The Neurobiology of Dopamine Signaling

The biochemistry of synaptic transmission, especially the neurobiology of dopamine signaling, is discussed.     

Helicobacter pylori in familial clusters based on antibody profile

Studies have shown a high prevalence of Helicobacter pylori infection in close communities and that intrafamilial spread during early childhood may be a route of transmission. A total of 72 household members from 21 families were enrolled in this study. Sera from individuals showed 50/72 (69.4%) seropositive for IgG against H. pylori by ELISA. Western blots showed diversity in the protein profiles with molecular masses ranging from approximately 8 to 130 kDa. Cohen's kappa statistical analysis of the blot patterns showed that nine families demonstrated similar profiles (100%), while 4 other families showed varying similarities (17-50%). The results support the hypothesis of intrafamilial transmission of H. pylori. Furthermore, serological studies can be used as an effective approach to determine the familial status in relation to H. pylori infection.     

Postnatal pre- and postexposure passive immunization strategies: protection of neonatal macaques against oral simian-human immunodeficiency virus challenge

Simian-human immunodeficiency viruses (SHIV) allow the evaluation of antiviral strategies that target the envelope glycoproteins of the human immunodeficiency virus 1 (HIV-1) in macaques. We previously protected neonates from oral challenge with cell-free SHIV-vpu+ by passive immunization with synergistic human neutralizing monoclonal antibodies (mAbs) (Baba et al., Nat Med 6:200-206, 2000). mAbs were administered prenatally to pregnant dams and postnatally to the neonates. Here, we used solely postnatal or postexposure mAb treatment, thus significantly reducing the amount of mAbs necessary. All neonatal monkeys were also protected with these abbreviated mAb regimens. Our results are directly relevant for humans because we used mAbs that target HIV-1 envelope glycoproteins. Thus, the large-scale use of passive immunization with neutralizing mAbs may be feasible in human neonates. The mAbs, being natural human proteins, can be expected to have low toxicity. Passive immunization has promise to prevent intrapartum as well as milk-borne virus transmission from HIV-1-infected women to their infants.     

Exploring the 3D molecular architecture of Escherichia coli type 1 pili

An integrated approach combining information gained by Fourier transformation, linear Markham superposition (real space) and mass-per-length measurement by scanning transmission electron microscopy was used to analyze the helical structure of the rod-like type 1 pili expressed by uropathogenic Escherichia coli strain W3110. The 3D reconstruction calculated from the experimental data showed the pili to be 6.9nm wide, right-handed helical tubes with a 19.31(+/-0.34)nm long helical repeat comprising 27 FimA monomers associated head-to-tail in eight turns of the genetic one-start helix. Adjacent turns of the genetic helix are connected via three binding sites making the pilus rod rather stiff. In situ immuno-electron microscopy experiments showed the minor subunit (FimH) mediating pilus adhesion to bladder epithelial cells to be the distal protein of the pilus tip, which had a spring-like appearance at higher magnification. The subunits FimG and FimF connect FimH to the FimA rod, the sequential orientation being FimA-FimF-FimG-FimH. The electron density map calculated at 18A resolution from an atomic model of the pilus rod (built using the pilin domain FimH together with the G1 strand of FimC as a template for FimA and applying the optimal helical parameters determined to the head-to-tail interaction model for pilus assembly) was practically identical with that of the actual 3D reconstruction.     

Polymorphonuclear leukocyte-myocyte interaction: an early event in collar-induced rabbit carotid intimal thickening

The importance of mononuclear leukocyte (MO) adhesion to dysfunctional endothelium and migration to the subendothelial space in the early phases of atherogenesis is well established. Few studies have addressed the relevance of polymorphonuclear leukocytes (PMNs) in the context of evolving lesions, and nothing is known about PMN interaction with vascular smooth muscle cells (SMCs). In this study, we investigated leukocyte/SMC interactions in a model of rabbit carotid injury induced by placement of a silastic collar. This procedure leads to the development of intimal thickening characterized by SMC accumulation preceded by an abundant leukocyte infiltration. By transmission electron microscopy and immunocytochemistry, we demonstrated the occurrence of PMN infiltration starting at 6 h and ceasing within 72 h after collar placement. A previously unknown extensive interaction between medial myocytes and PMNs was detected, referring to emperipolesis, an active phenomenon of cells engulfing other cells in a process other than phagocytosis. PMNs, but not MOs, were internalized by SMCs, which showed ultrastructural features intermediate between the true contractile and the fully synthetic phenotype without exhibiting any sign of injury. Emperipolesis preceded any detectable cell proliferation in the vessel wall and disappeared within 72 h, following the kinetic of PMN infiltration in the vessel wall. In summary, our findings show the occurrence of an active and selective interaction between PMNs and SMCs via emperipolesis during the early phases of intimal thickening after perivascular collaring. However, the overall etiology of the phenomena described in the present study and their pathophysiological significance should be further investigated.     

