Cultural-Biology: Systemic Consequences of <Emphasis Type="Italic">Our</Emphasis> Evolutionary Natural Drift as Molecular Autopoietic Systems

Our purpose in this essay is to introduce new concepts (dynamic architecture and dynamic ecological organism-niche unity, among other) in a wide and recursive view of the systemic consequences of the following biological facts that I (Maturana in Biology of cognition, 1970, Unity and diversity of man. Le Seuil, Paris, 1978; Maturana and Varela in Autopoiesis and cognition: the realization of the living. D. Riedel Publishing Co, Boston, 1980, El Árbol del Conocimiento: Las Bases Biológicas del Conocer Humano, 1a Edición. Editorial Universitaria, Santiago, 1984; Maturana and Mpodozis in Rev Chil Hist Nat 73:261–310, 2000) and we (Maturana and Dávila in Habitar humano: en seis ensayos de biología-cultural. Juan Carlos Sáez Editorial, Chile, 2008) have presented that can be resumed as: (1) that as living systems we human beings are molecular autopoietic system; (2) that living systems live only as long as they find themselves in a medium that provides them with all the conditions that make the realization of their living possible, that is, in the continuous conservation of their relation of adaptation to the circumstances in which they find themselves; (3) that as a living system exists only in a relation of adaptation with the medium that operates as its ecological niche, its reproduction necessarily occurs as a process of systemic duplication or multiplication of the ecological organism-niche unity that it integrates; (4) that the worlds of doings that we generate as languaging beings in our conversations, explanations, reflections and theories are part of our ecological niche; and (5) that we human beings as living beings that exist in languaging, are biological–cultural beings in which our cultural and our biological manners of existences can be distinguished but cannot be separated. Of the systemic consequences of these biological facts that we consider in this essay, we wish to mention two as the principal: (1) that the diversification of manners of living produced in biological evolution is the result of differential survival in a changing medium through the conservation of adaptation, and not through competitive survival of the best; and (2) that we in our living as languaging human beings (observers) are the epistemological fundament of all that we do and know as such.     

A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response

Targeted therapies have demonstrated efficacy against specific subsets of molecularly defined cancers. Although most patients with lung cancer are stratified according to a single oncogenic driver, cancers harbouring identical activating genetic mutations show large variations in their responses to the same targeted therapy. The biology underlying this heterogeneity is not well understood, and the impact of co-existing genetic mutations, especially the loss of tumour suppressors, has not been fully explored. Here we use genetically engineered mouse models to conduct a 'co-clinical' trial that mirrors an ongoing human clinical trial in patients with KRAS-mutant lung cancers. This trial aims to determine if the MEK inhibitor selumetinib (AZD6244) increases the efficacy of docetaxel, a standard of care chemotherapy. Our studies demonstrate that concomitant loss of either p53 (also known as Tp53) or Lkb1 (also known as Stk11), two clinically relevant tumour suppressors, markedly impaired the response of Kras-mutant cancers to docetaxel monotherapy. We observed that the addition of selumetinib provided substantial benefit for mice with lung cancer caused by Kras and Kras and p53 mutations, but mice with Kras and Lkb1 mutations had primary resistance to this combination therapy. Pharmacodynamic studies, including positron-emission tomography (PET) and computed tomography (CT), identified biological markers in mice and patients that provide a rationale for the differential efficacy of these therapies in the different genotypes. These co-clinical results identify predictive genetic biomarkers that should be validated by interrogating samples from patients enrolled on the concurrent clinical trial. These studies also highlight the rationale for synchronous co-clinical trials, not only to anticipate the results of ongoing human clinical trials, but also to generate clinically relevant hypotheses that can inform the analysis and design of human studies.     

Simulation of heat transfer in steel billets during continuous casting

This work is focused on the development of computational algorithms to create a simulator for solving the heat transfer during the continuous casting process of steel. The temperatures and the solid shell thickness profiles were calculated and displayed on the screen for a billet through a defined continuous casting plant (CCP). The algorithms developed to calculate billet temperatures, involve the solutions of the corresponding equations for the heat removal conditions such as radiation, forced convection, and conduction according to the billet position through the CCP. This is done by a simultaneous comparison with the kinematics model previously developed. A finite difference method known as Crank-Nicholson is applied to solve the two-dimensional computational array (2D model). Enthalpy (H_I,J) and temperature (T_I,J) in every node are updated at each step time. The routines to display the results have been developed using a graphical user interface (GUI) in the programming language C++. Finally, the results obtained are compared with those of industrial trials for the surface temperature of three steel casters with different plant configurations in different casting conditions.     

Immunogenicity of fatty acid anilides in rabbits and the pathogenesis of the Spanish toxic oil syndrome

Summary Fatty acid anilides, the major xenobiotic found in the cooking oils responsible for the Spanish toxic oil syndrome, are immunogenic for rabbits as ascertained by a skin test reaction, the characterization of specific antibodies against anilides and the immunofluorescent detection of anilide dependent antigens in tissue slices from treated animals.Acknowledgments. This work was supported by a grant from the Fondo de Investigaciones Sanitarias to the C.S.I.C. Programme on Toxic Oil Syndrome. We are indebted to Dr M. Studt and Dr E. Fernández-Alvarez, from the National Center for Organic Chemistry, C.S.I.C., for kindly providing the synthetic fatty acid anilides. We also wish to thank Prof. C. Gitler for helpful discussion.     

Effects of 2-β-D-glucosyl-4-hydroxy-7-methoxy-1,4-benzoxazin-3-one onSchizaphis graminum (rondani) (insecta,aphididae) feeding on artificial diets

Summary 2--Glucosyl-4-hydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA-Glc), the main hydroxamic acid from maize and wheat, and its aglucone, decreased survival ofSchizaphis graminum reared on artificial diets. Both compounds were toxic for aphids and acted as feeding deterrents, at concentrations as low as 1 mM. The natural concentrations of glucosides of hydroxamic acids in wheat leaves reach up to 6 mmoles/kg fresh weight, thus falling within the range in which DIMBOA-Glc causes delecterious effects to diet-fed aphids.To whom correspondence should be addressed. THis work was supported by grants from International Foundation for Science (484), Universidad de Chile (N-1654) and the Agency for International Development.     

Chaos in a long-term experiment with a plankton community

Mathematical models predict that species interactions such as competition and predation can generate chaos. However, experimental demonstrations of chaos in ecology are scarce, and have been limited to simple laboratory systems with a short duration and artificial species combinations. Here, we present the first experimental demonstration of chaos in a long-term experiment with a complex food web. Our food web was isolated from the Baltic Sea, and consisted of bacteria, several phytoplankton species, herbivorous and predatory zooplankton species, and detritivores. The food web was cultured in a laboratory mesocosm, and sampled twice a week for more than 2,300 days. Despite constant external conditions, the species abundances showed striking fluctuations over several orders of magnitude. These fluctuations displayed a variety of different periodicities, which could be attributed to different species interactions in the food web. The population dynamics were characterized by positive Lyapunov exponents of similar magnitude for each species. Predictability was limited to a time horizon of 15-30 days, only slightly longer than the local weather forecast. Hence, our results demonstrate that species interactions in food webs can generate chaos. This implies that stability is not required for the persistence of complex food webs, and that the long-term prediction of species abundances can be fundamentally impossible.     

Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae

The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation.     

Harvesting large amounts of Drosophila embryos at precisely defined stages

Summary A simple method is described which makes it possible to eliminate the retained eggs ofDrosophila melanogaster and to harvest a large amount of embryos at a defined stage of development. It is based upon carbon dioxide anesthesia, which brings about the expulsion of eggs remaining in the uterus.