Unraveling the Entry Mechanism of Baculoviruses and Its Evolutionary Implications

The entry of baculovirus budded virus into host cells is mediated by two distinct types of envelope fusion proteins (EFPs), GP64 and F protein. Phylogenetic analysis suggested that F proteins were ancestral baculovirus EFPs, whereas GP64 was acquired by progenitor group I alphabaculovirus more recently and may have stimulated the formation of the group I lineage. This study was designed to experimentally recapitulate a possible major step in the evolution of baculoviruses. We demonstrated that the infectivity of an F-null group II alphabaculovirus (Helicoverpa armigera nucleopolyhedrovirus [HearNPV]) can be functionally rescued by coinsertion of GP64 along with the nonfusogenic F^def (furin site mutated HaF) from HearNPV. Interestingly, HearNPV enters cells by endocytosis and, less efficiently, by direct membrane fusion at low pH. However, this recombinant HearNPV coexpressing F^def and GP64 mimicked group I virus not only in its EFP composition but also in its abilities to enter host cells via low-pH-triggered direct fusion pathway. Neutralization assays indicated that the nonfusogenic F proteins contribute mainly to binding to susceptible cells, while GP64 contributes to fusion. Coinsertion of GP64 with an F-like protein (Ac23) from group I virus led to efficient rescue of an F-null group II virus. In summary, these recombinant viruses and their entry modes are considered to resemble an evolutionary event of the acquisition of GP64 by an ancestral group I virus and subsequent adaptive inactivation of the original F protein. The study described here provides the first experimental evidence to support the hypothesis of the evolution of baculovirus EFPs.     

Rapid deterioration of Aquatic Warbler Acrocephalus paludicola habitats at the western margin of the breeding range

In the last German breeding area of the rapidly declining “Pomeranian” population of the Aquatic Warbler (Acrocephalus paludicola), the Lower Oder Valley National Park, we investigated changes in habitat suitability between 1993 and 2006 by combining monitoring results with repeated assessments of vegetation structure and composition, site conditions, and land use. Sites with recent Aquatic Warbler records showed shorter and sparser vegetation, a thinner litter layer, and a higher total plant species richness and cover of small and least competitive (CSR) species than abandoned or unoccupied sites. On a long-term study plot, during a period of late mowing and subsequent cessation of land use, vegetation height increased, the cover of CSR species decreased, and the site became abandoned by Aquatic Warblers. The probability of Aquatic Warbler occurrence was dependent on elevation and increased with the proportion of early mown or grazed area in the preceding year, with early use being most important on slightly higher elevated sites. This rapid deterioration of eutrophic habitats by delayed or discontinued land use is atypical for the majority of Aquatic Warbler breeding habitats. We conclude that both late or no land use and land use during the breeding season negatively affect the Pomeranian breeding sites and that a more sophisticated and flexible land management is urgently needed.     

Local Cerebral Glucose Utilization in Hypothermic and Hyperthermic Rats

Abstract: Local rates of glucose utilization in 38 regions of the CNS were measured in conscious, lightly restrained rats during normothermia (rectal temperature, 37.4 ± 0.1°C), hypothermia (31.8 ± 0.1°C), and hyperthermia (40.2 ± 0.3°C). In 34 of the 38 regions examined (the four exceptions being primary auditory nuclei in the lower brainstem), a significant relationship could be demonstrated between the rate of glucose utilization and body temperature. The magnitude of temperature-related alterations in glucose use displayed considerable regional heterogeneity. In hypothermic rats the reductions in glucose use were proportionately most marked (reduced 35–50% from normothermic) in thalamic nuclei, extrapyramidal and motor areas, septohippocampal formation, and some areas of neocortex and white matter; they were least pronounced in anterior hypothalamus (reduced by 13%), habenula (by 16%), and amygdala (by 22%). In hyperthermic rats, significantly increased glucose utilization was observed in only 16 of the 38 areas examined (e.g., hypothalamus, hippocampus, extrapyramidal system, and raphe nucleus), whereas in a number of major areas (such as the neocortex and thalamus) glucose use was minimally altered with hyperthermia. The regional heterogeneity in the alterations in glucose utilization suggests that caution must be exercised in the interpretation of autoradiographic 2-deoxyglucose investigations in which body temperature disturbances occur.     

