The role of colonization in the dynamics of patchy populations of a cyclic vole species

The crash phase of vole populations with cyclic dynamics regularly leads to vast areas of uninhabited habitats. Yet although the capacity for cyclic voles to re-colonize such empty space is likely to be large and predicted to have become evolved as a distinct life history trait, the processes of colonization and its effect on the spatio-temporal dynamics have been little studied. Here we report from an experiment with root voles (Microtus oeconomus) specifically targeted at quantifying the process of colonization of empty patches from distant source patches and its resultant effect on local vole deme size variation in a patchy landscape. Three experimental factors: habitat quality, predation risk and inter-patch distance were employed among 24 habitat patches in a 100 × 300-m experimental area. The first-born cohort in the spring efficiently colonized almost all empty patches irrespective of the degree of patch isolation and predation risk, but this was dependent on habitat quality. Just after the initial colonization wave the deme sizes in patches of the same quality were underdispersed relative to Poisson variance, indicating regulated (density-dependent) settlement. Towards the end of the breeding season local demographic processes acted to smooth out the initial post-colonization differences among source and colonization patches, and among patches of initially different quality. However, at this time demographic stochasticity had also given rise to a large (overdispersed) variation in deme sizes that may have contributed to an overshadowing of the effect of other factors. The results of this experiment confirmed our expectation that the space-filling capacity of voles is large. The costs associated with transience appeared to be so low, at least at the spatial scale considered in this experiment, that such costs are not likely to substantially constrain habitat selection and colonization in the increase phase of cyclic patchy populations.     

Complement-mediated lysis in vitro of newly excysted tapeworms: Hymenolepis diminuta, Hymenolepis microstoma, Hymenolepis nana and Hymenolepis citelli

Bøgh H., Christensen J.P.B. and Andreassen J. 1986. Complement-mediated lysis in vitro of newly excysted tapeworms: Hymenolepis diminuta, Hymenolepis microstoma, Hymenolepis nana and Hymenolepis citelii. International Journal for Parasitology16: 157–161. Newly excysted worms of Hymenolepis diminuta were lysed in 50% normal serum from all 13 animal species tested, including man. Since H. diminuta was neither lysed in complement inactivated serum—by heat or adding EDTA, LPS or CVF—nor in C5-deficient mouse serum, it is concluded that the lysis was associated with the complement cascade. It is shown that H. diminuta can activate the complement system via both the classical and alternative pathway. Furthermore, it is indicated that the lysis is independent of serum antibodies. Hymenolepis nana and H. citelli were also lysed in all normal sera tested, eight and six respectively, while newly excysted worms of H. microstoma were lysed in normal sera from 10 mammals and birds, but not in sera from its hosts, the mouse, rat and golden hamster. This indicates that the complement system of these three species differs from that of the other species tested in such a way that H. microstoma is able to avoid lysis in these sera.     

Abundant Genetic Overlap between Blood Lipids and Immune-Mediated Diseases Indicates Shared Molecular Genetic Mechanisms

Epidemiological studies suggest a relationship between blood lipids and immune-mediated diseases, but the nature of these associations is not well understood. We used genome-wide association studies (GWAS) to investigate shared single nucleotide polymorphisms (SNPs) between blood lipids and immune-mediated diseases. We analyzed data from GWAS (n~200,000 individuals), applying new False Discovery Rate (FDR) methods, to investigate genetic overlap between blood lipid levels [triglycerides (TG), low density lipoproteins (LDL), high density lipoproteins (HDL)] and a selection of archetypal immune-mediated diseases (Crohn’s disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, psoriasis and sarcoidosis). We found significant polygenic pleiotropy between the blood lipids and all the investigated immune-mediated diseases. We discovered several shared risk loci between the immune-mediated diseases and TG (n = 88), LDL (n = 87) and HDL (n = 52). Three-way analyses differentiated the pattern of pleiotropy among the immune-mediated diseases. The new pleiotropic loci increased the number of functional gene network nodes representing blood lipid loci by 40%. Pathway analyses implicated several novel shared mechanisms for immune pathogenesis and lipid biology, including glycosphingolipid synthesis (e.g. FUT2) and intestinal host-microbe interactions (e.g. ATG16L1). We demonstrate a shared genetic basis for blood lipids and immune-mediated diseases independent of environmental factors. Our findings provide novel mechanistic insights into dyslipidemia and immune-mediated diseases and may have implications for therapeutic trials involving lipid-lowering and anti-inflammatory agents.     

Inhibition of DNA decatenation, but not DNA damage, arrests cells at metaphase

DNA damage by double-strand breaks induces arrest during interphase in mammalian cells. It is not clear whether DNA damage can arrest cells in mitosis. We show here that three human cell lines, HeLa, U2OS, and HCT116, do not delay in mitosis in response to double-strand breaks induced during mitosis by gamma irradiation or by adriamycin. Durable arrest at metaphase occurs, however, with ICRF-193, a topoisomerase II inhibitor that does not damage DNA. Arrest with ICRF-193 is not accompanied by recruitment of Mad2 or Bub1 to kinetochores, nor by phosphorylation of the histone H2AX, indicating arrest by ICRF-193 is not due to activation of the spindle assembly checkpoint, nor is it a response to DNA damage. VP-16, another decatenation inhibitor, induces metaphase arrest only at concentrations well above those that induce DNA damage. We conclude that decatenation failure, but not DNA damage, creates metaphase arrest in mammalian cells.     

