Conformational dynamics of a lipid-interacting protein: MD simulations of saposin B

Saposin B is a water soluble alpha-helical protein which can bind to membranes and extract selected lipids, especially cerebroside sulfates. The X-ray structure of saposin B is homodimeric. There are two conformations of the dimer in the crystal-one with a closed central cavity (the AB dimer) and one (the CD dimer) with a more open cavity. We have conducted a series of short (5 ns) molecular dynamics simulations of saposin B, starting from both the AB and CD conformations and with/without bound lipid and/or water molecules within the central hydrophobic cavity. The more open (CD) dimer showed greater conformational drift than the AB dimer. The conformational drift was also somewhat higher in the absence of bound lipid. Two more extended (30 ns) simulations of AB and CD dimers were performed and analyzed in terms of changes in intersubunit packing within the dimers. The AB dimer remained largely unchanged in conformation over the duration of the extended simulation. In contrast, the CD dimer underwent a substantial conformational change corresponding to a 'scissor' motion of the two monomers so as to compress the central cavity to a more closed conformation than that seen in the AB dimer structure. A H-bond between the Q53 and Y54 side chains of the alpha3 helices of the two opposing monomers seems to hold the dimer in this 'scissor-closed' conformation. We suggest that a cycle of conformational changes, expanding and compressing the central cavity of the saposin B dimer, may play a key role in facilitating lipid extraction from bilayers.     

Identification of two mosquitocidal Bacillus cereus strains showing different host ranges

Mosquitocidal bacteria, M413 and C32 have been isolated from sediment samples collected from woodland and ditch, respectively. Gas chromatographic analysis of fatty acids methyl esters (GC-FAME) and 16S rRNA gene sequence alignment results showed these isolates belong to Bacillus cereus. The SDS-PAGE analysis of sporulated cultures of both isolates showed two major bands very similar in size. Interestingly, however, M413 is mainly toxic to 4th instars of Ochlerotatus taeniorhynchus whereas C32 is to those of Culex quinquefasciatus.     

GENETIC DIFFERENTIATION AMONG CHEWING LOUSE POPULATIONS (MALLOPHAGA: TRICHODECTIDAE) IN A POCKET GOPHER CONTACT ZONE (RODENTIA: GEOMYIDAE)

Genetic variation among populations of chewing lice (Geomydoecus actuosi) was examined in relation to chromosomal and electrophoretic variation among populations of their hosts (Thomomys bottae) at a contact zone. Louse demes were characterized by low levels of genetic heterozygosity (H? = 0.039) that may result from founder effects during primary infestation of hosts, compounded by seasonal reductions in louse population size. Louse populations sampled from different hosts showed high levels of genetic structuring both within and among host localities. Microgeographic differentiation of louse populations is high (mean F_ST = 0.092) suggesting that properties of this host–parasite system promote differentiation of louse populations living on different individual hosts. Among-population differentiation in lice (F_ST = 0.240) was similar to that measured among host populations (F_ST = 0.236), suggesting a close association between gene flow in pocket gophers and gene flow in their lice.     

Autophagy in stem cells

Autophagy is a highly conserved cellular process by which cytoplasmic components are sequestered in autophagosomes and delivered to lysosomes for degradation. As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining cellular homeostasis as well as remodeling during normal development, and dysfunctions in autophagy have been associated with a variety of pathologies including cancer, inflammatory bowel disease and neurodegenerative disease. Stem cells are unique in their ability to self-renew and differentiate into various cells in the body, which are important in development, tissue renewal and a range of disease processes. Therefore, it is predicted that autophagy would be crucial for the quality control mechanisms and maintenance of cellular homeostasis in various stem cells given their relatively long life in the organisms. In contrast to the extensive body of knowledge available for somatic cells, the role of autophagy in the maintenance and function of stem cells is only beginning to be revealed as a result of recent studies. Here we provide a comprehensive review of the current understanding of the mechanisms and regulation of autophagy in embryonic stem cells, several tissue stem cells (particularly hematopoietic stem cells), as well as a number of cancer stem cells. We discuss how recent studies of different knockout mice models have defined the roles of various autophagy genes and related pathways in the regulation of the maintenance, expansion and differentiation of various stem cells. We also highlight the many unanswered questions that will help to drive further research at the intersection of autophagy and stem cell biology in the near future.     

TIE-2/VEGF-R2 SAR and in vitro activity of C3-acyl dihydroindazolo[5,4-a]pyrrolo[3,4-c]carbazole analogs

Orally bioavailable, dual inhibitors of TIE-2/VEGF-R2 were identified by elaborating the C3/N13 SAR around a fused pyrrolodihydroindazolocarbazole scaffold. Analogs bearing a C3-thiophencarbonyl group were evaluated in enzymatic and cellular biochemical assays; two orally bioavailable analogs were further profiled in functional assays and found to inhibit microvessel growth in rat aortic explant cultures and inhibit Ang-1-stimulated chemotaxis of HUVECs.     

