A statistical investigation of normal regional intra-subject heterogeneity of brain metabolism and perfusion by F-18 FDG and O-15 H(2)O PET imaging

BACKGROUND: The definite evaluation of the regional cerebral heterogeneity using perfusion and metabolism by a single modality of PET imaging has not been well addressed. Thus a statistical analysis of voxel variables from identical brain regions on metabolic and perfusion PET images was carried out to determine characteristics of the regional heterogeneity of F-18 FDG and O-15 H(2)O cerebral uptake in normal subjects. METHODS: Fourteen normal subjects with normal CT and/or MRI and physical examination including MMSE were scanned by both F-18 FDG and O-15 H(2)O PET within same day with head-holder and facemask. The images were co-registered and each individual voxel counts (Q) were normalized by the gloabl maximal voxel counts (M) as R = Q/M. The voxel counts were also converted to z-score map by z = (Q - mean)/SD. Twelve pairs of ROIs (24 total) were systematically placed on the z-score map at cortical locations 15-degree apart and identically for metabolism and perfusion. Inter- and intra-subject correlation coefficients (r) were computed, both globally and hemispherically, from metabolism and perfusion: between regions for the same tracer and between tracers for the same region. Moments of means and histograms were computed globally along with asymmetric indices as their hemispherical differences. RESULTS: Statistical investigations verified with data showed that, for a given scan, correlation analyses are expectedly alike regardless of variables (Q, R, z) used. The varieties of correlation (r's) of normal subjects, showing symmetry, were mostly around 0.8 and with coefficient of variations near 10%. Analyses of histograms showed non-Gaussian behavior (skew = -0.3 and kurtosis = 0.4) of metabolism on average, in contrast to near Gaussian perfusion. CONCLUSION: The co-registered cerebral metabolism and perfusion z maps demonstrated regional heterogeneity but with attractively low coefficient of variations in the correlation markers

Protective Immunity to Listeria Monocytogenes Infection Mediated by Recombinant Listeria innocua Harboring the VGC Locus

In this study we propose a novel bacterial vaccine strategy where non-pathogenic bacteria are complemented with traits desirable for the induction of protective immunity. To illustrate the proof of principle of this novel vaccination strategy, we use the model organism of intracellular immunity Listeria. We introduced a, low copy number BAC-plasmid harbouring the virulence gene cluster (vgc) of L. monocytogenes (Lm) into the non-pathogenic L. innocua (L.inn) strain and examined for its ability to induce protective cellular immunity. The resulting strain (L.inn::vgc) was attenuated for virulence in vivo and showed a strongly reduced host detrimental inflammatory response compared to Lm. Like Lm, L.inn::vgc induced the production of Type I Interferon's and protection was mediated by Listeria-specific CD8+ T cells. Rational vaccine design whereby avirulent strains are equipped with the capabilities to induce protection but lack detrimental inflammatory effects offer great promise towards future studies using non-pathogenic bacteria as vectors for vaccination

Dietary and Behavioral Interventions Protect against Age Related Activation of Caspase Cascades in the Canine Brain

Lifestyle interventions such as diet, exercise, and cognitive training represent a quietly emerging revolution in the modern approach to counteracting age-related declines in brain health. Previous studies in our laboratory have shown that long-term dietary supplementation with antioxidants and mitochondrial cofactors (AOX) or behavioral enrichment with social, cognitive, and exercise components (ENR), can effectively improve cognitive performance and reduce brain pathology of aged canines, including oxidative damage and Aβ accumulation. In this study, we build on and extend our previous findings by investigating if the interventions reduce caspase activation and ceramide accumulation in the aged frontal cortex, since caspase activation and ceramide accumulation are common convergence points for oxidative damage and Aβ, among other factors associated with the aged and AD brain. Aged beagles were placed into one of four treatment groups: CON – control environment/control diet, AOX– control environment/antioxidant diet, ENR – enriched environment/control diet, AOX/ENR– enriched environment/antioxidant diet for 2.8 years. Following behavioral testing, brains were removed and frontal cortices were analyzed to monitor levels of active caspase 3, active caspase 9 and their respective cleavage products such as tau and semaphorin7a, and ceramides. Our results show that levels of activated caspase-3 were reduced by ENR and AOX interventions with the largest reduction occurring with combined AOX/ENR group. Further, reductions in caspase-3 correlated with reduced errors in a reversal learning task, which depends on frontal cortex function. In addition, animals treated with an AOX arm showed reduced numbers of cells expressing active caspase 9 or its cleavage product semaphorin 7A, while ENR (but not AOX) reduced ceramide levels. Overall, these data demonstrate that lifestyle interventions curtail activation of pro-degenerative pathways to improve cellular health and are the first to show that lifestyle interventions can regulate caspase pathways in a higher animal model of aging

