Towards a Liberal Biology The Pathology of University Biological Education

In this paper is offered a possible class-based or self-assessment exercise in Molecular Biology. It is intended to resemble a student essay except that it contains fifty mistakes which the student has to identify and rectify. The corrections and possible discussion points are also included. Experience from using this exercise with polytechnic undergraduates has indicated that 30 minutes is a suitable time to allocate for correction of the essay, the remainder of the class period then being available for discussion of any queries or points raised during the exercise.     

Introduction and evaluation of case-based learning in the first foundational course of an undergraduate medical curriculum

Case-based learning (CBL) has been proposed as an effective method to promote student knowledge and motivation. The timing and methods for implementation have varied among schools, and data regarding the effectiveness of this pedagogy compared to other learning modalities are inconclusive. We introduced five different cases in the first course of our medical school as part of small-group CBL, and monitored student satisfaction and performance in summative evaluations. We observed that (1) students were very satisfied with the CBL sessions; (2) performance in essay examinations was significantly higher in CBL topics, compared to non-CBL topics, as evaluated at the end of the course, and three months after course conclusion; and (3) there was a trend of higher performance in multiple-choice questions about CBL topics, but this was not statistically significant. Our results indicate that CBL is an acceptable pedagogy to be incorporated from the beginning of undergraduate medical education to promote acquisition and retention of knowledge, students’ interest in foundational sciences, and integration of basic science disciplines and clinical medicine. When evaluating knowledge acquired using the CBL method, integrative essays represent a valuable tool to assess the depth of comprehension and application of information.     

Seascape genetics: a coupled oceanographic-genetic model predicts population structure of Caribbean corals

Population genetics is a powerful tool for measuring important larval connections between marine populations [1-4]. Similarly, oceanographic models based on environmental data can simulate particle movements in ocean currents and make quantitative estimates of larval connections between populations possible [5-9]. However, these two powerful approaches have remained disconnected because no general models currently provide a means of directly comparing dispersal predictions with empirical genetic data (except, see [10]). In addition, previous genetic models have considered relatively simple dispersal scenarios that are often unrealistic for marine larvae [11-15], and recent landscape genetic models have yet to be applied in a marine context [16-20]. We have developed a genetic model that uses connectivity estimates from oceanographic models to predict genetic patterns resulting from larval dispersal in a Caribbean coral. We then compare the predictions to empirical data for threatened staghorn corals. Our coupled oceanographic-genetic model predicts many of the patterns observed in this and other empirical datasets; such patterns include the isolation of the Bahamas and an east-west divergence near Puerto Rico [3, 21-23]. This new approach provides both a valuable tool for predicting genetic structure in marine populations and a means of explicitly testing these predictions with empirical data.     

Transgenic and knock out mice in skeletal research. Towards a molecular understanding of the mammalian skeleton

Our understanding of the biology of the skeleton, like that of virtually every other subject in biology, has been transformed by recent advances in human and mouse genetics. Among mammals, mice are the most promising animals for this experimental work. Because extensive genetic information exists, many mouse mutations are known, and cells from early mouse developmental stages are accessible, scientists have developed transgenic mice - mice in which a gene is introduced or ablated in the germ line. Thus far, we have analyzed more than 100 different transgenic and knock out models with various skeletal phenotypes, covering the major aspects of both skeletal development and skeletal maintenance. Based on these results we here present a first perspective on transgenic and gene knock out animals in skeletal research, including insights in signaling pathways controlling endochondral bone formation, in the regulation of osteoblast function, osteoclastic bone resorption and in bone tumorigenesis, as well as the central control of bone formation. The use of transgenic mice to dissect and analyze regulatory mechanisms in bone cell physiology and the pathogenesis of human bone diseases is an extremely powerful experimental tool. The data presented here demonstrate that the successful convergence of novel genetic approaches with the established and fundamental knowledge of bone biology has made a beginning.     

How Darwinian reductionism refutes genetic determinism

Genetic determinism labels the morally problematical claim that some socially significant traits, traits we care about, such as sexual orientation, gender roles, violence, alcoholism, mental illness, intelligence, are largely the results of the operation of genes and not much alterable by environment, learning or other human intervention. Genetic determinism does not require that genes literally fix these socially significant traits, but rather that they constrain them within narrow channels beyond human intervention. In this essay we analyze genetic determinism in light of what is now known about the inborn error of metabolism phenylketonuria (PKU), which has for so long been the poster child 'simple' argument in favor of some form of genetic determinism. We demonstrate that this case proves the exact opposite of what it has been proposed to support and provides a strong refutation of genetic determinism in all its guises.     

