Tumour necrosis factor alpha restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice.

Schistosomiasis (bilharzia) is a parasitic disease caused by several species of schistosome worms (blood flukes). The key pathogenic event in this disease is the formation of granulomas around schistosome eggs trapped in portal venules of the liver. Granulomas are a distinctive form of chronic inflammation characterized by localized aggregation of activated macrophages around an inciting stimulus. Each granuloma evolves to form a fibrous scar; in schistosomiasis, the result is widespread hepatic fibrosis and portal hypertension. To identify the specific immune signal molecules necessary for granuloma formation, we studied schistosome infections in severe combined immunodeficient (SCID) mice, which have normal macrophages but lack functional B or T lymphocytes. Here we report that the immunoregulatory cytokine tumour necrosis factor alpha is necessary and sufficient to reconstitute granuloma formation in schistosome-infected SCID mice. Moreover, we find that the parasitic worms require tumour necrosis factor alpha for egg-laying and for excretion of eggs from the host. The implication of this latter result is that the parasite has adapted so successfully to its host that it uses a host-derived immunoregulatory protein as a signal for replication and transmission.     

Rapid switching to multiple antigenic and adhesive phenotypes in malaria.

Adhesion of parasitized erythrocytes to post-capillary venular endothelium or uninfected red cells is strongly implicated in the pathogenesis of severe Plasmodium falciparum malaria. Neoantigens at the infected red-cell surface adhere to a variety of host receptors, demonstrate serological diversity in field isolates and may also be a target of the host-protective immune response. Here we use sequential cloning of P. falciparum by micromanipulation to investigate the ability of a parasite to switch antigenic and cytoadherence phenotypes. Our data show that antigens at the parasitized cell surface undergo clonal variation in vitro in the absence of immune pressure at the rate of 2% per generation with concomitant modulations of the adhesive phenotype. A clone has the potential to switch at high frequency to a variety of antigenic and adhesive phenotypes, including a new type of cytoadherence behaviour, 'auto-agglutination' of infected erythrocytes. This rapid appearance of antigenic and functional heterogeneity has important implications for pathogenesis and acquired immunity.     

Superantigen implicated in dependence of HIV-1 replication in T cells on TCR V beta expression.

In the pathogenesis of AIDS it is not yet understood whether the small fraction of CD4+ T cells (approximately 1%) infected with the human immunodeficiency virus (HIV) are randomly targeted or not. Here we present evidence that human CD4 T-cell lines expressing selected T-cell antigen receptor V beta gene products can all be infected in vitro with HIV-1, but give markedly different titres of HIV-1 virion production. For example, V beta 12 T-cell lines from several unrelated donors reproducibly yielded up to 100-fold more gag gene product (p24gag antigen) than V beta 6.7a lines. This is consistent with a superantigen effect, because the V beta selectivity was observed with several divergent HIV-1 isolates, was dependent on antigen-presenting cells and on major histocompatibility complex (MHC) class II but was not MHC class II-restricted. The in vivo significance of these findings is supported by the preferential stimulation of V beta 12+ T cells by freshly obtained irradiated antigen-presenting cells from some HIV-1-seropositive but not HIV-1-negative donors. Moreover, cells from patients positive for viral antigen (gp120) were enriched in the V beta 12 subpopulation. V beta 12+ T cells were not deleted in AIDS patients, however, raising the possibility that a variety of mechanisms contribute to T-cell depletion. Our results indicate that a superantigen targets a subpopulation of CD4+ cells for viral replication.     

Mixed micelles in drug delivery.

Large disk-like mixed micelles composed of a drug and biological lipid are thermodynamically stable and represent a novel drug delivery system. Their unique physical properties are reflected in a significantly improved therapeutic index.     