Soil mobility of surface applied polyaromatic hydrocarbons in response to simulated rainfall

Polyaromatic hydrocarbons (PAHs) are emitted from a variety of sources and can accumulate on and within surface soil layers. To investigate the level of potential risk posed by surface contaminated soils, vertical soil column experiments were conducted to assess the mobility, when leached with simulated rainwater, of six selected PAHs (naphthalene, phenanthrene, fluoranthene, pyrene, benzo(e)pyrene and benzo(ghi)perylene) with contrasting hydrophobic characteristics and molecular weights/sizes. The only PAH found in the leachate within the experimental period of 26 days was naphthalene. The lack of migration of the other applied PAHs were consistent with their low mobilities within the soil columns which generally parallelled their log Koc values. Thus only 2.3% of fluoranthene, 1.8% of pyrene, 0.2% of benzo(e)pyrene and 0.4% of benzo(ghi)perylene were translocated below the surface layer. The PAH distributions in the soil columns followed decreasing power relationships with 90% reductions in the starting levels being shown to occur within a maximum average depth of 0.94 cm compared to an average starting depth of 0.5 cm. A simple predictive model identifies the extensive time periods, in excess of 10 years, required to mobilise 50% of the benzo(e)pyrene and benzo(ghi)perylene from the surface soil layer. Although this reduces to between 2 and 7 years for fluoranthene and pyrene, it is concluded that the possibility of surface applied PAHs reaching and contaminating a groundwater aquifer is unlikely

Bunyaviridae RNA Polymerases (L-Protein) Have an N-Terminal, Influenza-Like Endonuclease Domain, Essential for Viral Cap-Dependent Transcription

Bunyaviruses are a large family of segmented RNA viruses which, like influenza virus, use a cap-snatching mechanism for transcription whereby short capped primers derived by endonucleolytic cleavage of host mRNAs are used by the viral RNA-dependent RNA polymerase (L-protein) to transcribe viral mRNAs. It was recently shown that the cap-snatching endonuclease of influenza virus resides in a discrete N-terminal domain of the PA polymerase subunit. Here we structurally and functionally characterize a similar endonuclease in La Crosse orthobunyavirus (LACV) L-protein. We expressed N-terminal fragments of the LACV L-protein and found that residues 1-180 have metal binding and divalent cation dependent nuclease activity analogous to that of influenza virus endonuclease. The 2.2 Å resolution X-ray crystal structure of the domain confirms that LACV and influenza endonucleases have similar overall folds and identical two metal binding active sites. The in vitro activity of the LACV endonuclease could be abolished by point mutations in the active site or by binding 2,4-dioxo-4-phenylbutanoic acid (DPBA), a known influenza virus endonuclease inhibitor. A crystal structure with bound DPBA shows the inhibitor chelating two active site manganese ions. The essential role of this endonuclease in cap-dependent transcription was demonstrated by the loss of transcriptional activity in a RNP reconstitution system in cells upon making the same point mutations in the context of the full-length LACV L-protein. Using structure based sequence alignments we show that a similar endonuclease almost certainly exists at the N-terminus of L-proteins or PA polymerase subunits of essentially all known negative strand and cap-snatching segmented RNA viruses including arenaviruses (2 segments), bunyaviruses (3 segments), tenuiviruses (4–6 segments), and orthomyxoviruses (6–8 segments). This correspondence, together with the well-known mapping of the conserved polymerase motifs to the central regions of the L-protein and influenza PB1 subunit, suggests that L-proteins might be architecturally, and functionally equivalent to a concatemer of the three orthomyxovirus polymerase subunits in the order PA-PB1-PB2. Furthermore, our structure of a known influenza endonuclease inhibitor bound to LACV endonuclease suggests that compounds targeting a potentially broad spectrum of segmented RNA viruses, several of which are serious or emerging human, animal and plant pathogens, could be developed using structure-based optimisation

Architecture of an Antagonistic Tree/Fungus Network: The Asymmetric Influence of Past Evolutionary History

Compartmentalization and nestedness are common patterns in ecological networks. The aim of this study was to elucidate some of the processes shaping these patterns in a well resolved network of host/pathogen interactions.Based on a long-term (1972-2005) survey of forest health at the regional scale (all French forests; 15 million ha), we uncovered an almost fully connected network of 51 tree taxa and 157 parasitic fungal species. Our analyses revealed that the compartmentalization of the network maps out the ancient evolutionary history of seed plants, but not the ancient evolutionary history of fungal species. The very early divergence of the major fungal phyla may account for this asymmetric influence of past evolutionary history. Unlike compartmentalization, nestedness did not reflect any consistent phylogenetic signal. Instead, it seemed to reflect the ecological features of the current species, such as the relative abundance of tree species and the life-history strategies of fungal pathogens. We discussed how the evolution of host range in fungal species may account for the observed nested patterns.Overall, our analyses emphasized how the current complexity of ecological networks results from the diversification of the species and their interactions over evolutionary times. They confirmed that the current architecture of ecological networks is not only dependent on recent ecological processes

