPS was combined with Adriamycin on the Adriamycin-resistant, midkine (MK) gene expressing YCC-7 cell line, the growth inhibition rate increased up to 84%, while that for a single treatment of PPS or Adriamycin was 40% and 22%, respectively (p=0.001). When we combined Tranexamic acid and Adriamycin, we observed the synergistic effect in YCC-3 and YCC-7, while no combined effect was found in YCC-1. The combination of Lovastatin and Adriamycin did not show any combined effects in any of the cell lines. In conclusion, a synergistic anti-proliferative effect (chemo-sensitization) with combined chemo-biotherapy was found in cancer cells with specific biological target, MK. The anti-motility effect was the greatest when the gastric cancer cells expressed all the specific biological phenotypes.

Anticoagulants↗

Aristotle's biopolitics: a defense of biological teleology against biological nihilism.

Modern Darwinian biology seems to promote nihilism, for it seems to teach that there is no rationally discoverable standard in nature for giving meaning to life. The purpose of this article is to argue for a revival of Aristotle's biological teleology as a reasonable alternative to biological nihilism. The article begins with Edward Wilson's vain struggle against nihilism. Then it is argued that a teleological understanding of nature is assumed in the practice of medicine, as illustrated by one case from Oliver Sacks' neurological practice. The article then considers the importance of biological teleology for Aristotle's moral and political philosophy, and attention is given to some points of agreement and disagreement with contemporary sociobiologists. The main part of the article is then devoted to a defense of Aristotle's biology against the five objections that might be made by a Darwinian biologist. Finally, the article illustrates the practical implications of this issue for bioethics by considering the recent work of Engelhardt.

Animals↗

Biological Parts in Yeast Synthetic Biology: From Regulatory Elements to Predictive Design Platforms.

Yeasts, particularly Saccharomyces cerevisiae, are important eukaryotic chassis for synthetic biology because of their tractable genetics, versatile toolkits, and broad utility in metabolic engineering and functional genomics. Progress in this field has been driven by biological parts that enable programmable control of gene expression and cellular behavior. Early efforts focused mainly on promoters, terminators, and other regulatory elements for tuning individual genes. However, as engineering expanded to multigene pathways, genetic circuits, and dynamic regulatory systems, the limits of part-centric design became clear. Part performance is often shaped by genomic context, chromatin state, host physiology, and interactions with other components, which restricts modularity and predictability. In response, yeast synthetic biology is shifting toward integrated design frameworks combining multilayer regulation, standardized assembly, automated experimentation, and computational modeling. This review provides an integrated perspective on the evolution of biological parts across DNA-, RNA-, and protein-level regulation, connecting these advances with assembly frameworks, biofoundries, and machine learning to trace the trajectory from part-centric engineering toward predictive, system-level design in yeast synthetic biology.

Biofoundry↗

Clustering biological annotations and gene expression data to identify putatively co-regulated biological processes.

MOTIVATION: Functional profiling is a key step of microarray gene expression data analysis. Identifying co-regulated biological processes could help for better understanding of underlying biological interactions within the studied biological frame. RESULTS: We present herein an original approach designed to search for putatively co-regulated biological processes sharing a significant number of co-expressed genes. An R language implementation named "FunCluster" was built and tested on two gene expression data sets. A discriminatory functional analysis of the first data set, related to experiments performed on separated adipocytes and stroma vascular fraction cells of human white adipose tissue, highlighted the prevalent role of nonadipose cells in the synthesis of inflammatory and immunity molecules in human adiposity. On the second data set, resulting from a model investigating insulin coordinated regulation of gene expression in human skeletal muscle, FunCluster analysis spotlighted novel functional classes of putatively co-regulated biological processes related to protein metabolism and the regulation of muscular contraction. AVAILABILITY: Supplementary information about the FunCluster tool is available on-line at http://corneliu.henegar.info/FunCluster.htm.

Algorithms↗