Galactosemia: the good, the bad, and the unknown

Alpha-D-galactose is metabolized in species ranging from E. coli to mammals predominantly via a series of sequential reactions collectively known as the Leloir pathway. Deficiency of any one of these enzymes in humans results in a form of the inherited metabolic disorder, galactosemia, although the symptoms and severity depend upon the enzyme impaired, and the degree of functional deficiency (Tyfield and Walter, 2002, The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw Hill.). Studies of these enzymes, and the disorders associated with their loss, have led to a much deeper appreciation of the intricate and interwoven levels of regulation that govern their normal function. These insights have further identified likely mediators of outcome severity in patients, and have enabled a rational approach to the development of novel strategies of intervention.     

Superantigens: the good, the bad, and the ugly

Increasing evidence suggests that superantigens play a role in immune-mediated diseases. Superantigens are potent activators of CD4+ T cells, causing rapid and massive proliferation of cells and cytokine production. This characteristic of superantigens can be exploited in diseases where strong immunologic responses are required, such as in the B16F10 animal model of melanoma. Superantigen administration is able to significantly enhance ineffective anti-tumor immune responses, resulting in potent and long-lived protective anti-tumor immunity. However, superantigens are more well-known for the role they play in diseases. Studies using an animal model for neurologic demyelinating diseases such as multiple sclerosis show that superantigens can induce severe relapses and activate autoreactive T cells not involved in the initial bout of disease. This may also involve epitope spreading of disease. Superantigens have also been implicated in acute diseases such as food poisoning and TSS, and in chronic diseases such as psoriasis and rheumatoid arthritis. Viral superantigens are also involved in the disease process, including superantigens derived from human immunodeficiency virus and mouse mammary tumor virus. Finally, immunotherapies that ameliorate the role played by superantigens in disease are discussed.     

Making Forest of Bliss: The Film, the Book, the DVD, and the Breakthrough

Robert Gardner's and Àkos Östör's Making of Forest of Bliss (2002) is a combination book and DVD that contains eight teaching tools for better understanding Gardner's celebrated film Forest of Bliss. After the film was shot in 1985, filmmaker Gardner and anthropologist Östör recorded a conversation about each image and sound of the film while they screened it again in 1987, and remembered their filmmaking process on location in Benares, India. The feature length (89 minute) documentary about death ritual, reincarnation, the sacred Ganges River, and the very atmosphere of Benares is included as DVD, as are teaching tools such as frame grabs (still images from the film), a mathematically precise shot list, bibliography, important criticism and essays about the film, and the featured in-depth conversation between filmmaker Gardner and anthropological advisor Östör. This essay articulates the unique breakthroughs in pedagogy, cross-cultural studies, and multidisciplinary analysis such hybrid technology provides.     

Structures of the potassium-saturated, 2:1, and intermediate, 1:1, forms of a quadruplex DNA

Potassium can stabilize the formation of chair- or edge-type quadruplex DNA structures and appears to be the only naturally occurring cation that can do so. As quadruplex DNAs may be important in the structure of telomere, centromere, triplet repeat and other DNAs, information about the details of the potassium–quadruplex DNA interactions are of interest. The structures of the 1:1 and the fully saturated, 2:1, potassium–DNA complexes of d(GGTTGGTGTGGTTGG) have been determined using the combination of experimental NMR results and restrained molecular dynamics simulations. The refined structures have been used to model the interactions at the potassium binding sites. Comparison of the 1:1 and 2:1 potassium:DNA structures indicates how potassium binding can determine the folding pattern of the DNA. In each binding site potassium interacts with the carbonyl oxygens of both the loop thymine residues and the guanine residues of the adjacent quartet.     

Neuroscience, ethics, and national security: the state of the art

National security organizations in the United States, including the armed services and the intelligence community, have developed a close relationship with the scientific establishment. The latest technology often fuels warfighting and counter-intelligence capacities, providing the tactical advantages thought necessary to maintain geopolitical dominance and national security. Neuroscience has emerged as a prominent focus within this milieu, annually receiving hundreds of millions of Department of Defense dollars. Its role in national security operations raises ethical issues that need to be addressed to ensure the pragmatic synthesis of ethical accountability and national security.     

