A statistical model for the genetic origin of allometric scaling laws in biology

Many biological processes, from cellular metabolism to population dynamics, are characterized by particular allometric scaling (power-law) relationships between size and rate. Although such allometric relationships may be under genetic determination, their precise genetic mechanisms have not been clearly understood due to a lack of a statistical analytical method. In this paper, we present a basic statistical framework for mapping quantitative genes (or quantitative trait loci, QTL) responsible for universal quarter-power scaling laws of organic structure and function with the entire body size. Our model framework allows the testing of whether a single QTL affects the allometric relationship of two traits or whether more than one linked QTL is segregating. Like traditional multi-trait mapping, this new model can increase the power to detect the underlying QTL and the precision of its localization on the genome. Beyond the traditional method, this model is integrated with pervasive scaling laws to take advantage of the mechanistic relationships of biological structures and processes. Simulation studies indicate that the estimation precision of the QTL position and effect can be improved when the scaling relationship of the two traits is considered. The application of our model in a real example from forest trees leads to successful detection of a QTL governing the allometric relationship of third-year stem height with third-year stem biomass. The model proposed here has implications for genetic, evolutionary, biomedicinal and breeding research.     

Mathematical models, explanation, laws, and evolutionary biology

It is commonly agreed in the literature on laws of nature that there are at least two necessary conditions for lawhood--that a law must have empirical content and that it must be universal. The main reason offered for the requirement that laws be empirical is as follows: a priori statements are consistent with any imaginable set of observations, so they cannot be informative about the world and therefore they cannot provide explanations. However, we care about laws because we think that laws provide explanations and allow us to make predictions. Thus, if one of the functions of laws is to provide explanations and a priori propositions cannot fulfill this function, they cannot properly be viewed as laws. In this paper, I will aim to show that this argument for the claim that laws must be empirical does not work.     

Sober and Elgin on laws of biology: a critique

In this short discussion note, I discuss whether any of the generalizations made in biology should be construed as laws. Specifically, I examine a strategy offered by Elliot Sober (1997) and supported by Mehmet Elgin (2006) to reformulate certain biological generalizations so as to eliminate their contingency, thereby allowing them to count as laws. I argue that this strategy entails a conception of laws that is unacceptable on two counts: (1) Sober and Elgin’s approach allows the possibility of formulating laws describing any biological phenomenon whatsoever; and (2) on Sober and Elgin’s view, any interesting contrast between so-called laws and obviously accidental generalizations collapses. I conclude by offering suggestions to refine their view in order to avoid these theoretical problems.     

New perspectives on the biology of fragile X syndrome

Fragile X syndrome (FXS) is a trinucleotide repeat disorder caused by a CGG repeat expansion in FMR1, and loss of its protein product FMRP. Recent studies have provided increased support for the role of FMRP in translational repression via ribosomal stalling and the microRNA pathway. In neurons, particular focus has been placed on identifying the signaling pathways such as PI3K and mTOR downstream of group 1 metabotropic glutamate receptors (mGluR1/5) that regulate FMRP. New evidence also suggests that loss of FMRP causes presynaptic dysfunction and abnormal adult neurogenesis. In addition, studies on FXS stem cells especially induced pluripotent stem (iPS) cells and new sequencing efforts hold out promise for deeper understanding of the silencing process and mutation spectrum of FMR1.     

Generalizations about bacteriology: thermodynamic,open systems,genetic instructions,and evolution

Biological generalizations about bacteriology are discussed to provide a broad perspective of what we know about bacteria. Bacteriology (and possibly all biology) from an overall perspective can be researched and understood as observations and experimentations on mass and energy, which are themselves the products of evolutionary change for about 3.5–3.9 billion years. All organisms have mass, transform, store and use biochemical energy and obey the most fundamental of all laws-the laws of thermodynamics. Bacteria can be viewed as semi-permeable, thermodynamically open systems of mass, controlled by relatively small amounts of genetic instructions with lower entropy than their higher entropy, surrounding environments. Some fundamental properties describing bacterial life are also presented.     