A gene map of the rat derived from linkage analysis and related regions in the mouse and human genomes

We report the localization by linkage analysis in the rat genome of 148 new markers derived from 128 distinct known gene sequences, ESTs, and anonymous sequences selected in GenBank database on the basis of the presence of a repeated element. The composite linkage map of the rat contributed by our group integrates mapping information on a total of 370 different known genes, ESTs, and anonymous mouse or human sequences, and provides a valuable tool for comparative genome analysis. 206 and 254 homologous loci were identified in the mouse and human genomes respectively. Our linkage map, which combines both anonymous markers and gene markers, should facilitate the advancement of genetic studies for a wide variety of rat models characterized for complete phenotypes. The comparative genome mapping should define genetic regions in human likely to be homologous to susceptibility loci identified in rat and provide useful information for the identification of new potential candidates for genetic disorders. Received: 2 January 1999 / Accepted: 7 March 1999     

Sensitivity of genome-wide-association signals to phenotyping strategy: the PROP-TAS2R38 taste association as a benchmark

Natural genetic variation can have a pronounced influence on human taste perception, which in turn may influence food preference and dietary choice. Genome-wide association studies represent a powerful tool to understand this influence. To help optimize the design of future genome-wide-association studies on human taste perception we have used the well-known TAS2R38-PROP association as a tool to determine the relative power and efficiency of different phenotyping and data-analysis strategies. The results show that the choice of both data collection and data processing schemes can have a very substantial impact on the power to detect genotypic variation that affects chemosensory perception. Based on these results we provide practical guidelines for the design of future GWAS studies on chemosensory phenotypes. Moreover, in addition to the TAS2R38 gene past studies have implicated a number of other genetic loci to affect taste sensitivity to PROP and the related bitter compound PTC. None of these other locations showed genome-wide significant associations in our study. To facilitate further, target-gene driven, studies on PROP taste perception we provide the genome-wide list of p-values for all SNPs genotyped in the current study.     

Genomic classification using an information-based similarity index: application to the SARS coronavirus.

Measures of genetic distance based on alignment methods are confined to studying sequences that are conserved and identifiable in all organisms under study. A number of alignment-free techniques based on either statistical linguistics or information theory have been developed to overcome the limitations of alignment methods. We present a novel alignment-free approach to measuring the similarity among genetic sequences that incorporates elements from both word rank order-frequency statistics and information theory. We first validate this method on the human influenza A viral genomes as well as on the human mitochondrial DNA database. We then apply the method to study the origin of the SARS coronavirus. We find that the majority of the SARS genome is most closely related to group 1 coronaviruses, with smaller regions of matches to sequences from groups 2 and 3. The information based similarity index provides a new tool to measure the similarity between datasets based on their information content and may have a wide range of applications in the large-scale analysis of genomic databases.     

Human genome research and the public interest: progress notes from an American science policy experiment.

This essay reviews the efforts of the U.S. Human Genome Project to anticipate and address the ethical, legal, and social implications of new advances in human genetics. Since 1990, approximately $10 million has been awarded by the National Institutes of Health and the Department of Energy, in support of 65 research, education, and public discussion projects. These projects address four major areas of need: (1) the need for both client-centered assessments of new genetic services and for improved knowledge of the psychosocial and ethnocultural factors that shape clients' clinical genetic experiences; (2) the need for clear professional policies regarding human-subject research, clinical practice standards, and public health goals in human genetics; (3) the need for social policy protection against unfair access to and use of personal genetic information; and (4) the need for improved public and professional understanding and discussion of these issues. The Human Genome Project's goal is to have defined, by 1995, policy options and programs capable of addressing these needs.     

