[Evaluation of the German new back school: muscular physiological characteristics]. / Evaluation der Neuen Rückenschule : Muskulär-physiologische Merkmale.

BACKGROUND: According to the biopsychosocial approach of the German new back school the core objectives are sustainable improvement of physical and psychosocial health resources. Subjects with non-specific low back pain were investigated to evaluate the desired physical effects. METHODS: Coordinative and postural motor exercises were evaluated by means of surface electromyography (EMG). Applying a modified waiting group design 56 participants were examined 3 months before the start, at the beginning and at the end of the new back school program as well as 3 and 12 months after completion and the results were compared to a healthy control group (n=56) matched for age and body mass index (BMI). RESULTS: Initially significant group differences were found in 18 % of all statistical calculations of the static and 6 % of the dynamic test situations. Considering the trunk muscles the most frequent significant alterations from normative data were found in the lumbar multifidus muscle (static tests 29 % and dynamic tests 7 %). No relevant changes in the number of statistical results could be detected directly after completion of the new back school program. Nevertheless, at 12 months follow-up the number of significant differences to the normative data of the control group dropped by one third to 12 % of all calculations with static loads. CONCLUSION: The adjustment effects at 12 months follow-up indicate a delayed positive influence of the new back school program on muscular physiological parameters. Individuals with chronic non-specific back pain showed a long-term profit from participation in the new back school program due to the initiated orientation to a modified more active lifestyle.

Cross-sphere modelling to evaluate impacts of climate and land management changes on groundwater resources.

Climate change affects both water resources and agricultural production. With rising temperatures and decreasing summer precipitation, it is expected that agricultural production will be increasingly limited by drought. Where surface- or groundwater resources are available for irrigation, an increase in water withdrawals for irrigation is to be expected. Therefore, quantitative approaches are required to anticipate and manage the expected conflicts related to increased water abstraction for irrigation. This project aims to investigate how agricultural production, water demand for irrigation, runoff and groundwater dynamics are affected by future climate change and how climate change impacts combined with changes in agricultural water use affect groundwater dynamics. To answer these research questions, a comprehensive, loosely coupled model approach was developed, combining models from three disciplines: an agricultural plant growth model, a hydrological model and a hydrogeological model. The model coupling was implemented and tested for an agricultural area located in Switzerland in which groundwater plays a significant role in providing irrigation water. Our suggested modelling approach can be easily adapted to other areas. The model results show that yield changes are driven by drought limitations and rising temperatures. However, an increase in yield may be realized with an increase in irrigation. Simulation results show that the water requirement for irrigation without climate protection (RCP8.5) could increase by 40% by the end of the century with an unchanged growing season and by up to 80% with varietal adaptations. With climate change mitigation (RCP2.6) the increase in water demand for irrigation would be limited to 7%. The increase in irrigation (+12 mm) and the summer decrease in recharge rates (~20 mm/month) with decreasing summer precipitation causes a lowering of groundwater levels (40 mm) in the area in the late summer and autumn. This impact may be accentuated by an intensification of irrigation and reduced by extensification.

Rearrangement of structured RNA via branch migration structures catalysed by the highly related DEAD-box proteins p68 and p72.

RNA helicases, like their DNA-specific counterparts, can function as processive enzymes, unwinding RNA with a defined step size in a unidirectional fashion. Recombinant nuclear DEAD-box protein p68 and its close relative p72 are reported here to function in a similar fashion, though the processivity of both RNA helicases appears to be limited to only a few consecutive catalytic steps. The two proteins resemble each other also with regard to other biochemical properties. We have found that both proteins exhibit an RNA annealing in addition to their helicase activity. By using both these activities the enzymes are able in vitro to catalyse rearrangements of RNA secondary structures that otherwise are too stable to be resolved by their low processive helicase activities. RNA rearrangement proceeds via protein induced formation and subsequent resolution of RNA branch migration structures, whereby the latter step is dependent on ATP hydrolysis. The analysed DEAD-box proteins are reminiscent of certain DNA helicases, for example those found in bacteriophages T4 and T7, that catalyse homologous DNA strand exchange in cooperation with the annealing activity of specific single strand binding proteins.

Structure and expression of the human p68 RNA helicase gene.

