Fragments formed by the side chain cleavage of a 20-aryl analog of 20alpha-hydroxycholesterol by adrenal mitochondria.

An analog of 20alpha-hydroxycholesterol, (20R)-20-phenyl-5-pregnene-3beta,20-diol, which is completely substituted at C-22 was prepared with radioisotopes at various positions. The analog labeled with 3H at C-M and 14C at C-4 and C-IU was converted into radioactive pregnenolone by an enzyme preparation derived from adrenal mitochondria. Cleavage of the phenyl analog labeled with 3H in the aromatic ring by the same enzyme preparation led to the formation of [3H]phenol. Using the substrate doubly labeled with 14C at C-4 and 3H in the aromatic ring, it appeared that the products of the reactions, pregnenolone and phenol, were formed in equal amounts. During incubation of the side chain labeled substrate, another labeled fragment was formed. It was identified as acetophenone, a product resulting from cleavage of the C17,20 bond. The steroidal fragment corresponding to this C8 ketone was traced using nuclear label analog. From its nonpolar chromatographic properties it appears to be a C-17-deoxy-C19 steroid.     

Can natural enemies enforce geographical range limits?

We develop a simple mathematical model to investigate the question as to whether a specialised consumer can be responsible for creating a range limit in the population of its dynamic resource. The model is most attuned for parasitoid-host relationships, but the central results should apply to a broad range of systems. Specifically, at the beginning of each simulation host and parasitoid populations are distributed at random along a string of patches. In each discrete generation and for each patch, host and parasitoid populations grow and interact, and then a constant fraction of those remaining disperses one or more patch distances in either direction according to a geometric distribution. We iterate the model 200 generations, and in any generation for any patch, either host and/or parasitoid can go locally extinct if its population falls below a threshold density. We find that a specialised parasitoid can enforce a limit, and it is even more likely to fragment its host population. The two most important conditions for parasitoid-enforced range limits are: 1) the theoretical host equilibrium density in the presence of the parasitoid be very small at sites eliminated from the host's range, and 2) the parasitoid disperses at high rates. We close by discussing our findings for specialist and generalist natural enemies, and the relevance of our study to the wealth of investigations on the causes of geographical range limits.     

Impact of ecological factors on the initial invasion of Bt transgenes into wild populations of birdseed rape (Brassica rapa)

The inevitable escape of transgenic pollen from cultivated fields will lead to the emergence of transgenic crop-wild plant hybrids in natural patches of wild plants. The fate of these hybrids and that of the transgene depend on their ability to compete with their wild relatives. Here we study ecological factors that may enhance the fitness of genetically modified hybrids relative to wild plants for a Bacillus thuringiensis (Bt) transgene conferring resistance to insects. Mixed stands of wild plants and first-generation hybrids were grown under different conditions of herbivore pressure and density, with Bt oilseed rape (Brassica napus) as the crop and B. rapa as the wild recipient. Biomass and fitness components were measured from plant germination to the germination of their offspring. The frequency of transgenic seedlings in the offspring generation was estimated using the green fluorescent protein marker. The biomass of F₁ Bt-transgenic hybrids relative to that of wild-type plants was found to be sensitive to both plant density and herbivore pressure, but herbivore pressure appeared as the major factor enhancing their relative fitnesses. In the absence of herbivore pressure, Bt hybrids produced 6.2-fold fewer seeds than their wild neighbors, and Bt plant frequency fell from 50% to 16% within a single generation. Under high herbivore pressure, Bt hybrids produced 1.4-fold more seeds, and Bt plant frequency was 42% in the offspring generation. We conclude that high-density patches of highly damaged wild plants are the most vulnerable to Bt-transgene invasion. They should be monitored early to detect potential transgene spread.     

EBV and systemic lupus erythematosus: a new perspective

We have proposed that EBV uses mature B cell biology to access memory B cells as a site of persistent infection. A central feature of this model is that EBV adapts its gene expression profile to the state of the B cell it resides in and that the level of infection is stable over time. This led us to question whether changes in the behavior or regulation of mature B cells would alter the state of EBV persistence. To investigate this, we studied the impact of systemic lupus erythematosus (SLE), a disease characterized by immune dysfunction, on EBV infection. We show that patients with SLE have abnormally high frequencies of EBV-infected cells in their blood, and this is associated with the occurrence of SLE disease flares. Although patients with SLE have frequencies of infected cells comparable to those seen in immunosuppressed patients, in SLE the effect was independent of immunosuppressive therapy. Aberrant expression of viral lytic (BZLF1) and latency (latency membrane proteins 1 and 2a) genes was also detected in the blood of SLE patients. We conclude that the abnormal regulation of EBV infection in SLE patients reflects the sensitivity of the virus to perturbation of the immune system.     