Applications of computational algorithm tools to identify functional SNPs in cytokine genes

Understanding the functions of single nucleotide polymorphisms (SNPs) can greatly help to understand the genetics of the human phenotype variation and especially the genetic basis of human complex diseases. However, how to identify functional SNPs from a pool containing both functional and neutral SNPs is challenging. In this study, we analyzed the genetic variations that can alter the expression and function of a group of cytokine proteins using computational tools. As a result, we extracted 4552 SNPs from 45 cytokine proteins from SNPper database. Of particular interest, 828 SNPs were in the 5'UTR region, 961 SNPs were in the 3' UTR region, and 85 SNPs were non-synonymous SNPs (nsSNPs), which cause amino acid change. Evolutionary conservation analysis using the SIFT tool suggested that 8 nsSNPs may disrupt the protein function. Protein structure analysis using the PolyPhen tool suggested that 5 nsSNPs might alter protein structure. Binding motif analysis using the UTResource tool suggested that 27 SNPs in 5' or 3'UTR might change protein expression levels. Our study demonstrates the presence of naturally occurring genetic variations in the cytokine proteins that may affect their expressions and functions with possible roles in complex human disease, such as immune diseases.     

Emil du Bois-Reymond vs Ludimar Hermann

This essay recounts a controversy between a pioneer electrophysiologist, Emil du Bois-Reymond (1818-1896), and his student, Ludimar Hermann (1838-1914). Du Bois-Reymond proposed a molecular explanation for the slight electrical currents that he detected in frog muscles and nerves. Hermann argued that du Bois-Reymond's 'resting currents' were an artifact of injury to living tissue. He contested du Bois-Reymond's molecular model, explaining his teacher's observations as electricity produced by chemical decomposition. History has painted Hermann as the wrong party in this dispute. I seek to set the record straight.     

一个可用于复杂大群体的可视化系谱绘制和分析软件

对于在遗传研究和家系研究中大的系谱结构图还很难分析。系谱的绘制通常是遗传性状的分析研究的第一步。系图可以反映整个群体的结构、每个个体之间的相互关系以及基因流的走向,便于理解遗传性状的本质。因为所用家系数目的增大和复杂性的增加,绘制1个清晰的系谱有时变得十分困难。因此开发了1种名为Pedigraph软件,可以解决这个问题。Pedigraph能够完成对于大的复杂的群体的系谱绘制工作,并能进行相应的系谱分析。初步的测试表明这个软件在研究动植物的遗传育种中是1个有用的工具,同时它也可以用于人类的群体和历史等方面的研究。     

BioManager: the use of a bioinformatics web application as a teaching tool in undergraduate bioinformatics training

The completion of the human genome project, and other genome sequencing projects, has spearheaded the emergence of the field of bioinformatics. Using computer programs to analyse DNA and protein information has become an important area of life science research and development. While it is not necessary for most life science researchers to develop specialist bioinformatic skills (including software development), basic skills in the application of common bioinformatics software and the effective interpretation of results are increasingly required by all life science researchers. Training in bioinformatics is increasingly occurring within the university system as part of existing undergraduate science and specialist degrees. One difficulty in bioinformatics education is the sheer number of software programs required in order to provide a thorough grounding in the subject to the student. Teaching requires either a well-maintained internal server with all the required software, properly interfacing with student terminals, and with sufficient capacity to handle multiple simultaneous requests, or it requires the individual installation and maintenance of every piece of software on each computer. In both cases, there are difficult issues regarding site maintenance and accessibility. In this article, we discuss the use of BioManager, a web-based bioinformatics application integrating a variety of common bioinformatics tools, for teaching, including its role as the main bioinformatics training tool in some Australian and international universities. We discuss some of the issues with using a bioinformatics resource primarily created for research in an undergraduate teaching environment.     

Interactive computer graphics in the study of human body planar motion under free fall conditions

A computer program utilizing interactive graphics was developed in order to study the planar motion of a five-segment model of the human body. By providing instantaneous feedback and convenient graphical representation of the body, the program allows the user to quickly simulate and study body motions of interest. Consequently, the model is a useful tool for the researcher and may be readily employed for student instructional purposes.The configuration of the model, and the derivation and validation of the equations of motion, are included. Several options provided by the simulation are described.     