Density-dependent dispersal and spatial population dynamics

The synchronization of the dynamics of spatially subdivided populations is of both fundamental and applied interest in population biology. Based on theoretical studies, dispersal movements have been inferred to be one of the most general causes of population synchrony, yet no empirical study has mapped distance-dependent estimates of movement rates on the actual pattern of synchrony in species that are known to exhibit population synchrony. Northern vole and lemming species are particularly well-known for their spatially synchronized population dynamics. Here, we use results from an experimental study to demonstrate that tundra vole dispersal movements did not act to synchronize population dynamics in fragmented habitats. In contrast to the constant dispersal rate assumed in earlier theoretical studies, the tundra vole, and many other species, exhibit negative density-dependent dispersal. Simulations of a simple mathematical model, parametrized on the basis of our experimental data, verify the empirical results, namely that the observed negative density-dependent dispersal did not have a significant synchronizing effect.     

Hymenolepis microstoma: direct life cycle in immunodeficient mice

The mouse bile duct tapeworm Hymenolepis microstoma requires beetles as the obligatory intermediate host. However, when congenitally athymic NMRI-nu mice were infected with the mature tapeworm and allowed to eat their own faeces with tapeworm eggs, the oncospheres penetrated the intestinal tissue and developed to cysticercoids. After excysting, growth to adult worms occurs in the lumen of the small intestine and bile duct. Furthermore, the same happened when NMRI-nu mice, non-obese diabetic severe combined immunodeficiency (NOD/Shi-scid) mice and NOD/Shi-scid, IL-2 Rgamma(null) (NOG) mice were orally inoculated with shell-free eggs of this parasite. Differences between the cysticercoids of H. microstoma and H. nana developed in the mouse intestinal tissues were: (i) the time course for the development of fully matured cysticercoids of H. microstoma in mice was about 11 days but only 4 days for H. nana; and (ii) cysticercoids of H. microstoma developed in mice had a tail while those of H. nana had none.     

Nonlinear decrease over time in N-acetyl aspartate levels in the absence of neuronal loss and increases in glutamine and glucose in transgenic Huntington's disease mice

Mice transgenic for exon I of mutant huntingtin, with 141 CAG repeats, exhibit a profound symptomatology characterized by weight loss, motor disorders, and early death. We performed longitudinal analysis of metabolite levels in these mice using NMR spectroscopy in vivo and in vitro. These mice exhibited a large (53%), nonlinear drop in in vivo N-acetyl aspartate (NAA) levels over time, commencing at approximately 6 weeks of age, coincident with onset of symptoms. These drops in NAA levels occurred in the absence of neuronal death as measured by postmortem Nissl staining and neuronal counting but in the presence of nuclear inclusion bodies. In addition to decreased NAA, these mice showed a large elevation of glucose in the brain (600%) consistent with a diabetic profile and elevations in blood glucose levels both before and after glucose loading. In vitro NMR analysis revealed significant increases in glutamine (100%), taurine (95%) cholines (200%), and scyllo-inositol (333%) and decreases in glutamate (24%) and succinate (47%). These results lead to two conclusions. NAA is reflective of the health of neurons and thus is a noninvasive marker, with a temporal progression similar to nuclear inclusion bodies and symptoms, of neuronal dysfunction in transgenic mice. Second, the presence of elevated glutamine is evidence of a profound metabolic defect. We present arguments that the elevated glutamine results from a decrease in neuronal-glial glutamate-glutamine cycling and a decrease in glutaminase activity.     

Malonate and 3-nitropropionic acid neurotoxicity are reduced in transgenic mice expressing a caspase-1 dominant-negative mutant

Increasing evidence implicates caspase-1-mediated cell death as a major mechanism of neuronal death in neurodegenerative diseases. In the present study we investigated the role of caspase-1 in neurotoxic experimental animal models of Huntington's disease (HD) by examining whether transgenic mice expressing a caspase-1 dominant-negative mutant are resistant to malonate and 3-nitropropionic acid (3-NP) neurotoxicity. Intrastriatal injection of malonate resulted in significantly smaller striatal lesions in mutant caspase-1 mice than those observed in littermate control mice. Caspase-1 was significantly activated following malonate intrastriatal administration in control mice but significantly attenuated in mutant caspase-1 mice. Systemic 3-NP treatment induced selective striatal lesions that were significantly smaller within mutant caspase-1 mice than in littermate control mice. These results provide further evidence of a functional role for caspase-1 in both malonate- and 3-NP-mediated neurotoxin models of HD.