The GDB Human Genome Data Base anno 1994.

In 1991 the Genome Data Base at Johns Hopkins University School of Medicine was selected as the central repository for mapping data from the Human Genome Project, and was funded by NIH and DOE under a three year award. GDB has now finished 28 months of Federally funded operation. During this period a great deal of progress and many internal changes have taken place. In addition, many changes have also occurred in the external environment, and GDB has adapted its strategies to play an appropriate role in those changes as well. Recognizing the central role of mapping information in the genome project, it is important that GDB respond aggressively to the increasing demands of genomic researchers, as well as formulate a program of response to a number of long standing, but still unmet, needs of that community. It is even more important that GDB provide leadership in the genome informatics enterprise. Three themes described here are dominant in our future plans and represent the essence of the major changes made in the past year. They include: enhanced data acquisition, better map representation, and full integration into the collection of genomic databases.     

MHC superfamily structure and the immune system

During the past year, a plethora of structural information has provided detailed insights into the interactions between classical MHC class I molecules and their cognate receptors on T cells. Likewise, there have been major advances in our knowledge of the structures and functions of five nonclassical MHC-like molecules: HLA-DM (murine H2-M), HLA-E, HFE, ZAG and MIC-A.     

Did Darwin really answer Paley’s question?

It is commonly thought that natural selection explains the rise of adaptive complexity. Razeto-Barry and Frick (2011) have recently argued in favour of this view, dubbing it the Creative View. I argue that the Creative View is mistaken if it claims that natural selection serves to answer Paley’s question. This is shown by a case that brings out the contrastive structure inherent in this demand for explanation. There is, however, a rather trivial sense in which specific environmental conditions are crucial for the rise of specific adaptations, but this is hardly what opponents of the Creative View are denying.     

Acrokeratoelastoidosis

Summary Acrokeratoelastoidosis is a peculiar palmo-plantar keratosis which was first described in 1952 by the Brasilian dermatologist Costa. Since then several patients have been observed, most of them in South America. During the past year we have had occasion to observe this disease in a large German kindred as well.     

Complexity,adaptive complexity and the Creative View of natural selection

In this paper, I respond to arguments proposed by Brunnander in this journal issue concerning my position regarding the Creative View of natural selection (Razeto-Barry & Frick, 2011). Brunnander argues that (i) the Creative View we defend does not serve to answer William Paley’s question because (ii) Paley’s question is “why there are complex things rather than simple ones” and (iii) natural selection cannot answer this question. Brunnander’s arguments for (iii) defend a Non-creative View of natural selection (sensu Razeto-Barry & Frick, 2011). Here I claim that Brunnander’s arguments for (iii) are mistaken and I also argue that even accepting (iii) we do not have to accept (i), given that statement (ii) is historically and conceptually flawed. Thus here I analyze Paley’s question from a historical point of view and from a contemporary perspective in a quest for the potential conceptual relevance of Paley’s question today. In this vein I argue that from a contemporary point of view statement (iii) may be correct but for different reasons than those adduced by Brunnander.     

Sodium-calcium exchange.

During the past year, significant advances have been made in the investigation of molecular, kinetic and electrophysiological aspects of Na(+)-Ca2+ exchange. The cardiac and retinal exchangers have been cloned and structure-function studies have begun.     

Telomeres and telomerase: broad effects on cell growth.

During the past year, major advances have been made in understanding the link between telomerase expression and cell immortality. Studies of yeast telomeres have revealed an unexpected role for the non-homologous end-joining machinery in telomere maintenance and have provided the first definitive evidence that telomeres play a critical role in meiosis. Identification of new telomere proteins has led to a better understanding of vertebrate telomere structure and function.     

Genomics and proteomics converge on Helicobacter pylori

During the past year, a series of studies have provided new perspectives about genetic diversity in Helicobacter pylori. The results illustrate how the current revolution in genomics and proteomics is being used to understand how this organism co-evolves with its host. The approaches should have broad applications to other host-bacterium relationships.     

Protein phosphatase 2A: a panoply of enzymes

Protein phosphatase 2A describes an extended family of intracellular protein serine/threonine phosphatases sharing a common catalytic subunit that regulates a variety of processes by means of diverse regulatory subunits. During the past year, studies have shown that protein phosphatase 2A influences events ranging from the initiation of DNA replication to vertebrate axis formation to apoptosis.     

Computer-aided instruction at the Ottawa General Hospital

We have reviewed our experiences with the first systematic use of CAI at the University of Ottawa Medical School. The Bleich acid-base and electrolyte program was employed by senior clinical clerks in the Department of Medicine during the past year using APL version of the program, an IBM 360-65 computer linked by acoustic coupler to the typewriter-style IBM 2741 terminal. We have been impressed with the importance of: (1) minimizing technical difficulties, (2) enhancing the teaching capacity of the program (as opposed to its consultant function) and (3) carefully ensuring that the user understands its limitations. This pilot project in clinical CAI has identified problems which will likely be experienced in other medical centres and has suggested important areas for further development.     

Genetic variation and quasi-species.

During the past year the relative fitness, that is, overall replication ability, and the fitness gain of animal virus variants have been quantified, providing new insight into the dynamics for the generation of RNA virus quasi-species. Measurements of mutant frequencies and rates of genetic diversification have confirmed the extreme complexity of RNA virus and retrovirus populations.     

Papillomaviruses and human oncogenesis.

During the past year, significant advances have been made in understanding the functions of the oncoproteins, E6 and E7, of human papillomaviruses that are associated with malignant genital tumors. In addition, important new information is now available on the responses of both the keratinocyte and of the individual following papillomavirus infection.     

Microbial hemicellulases

Hemicellulases are a diverse group of enzymes that hydrolyze hemicelluloses--one of the most abundant groups of polysaccharide in nature. These enzymes have many biotechnological applications and their structure/function relationships are a subject of intense research. During the past year, new high-resolution structures of catalytic and non-catalytic domains of hemicellulases have been elucidated, and, together with biochemical studies, they reveal the principles of catalysis and specificity for these enzymes.     

Trade-offs between pathogen and herbivore resistance

During the past year genetic and pharmacological experiments have revealed a molecular basis for the cross-talk between signaling pathways mediating pathogen and herbivore resistance. These findings provide considerable insight into the apparently contradictory results reported for trade-offs between pathogen and herbivore resistance.     

Bacterial adhesins: structural studies reveal chaperone function and pilus biogenesis

During the past year, remarkable progress has been made in understanding how periplasmic chaperones fold and protect protein modules that are destined for assembly into adhesive pili in Gram-negative bacteria. The first two three-dimensional structures of complexes of periplasmic chaperones with substrate pilus subunits have revealed much about the structural basis for chaperone-mediated folding and aggregation prevention, and have provided insight into the structure of adhesive pili.     

Mechanisms for ATP-dependent chromatin remodelling

During the past year, major advances have been made towards understanding the function of ATP-dependent chromatin-remodelling activities both in vitro and in vivo. These suggest that ATP-dependent chromatin-remodelling activities are capable of both altering the structure of individual nucleosomes and acting in concert with other forms of chromatin-modifying enzymes, to regulate the formation and decondensation of chromatin fibres.     

Virulence gene regulation by peptides in staphylococci and other Gram-positive bacteria

In staphylococci, autoinducing peptides activate agr. a global regulator of the expression of genes encoding virulence factors and other exoproteins. During the past year, there have been major advances in the structure-function analysis of these peptides and the regulation of a virulence factor by an autoinducing peptide in pneumococci has been demonstrated.