Nuclear DEAD box protein p68 is immunologically related to SV40 large tumour antigen and both proteins possess RNA helicase activity. In this report, we describe the structural organisation of the human p68 gene and aspects of the regulation of its expression. Northern blot and primer extension analyses indicate that, although its level is variable, the p68 RNA helicase appears to be expressed from a single transcription start site in all tissues tested. Sequence analysis revealed that the p68 promoter harbours a 'TATA', a 'CAAT' and an initiator element and contains high affinity binding sites for Sp1, AP-2, CRE and Myc. This and functional promoter analyses in transient expression assays suggest that transcriptional regulation of the p68 gene is complex. Furthermore, there are indications that p68 expression is also regulated post-transcriptionally. Steady-state pools of poly(A)(+)RNA from human cells contain completely spliced p68 mRNA and alternatively spliced forms that contain introns 8-11 or 8-12 (from a total of 12 introns) and are not translated. Analysis of a conditionally p68-overproducing HeLa cell line points to negative autoregulation at the level of splicing, which is confirmed by a recently reported association of p68 with spliceosomes in human cells.

Timekeeping in genetically programmed aging.

Genetically programmed aging, with its cellular genetic switching implied by the in vitro Hayflick limit, requires additional timing devices to coordinate the switching processes within the different cells of a highly complex life form. Evolutionary arguments have been presented elsewhere to support the need for a centralized timing mechanism as against a localized mean-field alternative. Extensive evidence is now available for the role of the pineal gland and its secreted melatonin in the aging process. The nightly melatonin peak changes with age, thus providing a potential signal to inform all of the cells in the organism of its age. Here it is hypothesized that the decoding of this "durational signal" at the cellular level is carried out with the aid of the sleep induced pCO2 changes in the blood. To test this hypothesis, modifications of the in vitro Hayflick experiment and of the in vivo Pierpaoli longevity experiment involving rhythmic addition of melatonin and pH manipulations are proposed.

Chaos in coupled optimizers.

Autonomous optimizers, a subclass of dynamical systems, arise on the intersection between artificial intelligence and deductive biology. Two simple optimizers coupled symmetrically à la Rashevsky give rise to chaotic attractors and (possibly) cloud attractors. More complicated autonomous optimizers (endowed with internal simulation) will be subject to more complicated interactional function changes. Humanistic ideas of Mead and Bateson may come within scientific reach. Conversely, the physical measurement problem may turn out to belong partly to the humanities.

Artificial life extension. The epigenetic approach.

An epigenetic approach starts out from the direct (rather than the underlying genetic) causes. An epigenetic approach to aging has little chance of succeeding before a minimum amount of knowledge has been accumulated on the "genetic programming" that is currently believed to underlie aging. Two recent advances, one empirical and one theoretical, jointly brighten the prospect. The empirical one is the discovery that melatonin functions as an aging-controlling hormone in mammals. In 1979, Dilman and co-workers isolated a biologically active pineal extract (epithalamin) in rats which, as they later showed, stimulates melatonin production. Pierpaoli and co-workers in 1987 directly administered melatonin to mice. Both groups observed a surprising 25-percent increase of life span in conjunction with a postponed senescence. A similar effect was also achieved with an engraftment of young pineal tissue into the thymus of old mice by Pierpaoli's group. Beneficial effects of epithalamin in humans were reported by Dilman's group. The second advance is a deductive evolution-theoretical approach to aging discovered in 1988. In populations living in a niche with a fixed carrying capacity, any individual is in the long run replaced by a single successor. It follows that, as the expected cumulative number of adult progeny of the same sex approaches unity as a function of life time of the progenitor, the latter's survivability must approach zero if the sum is to remain unity. A physiological prediction follows: a centralized physicochemical clock--like a sedimentation process--must exist somewhere in the organism controlling a secreted substance that reaches all cells. In this way, the pineal coacervates and the pineal's hormonal product melatonin were arrived at on an independent route again. While melatonin as a drug has been used on human volunteers for decades, its anti-aging effect has yet to be proved. Detailed hormone profiles in different age groups and under different life styles have to be performed. A modified Hayflick in vitro experiment is also needed to elucidate the mechanism by which melatonin works in cells.

Recursive evolution.

