Homology a personal view on some of the problems

There are many problems relating to defining the terminology used to describe various biological relationships and getting agreement on which definitions are best. Here, I examine 15 terminological problems, all of which are current, and all of which relate to the usage of homology and its associated terms. I suggest a set of definitions that are intended to be totally consistent among themselves and also as consistent as possible with most current usage.     

A personal view on the early history of the insulin-like growth factors

Salmon and Daughaday, when trying to set up an in vitro assay for Growth Hormone (GH), failed to obtain a direct effect on sulphate uptake in cartilage of hypophysectomized (hypox) rats. They recognised that this was not the consequence of poor methodology or materials, but an encrypted message from the examined system. They decided to turn around and to try and decipher it. Treatment with GH appeared to render hypox rat serum active in stimulating sulphation in hypox rat cartilage. They proposed that GH induced an intermediary substance, responsible for this biological effect: sulphation factor (SF), later renamed to Somatomedin(s) (SM). This hypothesis met with great criticism and very few took on to study this hypothetical substance. Besides disbelief, slow progress was also due to initial lack of a practical assay and to the failure to find a tissue with enriched concentration from which to extract the activity. From experimental evidence, the concept gradually evolved that SF/SM was insulin-like and might be identical to NSILA (non-suppressible insulin-like activity). This again generated controversy. This characteristic was too far away from the known effects of GH to be readily acceptable as a physiological phenomenon. The subsequent recognition of the distinct characteristics of the receptors for SM/NSILA and insulin, the discovery of the SM/NSILA binding proteins and, much later, a beginning understanding of their interactions, modifications and breakdown, have gradually resolved this apparent contradiction. When the sequence of two NSILA molecules became known, they were named IGF-I and -II. Structural similarity with proinsulin and identity of IGF-I with SM-C and -A were established and it was found that Multiplication Stimulating Activity (MSA), a growth factor isolated from fetal calf serum and subsequently from conditioned media of a rat liver cell line, was the rat equivalent of IGF-II. Structure-function relations could be studied, a quest which is not yet brought to an end. Meanwhile, the endocrine profile of SF/SM had gradually emerged by measuring plasma levels with bioassays. The main determinants were found to be age, body size, GH and the nutritional state. Later, radioimmunoassays were developed, enabling consolidation and detailing of these early observations, and allowing explorations at the tissue level. As another aspect of the endocrine paradigm, in vivo effects of IGFs were studied. The initial demonstration of an effect of crude preparations on longitudinal growth in experimental animals raised heavy scepticism, since the effect might have been an artefact caused by contaminants. It took confirmation with highly purified preparations and biosynthetic IGF-I to ease this concern. Still, not until recent years it was demonstrated, by knocking out the genes, that a true physiological and not a pharmacological effect had been induced previously. When it was found that most tissues produce SMs and are sensitive to their actions, the concept emerged that IGFs may have para- and autocrine functions. Early experiments with combinations of growth factors in cell cultures had begun to define their specific roles in the cell cycle as competence or progression factors. SM-C fell in the latter category. Still, the awareness grew that, for obtaining physiologically meaningful results on the role of IGFs in complex, dynamic and tissue-specific environments, involving interactions of many hormones and growth factors, the intactness of tissue was a prerequisite. One result of this approach was the discovery of a direct interaction of GH with cartilage, leading, in concert with IGFs, to a clonal expansion of the cartilage cells of the growth plate. The isolation and sequencing of the IGF-I and -II genes, and later, of six IFG-BPs initiated the gradual elucidation of structure and function at the DNA and RNA level and the study of natural and synthetic IGF-variants. The generation of transgenic animals became feasible     

Animal behavior and the captive management of wild mammals: A personal view

Behaviorists can undertake noninvasive studies of zoo animals using only the simplest of research tools, unlike those biologists who are concerned with functions below the level of the whole, living organism. With careful interpretation, the results of behavioral studies can be applied to improve the management, husbandry, and exhibition of wild mammals in captivity. This often involves comparisons with research results obtained from studies of animals in the wild, since the behavior of captive specimens may in some measure be altered. Examples are given involving the breeding biology or social organization of three species: (1) barasingha or swamp deer (Cervus duvauceli), (2) mongoose lemur (Lemur mongoz), and (3) drill (Papio leucophaeus). Suggestions are made to improve the allocation of time and resources for research by zoo personnel, including a greater reliance on cooperative efforts to solve problems of common interest.     