Mice transgenic for exon 1 of Huntington's disease: properties of cholinergic and dopaminergic pre-synaptic function in the striatum

In Huntington's disease (HD), neuronal loss is most prominent in the striatum leading to emotional, cognitive and progressive motor dysfunction. The R6/2 mice, transgenic for exon 1 of the HD gene, develop a neurological phenotype with similarities to these features of HD. In striatal tissue, electrically evoked release of tritiated acetylcholine (ACh) and dopamine (DA) were compared in wild-type (WT) and R6/2 mice. In R6/2 mice, the evoked release of ACh, its M2 autoreceptor-mediated maximum inhibition and its dopamine D2 heteroreceptor-mediated maximum inhibition was diminished to 51%, 74% and 87% of controls, respectively. Also, the activities of choline acetyltransferase and of synaptosomal high-affinity choline uptake decreased progressively with age in these mice. In the DA release model, however, electrical stimulation elicited equal amounts of [3H]-DA both in WT and R6/2 mice. Moreover, high-affinity DA uptake into striatal slices was similar in WT and R6/2 mice. In order to confirm these findings in vivo, intrastriatal levels of extracellular DA were measured by intracerebral microdialysis in freely moving mice: striatal DA levels were found to be equal in WT and R6/2 mice. In conclusion, in the transgenic R6/2 mice changes occur mainly in striatal cholinergic neurones and their pre-synaptic modulation, but not in the dopaminergic afferent terminals. Whether similar events also contribute to the pathogenesis of HD in humans has to be established.     

Mutation of the RGD sequence does not affect plasma membrane association and growth inhibitory effects of elevated IGFBP-2 in vivo

Vacuolar sequestration or cellular extrusion of glutathione-conjugated xenobiotics and catabolites by ATP-binding cassette (ABC) transporters is an important detoxification mechanism operating in many species. In this study, we show that the yeast ABC transporter Bpt1p, a paralogue of Ycf1p, acts as an ATP-dependent vacuolar pump for glutathione conjugates. Bpt1p, which is inhibited by vanadate and glibenclamide, accounts for one third of the total vacuolar transport of glutathione conjugates. Furthermore, immunoblot analyses show that Bpt1p levels are strongly elevated in early stationary phase, consistent with a function of Bpt1p in vacuolar detoxification.     

The Impact of the Latest Danian Event on Planktic Foraminiferal Faunas at ODP Site 1210 (Shatsky Rise,Pacific Ocean)

The marine ecosystem has been severely disturbed by several transient paleoenvironmental events (<200 kyr duration) during the early Paleogene, of which the Paleocene-Eocene Thermal Maximum (PETM, ~56 Ma) was the most prominent. Over the last decade a number of similar events of Paleocene and Eocene age have been discovered. However, relatively little attention has been paid to pre-PETM events, such as the “Latest Danian Event” ("LDE", ~62.18 Ma), specifically from an open ocean perspective. Here we present new foraminiferal isotope (δ¹³C, δ¹⁸O) and faunal data from Ocean Drilling Program (ODP) Site 1210 at Shatsky Rise (Pacific Ocean) in order to reconstruct the prevailing paleoceanographic conditions. The studied five-meter-thick succession covers ~900 kyr and includes the 200-kyr-lasting LDE. All groups surface dwelling, subsurface dwelling and benthic foraminifera show a negative δ¹³C excursion of >0.6‰, similar in magnitude to the one previously reported from neighboring Site 1209 for benthic foraminifera. δ¹⁸O-inferred warming by 1.6 to 2.8°C (0.4–0.7‰ δ¹⁸O measured on benthic and planktic foraminiferal tests) of the entire water column accompanies the negative δ¹³C excursion. A well stratified upper ocean directly before and during the LDE is proposed based on the stable isotope gradients between surface and subsurface dwellers. The gradient is less well developed, but still enhanced after the event. Isotope data are supplemented by comprehensive planktic foraminiferal faunal analyses revealing a dominance of Morozovella species together with Parasubbotina species. Subsurface-dwelling Parasubbotina shows high abundances during the LDE tracing changes in the strength of the isotope gradients and, thus, may indicate optimal living conditions within a well stratified surface ocean for this taxon. In addition, distinct faunal changes are reported like the disappearance of Praemurica species right at the base of the LDE and the continuous replacement of M. praeangulata with M. angulata across the LDE.     