A synopsis of the sawflies (Hymenoptera: Symphyta) of America south of the United States: introduction, Xyelidae, Pamphiliidae, Cimbicidae, Diprionidae, Xiphydriidae, Siricidae, Orussidae, Cephidae

Abstract Eight families of Symphyta for the Western Hemisphere south of the United States are reviewed: Xyelidae (one genus, two species), Pamphiliidae (one genus, four species), Cimbicidae (five genera, nine species), Diprionidae (three genera, thirteen species), Xiphydriidae (four genera, seventeen species), Siricidae (six genera, nine species), Orussidae (five genera, twelve species), and Cephidae (one genus, one species). New taxa are Acantholyda nigrostigmata (Pamphiliidae); Zadiprionfalsus, Neodiprion bicolor, N.equalis, N.omosus (Diprionidae); Derecyrta circularis, Steirocephala lateralba (Xiphydriidae); Sirotremex, S.flammeus (Siricidae); and Ophrynopus depressatus, O.plaumanni (Orussidae). Lopesiana is a new name for Lopesia Conde (Cimbicidae). Three new combinations and six new synonyms are proposed. The Xyelidae, Pamphiliidae, Diprionidae, Siricidae and Cephidae are primarily northern groups with southern extensions into Mexico, Central America and/or Cuba. The Cimbicidae, Xiphydriidae and Orussidae are more generally distributed throughout the neotropics. Keys to families, genera and species are provided.     

Postcolonial France: race,Islam, and the future of the republic

Abstract

The study explored feelings of European identity and attitudes towards Europe manifested in two groups within the British population: the indigenous white British population (N?=?58) and the South-Asian ethnic minority (N?=?44). A social survey approach was used with scales to evaluate British, European and ethnic identities and also attitudes towards Europe. Perceived compatibility of identities was also assessed using a visual representation of identities task. Previous research findings were confirmed with the indigenous white British respondents, who displayed a strong sense of national identity negatively correlated with European identity. In contrast, the South Asian respondents displayed positive feelings of identification on all three levels, and a British identity that correlated positively with European identification.     

Onto-Tools,the toolkit of the modern biologist: Onto-Express,Onto-Compare,Onto-Design and Onto-Translate

Onto-Tools is a set of four seamlessly integrated databases: Onto-Express, Onto-Compare, Onto-Design and Onto-Translate. Onto-Express is able to automatically translate lists of genes found to be differentially regulated in a given condition into functional profiles characterizing the impact of the condition studied upon various biological processes and pathways. OE constructs functional profiles (using Gene Ontology terms) for the following categories: biochemical function, biological process, cellular role, cellular component, molecular function and chromosome location. Statistical significance values are calculated for each category. Once the initial exploratory analysis identified a number of relevant biological processes, specific mechanisms of interactions can be hypothesized for the conditions studied. Currently, many commercial arrays are available for the investigation of specific mechanisms. Each such array is characterized by a biological bias determined by the extent to which the genes present on the array represent specific pathways. Onto-Compare is a tool that allows efficient comparisons of any sets of commercial or custom arrays. Using Onto-Compare, a researcher can determine quickly which array, or set of arrays, covers best the hypotheses studied. In many situations, no commercial arrays are available for specific biological mechanisms. Onto-Design is a tool that allows the user to select genes that represent given functional categories. Onto-Translate allows the user to translate easily lists of accession numbers, UniGene clusters and Affymetrix probes into one another. All tools above are seamlessly integrated. The Onto-Tools are available online at http://vortex.cs.wayne.edu/Projects.html.     

Pasteur, Pastorians, and the dawn of immunology: the importance of specificity

Throughout his career, the problems that attracted Louis Pasteur almost invariably involved considerations of specificity of structure and/or of action. Thus, his work on asymmetric crystals showed that chemical form not only specifies crystalline structure, but affects the affinity of ferments as well. In his studies of diseases of silkworms, of beer, and of wine, he could unerringly distinguish with the microscope the specific agents of disease. From this emerged his concept of the specificity of species and against the nonspecificity of spontaneous generation, whence the germ theory of disease. It was in the new field of immunology, however, where the manifestations of an exquisite specificity were most clearly seen. Here, Pasteur's vaccines worked because he chose the specific pathogen in order to induce a specific immunity, and he succeeded each time. But the two most prominent Pastorian successors in immunology, Elie Metchnikoff and Jules Bordet, were not equally successful. Although each contributed significantly to the birth of immunology, each advanced a theory that neglected the principle of specificity and paid a price in consequence. Metchnikoff's phagocytic theory of immunity could not survive the demonstrable specificity of humoral antibodies, while Bordet's physical adsorptive concept of the antibody-cell interaction quickly fell to Paul Ehrlich's demonstration of the stereochemical determination of immunological specificity.