热力系统的熵分析

根据热力学第二定律,应用熵平衡法对热力系统进行分析和设计。作为实例,应用此方法分析以溴化锂—水为工质的单级制冷系统和单级热转换器系统。结果表明,熵平衡法不仅可以获得如能量法和(火用)分析法相同的结果,而且还可清晰地揭示系统中各个过程的不可逆性,对系统性能系数和效率的影响。该系数和效率仅取决于过程的性质而与环境条件无关。     

Spectral analysis of phylogenetic data

The spectral analysis of sequence and distance data is a new approach to phylogenetic analysis. For two-state character sequences, the character values at a given site split the set of taxa into two subsets, a bipartition of the taxa set. The vector which counts the relative numbers of each of these bipartitions over all sites is called a sequence spectrum. Applying a transformation called a Hadamard conjugation, the sequence spectrum is transformed to the conjugate spectrum. This conjugation corrects for unobserved changes in the data, independently from the choice of phylogenetic tree. For any given phylogenetic tree with edge weights (probabilities of state change), we define a corresponding tree spectrum. The selection of a weighted phylogenetic tree from the given sequence data is made by matching the conjugate spectrum with a tree spectrum. We develop an optimality selection procedure using a least squares best fit, to find the phylogenetic tree whose tree spectrum most closely matches the conjugate spectrum. An inferred sequence spectrum can be derived from the selected tree spectrum using the inverse Hadamard conjugation to allow a comparison with the original sequence spectrum. A possible adaptation for the analysis of four-state character sequences with unequal frequencies is considered. A corresponding spectral analysis for distance data is also introduced. These analyses are illustrated with biological examples for both distance and sequence data. Spectral analysis using the Fast Hadamard transform allows optimal trees to be found for at least 20 taxa and perhaps for up to 30 taxa. The development presented here is self contained, although some mathematical proofs available elsewhere have been omitted. The analysis of sequence data is based on methods reported earlier, but the terminology and the application to distance data are new.     

Effects of corpora cardiaca extract,furosemide and ion substitution on sodium and chloride flux in perfused Malpighian tubules ofLocusta

Treatment with the co-transport inhibitor, furosemide decreased³⁶Cl^– flux across perfused Malpighian tubules ofLocusta. However, exclusion of³⁶Cl^– from the bathing medium had not effect on²²Na⁺ flux whereas substitution of bathing medium Na⁺ by K⁺ increased³⁶Cl^– flux. Diuretic extract of corpora cardiaca increased²²Na⁺ (by 106%) and³⁶Cl^– (by 335%) fluxes differentially.     

The effect of scale changes on repetitive patterns: Influence of 6-aminonicotinamide on feather germ number

There are many examples of patterned developing systems which are size invariant: if the total size of the system is reduced, then the pattern responds by changing its scale in such a way that the number of pattern elements remains constant. This phenomenon is one of the bases which underaly the formulation of the concept of positional information, one of the great unifying ideas in developmental biology. However, there are less common examples of patterns which are size dependent. In these, alterations of overall size lead to a reduction in pattern elements. Such size-dependent patterns are therefore of theoretical interest. Here we describe how the number of feather germs along the wing bud of the developing chick embryo responds to shortening of the limb, and consider the implications of these observations.     

Photoreceptor damage following exposure to excess riboflavin

Flavins generate oxidants during metabolism and when exposed to light. Here we report that the photoreceptor layer of retinas from black-eyed rats is reduced in size by a dietary regime containing excess riboflavin. The effect of excess riboflavin was dose-dependent and was manifested by a decrease in photoreceptor length. This decrease was due in part to a reduction in the thickness of the outer nuclear layer, a structure formed from stacked photoreceptor nuclei. These changes were accompanied by an increase in photoreceptor outer segment autofluorescence following illumination at 328 nm, a wavelength that corresponds to the excitation maxima of oxidized lipopigments of the retinal pigment epithelium.     

Extraordinary levels of cadmium and zinc in a marine sponge,Tedania charcoti Topsent: inorganic chemical defense agents

The Antarctic marine spongeTedania charcoti has been shown to contain extraordinarily high natural concentrations of cadmium and zinc, which have in turn been correlated to the ability of the crude ethanol extract to modulate protein phosphorylation in chicken forebrain and to inhibit the growth of several test bacteria.