Composite analysis of black duck breeding population surveys in eastern North America

Waterfowl are monitored in eastern Canada and the northeastern United States with 2 surveys: a transect survey from fixed-wing aircraft and a plot survey conducted from helicopters. The surveys vary in extent, but overlap exists in a core area of 9 strata covering portions of all provinces from Ontario east to Newfoundland. We estimated population change for American black ducks (Anas rubripes) and mallards (Anas platyrhynchos) from these surveys using a log-linear hierarchical model that accommodates differences in sample design and visibility associated with these survey methods. Using a combined analysis of the surveys based on total indicated birds, we estimate the American black duck population to be 901,700 (95% CI: 715,200–1,274,000) in 2011, with 526,900 (95% CI: 357,500–852,300) mallards in the surveyed area. Precision of estimates varies widely by species and region, with transect surveys providing less precise results than plot surveys for black ducks in areas of overlap. The combined survey analysis for black ducks in the eastern survey region produced estimates with an average yearly coefficient of variation (CV) of 12.1% for the entire area and an average CV of 6.9% in the plot survey area. Mallards, which had a more limited distribution in the region, had an average yearly CV of 22.1% over the entire region, and an average CV of 27.7% in the plot survey area. Hierarchical models provide a rich framework for analyzing and combining results from complex survey designs, providing useful spatial and temporal information on population size and change in these economically important species. © 2012 The Wildlife Society.     

Pliocene coastal palaeomorphology and ostracod faunas of the Bass Strait hinterland,southeast Australia

Early to late Pliocene sedimentary strata present across the northern Bass Strait hinterland, southeastern Australia yield extensive fossil proxy data relevant to the interpretation of high sea level coastal palaeomorphology. Within the Pliocene Whalers Bluff Formation exposed in coastal cliffs near the township of Portland, Victoria, marine microfossil faunas delineate two broad cycles of deposition. Both these sedimentary cycles are bound below by unconformity surfaces. Within the lower sedimentary cycle, a basal stress-tolerant (low diversity) marginal marine microfossil fauna devoid of ostracods and suggestive of bottom-water hypoxia, is succeeded by a diverse shallow marine ostracod fauna dominated by stenohaline species indicative of a sheltered (but open) oceanic embayment. This lower sedimentary cycle has an early Pliocene (Zanclean) age. Equivalent shallow marine (e.g. coastal embayment) deposits occur broadly across the coastal hinterland of southeastern Australia—reflecting the generally higher global sea levels of this time. The upper cycle in the cliff exposures at Portland is late Pliocene (Piacenzian) in age. Equivalent deposits across the Bass Strait hinterland are restricted to former incised river valley settings. Euryhaline estuarine/coastal lagoon Ostracoda are present throughout the upper cycle in the Portland cliffs. These are associated with a low diversity microfauna at the base of the upper cycle and a high diversity microfauna towards the top of the cycle. Early Pliocene coastal marine deposits can be distinguished from late Pliocene coastal marine deposits across the northern Bass Strait hinterland on the basis of the presence or absence of certain open marine (‘stenohaline’) ostracod species.     

Inter‐oceanic variation in patterns of host‐associated divergence in a seabird ectoparasite

Aim Parasites with global distributions and wide host spectra provide excellent models for exploring the factors that drive parasite diversification. Here, we tested the relative force of host and geography in shaping population structure of a widely distributed and common ectoparasite of colonial seabirds, the tick Ixodes uriae. Location Two natural geographic replicates of the system: numerous seabird colonies of the North Pacific and North Atlantic Ocean basins. Methods Using eight microsatellite markers and tick samples from a suite of multi‐specific seabird colonies, we examined tick population structure in the North Pacific and compare patterns of diversity and structure to those in the Atlantic basin. Analyses included population genetic estimations of diversity and population differentiation, exploratory multivariate analyses, and Bayesian clustering approaches. These different analyses explicitly took into account both the geographic distance among colonies and host use by the tick. Results Overall, little geographic structure was observed among Pacific tick populations. However, host‐related genetic differentiation was evident, but was variable among host types and lower than in the North Atlantic. Main conclusions Tick population structure is concordant with the genetic structure observed in seabird host species within each ocean basin, where seabird populations tend to be less structured in the North Pacific than in the North Atlantic. Reduced tick genetic structure in the North Pacific suggests that host movement among colonies, and thus tick dispersal, is higher in this region. In addition to information on parasite diversity and gene flow, our findings raise interesting questions about the subtle ways that host behaviour, distribution and phylogeographic history shape the genetics of associated parasites across geographic landscapes.