In evolutionary systems in which the units (individuals) are generated by a morphogenetic process, unbiased "mosaic type" mutability of the phenotype is not possible (Waddington's principle). The question is whether this unavoidable "channeling" can itself be made plastic through provision of alternative morphogeneses possessing differing "hot spots." If so, plasticity would not only be reestablished, but be established at a higher level. Plasticity itself would be plastic. The property of ultrasplasticity is evolutionarily necessary and stable, but perhaps not possible. Ultraplastic systems form a subclass of "temporal brains" as described in deductive biology. Many of their properties have yet to be discovered.

An artificial cognitive map system.

A blueprint for a geometric information processor is described. The system essentially combines a digital scan converter with a digital flight simulator. The latter's 'local' (Poincaréan) rather than standing (Helmholtzian) display may have advantages in 3-dimensional diagnostic imaging. At the same time, the system provides a technologically realizable abstract model in terms of which to express (and perhaps eventually explain) the experimental results of O'Keefe and Nadel on the functioning of the hippocampus in the mammalian brain.

Ultraperspective and endophysics.

Ultraperspective is the capability of human beings to step into the shoes of another person. Endophysics is the science of those physical properties of the world which exist not from the outside but only form the inside. Both have in common the adoption of an 'exterior' position. In the one case, the exteriority is 'horizontal', in the other, 'vertical'. Ultraperspective is a macroscopic concept, endophysics a microscopic one. Both can be implemented in computer models. Novel experiments can be set up in either domain: animals acquiring the status of human persons, and objective features of the physical world acquiring the status of an observer-specific mirage. Mead an Levinas, and Einstein and Bohr, are the protagonists. In the age of computer-assisted enlightenment, a new look at the ethical roots of science appears justified.

Computer faces: the human Lorenz matrix.

Realistic Ekman-type faces were generated by a computer program. Twenty primary parameters (muscle tensions and opening factors), each continuous, were used. Non-linear combination of the primary parameters permits the generation of meaningful faces each governed by a single combined parameter (intensity-parameter). Five major meaningful faces were distinguished, "friendliness", "surprise", "disgust", "anger" and "grief". In contrast to the experiments of Ekman, who combined subregions of photographed meaningful faces by hand, mixing can be done in the computer both more easily and, it turns out, more naturally. Mixed facial expressions in an animal were first drawn in matrix form by Lorenz. A consistent interpretation is possible if the linearly superposed displays are assumed to indicate the state of an autonomous optimizer with n linearly independent subfunctionals. An instant display of a vector in n-dimensional space using faces was already proposed by Chernoff. The present faces have the asset that only "natural" parameters are used. This means that no longer only a single point in n-dimensional space can be displayed, but also a meaningful succession of such points--that is, a whole trajectory.

Some remarks on the experimental realization of a mind machine.

The brain not only makes use of measuring apparatuses, but perhaps has the potential to serve as one itself. Since Einstein-Podolsky-Rosen correlations must be absent between observer and object in order for a quantum state to become reducible, it is tempting to perturb measurements by changing the quantum state of the brain. The latter would then be part of the measurement. What kind of effects would one expect? It appears that a new psychophysical problem has been opened up, since any observable consequences would be confined to the subjectivity of the observer.

The relativist stance.

The two mindsets of absolutism and relativism are juxtaposed, and the relational or relativist stance is vindicated. The only 'absolute' entity which undeniably exists, consciousness has the reality of a dream. The escape hatch from this prison is relational, as Descartes and Levinas found out: Unfalsified relational consistency implies exteriority. Exteriority implies infinite power which in turn makes compassion inevitable. Aside from ethics as a royal way to enlightenment, a new technology called 'deep technology' may be accessible. It changes the whole world in a demonstrable fashion by manipulation of the micro frame--that is, the observer-world interface.

Slower aging in women: a proposed evolutionary explanation.

Differential female longevity is so far unexplained in evolutionary terms. The theory of evolutionarily necessary aging which goes back to Wallace appears to be up to the task. In this theory, aging minimizes competition between forebear and offspring. The aging equation which is implicit contains the well-known empirical Gompertz law as a special case. Moreover, its parameters are automatically sex-specific. It is shown that the slower aging of the female members of two species of mammals, humans and sperm whales, can be 'predicted' on the basis of this equation. A prediction of effective human monogamy under archaic conditions is obtained as a corollary. The analogous if opposite prediction for sperm whales (strong promiscuity) is empirically testable.

A predictive model for life expectancy curves.