Ecology drives the worldwide distribution of human diseases

Identifying the factors underlying the origin and maintenance of the latitudinal diversity gradient is a central problem in ecology, but no consensus has emerged on which processes might generate this broad pattern. Interestingly, the vast majority of studies exploring the gradient have focused on free-living organisms, ignoring parasitic and infectious disease (PID) species. Here, we address the influence of environmental factors on the biological diversity of human pathogens and their global spatial organization. Using generalized linear multivariate models and Monte Carlo simulations, we conducted a series of comparative analyses to test the hypothesis that human PIDs exhibit the same global patterns of distribution as other taxonomic groups. We found a significant negative relationship between latitude and PID species richness, and a nested spatial organization, i.e., the accumulation of PID species with latitude, over large spatial scales. Additionally, our results show that climatic factors are of primary importance in explaining the link between latitude and the spatial pattern of human pathogens. Based on our findings, we propose that the global latitudinal species diversity gradient might be generated in large part by biotic interactions, providing strong support for the idea that current estimates of species diversity are substantially underestimated. When parasites and pathogens are included, estimates of total species diversity may increase by more than an order of magnitude.     

New species of Dicyemennea (phylum: Dicyemida) in deep-water Graneledone (Mollusca: Cephalopoda: Octopoda) from the Antarctic

Two new species of dicyemids are described from 2 species of deep benthic cephalopods, Graneledone antarctica and G. macrotyla, collected in the Southern Ocean south of the Antarctic Convergence. Dicyemennea bathybenthum n. sp. was found in G. antarctica. It is a medium-sized dicyemid whose length does not exceed 1,000 microm. The calotte is bluntly rounded or conical in small individuals, but the shape becomes discoidal in large individuals. Nematogens and vermiform embryos have 23 peripheral cells. An anterior abortive axial cell is present in vermiform embryos. Other stages in the life cycle were not observed. Dicyemennea dorycephalum n. sp. was found in G. macrotyla. It is a medium to large dicyemid that rarely exceeds 4,000 microm. The calotte is distinctly pointed, similar in shape to a spearhead. Vermiform stages typically have either 25 or 27 peripheral cells. An anterior abortive axial cell is present in vermiform embryos. Infusoriform embryos have 37 cells, the refringent bodies are solid in composition, and 2 nuclei are present in each urn cell.     

Leucine-induced hypoglycemia in a family: effect of diphenylhydantoin, oxprenolol, and diazoxide

The present report describes a mother and 2 children with leucine-induced hypoglycemia (LIH). Hypoglycemic episodes following high-protein meals first appeared at age 4-7 months. Leucine-stimulation tests triggered marked hyperinsulinism and hypoglycemia in the children and a milder but abnormal response in the mother. To evaluate the therapeutic effects and to study the mechanism of hyperinsulinism in LIH, the leucine test was repeated under treatment with diphenylhydantoin, oxprenolol (a beta-blocker), and diazoxide. Diazoxide abolished hyperinsulinism; diphenylhydantoin did not affect the response to leucine; and oxprenolol, tested in the mother only, increased hyperinsulinism and hypoglycemia. Our results indicate that LIH is an autosomal dominant disorder; LIH may persist into adulthood with milder clinical symptoms and chemical response to leucine; diazoxide is the treatment of choice in LIH. Considering the effects of the three agents on stimulated release of insulin, it is concluded that leucine triggers hyperinsulinism by a mechanism different from that of glucose and beta-adrenergic receptors.     

The penetration of a dinucleoside monophosphate into rabbit blood cells in vitro

Uridylyl 3′-5′[¹⁴C] adenosine and uridylyl 2′-5′[¹⁴C] adenosine penetrate into rabbit blood cell sap at the same rate. No enzymatic or chemical hydrolysis of the dinucleoside monophosphates was observed.