Systems biology perspectives on cerebellar long-term depression

Long-term depression (LTD) at parallel fiber-Purkinje cell (PF-PC) synapses is thought to be the cellular correlate of cerebellar associative learning. The molecular processes are, in brief, phosphorylation of AMPA-type glutamate receptors (AMPARs) and their subsequent removal from the surface of the PF-PC synapse. In order to elucidate the fundamental mechanisms for cerebellar LTD and further the understanding of its computational role, we have investigated its systems biology and proposed the following hypotheses, some of which have already been experimentally verified: (1) due to the mitogen-activated protein kinase (MAPK)-protein kinase C (PKC) positive feedback loop, phosphorylation of AMPARs is an all-or-none event; (2) the inositol 1,4,5-triphosphate receptor detects concurrent PF and climbing fiber inputs, forming the cellular basis for associative learning, and (3) the local concentration of nitric oxide in the PC dendrite reflects the relevance of a given context, enabling context-dependent selection of learning modules within the cerebellum. In this review, we first introduce theoretical studies on cerebellar LTD, mainly focusing on our own published work, followed by a discussion of the effects of stochasticity, localization, diffusion, and scaffolding. Neurons embody two features that are apparently contradictory, yet necessary for synaptic memory: stability and plasticity. We will also present models for explaining how neurons solve this dilemma. In the final section, we propose a conceptual model in which a cascade of excitable dynamics with different time scales, i.e., Ca(2+)-induced Ca(2+) release, the MAPK-PKC positive feedback loop, and protein kinase Mzeta (PKMzeta)-induced PKMzeta synthesis, provides a mechanism for stable memory that is still amenable to modifications.     

Gravitational biology within the German Space Program: goals, achievements, and perspectives

Summary. Gravity plays an important role for the evolution, orientation and development of organisms. Most of us, however, tend to overlook its importance because – due to its constant presence from the beginning of evolution some 4 billion years ago – this environmental parameter is almost hardwired into our interpretation of reality. This negligence of gravity is the more surprising as we all have our strong fights with this factor, especially during the very early and again during the late phases of our lives. On the other hand, scientists have been fascinated to observe the effects of gravity especially on plants and microorganisms for more than a hundred years, since Darwin and Sachs demonstrated the role of the root cap for downward growing plants. Different experimental approaches are nowadays available in order to change the influence of gravity and to study the corresponding influences on the physiology of biological systems. With the advent of spaceflight, a long-term nearly nullification of gravity is possible. Utilisation of this so-called “microgravity” condition for research in life sciences thus became an important asset in the space programs of various space agencies around the world. The German Space Life Sciences Program is managed – like all other space programs and activities in Germany – by the German Aerospace Center (DLR) in its role as space agency for Germany. Within the current space program, approved by the German government in May 2001, the overall goal for its life sciences part was defined as to gain scientific knowledge and to disclose new application potential by research under space conditions, especially by utilising the microgravity environment of the International Space Station. Three main scientific fields have been identified in collaboration with the scientific community: integrative human physiology, biotechnological applications of the microgravity environment, and fundamental biology of gravity and radiation responses (i.e., gravitational and radiation biology). In the present contribution, specific goals as well as achievements and perspectives of research in gravitational biology are given. In addition, some information is provided on spaceflight opportunities available. Correspondence and reprints: German Aerospace Center (DLR), Space Agency, P.O. Box 300364, 53183 Bonn, Federal Republic of Germany.     

Theoretical molecular biology: prospectives and perspectives

I briefly discuss some aspects of theoretical molecular biology. Specifically, I include the issues of searches for homologies via string matchings, for patterns of specific nucleotide groupings and of sequence-structure relationship. The various approaches developed in order to achieve this end are described, attempting to convey some of the excitement in this quickly growing field.     

Role of cilia in normal pancreas function and in diseased states

Primary cilia play an essential role in modulating signaling cascades that shape cellular responses to environmental cues to maintain proper tissue development. Mutations in primary cilium proteins have been linked to several rare developmental disorders, collectively known as ciliopathies. Together with other disorders associated with dysfunctional cilia/centrosomes, affected individuals have increased risk of developing metabolic syndrome, neurologic disorders, and diabetes. In pancreatic tissues, cilia are found exclusively in islet and ductal cells where they play an essential role in pancreatic tissue organization. Their absence or disorganization leads to pancreatic duct abnormalities, acinar cell loss, polarity defects, and dysregulated insulin secretion. Cilia in pancreatic tissues are hubs for cellular signaling. Many signaling components, such as Hh, Notch, and Wnt, localize to pancreatic primary cilia and are necessary for proper development of pancreatic epithelium and β‐cell morphogenesis. Receptors for neuroendocrine hormones, such as Somatostatin Receptor 3, also localize to the cilium and may play a more direct role in controlling insulin secretion due to somatostatin's inhibitory function. Finally, unique calcium signaling, which is at the heart of β‐cell function, also occurs in primary cilia. Whereas voltage‐gated calcium channels trigger insulin secretion and serve a variety of homeostatic functions in β‐cells, transient receptor potential channels regulate calcium levels within the cilium that may serve as a feedback mechanism, regulating insulin secretion. This review article summarizes our current understanding of the role of primary cilia in normal pancreas function and in the diseased state. Birth Defects Research (Part C) 102:126–138, 2014. © 2014 Wiley Periodicals, Inc.     