Life expectancy curves have a characteristic ominous shape that has fascinated scientists for centuries. Medawar was the first to explain this shape, specifically the steeply rising proneness of an average individual to die as a function of age, in evolutionary terms. The idea was that the "selective value" of the individual decreases as it has triggered other individuals taking its place (and carrying its genes) into existence. We demonstrate that this idea can be turned into a quantitative model. The resulting 4-parameter function reproduces well two well-known life expectancy curves from the first half of this century. Moreover, the easily interpretable parameters (3 of the 4) seem intuitively reasonable.

Chaos in physiology.

A bird's eye view of the role of nontrivial dynamical phenomena in physiological systems is presented. Many levels in the physiological hierarchy are affected. It appears that physiology has a particularly high affinity to chaos. The old central place of physiology in the circle of sciences can perhaps be regained if the two disciplines join resources. Even physics may turn out to be dependent on the chaotic micro dynamics of the brain.

Arsenite-induced apoptosis of human neuroblastoma cells requires p53 but occurs independently of c-Jun.

Arsenite treatment of human SH-SY5Y neuroblastoma cells leads to an upregulation of caspase-3/7 activity and to the fragmentation of chromatin that is accompanied by elevated p53 and c-Jun levels. Expression of a truncated mutant of p53, p53DD, which interfered with the oligomerization of p53, suppressed the arsenite-induced upregulation of caspase-3/7 activity and the fragmentation of chromatin, indicating that p53 is required for arsenite-induced cell death. These data were corroborated by knockdown experiments of p53 following expression of a p53-specific short hairpin RNA. Likewise, expression of either p53DD or knockdown of p53 prevented caspase-3/7 activation and chromatin fragmentation induced by nutlin-3, a compound that prevents the interaction between p53 and the E3 ubiquitin ligase MDM2. Transcriptional upregulation of a chromatin-embedded p53-responsive reporter gene in either arsenite or nutlin-3 stimulated neuroblastoma cells revealed that the transcriptional activity of p53 was increased under these conditions. Expression of a c-Jun-specific short hairpin RNA failed to impair arsenite-induced caspase-3/7 activation and fragmentation of chromatin. Likewise, inhibition of c-Jun target gene expression by expression of a dominant-negative mutant of c-Jun did not interfere with arsenite-induced caspase-3/7 activation and chromatin fragmentation. However, this approach successfully reduced caspase-3/7 activity induced as a result of forced expression of a constitutively active mutant of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase (MEKK)-1. Together, these data show that the upregulation of p53 is causally linked with arsenite-induced cell death in neuroblastoma cells, whereas the upregulation of c-Jun is not part of this apoptotic signaling cascade.

Is the mind-body interface microscopic?

This paper puts forward the hypothesis that consciousness might be linked to matter in a way which is more sophisticated than the traditional macroscopic Cartesian hypothesis suggests. Advances in the biophysics of the nervous system, not only on the level of its macroscopic functioning but also on the level of individual ion channels, have made the question of 'how finely' consciousness is tied to matter and its dynamics more important. Quantum mechanics limits the attainable resolution and puts into doubt the idea of an infinitely fine-woven attachment. A recent approach to physics rekindles such a rationalist hope. 'Endophysics' focuses on the global implications of microscopic computer simulations of chemical and biophysical processes. A complete 'artificial universe' can be set up in the computer. It produces non-classical and nonlocal effects inside--on the 'interface' that exists between an internal observer ('fluid neuron') and the rest of the world. This interface is finer than any brain property to which the status of the mind-body interface has been attributed hitherto. A new class of experiments becomes possible in the artificial world and, by analogy, in the real world. Magnetic resonance imaging experiments, routinely performed under open-loop conditions, can be repeated under psychophysical (closed-loop) conditions--in search for microscopically induced changes in the perceived and measured structure of the world.

Does a centralized clock for ageing exist?

It is proposed that a centralized clock controlling ageing is located in the pineal gland with the calcification process occurring there providing a highly accurate bio-inorganic timing mechanism and the secreted melatonin carrying a signal to all cells in the organism. An explicit programme of data gathering and experiments suitable for the falsification of the proposal, which is consistent with presently known anatomical and physiological facts, is presented. The underlying motivation comes from evolutionary biology and the invariance, that is the allometry, of life expectancy curves.