Chronobiology: a frontier in biology and medicine

On the occasion of Franz Halberg's 70th birthday, some of his many achievements are reviewed. We provide a historical background to the development of chronobiology; offer insight into the current state of this new science; and sketch the promise of this discipline for health care and cure. As a tribute to Franz Halberg, in an era of fast-growing technology, an attempt is made to describe his perspective of tomorrow's medicine and biology. The many students he trained throughout his productive career face the challenge of deserving the trust he placed in them and of further implementing his vision. A leader in social pediatrics put it aptly: it will take several generations of researchers to study and master his life's work.     

Contemporary evolution meets conservation biology II: impediments to integration and application

Conservation biology needs to be concerned not just with exogenous threats to populations, but also with the changing nature of populations themselves. In a previous review paper, we highlighted evolution in contemporary time (years to decades) as a largely overlooked aspect of population responses to environmental perturbations. We argued that these responses might affect the fate of natural, managed and exotic populations. In the present review, we discuss issues that may limit the integration of contemporary evolution into conservation biology—with the intent that recognition of these limitations may foster research, discussion and resolution. In particular, we consider (1) alternative perceptions of “evolutionary” and “ecological” time, (2) the role of contemporary evolution as an ecological process, (3) fitness as a bridge between evolution and conservation, and (4) challenges faced by conservation strategies based on gene flow estimation or manipulation. We close by highlighting some situations in which current conservation approaches and contemporary evolution may require reconciliation.     

Kleisli: a new tool for data integration in biology.

One of the central problems in bioinformatics is data retrieval and integration. The existing biological databases are geographically distributed across the Internet, complex and heterogeneous in data types and data structures, and constantly changing. With the current rapid growth of biomedical data, the challenge is how large volumes of data retrieved from multiple databases can be transformed and integrated automatically and flexibly. This article describes a powerful new tool, the Kleisli system, for complex queries across multiple databases and data integration.     

Mathematical models for excitable systems in biology and medicine.

The excitable systems play a very important role in Biology and Medicine. Phenomena such as the transmission of impulses between neurons, the cardiac arrhythmia, the aggregation of amoebas, the appearance of organized structures in the cortex of egg cells, all derive from the activity of excitable media. In the first part of this work a general definition of excitable system is given; we then analyze some cases of excitability, distinguishing between electrical and chemical excitability and comparing experimental observations with simulations carried out by appropriate mathematical models. Such models are almost always formulated by partial differential equations of "reaction-diffusion" type and they have the characteristic to describe propagations of electrical waves (neurons, pacemaker cardiac cells, pancreatic b-cells) or chemical and mechanical waves (propagation of Ca++ waves or mechanical waves in the endoplasmic reticulum). The aim is to put in evidence that the biological systems can show not only excitability of electrical type, but also excitability of chemical nature, which can be observed in the first steps of development of egg cells or, for example, in the formation of pigments in vertebrate skin or in clam shells.     

Trade-offs in thermal adaptation: the need for a molecular to ecological integration

Through functional analyses, integrative physiology is able to link molecular biology with ecology as well as evolutionary biology and is thereby expected to provide access to the evolution of molecular, cellular, and organismic functions; the genetic basis of adaptability; and the shaping of ecological patterns. This paper compiles several exemplary studies of thermal physiology and ecology, carried out at various levels of biological organization from single genes (proteins) to ecosystems. In each of those examples, trade-offs and constraints in thermal adaptation are addressed; these trade-offs and constraints may limit species' distribution and define their level of fitness. For a more comprehensive understanding, the paper sets out to elaborate the functional and conceptual connections among these independent studies and the various organizational levels addressed. This effort illustrates the need for an overarching concept of thermal adaptation that encompasses molecular, organellar, cellular, and whole-organism information as well as the mechanistic links between fitness, ecological success, and organismal physiology. For this data, the hypothesis of oxygen- and capacity-limited thermal tolerance in animals provides such a conceptual framework and allows interpreting the mechanisms of thermal limitation of animals as relevant at the ecological level. While, ideally, evolutionary studies over multiple generations, illustrated by an example study in bacteria, are necessary to test the validity of such complex concepts and underlying hypotheses, animal physiology frequently is constrained to functional studies within one generation. Comparisons of populations in a latitudinal cline, closely related species from different climates, and ontogenetic stages from riverine clines illustrate how evolutionary information can still be gained. An understanding of temperature-dependent shifts in energy turnover, associated with adjustments in aerobic scope and performance, will result. This understanding builds on a mechanistic analysis of the width and location of thermal windows on the temperature scale and also on study of the functional properties of relevant proteins and associated gene expression mechanisms.     