Synthetic biology and genetic causation

Synthetic biology research is often described in terms of programming cells through the introduction of synthetic genes. Genetic material is seemingly attributed with a high level of causal responsibility. We discuss genetic causation in synthetic biology and distinguish three gene concepts differing in their assumptions of genetic control. We argue that synthetic biology generally employs a difference-making approach to establishing genetic causes, and that this approach does not commit to a specific notion of genetic program or genetic control. Still, we suggest that a strong program concept of genetic material can be used as a successful heuristic in certain areas of synthetic biology. Its application requires control of causal context, and may stand in need of a modular decomposition of the target system. We relate different modularity concepts to the discussion of genetic causation and point to possible advantages of and important limitations to seeking modularity in synthetic biology systems.     

The origin of allometric scaling laws in biology

The empirical rules relating metabolic rate and body size are described in terms of (i) a scaling exponent, which refers to the ratio of the fractional change in metabolic rate to a change in body size, (ii) a proportionality constant, which describes the rate of energy expenditure in an organism of unit mass. This article integrates the chemiosmotic theory of energy transduction with the methods of quantum statistics to propose a molecular mechanism which, in sharp contrast to competing models, explains both the variation in scaling exponents and the taxon-specific differences in proportionality constants. The new model is universal in the sense that it applies to unicellular organisms, plants and animals.     

Marking hard-shelled gastropods: tag loss, impact on life-history traits, and perspectives in biology

Abstract. Individual marking has long been used in many fields of biology. However, capture–mark–recapture (CMR) studies are not evenly distributed among taxonomic groups, with most studies focusing on vertebrates. For example, a limited number of studies have been conducted in gastropods, in sharp contrast to their important role as biological models or exploited natural resources. The lack of standard, validated marking techniques certainly contributes to the limited use of CMR. In this article, we evaluate two fundamental requirements for a marking technique to be suitable, i.e., tag loss (two experiments) and impact on life-history traits (survival, growth, and fecundity, in three experiments). Five marking techniques for hard-shelled gastropods were tested in the freshwater snail Physa acuta (Pulmonata). The tag-loss rate per month was lower for glued plastic marks (0.01) than for paint marks (0.03–0.07), and the tag-loss rate varied among colors (gouache paint). Under laboratory conditions, the life-history traits were not significantly affected by marking. We thus recommend using glued plastic marks for long-term studies, and paint marks for mass marking, with double marking to account for tag-loss rate. Based on an extensive literature survey, we also review current CMR practices in gastropod studies and suggest general improvements that would prove useful in both this group and invertebrates in general.     

BioMEMS and cellular biology: perspectives and applications

The ability to culture cells has revolutionized hypothesis testing in basic cell and molecular biology research. It has become a standard methodology in drug screening, toxicology, and clinical assays, and is increasingly used in regenerative medicine. However, the traditional cell culture methodology essentially consisting of the immersion of a large population of cells in a homogeneous fluid medium and on a homogeneous flat substrate has become increasingly limiting both from a fundamental and practical perspective. Microfabrication technologies have enabled researchers to design, with micrometer control, the biochemical composition and topology of the substrate, and the medium composition, as well as the neighboring cell type in the surrounding cellular microenvironment. Additionally, microtechnology is conceptually well-suited for the development of fast, low-cost in vitro systems that allow for high-throughput culturing and analysis of cells under large numbers of conditions. In this interview, Albert Folch explains these limitations, how they can be overcome with soft lithography and microfluidics, and describes some relevant examples of research in his lab and future directions.     

Effect of European wheat striate mosaic, acquired by feeding on diseased plants, on the biology of its planthopper vector Javesella pellucida

Ten lines of Javesella pellucida transmitted European wheat striate mosaic (EWSM) from diseased plants with an average efficiency of 31% compared to 10% efficiency for eleven lines of J. dubia. The effect on J. pellucida of EWSM, acquired through feeding on diseased plants by first and second instar nymphs, was studied in two outbred lines of hoppers. Three categories were compared: hoppers that fed on diseased plants for 7 days and became infective, hoppers that fed similarly but did not become infective, and control hoppers never fed on diseased plants and which were non-infective. No statistically significant variation was found between these three categories in survival of nymphs to adulthood, adult longevity of either sex, total, and rate of, egg production per female, or survival of eggs to eclosion. Transovarial transmission of EWSM occurred in 6 to 43% of the progenies of infective females of J. pellucida.