Outcomes of Brood Parasite–Host Interactions Mediated by Egg Matching: Common Cuckoos Cuculus canorus versus Fringilla Finches

Antagonistic species often interact via matching of phenotypes, and interactions between brood parasitic common cuckoos (Cuculus canorus) and their hosts constitute classic examples. The outcome of a parasitic event is often determined by the match between host and cuckoo eggs, giving rise to potentially strong associations between fitness and egg phenotype. Yet, empirical efforts aiming to document and understand the resulting evolutionary outcomes are in short supply.We used avian color space models to analyze patterns of egg color variation within and between the cuckoo and two closely related hosts, the nomadic brambling (Fringilla montifringilla) and the site fidelic chaffinch (F. coelebs). We found that there is pronounced opportunity for disruptive selection on brambling egg coloration. The corresponding cuckoo host race has evolved egg colors that maximize fitness in both sympatric and allopatric brambling populations. By contrast, the chaffinch has a more bimodal egg color distribution consistent with the evolutionary direction predicted for the brambling. Whereas the brambling and its cuckoo host race show little geographical variation in their egg color distributions, the chaffinch's distribution becomes increasingly dissimilar to the brambling's distribution towards the core area of the brambling cuckoo host race.High rates of brambling gene flow is likely to cool down coevolutionary hot spots by cancelling out the selection imposed by a patchily distributed cuckoo host race, thereby promoting a matching equilibrium. By contrast, the site fidelic chaffinch is more likely to respond to selection from adapting cuckoos, resulting in a markedly more bimodal egg color distribution. The geographic variation in the chaffinch's egg color distribution could reflect a historical gradient in parasitism pressure. Finally, marked cuckoo egg polymorphisms are unlikely to evolve in these systems unless the hosts evolve even more exquisite egg recognition capabilities than currently possessed

How long do nosocomial pathogens persist on inanimate surfaces? A systematic review

BACKGROUND: Inanimate surfaces have often been described as the source for outbreaks of nosocomial infections. The aim of this review is to summarize data on the persistence of different nosocomial pathogens on inanimate surfaces. METHODS: The literature was systematically reviewed in MedLine without language restrictions. In addition, cited articles in a report were assessed and standard textbooks on the topic were reviewed. All reports with experimental evidence on the duration of persistence of a nosocomial pathogen on any type of surface were included. RESULTS: Most gram-positive bacteria, such as Enterococcus spp. (including VRE), Staphylococcus aureus (including MRSA), or Streptococcus pyogenes, survive for months on dry surfaces. Many gram-negative species, such as Acinetobacter spp., Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Serratia marcescens, or Shigella spp., can also survive for months. A few others, such as Bordetella pertussis, Haemophilus influenzae, Proteus vulgaris, or Vibrio cholerae, however, persist only for days. Mycobacteria, including Mycobacterium tuberculosis, and spore-forming bacteria, including Clostridium difficile, can also survive for months on surfaces. Candida albicans as the most important nosocomial fungal pathogen can survive up to 4 months on surfaces. Persistence of other yeasts, such as Torulopsis glabrata, was described to be similar (5 months) or shorter (Candida parapsilosis, 14 days). Most viruses from the respiratory tract, such as corona, coxsackie, influenza, SARS or rhino virus, can persist on surfaces for a few days. Viruses from the gastrointestinal tract, such as astrovirus, HAV, polio- or rota virus, persist for approximately 2 months. Blood-borne viruses, such as HBV or HIV, can persist for more than one week. Herpes viruses, such as CMV or HSV type 1 and 2, have been shown to persist from only a few hours up to 7 days. CONCLUSION: The most common nosocomial pathogens may well survive or persist on surfaces for months and can thereby be a continuous source of transmission if no regular preventive surface disinfection is performed

Coronary artery calcium screening: current status and recommendations from the European Society of Cardiac Radiology and North American Society for Cardiovascular Imaging

Current guidelines and literature on screening for coronary artery calcium for cardiac risk assessment are reviewed for both general and special populations. It is shown that for both general and special populations a zero score excludes most clinically relevant coronary artery disease. The importance of standardization of coronary artery calcium measurements by multi-detector CT is discussed