Applications of living systems theory

Living systems theory identifies basic principles that underlie the structure and processes of living things and relates them to the nonliving physical world, integrating and bringing order to the ever-growing mass of empirical data about them. In addition, living systems models and methodology are useful in empirical research on the great variety of systems of interest to psychology and related fields and in study of individual systems at any of the eight levels of living systems.FromAnalysis of Dynamic Psychological Systems, Volume 2: Methods and Applications, edited by Ralph L. Levine and Hiram E. Fitzgerald, Plenum Press, New York, 1992.     

Resource-based niches provide a basis for plant species diversity and dominance in arctic tundra.

Ecologists have long been intrigued by the ways co-occurring species divide limiting resources. Such resource partitioning, or niche differentiation, may promote species diversity by reducing competition. Although resource partitioning is an important determinant of species diversity and composition in animal communities, its importance in structuring plant communities has been difficult to resolve. This is due mainly to difficulties in studying how plants compete for below-ground resources. Here we provide evidence from a 15N-tracer field experiment showing that plant species in a nitrogen-limited, arctic tundra community were differentiated in timing, depth and chemical form of nitrogen uptake, and that species dominance was strongly correlated with uptake of the most available soil nitrogen forms. That is, the most productive species used the most abundant nitrogen forms, and less productive species used less abundant forms. To our knowledge, this is the first documentation that the composition of a plant community is related to partitioning of differentially available forms of a single limiting resource.     

Internal brain state regulates membrane potential synchrony in barrel cortex of behaving mice

Internal brain states form key determinants for sensory perception, sensorimotor coordination and learning. A prominent reflection of different brain states in the mammalian central nervous system is the presence of distinct patterns of cortical synchrony, as revealed by extracellular recordings of the electroencephalogram, local field potential and action potentials. Such temporal correlations of cortical activity are thought to be fundamental mechanisms of neuronal computation. However, it is unknown how cortical synchrony is reflected in the intracellular membrane potential (V(m)) dynamics of behaving animals. Here we show, using dual whole-cell recordings from layer 2/3 primary somatosensory barrel cortex in behaving mice, that the V(m) of nearby neurons is highly correlated during quiet wakefulness. However, when the mouse is whisking, an internally generated state change reduces the V(m) correlation, resulting in a desynchronized local field potential and electroencephalogram. Action potential activity was sparse during both quiet wakefulness and active whisking. Single action potentials were driven by a large, brief and specific excitatory input that was not present in the V(m) of neighbouring cells. Action potential initiation occurs with a higher signal-to-noise ratio during active whisking than during quiet periods. Therefore, we show that an internal brain state dynamically regulates cortical membrane potential synchrony during behaviour and defines different modes of cortical processing.     

Prolonged suppression of ecosystem carbon dioxide uptake after an anomalously warm year

Terrestrial ecosystems control carbon dioxide fluxes to and from the atmosphere through photosynthesis and respiration, a balance between net primary productivity and heterotrophic respiration, that determines whether an ecosystem is sequestering carbon or releasing it to the atmosphere. Global and site-specific data sets have demonstrated that climate and climate variability influence biogeochemical processes that determine net ecosystem carbon dioxide exchange (NEE) at multiple timescales. Experimental data necessary to quantify impacts of a single climate variable, such as temperature anomalies, on NEE and carbon sequestration of ecosystems at interannual timescales have been lacking. This derives from an inability of field studies to avoid the confounding effects of natural intra-annual and interannual variability in temperature and precipitation. Here we present results from a four-year study using replicate 12,000-kg intact tallgrass prairie monoliths located in four 184-m(3) enclosed lysimeters. We exposed 6 of 12 monoliths to an anomalously warm year in the second year of the study and continuously quantified rates of ecosystem processes, including NEE. We find that warming decreases NEE in both the extreme year and the following year by inducing drought that suppresses net primary productivity in the extreme year and by stimulating heterotrophic respiration of soil biota in the subsequent year. Our data indicate that two years are required for NEE in the previously warmed experimental ecosystems to recover to levels measured in the control ecosystems. This time lag caused net ecosystem carbon sequestration in previously warmed ecosystems to be decreased threefold over the study period, compared with control ecosystems. Our findings suggest that more frequent anomalously warm years, a possible consequence of increasing anthropogenic carbon dioxide levels, may lead to a sustained decrease in carbon dioxide uptake by terrestrial ecosystems.     

Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors

Investigation of the human antibody response to influenza virus infection has been largely limited to serology, with relatively little analysis at the molecular level. The 1918 H1N1 influenza virus pandemic was the most severe of the modern era. Recent work has recovered the gene sequences of this unusual strain, so that the 1918 pandemic virus could be reconstituted to display its unique virulence phenotypes. However, little is known about adaptive immunity to this virus. We took advantage of the 1918 virus sequencing and the resultant production of recombinant 1918 haemagglutinin (HA) protein antigen to characterize at the clonal level neutralizing antibodies induced by natural exposure of survivors to the 1918 pandemic virus. Here we show that of the 32 individuals tested that were born in or before 1915, each showed seroreactivity with the 1918 virus, nearly 90 years after the pandemic. Seven of the eight donor samples tested had circulating B cells that secreted antibodies that bound the 1918 HA. We isolated B cells from subjects and generated five monoclonal antibodies that showed potent neutralizing activity against 1918 virus from three separate donors. These antibodies also cross-reacted with the genetically similar HA of a 1930 swine H1N1 influenza strain, but did not cross-react with HAs of more contemporary human influenza viruses. The antibody genes had an unusually high degree of somatic mutation. The antibodies bound to the 1918 HA protein with high affinity, had exceptional virus-neutralizing potency and protected mice from lethal infection. Isolation of viruses that escaped inhibition suggested that the antibodies recognize classical antigenic sites on the HA surface. Thus, these studies demonstrate that survivors of the 1918 influenza pandemic possess highly functional, virus-neutralizing antibodies to this uniquely virulent virus, and that humans can sustain circulating B memory cells to viruses for many decades after exposure-well into the tenth decade of life.     

Tackling heart failure in the twenty-first century

Heart failure, or congestive heart failure, is a condition in which the heart cannot supply the body's tissues with enough blood. The result is a cascade of changes that lead to severe fatigue, breathlessness and, ultimately, death. In the past quarter century, much progress has been made in understanding the molecular and cellular processes that contribute to heart failure, leading to the development of effective therapies. Despite this, chronic heart failure remains a major cause of illness and death. And because the condition becomes more common with increasing age, the number of affected individuals is rising with the rapidly ageing global population. New treatments that target disease mechanisms at the cellular and whole-organ level are needed to halt and reverse the devastating consequences of this disease.     

A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25

Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 x 10(-10)). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 x 10(-20) overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines, and they bind to N'-nitrosonornicotine and potential lung carcinogens. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets.