Acquired immunity and epidemiology of Schistosoma haematobium

Human immune responses to schistosome infection have been characterized in detail. But there has been controversy over the relative importance of ecological factors (variation in exposure to infection) and immunological factors (acquired immunity) in determining the relationships between levels of infection and age typically found in areas where infection is endemic. Independent effects of exposure and age on the rates of reinfection with Schistosoma haematobium after chemotherapy have been demonstrated in the Gambia and Zimbabwe. This age effect could be the result of acquired immunity to infection. Indeed, allowing for variation in exposure and age, low rates of reinfection in the Gambia are correlated with high amounts of specific IgE antibodies--human IgE can kill S. mansoni schistosomulae in vitro. Further, animals can acquire immunologically mediated resistance to S. mansoni infection, although nonimmunological factors could also be involved. Acquisition of this immunity seems to be related to the cumulative effects of repeated infection and provides only partial protection. These characteristics are consistent with immuno-epidemiological data for both S. mansoni and S. haematobium infections of humans. We have now analysed age-prevalence data for human infection with S. haematobium, and find patterns of variation that are indeed consistent with the epidemiological effects of acquired immunity predicted by mathematical models.     

Descartes’s changing mind

Descartes is always concerned about knowledge. However, the Galileo affair in 1633, the reactions to his Discourse on method, and later his need to reply to objections to his Meditations provoked crises in Descartes’s intellectual development the import of which has not been sufficiently recognized. These events are the major reasons why Descartes’s philosophical position concerning how we know and what we may know is radically different at the end of his life from what it was when he began. We call this later position Descartes’s epistemic stance and contrast it with his earlier methodological, metaphysical realism. Yet Descartes’s epistemic views cannot be separated from other aspects of his work, for example, his views concerning God, causality, metaphysics, and the nature of science. A further meta-implication is that serious errors await any scholar who cites early Cartesian texts in support of late Cartesian positions, or who uses later texts in conjunction with early ones to support a reading of Descartes’s philosophy.     

Preferential hydrophobic interactions are responsible for a preference of D-amino acids in the aminoacylation of 5'-AMP with hydrophobic amino acids.

We have studied the chemistry of aminoacyl AMP to model reactions at the 3' terminus of aminoacyl tRNA for the purpose of understanding the origin of protein synthesis. The present studies relate to the D, L preference in the esterification of 5'-AMP. All N-acetyl amino acids we studied showed faster reaction of the D-isomer, with a generally decreasing preference for D-isomer as the hydrophobicity of the amino acid decreased. The beta-branched amino acids, Ile and Val, showed an extreme preference for D-isomer. Ac-Leu, the gamma-branched amino acid, showed a slightly low D/L ratio relative to its hydrophobicity. The molecular basis for these preferences for D-isomer is understandable in the light of our previous studies and seems to be due to preferential hydrophobic interaction of the D-isomer with adenine. The preference for hydrophobic D-amino acids can be decreased by addition of an organic solvent to the reaction medium. Conversely, peptidylation with Ac-PhePhe shows a preference for the LL isomer over the DD isomer.     

Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome.

The inherited osteolyses or 'vanishing bone' syndromes are a group of rare disorders of unknown etiology characterized by destruction and resorption of affected bones. The multicentric osteolyses are notable for interphalangeal joint erosions that mimic severe juvenile rheumatoid arthritis (OMIMs 166300, 259600, 259610 and 277950). We recently described an autosomal recessive form of multicentric osteolysis with carpal and tarsal resorption, crippling arthritic changes, marked osteoporosis, palmar and plantar subcutaneous nodules and distinctive facies in a number of consanguineous Saudi Arabian families. We localized the disease gene to 16q12-21 by using members of these families for a genome-wide search for homozygous-by-descent microsatellite markers. Haplotype analysis narrowed the critical region to a 1.2-cM region that spans the gene encoding MMP-2 (gelatinase A, collagenase type IV; (ref. 3). We detected no MMP2 enzymatic activity in the serum or fibroblasts of affected family members. We identified two family-specific homoallelic MMP2 mutations: R101H and Y244X. The nonsense mutation effects a deletion of the substrate-binding and catalytic sites and the fibronectin type II-like and hemopexin/TIMP2 binding domains. Based on molecular modeling, the missense mutation disrupts hydrogen bond formation within the highly conserved prodomain adjacent to the catalytic zinc ion.     

Why the Afshar experiment does not refute complementarity

A modified version of Young's experiment by Shahriar Afshar demonstrates that, prior to what appears to be a “which-way” measurement, an interference pattern exists. Afshar has claimed that this result constitutes a violation of the Principle of Complementarity. This paper discusses the implications of this experiment and considers how Cramer's Transactional Interpretation easily accommodates the result. It is also shown that the Afshar experiment is analogous in key respects to a spin one-half particle prepared as “spin up along x”, subjected to a nondestructive confirmation of that preparation, and post-selected in a specific state of spin along z. The terminology “which-way” or “which-slit” is critiqued; it is argued that this usage by both Afshar and his critics is misleading and has contributed to confusion surrounding the interpretation of the experiment. Nevertheless, it is concluded that Bohr would have had no more problem accounting for the Afshar result than he would in accounting for the aforementioned pre- and post-selection spin experiment, in which the particle's preparation state is confirmed by a nondestructive measurement prior to post-selection. In addition, some new inferences about the interpretation of delayed choice experiments are drawn from the analysis.     

Using genetically-defined rodent strains for the identification of hippocampal traits relevant for two-way avoidance behavior: a non-invasive approach

Summary Genetically-defined rodent strains permit the identification of hippocampal traits which are of functional relevance for the performance of two-way avoidance behavior. This is exemplified here by analyzing the relationship between infrapyramidal mossy fibers (a tiny projection terminating upon the basal dendrites of hippocampal pyramidal neurons) and two-way avoidance learning in about 800 animals. The necessary steps include 1) identification of structural traits sensitive to selective breeding for extremes in two-way avoidance, 2) testing the robustness of the associations found by studying individual and genetical correlations between hippocampal traits and behavior, 3) establishing causal relationships by Mendelian crossing of strains with extreme structural traits and studying the behavioral consequences of such structural randomization, 4) confirming causal relationships by manipulating the structural variable in inbred (isogenic) strains, thereby eliminating the possibility of genetic linkage, and 5) ruling out the possibility of spurious associations by studying the correlations between the hippocampal trait and other behaviors known to depend on hippocampal functioning.In comparison with the classical lesion approach for identifying relationships between brain and behavior, the present procedure appears to be superior in two aspects: it is non-invasive, and it focuses automatically on those brain traits which are used by natural selection to shape behaviorally-defined animal populations, i.e., it reveals the natural regulators of behavior.     

The effect of ethanol on the biosynthesis and regulation of opioid peptides

Summary Alcoholism and alcohol abuse are serious health problems. Alcohol is known to influence the activity of a number of biological systems, for example the hormonal and neuronal systems. One of the biological systems whose activity is greatly influenced by alcohol is the endogenous opiate system. Alcohol modifies the function of both opiate receptors and opioid peptides. In fact it has been proposed that many of the effects of ethanol are mediated by its effects on the endogenous opiate system. This review will present results from various laboratories on the effects of acute and chronic ethanol treatments on various species, and on the release, biosynthesis and post-translational processing of the endorphins, enkephalins and dynorphins, the three known families of endogenous opioid peptides. Furthermore, the effect of acute and chronic ethanol consumption on the -endorphin system in man, and the possible implications of the functional activity of the endogenous opiate system for the genetic predisposition to alcoholism will be discussed.     

Methodological foundations of systems methodologies

In social systems science generally, and in management science particularly, recent developments in the variety of types of specific problem-solving methodologies (under the rubric of hard and soft systems approaches) have given an impetus to a line of inquiry, as well as debate on the nature of those methodologies. On the one hand, there has been the view that what we are witnessing is a form of Kuhnian crisis. On the other hand, a complementarist view of developments has been argued and a contingency approach proposed. But one thing has been common among the competing views: a belief that the prospects for further advances in the design and application of those methodologies, and in resolving the current controversies, lie in serious attempts to reconsider and clarify the underlying metatheoretical assumptions and concerns. This paper is an attempt to contribute to such an endeavor. A brief exposition of three methodological foundations (namely, empiricism, hermeneutics, and critique) is made, not only with the purpose of highlighting the nature as well as the limits of their epistemological and ethical claims, but also as a basis for illuminating both the nature of contemporary work on systems inquiry, design, and problem solving and the ongoing debate on what constitutes appropriate criteria for choice of specific methodologies.     

The contents of the pygidial gland of the primitive antNothomyrmecia macrops (Hymenoptera:Formicidae)

Summary The principal constituent of the pygidial gland ofNothomyrmecia macrops is 3,7-dimethyloct-6-en-2-one, a substance not previously identified in insects. Also identified were 2,6-dimethylhept-5-enal, 2-nonanone, indole, -dodecalactone, and the hydrocarbons pentadecane, heptadecane, heptadecene and heptadecadiene, all in low nanogram quantities.