Origins of gene, genetic code, protein and life: comprehensive view of life systems from a GNC-SNS primitive genetic code hypothesis

We have investigated the origin of genes, the genetic code, proteins and life using six indices (hydropathy, α-helix, β-sheet and β-turn formabilities, acidic amino acid content and basic amino acid content) necessary for appropriate three-dimensional structure formation of globular proteins. From the analysis of microbial genes, we have concluded that newly-born genes are products of nonstop frames (NSF) on antisense strands of microbial GC-rich genes [GC-NSF(a)] and from SNS repeating sequences [(SNS)_n] similar to the GC-NSF(a) (S and N mean G or C and either of four bases, respectively). We have also proposed that the universal genetic code used by most organisms on the earth presently could be derived from a GNC-SNS primitive genetic code. We have further presented the [GADV]-protein world hypothesis of the origin of life as well as a hypothesis of protein production, suggesting that proteins were originally produced by random peptide formation of amino acids restricted in specific amino acid compositions termed as GNC-, SNS and GC-NSF(a)-0th order structures of proteins. The [GADV]-protein world hypothesis is primarily derived from the GNC-primitive genetic code hypothesis. It is also expected that basic properties of extant genes and proteins could be revealed by considerations based on the scenario with four stages This review is a modified English version of the paper, which was written in Japanese and published inViva Origino 2001 29 66–85.     

A view from the NIH bridge: perspectives of a program officer

This essay is written from my perspective as a program officer for research and training activities at the National Institute of General Medical Sciences (NIGMS) for almost 27 yr. It gives a bird's-eye view of the job of a program officer, which includes providing advice to applicants and grantees, making funding recommendations, overseeing grantees' progress, facilitating scientific opportunities in specific areas of program responsibility, and shaping NIGMS and National Institutes of Health (NIH) policy. I have highlighted the numerous rewards of serving as a program officer, as well as some of the difficulties. For those who may be considering a position as an NIH program officer now or in the future, I've also described the qualities and qualifications that are important for such a career choice. Finally, this essay addresses some of the challenges for the NIH and the research community in the years ahead as we simultaneously face exciting scientific opportunities and tighter budgets.     

Bioethics and animal research: a personal perspective and a note on the contribution of Fritz Jahr

Reviewing fundamental aspects of bioethics and outlining the work of the Bioethics Program of the Pan American Health Organization, this paper draws attention to the work of a forgotten pioneer- Fritz Jahr- who coined the term bioethics in 1927 and anticipated many of the arguments and discussions now current in biological research involving animals.     

Microsporidia and the Society for Invertebrate Pathology [corrected]: a personal point of view

In this overview, I trace the history of the study of microsporidia, with special emphasis on the collegial relationships that developed at the international level and were fostered by the establishment of the Society for Insect Pathology, which later became the Society for Invertebrate Pathology. Study of these organisms of invertebrates in the early days seemed to be mere curiosities, but it soon became clear that they were major disease-causing agents in insects, and later even in vertebrates, especially humans with compromised immune systems. Though microsporidia have not proven effective as pesticides, they do play a role in the regulation of insect populations, especially insects such as the gypsy moth, grasshoppers, and occasionally mosquitoes.     

A remark on sensory deprivation from the point of view of organismic sets

It is shown that from the definition of organismic sets (Rashevsky,Organismic Sets. Some Reflections on the Nature of Life and Society, Holland, Michigan, Mathematical Biology, Inc. and Grosse Pointe, Michigan, J. M. Richards Laboratory) a complete sensory deprivation of an organismic set of ordern=2 should result in malfunctioning of the set. A generalization to higher order sets is suggested.     

植物盐胁迫应答蛋白质组学研究的技术策略

土壤盐渍化是限制植物生长和分布的关键因素之一.揭示植物响应盐胁迫的分子机理是借助分子生物学手段提高植物耐盐性的基础,也是当前植物生理与分子生态学研究的热点问题.高通量的蛋白质组学技术体系包括双向电泳技术、蓝色自然胶电泳技术、双向荧光差异凝胶电泳技术、液相色谱技术,以及各种生物质谱技术,已经被广泛应用于植物应答盐胁迫研究,为解析植物耐盐分子机制提供了重要信息.本文综述了应用于植物盐胁迫响应蛋白质组学研究的技术策略.     

A personal view on systems medicine and the emergence of proactive P4 medicine: predictive, preventive, personalized and participatory

Systems biology and the digital revolution are together transforming healthcare to a proactive P4 medicine that is predictive, preventive, personalized and participatory. Systems biology - holistic, global and integrative in approach - has given rise to systems medicine, a systems approach to health and disease. Systems medicine promises to (1) provide deep insights into disease mechanisms, (2) make blood a diagnostic window for viewing health and disease for the individual, (3) stratify complex diseases into their distinct subtypes for a impedance match against proper drugs, (4) provide new approaches to drug target discovery and (5) generate metrics for assessing wellness. P4 medicine, the clinical face of systems medicine, has two major objectives: to quantify wellness and to demystify disease. Patients and consumers will be a major driver in the realization of P4 medicine through their participation in medically oriented social networks directed at improving their own healthcare. P4 medicine has striking implications for society - including the ability to turn around the ever-escalating costs of healthcare. The challenge in bringing P4 medicine to patients and consumers is twofold: first, inventing the strategies and technologies that will enable P4 medicine and second, dealing with the impact of P4 medicine on society - including key ethical, social, legal, regulatory, and economic issues. Managing the societal problems will pose the most significant challenges. Strategic partnerships of a variety of types will be necessary to bring P4 medicine to patients.     