Shifts in phenology due to global climate change: the need for a yardstick

Climate change has led to shifts in phenology in many species distributed widely across taxonomic groups. It is, however, unclear how we should interpret these shifts without some sort of a yardstick: a measure that will reflect how much a species should be shifting to match the change in its environment caused by climate change. Here, we assume that the shift in the phenology of a species' food abundance is, by a first approximation, an appropriate yardstick. We review the few examples that are available, ranging from birds to marine plankton. In almost all of these examples, the phenology of the focal species shifts either too little (five out of 11) or too much (three out of 11) compared to the yardstick. Thus, many species are becoming mistimed due to climate change. We urge researchers with long-term datasets on phenology to link their data with those that may serve as a yardstick, because documentation of the incidence of climate change-induced mistiming is crucial in assessing the impact of global climate change on the natural world.     

Developmental biology meets with reproductive engineering; interdisciplinary science area as a breakthrough.

It has been postulated many times that different scientific topics and strategies often encounter each other, which create cutting edge research field resulting in further significant progresses of science. This was also a lesson bestowed by Prof. Raymond Wegmann where he created innovative research field for biology, molecular biology and biochemistry-biophysics. Progresses of developmental biology were boosted by molecular biology and reproductive engineering where ES cells and embryonic manipulation are necessary. There are no questions about the utility of their technologies. Reviews on their contributions with respect to the condition of genome manipulation are addressed.     

Technetium in biology and medicine

Although twenty-eigth radionuclides of technetium have been prepared, only technetium-99m, technetium-99 and technetium-95m have so far become important.Technetium-99, available in large amounts, is used in the study of the physical and chemical properties of the element, and offers the possibility of many industrial applications where its radioactivity does not create serious problems. With the increase in the use of nuclear power, however, more and more technetium-99 is being produced which is entering into the environment. This has resulted in increased interest in the biogeochemical behaviour of this radionuclide during recent years.The ideal physical properties, half-life of 6 hours and monochromatic gamma emission of 140 kev, and the versatile chemistry of technetium-99m have recently made it the radiotracer of choice for the external noninvasive imaging of almost all internal organs of the body. In the preparation of technetium- 99m radiopharmaceuticals and in the interpretation of their biological behaviour, the chemistry of technetium-99 has so far served as a guide. Similarly assumptions have been made that technetium-95m and technetium-99 have identical biogeochemical behaviour. We have shown that even the radioisomers, technetium-99m and technetium-99, have different chemical properties. These results suggest that in the study of the biological and environmental behaviour of technetium, a rigorous knowledge of the chemistry of each radionuclide is needed.     

Mitochondria in biology and medicine

Ever since the first diagnosis of a mitochondrial disease in 1959 (Ernster et al., 1959), the interest for mitochondrial cytopathies has continued to increase. Originally it was believed that the condition was very rare and primarily effected high-energy requiring tissues resulting in a select few pathologies (Luft, 1994). Since 1959, the understanding of mitochondrial cytopathies has evolved immensely and mitochondrial cytopathies are now known to be the largest group of metabolic diseases and to be resulting in a wide variety of pathologies. "Mitochondria in Biology and Medicine" was the title of the first annual conference of Society of Mitochondrial Research and Medicine - India. The conference was organized by A. S. Sreedhar, Keshav Singh and Kumarasamy Thangaraj, and was held at The Centre for Cellular and Molecular Biology (CCMB) Hyderabad, India, during 9-10 December 2011. The conference featured talks from internationally renowned scientists within the field of mitochondrial research and offered both students and fellow researchers a comprehensive update to the newest research within the field. This paper summarizes key outcomes of the presentations.     

Chronobiology in the diagnosis and treatment of mesor-hypertension.

An elevation of systolic and diastolic bloodpressure to values regarded as abnormal ones on the basis of conventional criteria was recognized by self-measurement. For both systolic and diastolic blood pressure, the overall means adjusted for rhythms, the so-called mesors, also were elevated in the light of their response to treatment: these mesors were found to be lowered with statistical significance when values during treatment were compared by an objective test with values measured before treatment. Individualized rhythmometry quantitatively characterizes a predictalbe portion of the variability in human blood pressure and tests for the statistical significance of changes in blood pressure as a function of the treatment and also as a function of the circadian timing of such treatment. The case report thus illustrates an individualized chronotherapy of systolic and diastolic mesor-hypertension, diagnosed retrospectively from the tested effect of hydrochlorothiazide. In the case reported, and perhaps routinely, computer-analyzed self-measurements can serve 1) to prescribe the right kind and amount with the right timing, for a given therapy, and 2) for diagnosis and prevention as well (Meyer et al.; Halberg et al.).