Distribution records and comments on fleas in southwestern South Dakota

From October 2003 through April 2006, we collected 565 fleas incidental to a distribution survey of mammals in southwestern South Dakota. Sixty-one specimens, representing 18 species of mammals, possessed 20 species of fleas. The geographic distributions of these flea species revealed 8 new records for the Black Hills and its adjacent grasslands. Four species— Megarthroglossus divisus, Stenoponia americana, Odontopsyllus dentatus, and Amaradix euphorbi —constitute new records for South Dakota, thus increasing the state’s known flea fauna to 42 species. Hunters, trappers, and field biologists should be aware that serosurveillance during the 1990s revealed the presence of sylvatic plague and tularemia in the Black Hills area. Desde octubre de 2003 hasta abril de 2006, colectamos 565 pulgas de manera incidental durante un estudio de la distribución de mamíferos en el suroeste del estado de Dakota del Sur. Los 61 especímenes, que representaban 18 especies de mamíferos, albergaban 20 especies de pulgas. Sus distribuciones geográficas revelaron 8 nuevos registros para las Colinas Negras (Black Hills) y las praderas adyacentes. Cuatro de estas especies ( Megarthroglossus divisus, Stenoponia americana, Odontopsyllus dentatus y Amaradix euphorbi ) constituyen nuevos registros para Dakota del Sur. Esto aumenta el número de especies de pulgas conocidas del estado a 42 especies. Los cazadores, tramperos y biólogos de campo deben estar conscientes de que la vigilancia serológica durante la década de los 1990 reveló la presencia de la plaga silvática y la tularemia en el área de las Colinas Negras.     

Movement of internalized ligand-receptor complexes along a continuous endosomal reticulum

Complexes of cell-surface receptors and their ligands are commonly internalized by endocytosis and enter a prelysosomal endosomal pathway for further processing. Fluorescence microscopy and video recording of living cells to trace the passage of ligand-receptor complexes has identified the endosomal compartment as an extensive network of tubular cisternae. Endocytosed material entering this reticulum enters discrete swellings, identified as multivesicular bodies by electron microscopy, which move along the reticulum towards the pericentriolar area.     

A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors

The amyloid proteins isolated from neuritic plaques and the cerebrovasculature of Alzheimer's disease are self-aggregating moieties termed A4 protein and beta-protein, respectively. A putative A4 amyloid precursor (herein termed A4(695] has been characterized by analysis of a human brain complementary DNA. We report here the sequence of a closely related amyloid cDNA, A4(751), distinguished from A4(695) by the presence of a 168 base-pair (bp) sequence which adds 57 amino acids to, and removes one residue from, the predicted A4(695) protein. The peptide predicted from this insert is very similar to the Kunitz family of serine proteinase inhibitors. The two A4-specific messenger RNAs are differentially expressed: in a limited survey, A4(751) mRNA appears to be ubiquitous, whereas A4(695) mRNA has a restricted pattern of expression which includes cells from neuronal tissue. These data may have significant implications for understanding amyloid deposition in Alzheimer's disease.     

Identification of receptor contact site involved in receptor-G protein coupling

The mammalian G proteins transduce information from extracellular signals, including neurotransmitters, hormones and sensory stimuli, into regulation of effector enzymes or ion channels within cells. Triggered by appropriate extracellular signals, receptor proteins specifically activate members of the G protein family by catalysing replacement of GDP by GTP at the guanine nucleotide binding site. Like the receptor proteins, the heterotrimeric G proteins exhibit impressive structural similarities, suggesting that all receptor-G protein interactions use homologous structural elements and a single molecular mechanism. Topologically equivalent portions of each G protein may therefore interact with the appropriate receptor. We recently predicted the secondary structure of a composite G protein alpha-chain and proposed that a predicted amphipathic alpha-helix at the extreme carboxy-terminus of the polypeptide directly contacts receptors. This proposal has now been confirmed by sequencing complementary DNAs of the gene that encodes the alpha-chain (alpha s) of the stimulatory regulator (Gs) of adenylyl cyclase in wild-type cells and in a mutant mouse S49 lymphoma cell line, unc, in which Gs cannot be activated by hormone receptors. The sequences reveal a point mutation in the unc gene that substitutes a proline residue for an arginine near the carboxy-terminus of the alpha s-polypeptide. Expression of recombinant alpha s-unc in genetically alpha s-deficient S49 cells reproduces the unc phenotype.     

