Decrease in cardiac output and muscle sympathetic activity during vasovagal syncope

The importance of cardiac output (CO) to blood pressure level during vasovagal syncope is unknown. We measured thermodilution CO, mean blood pressure (MBP), and leg muscle mean sympathetic nerve activity (MSNA) each minute during 60 degrees head-up tilt in 26 patients with recurrent syncope. Eight patients tolerated tilt (TT) for 45 min (mean age 60 +/- 5 yr) and 15 patients developed syncope during tilt (TS) (mean age 58 +/- 4 yr, mean tilt time 15.4 +/- 2 min). In TT patients, CO decreased during the first minute of tilt (from 3.2 +/- 0.2 to 2.5 +/- 0.3 l x min(-1) x m(-2), P = 0.001) and thereafter remained stable between 2.5 +/- 0.3 (P = 0.001) and 2.4 +/- 0.2 l x min(-1) x m(-2) (P = 0.004) at 5 and 45 min, respectively. In TS patients, CO decreased during the first minute (from 3.3 +/- 0.2 to 2.7 +/- 0.1 l x min(-1) x m(-2), P = 0.02) and was stable until 7 min before syncope, falling to 2.0 +/- 0.2 at syncope (P = 0.001). Regression slopes for CO versus time during tilt were -0.01 min(-1) in TT versus -0.1 l x min(-1) x m(-2) x min(-1) in TS (P = 0.001). However, MBP was more closely correlated to total peripheral resistance (R = 0.56, P = 0.001) and MSNA (R = 0.58, P = 0.001) than CO (R = 0.32, P = 0.001). In vasovagal reactions, a progressive decline in CO may contribute to hypotension some minutes before syncope occurs.     

Biofilm Consumption and Variable Diet Composition of Western Sandpipers (Calidris mauri) during Migratory Stopover

Many shorebird species undertake long-distance migrations punctuated by brief stays at food-rich, estuarine stopover locations. Understanding use of these food resources helps guide conservation and responsible development decisions. We determined the extent and degree to which Western Sandpiper (Calidris mauri) utilized biofilm as a food resource across a large and variable stopover location during northward (spring) migration. We investigated the spatial heterogeneity in diet composition, to determine whether shorebirds were consistently feeding on biofilm or whether diet varied between naturally and anthropogenically delineated sites. We used stable isotope analysis to estimate that biofilm conservatively comprised 22% to 53% of Western Sandpiper droppings across all sampling sites and that prey composition differed significantly between areas within the stopover location. Widespread biofilm consumption demonstrates the importance of biofilm as a dietary component. Variable diet composition suggests that habitat heterogeneity may be an important component of high quality stopover locations in the context of “state-dependant trade-offs” of Western Sandpiper population sub-groups. Future management decisions must consider and address potential impacts on the biofilm community throughout a stopover location, as single site studies of diet composition may not be adequate to develop effective management strategies for entire stopover sites.     

SirT1 catalytic activity is required for male fertility and metabolic homeostasis in mice

The protein encoded by the sirt1 gene is an enzyme, SirT1, that couples the hydrolysis of NAD(+) to the deacetylation of acetyl-lysine residues in substrate proteins. Mutations of the sirt1 gene that fail to encode protein have been introduced into the mouse germ line, and the animals homozygous for these null mutations have various physiological abnormalities. To determine which of the characteristics of these sirt1(-/-) mice are a consequence of the absence of the catalytic activity of the SirT1 protein, we created a mouse strain carrying a point mutation (H355Y) that ablates the catalytic activity but does not affect the amount of the SirT1 protein. Mice carrying point mutations in both sirt1 genes, sirt1(Y/Y), have a phenotype that is overlapping but not identical to that of the sirt1-null animals. The sirt1(Y/Y) phenotype is significantly milder than that seen in the sirt1(-/-) animals. For example, female sirt1(Y/Y) animals are fertile, while sirt1(-/-) females are sterile. On the other hand, both sirt1(-/-) and sirt1(Y/Y) male mice are sterile and hypermetabolic. We report that sirt1(Y/Y) mice respond aberrantly to caloric restriction, although the effects are more subtle than seen in sirt1(-/-) mice. Thus, the SirT1 protein has functions that can be attributed to the catalytic activity of the protein, as well as other functions that are conferred by the protein itself.     

Consumer-resource coupling in wet-dry tropical rivers

1. Despite implications for top-down and bottom-up control and the stability of food webs, understanding the links between consumers and their diets remains difficult, particularly in remote tropical locations where food resources are usually abundant and variable and seasonal hydrology produces alternating patterns of connectivity and isolation. 2. We used a large scale survey of freshwater biota from 67 sites in three catchments (Daly River, Northern Territory; Fitzroy River, Western Australia; and the Mitchell River, Queensland) in Australia's wet-dry tropics and analysed stable isotopes of carbon (δ(13) C) to search for broad patterns in resource use by consumers in conjunction with known and measured indices of connectivity, the duration of floodplain inundation, and dietary choices (i.e. stomach contents of fish). 3. Regression analysis of biofilm δ(13) C against consumer δ(13) C, as an indicator of reliance on local food sources (periphyton and detritus), varied depending on taxa and catchment. 4. The carbon isotope ratios of benthic invertebrates were tightly coupled to those of biofilm in all three catchments, suggesting assimilation of local resources by these largely nonmobile taxa. 5. Stable C isotope ratios of fish, however, were less well-linked to those of biofilm and varied by catchment according to hydrological connectivity; the perennially flowing Daly River with a long duration of floodplain inundation showed the least degree of coupling, the seasonally flowing Fitzroy River with an extremely short flood period showed the strongest coupling, and the Mitchell River was intermediate in connectivity, flood duration and consumer-resource coupling. 6. These findings highlight the high mobility of the fish community in these rivers, and how hydrological connectivity between habitats drives patterns of consumer-resource coupling.     