ASYMMETRIC VIABILITY OF RECIPROCAL-CROSS HYBRIDS BETWEEN CRESTED AND MARBLED NEWTS (TRITURUS CRISTATUS AND T. MARMORATUS)

Hybridization between divergent lineages often results in reduced hybrid viability. Here we report findings from a series of independent molecular analyses over several seasons on four life stages of F₁ hybrids between the newts Triturus cristatus and T. marmoratus . These two species form a bimodal hybrid zone of broad overlap in France, with F₁ hybrids making up about 4% of the adult population. We demonstrate strong asymmetry in the direction of the cross, with one class ( cristatus -mothered) making up about 90% of F₁ hybrids. By analyzing embryos and hatchlings, we show that this asymmetry is not due to prezygotic effects, as both classes of hybrid embryos are present at similar frequencies, implicating differential selection on the two hybrid classes after hatching. Adult F₁ hybrids show a weak Haldane effect overall, with a 72% excess of females. The rarer marmoratus -mothered class, however, consists entirely of males. The absence of females from this class of adult F₁ hybrids is best explained by an incompatibility between the cristatus X chromosome and marmoratus cytoplasm. It is thus important to distinguish the two classes of reciprocal-cross hybrids before making general statements about whether Haldane's rule is observed.     

Novel roles for hERG K+ channels in cell proliferation and apoptosis

The human ether-a-go-go-related gene potassium channel (hERG, Kv11.1, KCNH2) has an essential role in cardiac action potential repolarization. Electrical dysfunction of the voltage-sensitive ion channel is associated with potentially lethal ventricular arrhythmias in humans. hERG K⁺ channels are also expressed in a variety of cancer cells where they control cell proliferation and apoptosis. In this review, we discuss molecular mechanisms of hERG-associated cell cycle regulation and cell death. In addition, the significance of hERG K⁺ channels as future drug target in anticancer therapy is highlighted.     

CHANGES IN BLOOD FLOW IN THE COMPONENT STRUCTURES OF THE DOG BRAIN DURING POSTNATAL MATURATION

Abstract— Blood flow was measured quantitatively in 35 structures of the brains of dogs of various ages from birth to maturity. In general, values were low at birth and rose to maximal levels between 3 and 7 weeks of postnatal age; declines from the peak levels then followed until values characteristic of maturity were attained by 13 weeks of postnatal age. From relatively uniform perfusion rates throughout the brain at birth there gradually emerged a marked heterogeneity, in parallel with the structural and functional maturation and differentiation known to occur in the brain during this period of life. Our observations may reflect the summation of the changes in energy demands associated on the one hand with biosynthetic processes essential for growth and development and with the support for progressively increasing functional activities on the other.     

Field resistance of codling moth against Cydia pomonella granulovirus (CpGV) is autosomal and incompletely dominant inherited

The current appearance of local codling moth populations with resistance to Cydia pomonella granulovirus (CpGV) is an impediment to continuous CpGV application. Therefore, crossing experiments have been performed in order to gain information about the inheritance of resistance. Evidence is presented that the observed field resistance is stably inherited even under non-selective conditions in the laboratory. Offspring of reciprocal F(1) crosses between a susceptible ('S') and a resistant ('R') strain and backcrosses between F(1) and S were bioassayed at different CpGV concentrations. The resistant strain showed 100 times lower susceptibility in 7-day bioassays. The responses of the reciprocal crosses (male S x female R and female S x male R) did not differ significantly, indicating that resistance is autosomally inherited. The median lethal concentration for the F(1) progeny was intermediate between those of its parental strains. Mortality data obtained from the backcrosses suggested that inheritance of resistance is due to a non-additive, polygenic trait.