Age-related differences in the effect of in vivo administration of indomethacin on hemopoietic cell lineages of the spleen and bone marrow of mice

During 21 days of indomethacin treatment, erythroid cells in the spleens of both young adult and older mice, and in the bone marrow of young adult mice, were increased significantly early, in treatment, relative to age-matched control organs, and remained high throughout treatment. During drug exposure, the numbers of myeloid cells in young adult bone marrow, but not spleen, were reduced, but in older mice these cells were elevated in both organs. Lymphoid cells in the young adult and older mouse spleens decreased and increased, respectively, during treatment, but were unchanged and decreased, respectively, in the bone marrow of young adult and older mice. Monocytemacrophage cells in the spleen were elevated but unchanged in the bone marrow of both age groups. During 14 days of indomethacin treatment of houng adult mice, the proportions of precursor cells in DNA synthesis of only the splenic erythroid lineage were increased. Thus, the major hemopoietic lineages in both the bone marrow and spleen are affected by exposure to indomethacin in a time-dependent and age-dependent manner. For all lineages studied, those of the bone marrow were least disturbed, and/or were first to recover, even during continued drug exposure.     

Human hepatitis B vaccine from recombinant yeast

The worldwide importance of human hepatitis B virus infection and the toll it takes in chronic liver disease, cirrhosis and hepatocarcinoma, make it imperative that a vaccine be developed for worldwide application. Human hepatitis B vaccines are presently prepared using hepatitis B surface antigen (HBsAg) that is purified from the plasma of human carriers of hepatitis B virus infection. The preparation of hepatitis B vaccine from a human source is restricted by the available supply of infected human plasma and by the need to apply stringent processes that purify the antigen and render it free of infectious hepatitis B virus and other possible living agents that might be present in the plasma. Joint efforts between our laboratories and those of Drs W. Rutter and B. Hall led to the preparation of vectors carrying the DNA sequence for HBsAg and antigen expression in the yeast Saccharomyces cerevisiae. Here we describe the development of hepatitis B vaccine of yeast cell origin. HBsAg of subtype adw was produced in recombinant yeast cell culture, and the purified antigen in alum formulation stimulated production of antibody in mice, grivet monkeys and chimpanzees. Vaccinated chimpanzees were totally protected when challenged intravenously with either homologous or heterologous subtype adr and ayw virus of human serum source. This is the first example of a vaccine produced from recombinant cells which is effective against a human viral infection.     

Plasmodium falciparum strain-specific antibody blocks binding of infected erythrocytes to amelanotic melanoma cells

An important feature of Plasmodium falciparum malaria which differentiates it from other human malarias is that erythrocytes infected with trophozoites and schizonts are not present in the peripheral blood but are sequestered along capillary and venular endothelium. Infected erythrocytes attach via parasite-induced ultrastructural modifications on the surface of the infected cells, called 'knobs'. This sequestration may be important for parasite survival because it prevents infected erythrocytes from circulating through the spleen where they could be eliminated. We have established an in vitro correlate of sequestration and used it to demonstrate that immune sera from repeatedly infected Aotus monkeys inhibit binding of infected erythrocytes to endothelial cells. We have investigated whether antiserum that blocks binding of one isolate of P. falciparum to target cells can block or reverse binding of other isolates. We report here that sera which block or reverse binding are strain-specific, indicating that the corresponding antigens on the surface of the infected erythrocytes are strain (isolate)-specific.