Incomplete feminisation by the microsporidian sex ratio distorter,Nosema granulosis,and reduced transmission and feminisation efficiency at low temperatures

We investigated the effects of temperature on transovarial transmission and feminisation by Nosema granulosis, a microsporidian sex ratio distorter of the brackish water amphipod Gammarus duebeni. There was no difference in parasite transmission efficiency to the F(1) eggs of infected females maintained under two temperature conditions, 5 and 10 degrees C (89 and 86%, respectively). When F(1) individuals were screened as adults, the proportion infected was also similar at both temperatures (74 and 75%, respectively). However, transmission to the eggs of the F(2) generation was significantly reduced at low temperatures (61% at 5 degrees C and 91% at 10 degrees C). In addition, feminisation efficiency was reduced substantially at low temperatures; at 10 degrees C, a calculated 85% of infected males were feminised, but at 5 degrees C only 49% were feminised. This is the first evidence for incomplete feminisation and temperature-dependent transmission and feminisation by this sex ratio distorter. We examine the consequences for parasite spread and maintenance in natural populations using a model to predict parasite prevalence in large populations. Reduced feminisation at low temperatures impedes the spread of the parasite so that it attains a substantially lower frequency, or may even be excluded, from host populations.     

Learning and memory in disease vectors

All animals can learn to some extent and it should not be surprising to discover that important vectors can also be influenced by experience. The potential effect of memory on vector behaviour, particularly vectorial capacity, has barely been investigated. Yet, how a population of blood-feeding insects distributes between available resources has important epidemiological consequences. Several recent studies have shown that behaviour during oviposition site-selection, host location and even host choice can be influenced by the environment or by experience after eclosion. The significance of these studies and their consequences for epidemiology and control are considered here.     

Cryptosporidium hominis n. sp. (Apicomplexa: Cryptosporidiidae) from Homo sapiens

The structure and infectivity of the oocysts of a new species of Cryptosporidium from the feces of humans are described. Oocysts are structurally indistinguishable from those of Cryptosporidium parvum. Oocysts of the new species are passed fully sporulated, lack sporocysts. and measure 4.4-5.4 microm (mean = 4.86) x 4.4-5.9 microm (mean = 5.2 microm) with a length to width ratio 1.0-1.09 (mean 1.07) (n = 100). Oocysts were not infectious for ARC Swiss mice, nude mice. Wistar rat pups, puppies, kittens or calves, but were infectious to neonatal gnotobiotic pigs. Pathogenicity studies in the gnotobiotic pig model revealed significant differences in parasite-associated lesion distribution (P = 0.005 to P = 0.02) and intensity of infection (P = 0.04) between C. parvum and this newly described species from humans. In vitro cultivation studies have also revealed growth differences between the two species. Multi-locus analysis of numerous unlinked loci, including a preliminary sequence scan of the entire genome demonstrated this species to be distinct from C. parvum and also demonstrated a lack of recombination, providing further support for its species status. Based on biological and molecular data, this Cryptosporidium infecting the intestine of humans is proposed to be a new species Cryptosporidium hominis n. sp.     

Ecology,development and pathogenicity of Buddenbrockia plumatellae Schröder, 1910 (Myxozoa,Malacosporea) (syn. Tetracapsula bryozoides) and establishment of Tetracapsuloides n. gen. for Tetracapsula bryosalmonae

Buddenbrockia plumatellae, an enigmatic worm-like myxozoan, was observed as continuously writhing free and attached 'worms' and as free mature spores in the coelom of the freshwater bryozoans Plumatella fungosa, Hyalinella punctata, and Fredericella sp. 'Worm' numbers could double every three days. 'Worms' and spores could be expelled from colonies by external pressure. Some mature 'worms' exited actively, entraining release of free spores, and gradually ceased movement outside the host. Bryozoans sealed off infected regions of the colony. Infected colonies grew slowly, produced no statoblasts, and eventually regressed and died. Transmission was not achieved and prevalence was low. Electron microscopy of 'worms' revealed a single layer of mural cells on a fibrous basal lamina overlying four longitudinal muscle blocks and an inner sheet of two types of proliferating cells, an organization indicative of the bilaterian ancestry of the Myxozoa. Primary type A cells were attached directly by striated tubules to mural cells at positions between muscle blocks. Secondary type A cells had a secretory function. Type B cells underwent meiosis and subsequently developed to typical malacosporean myxozoan spores filling the internal cavity of the 'worms'. External tubes were formed during capsulogenesis in 'worms' from Fredericella sp. Tetracapsula bryozoides is synonymised with Buddenbrockia plumatellae and a new genus is proposed for Tetracapsula bryosalmonae.