A career at the interface of cell and developmental biology: a view from the crest

Just as neural crest cells migrate great distances through the embryo, my journey has taken me from a childhood in a distant land to a career as a biologist. My mentoring relationships have shaped not only the careers of my trainees, but also the trajectory of my own science. One of the most satisfying aspects of mentoring comes from helping to empower the next generation of scientists to do more tomorrow than is possible today. This, together with a passion for discovery and learning new things, motivates me and makes science such a rewarding career.First, let me say how honored I am to receive the Women in Cell Biology Senior Award. I am particularly thankful to my former postdoctoral fellows and students. I have learned as much, or more, from them as they have from me and take great pride and vicarious pleasure from their successes. My goal as a mentor has been to impart an enthusiasm for science and for the satisfaction it can bring at both a professional and personal level. It is the pleasure of discovery and the bonds of collegiality that make being a scientist not only a worthwhile and interesting but also a very fulfilling career.When looking back upon my life as a biologist, many of the “choices” made along my career path were more of a random walk than a premeditated trajectory. Perhaps the most important and constant influences come from my family background, wonderful friends and colleagues, and an inherent interest in the natural world. For me, these were mixed with a good deal of luck and the generous mentorship of valued colleagues.     

The livestock reservoir for antimicrobial resistance: a personal view on changing patterns of risks,effects of interventions and the way forward

The purpose of this review was to provide an updated overview on the use of antimicrobial agents in livestock, the associated problems for humans and current knowledge on the effects of reducing resistance in the livestock reservoir on both human health and animal production. There is still limiting data on both use of antimicrobial agents, occurrence and spread of resistance as well as impact on human health. However, in recent years, emerging issues related to methicillin-resistant Staphylococcus aureus, Clostridium difficile, Escherichia coli and horizontally transferred genes indicates that the livestock reservoir has a more significant impact on human health than was estimated 10 years ago, where the focus was mainly on resistance in Campylobacter and Salmonella. Studies have indicated that there might only be a marginal if any benefit from the regular use of antibiotics and have shown that it is possible to substantially reduce the use of antimicrobial agents in livestock production without compromising animal welfare or health or production. In some cases, this should be done in combination with other measures such as biosecurity and use of vaccines. To enable better studies on both the global burden and the effect of interventions, there is a need for global harmonized integrated and continuous surveillance of antimicrobial usage and antimicrobial resistance, preferably associated with data on production and animal diseases to determine the positive and negative impact of reducing antimicrobial use in livestock.     

A neurobiological model of the recovery strategies from perturbed walking

This paper proposes a human mimetic neuro-musculo-skeletal model to simulate the recovery reactions from perturbations during walking. The computational model incorporates nonlinear viscoelastic muscular mechanics, supraspinal control of the center-of-mass, spinal pattern generator including muscle synergy network, spinal reflexes, and long-loop reflexes. Especially the long-loop reflexes specify recovery strategies based on the experimental observations [Schillings, A.M., van Wezel, B.M.H., Mulder, T.H., Duysen, J., 2000. Muscular responses and movement strategies during stumbling over obstacles. J. Neurophysiol. 83, 2093–2102; Eng, J.J., Winter, D.A., Patla, A.E., 1994. Strategies for recovery from a trip in early and late swing during human walking. Exp. Brain Res. 102, 339–349]. The model demonstrates two typical recovery strategies, i.e., elevating and lowering strategies against pulling over a swing leg. Sensed perturbation triggers a simple tonic pulse from the cortex. Depending on the swing phase, the tonic pulse activates a different compound of muscles over lower limbs. The compound induces corresponding recovery strategies. The reproduction of principal recovery behaviors may support the model's proposed functional and/or anatomical correspondence.     

A view from the forest floor: the impact of logging on indigenous peoples in Brazil

The social impact of the mahogany trade on the indigenous peoples of Brazil is described. Emphasis is placed on the violence directed against Indians and the consequences of the destruction of their environment which results from the trade. Also mentioned are the judicial issues regarding the illegal extraction of mahogany from protected areas and several of the court cases against logging companies. A moratorium on mahogany logging in Brazil is advocated as is the right of indigenous peoples to control their lands and resources as the way to conserve their environment.