The Basques according to polymorphic Alu insertions

Polymorphic Alu insertions provide a set of DNA markers of interest in human population genetics. Approximately 1000-2000 of these insertions have not reached fixation within the human genome. Each one of these polymorphic loci most probably resulted from a unique insertional event, and therefore all individuals possessing the insertion are related by descent not just state. In addition, the direction of mutational change is toward the gain of the Alu element at a particular locus. Therefore, the improved knowledge of both the ancestral state and the direction of mutational change greatly facilitates the analysis of population relationships. As a result, Alu insertion polymorphisms represent a significant tool for population genetic studies. In this study, polymorphic Alu insertions have been employed to ascertain phylogenetic relationships among Basque groups and worldwide populations. The Basques are considered to be a geographic isolate with a unique language and customs. They may be direct descendants of Cro-Magnon enclaves from the upper Paleolithic (38,000 to 10,000 years). The Basques are distributed among narrow valleys in northeastern Spain with little migration between them until recently. This characteristic may have had an effect on allelic frequency distributions. With the aim of studying this possible effect, we have analyzed six autosomal polymorphic Alu loci from four different sites within the Spanish Basque region in order to ascertain any genetic heterogeneity among the Basques. The results are consistent with a lack of homogeneity among these four autochthonous Basque groups.     

Delivering the goods: viral and non-viral gene therapy systems and the inherent limits on cargo DNA and internal sequences

Viruses have long been considered to be the most promising tools for human gene therapy. However, the initial enthusiasm for the use of viruses has been tarnished in the light of potentially fatal side effects. Transposons have a long history of use with bacteria in the laboratory and are now routinely applied to eukaryotic model organisms. Transposons show promise for applications in human genetic modification and should prove a useful addition to the gene therapy tool kit. Here we review the use of viruses and the limitations of current approaches to gene therapy, followed by a more detailed analysis of transposon length and the physical properties of internal sequences, which both affect transposition efficiency. As transposon length increases, transposition decreases: this phenomenon is known as length-dependence, and has implications for vector cargo capacity. Disruption of internal sequences, either via deletion of native DNA or insertion of exogenous DNA, may reduce or enhance genetic mobility. These effects may be related to host factor binding, essential spacer requirements or other influences yet to be elucidated. Length-dependence is a complex phenomenon driven not simply by the distance between the transposon ends, but by host proteins, the transposase and the properties of the DNA sequences encoded within the transposon.     

An essay on the evolution of cognition: Constructing a theoretical conceptual framework

In this essay we provide an interdisciplinary approach to the problem of the evolution of human cognition and suggest the theoretical framework of genetic system theory (GST) for organizing the relevant content of several disciplines. This bio-social-cultural theory is based on the assumption that organisms are dynamic systems which interact with one another and their environment and are themselves composed of dynamic internal relations at several levels. Special emphasis will be placed upon these internal cellular and molecular mechanisms underlying the physiological mechanisms of learning and memory. The human individual organism is emphasized because in its experiential activity over time it is the site of integration for social, and cultural stimuli and because of its unique properties among living things. The primary disciplines for our discussion are drawn from the biological, social, and humanistic sciences and several concrete examples are given from each science.     

Race, ethnicity, and health: can genetics explain disparities?

Over the past decade, numerous studies have documented profound racial and ethnic disparities in disease in the United States. This essay examines how popular and scientific concepts of race and ethnicity converge with dominant understandings of genetics to inform the design and interpretation of research, public health policy, and medical practice. Although there is some acknowledgment in the biomedical community that racial and ethnic categories are social and not genetic, ideas about race and ethnicity that circulate in biomedicine are contradictory. Thus, in practice genetic explanations for observed differences are common both in the scientific literature and in popular media accounts of biomedical research. Such explanations naturalize racial and ethnic difference and create a conceptual barrier to developing a research program that explores the complex ways in which social inequality and experiences of racial discrimination interact with human biology to influence patterns of disease. Importantly, genetically based ideas lead to disease prevention policies that are bound to be ineffective.     

LSHGD: A database for human leprosy susceptible genes

Studies aiming to explore the involvement of host genetic factors to determine susceptibility to develop disease and individual's response to the infection with Mycobacterium leprae have increased in recent years. To address this issue, we have developed a Leprosy Susceptible Human Gene Database (LSHGD) to integrate leprosy and human associated 45 genes by profound literature search. This will serve as a user-friendly and interactive platform to understand the involvement of human polymorphisms (SNPs) in leprosy, independent genetic control over both susceptibility to leprosy and its association with multi-drug resistance of M. leprae. As the first human genetic database in leprosy it aims to provide information about the associated genes, corresponding protein sequences, available three dimensional structures and polymorphism related to leprosy. In conclusion, this will serve as a multifunctional valuable tool and convenient information platform which is freely available at http://www.vit.ac.in/leprosy/leprosy.htm and enables the user to retrieve information of their interest.