Microbial communities in contaminated sediments, associated with bioremediation of uranium to submicromolar levels

Microbial enumeration, 16S rRNA gene clone libraries, and chemical analysis were used to evaluate the in situ biological reduction and immobilization of uranium(VI) in a long-term experiment (more than 2 years) conducted at a highly uranium-contaminated site (up to 60 mg/liter and 800 mg/kg solids) of the U.S. Department of Energy in Oak Ridge, TN. Bioreduction was achieved by conditioning groundwater above ground and then stimulating growth of denitrifying, Fe(III)-reducing, and sulfate-reducing bacteria in situ through weekly injection of ethanol into the subsurface. After nearly 2 years of intermittent injection of ethanol, aqueous U levels fell below the U.S. Environmental Protection Agency maximum contaminant level for drinking water and groundwater (<30 microg/liter or 0.126 microM). Sediment microbial communities from the treatment zone were compared with those from a control well without biostimulation. Most-probable-number estimations indicated that microorganisms implicated in bioremediation accumulated in the sediments of the treatment zone but were either absent or in very low numbers in an untreated control area. Organisms belonging to genera known to include U(VI) reducers were detected, including Desulfovibrio, Geobacter, Anaeromyxobacter, Desulfosporosinus, and Acidovorax spp. The predominant sulfate-reducing bacterial species were Desulfovibrio spp., while the iron reducers were represented by Ferribacterium spp. and Geothrix spp. Diversity-based clustering revealed differences between treated and untreated zones and also within samples of the treated area. Spatial differences in community structure within the treatment zone were likely related to the hydraulic pathway and to electron donor metabolism during biostimulation.     

Comparison of mandelate dehydrogenases from various strains of Acinetobacter calcoaceticus: similarity of natural and 'evolved' forms

In previous work it had been shown that Acinetobacter calcoaceticus wild-type strain NCIB 8250 had only an L-mandelate deydrogenase but it could give rise to mutants that contained an evolved D-mandelate dehydrogenase; conversely, wild-type strain EBF 65/65 had only a D-mandelate dehydrogenase but gave rise to mutants that possessed an evolved L-mandelate dehydrogenase. Several other wild-type strains of A. calcoaceticus have now been shown to grow on both enantiomers of mandelate. In every case the L-mandelate dehydrogenases were found to be much more heat-stable and insensitive to inhibition by p-chloromercuribenzoate than were the D-mandelate dehydrogenases when measured in bacterial extracts. All the D-mandelate dehydrogenases in the wild-type strains were inactivated to about the same extent by an antiserum that had been raised in a rabbit against an evolved D-mandelate dehydrogenase. An evolved D-mandelate deydrogenase (from a mutant strain derived from strain NCIB 8250) and an original D-mandelate dehydrogenase (from a mutant strain derived from strain EBF 65/65) were purified to homogeneity by the same procedure and were indistinguishable as judged by immunological cross-reactivity of the native and the sodium-dodecyl-sulphate-denatured enzymes, solubility in cholate, net charge at pH 7.5, pI value, salting-out properties, Mr value, apparent K(m) value for D-mandelate, heat-stability and sensitivity to p-chloromercuribenzoate. The most likely explanation for the appearance of evolved mandelate dehydrogenases in strains of A. calcoaceticus is that cryptic genes become expressed.     

The crystal structure of plasminogen activator inhibitor 2 at 2.0 A resolution: implications for serpin function.

BACKGROUND: Plasminogen activator inhibitor 2 (PAI-2) is a member of the serpin family of protease inhibitors that function via a dramatic structural change from a native, stressed state to a relaxed form. This transition is mediated by a segment of the serpin termed the reactive centre loop (RCL); the RCL is cleaved on interaction with the protease and becomes inserted into betasheet A of the serpin. Major questions remain as to what factors facilitate this transition and how they relate to protease inhibition. RESULTS: The crystal structure of a mutant form of human PAI-2 in the stressed state has been determined at 2.0 A resolution. The RCL is completely disordered in the structure. An examination of polar residues that are highly conserved across all serpins identifies functionally important regions. A buried polar cluster beneath betasheet A (the so-called 'shutter' region) is found to stabilise both the stressed and relaxed forms via a rearrangement of hydrogen bonds. CONCLUSIONS: A statistical analysis of interstrand interactions indicated that the shutter region can be used to discriminate between inhibitory and non-inhibitory serpins. This analysis implied that insertion of the RCL into betasheet A up to residue P8 is important for protease inhibition and hence the structure of the complex formed between the serpin and the target protease.     

Epidermal capillariasis in South African clawed frogs (Xenopus laevis)

Significant morbidity and mortality of South African clawed frogs, Xenopus laevis, can be caused by parasitism of the epidermis by a capillarid nematode. These worms produce an erosive dermatitis that is complicated by infection with gram-negative microorganisms. The nematode apparently has a direct life cycle that can be completed within the epidermis of the frog. These characteristics are suggested by the lack of an intermediate host and failure to detect visceral migration. Another unique feature of the parasite was the presence of larvated eggs, in utero. Some have named the parasite Capillaria xenopodis, whereas others called it Pseudocapillaroides xenopi to distinguish it form the typical members of the genus Capillaria.