Cortical tau is associated with microstructural imaging biomarkers of neurite density and dendritic complexity in Alzheimer's disease

INTRODUCTION: In Alzheimer's disease (AD), hyperphosphorylated tau is closely associated with focal neurodegeneration, but the mechanism remains uncertain. METHODS: We quantified cortical microstructure using neurite orientation dispersion and density imaging in 14 individuals with young onset AD. Diffusion tensor imaging measured mean diffusivity (MD). Amyloid beta and tau positron emission tomography were acquired and associations with microstructural measures were assessed. RESULTS: When regional volume was adjusted for, in the medial temporal lobe there was a significant negative association between neurite density and tau (partial R2  = 0.56, p = 0.008) and between orientation dispersion and tau (partial R2  = 0.66, p = 0.002), but not between MD and tau. In a wider cortical composite, there was an association between orientation dispersion and tau (partial R2  = 0.43, p = 0.030), but not between other measures and tau. DISCUSSION: Our findings are consistent with tau causing first dendritic pruning (reducing dispersion/complexity) followed by neuronal loss. Advanced magnetic resonance imaging (MRI) microstructural measures have the potential to provide information relating to underlying tau deposition

How much choice is there in housing choice vouchers? Neighborhood risk and free market rental housing accessibility for active drug users in Hartford, Connecticut

<p>Abstract</p> <p>Background</p> <p>Since the mid-1970s, the dominant model for U.S. federal housing policy has shifted from unit-based programs to tenant based vouchers and certificates, intended to allow recipients a choice in their housing and neighborhoods. Surprisingly little research has examined the question of where those with Section 8 housing vouchers are able to live, but some research suggests that voucher holders are more likely to reside in distressed neighborhoods than unsubsidized renter households. Further, federal housing policy has limited drug users' access to housing subsidies. In turn, neighborhood disorder has been associated with higher levels of injection drug risk behaviors, and higher drug-related mortality. This paper explores rental accessibility and neighborhood characteristics of advertised rental housing in Hartford CT.</p> <p>Methods</p> <p>Brief telephone interviews were conducted with landlords or management companies with units to rent in Hartford to explore housing accessibility measured as initial move in costs, credit and criminal background checks, and whether rental subsidies were accepted. These data were supplemented with in-depth interviews with landlords, shelter staff and active users of heroin, crack or cocaine. Apartments for rent were geocoded and mapped using <b>ArcGIS</b>. We used location quotients to identify areas where low-income rental housing is concentrated. Finally, we mapped apartments in relation to drug and violent arrest rates in each neighborhood.</p> <p>Results</p> <p>High security deposits, criminal background and credit checks limit housing accessibility even for drug users receiving vouchers. While most landlords or management companies accepted housing subsidies, several did not. Voucher units are concentrated in neighborhoods with high poverty neighborhoods. Landlords reported little incentive to accept rental subsidies in neighborhoods with low crime rates, but appreciated the guarantee provided by Section 8 in high crime neighborhoods that were less likely to attract applicants with good jobs and credit.</p> <p>Conclusion</p> <p>Housing vouchers in themselves do not greatly improve recipients' choice of neighborhood and voucher units are concentrated in the most distressed neighborhoods. Policy changes are needed to increase landlords' incentives to accept housing subsidies. Interventions to improve neighborhood conditions are needed to improve the probability of success for those recovering from drug addictions.</p

Use of a Semi-field System to Evaluate the Efficacy of Topical Repellents under user Conditions Provides a Disease Exposure free Technique Comparable with Field Data.

Before topical repellents can be employed as interventions against arthropod bites, their efficacy must be established. Currently, laboratory or field tests, using human volunteers, are the main methods used for assessing the efficacy of topical repellents. However, laboratory tests are not representative of real life conditions under which repellents are used and field-testing potentially exposes human volunteers to disease. There is, therefore, a need to develop methods to test efficacy of repellents under real life conditions while minimizing volunteer exposure to disease. A lotion-based, 15% N, N-Diethyl-3-methylbenzamide (DEET) repellent and 15% DEET in ethanol were compared to a placebo lotion in a 200 sq m (10 m x 20 m) semi-field system (SFS) against laboratory-reared Anopheles arabiensis mosquitoes and in full field settings against wild malaria vectors and nuisance-biting mosquitoes. The average percentage protection against biting mosquitoes over four hours in the SFS and field setting was determined. A Poisson regression model was then used to determine relative risk of being bitten when wearing either of these repellents compared to the placebo. Average percentage protection of the lotion-based 15% DEET repellent after four hours of mosquito collection was 82.13% (95% CI 75.94-88.82) in the semi-field experiments and 85.10% (95% CI 78.97-91.70) in the field experiments. Average percentage protection of 15% DEET in ethanol after four hours was 71.29% (CI 61.77-82.28) in the semi-field system and 88.24% (84.45-92.20) in the field. Semi-field evaluation results were comparable to full-field evaluations, indicating that such systems could be satisfactorily used in measuring efficacy of topically applied mosquito repellents, thereby avoiding risks of exposure to mosquito-borne pathogens, associated with field testing

Water induced sediment levitation enhances downslope transport on Mars

On Mars, locally warm surface temperatures (~293 K) occur, leading to the possibility of (transient) liquid water on the surface. However, water exposed to the martian atmosphere will boil, and the sediment transport capacity of such unstable water is not well understood. Here, we present laboratory studies of a newly recognized transport mechanism: “levitation” of saturated sediment bodies on a cushion of vapor released by boiling. Sediment transport where this mechanism is active is about nine times greater than without this effect, reducing the amount of water required to transport comparable sediment volumes by nearly an order of magnitude. Our calculations show that the effect of levitation could persist up to ~48 times longer under reduced martian gravity. Sediment levitation must therefore be considered when evaluating the formation of recent and present-day martian mass wasting features, as much less water may be required to form such features than previously thought

Access to housing subsidies, housing status, drug use and HIV risk among low-income U.S. urban residents

<p>Abstract</p> <p>Background</p> <p>Much research has shown an association between homelessness and unstable housing and HIV risk but most has relied on relatively narrow definitions of housing status that preclude a deeper understanding of this relationship. Fewer studies have examined access to housing subsidies and supportive housing programs among low-income populations with different personal characteristics. This paper explores personal characteristics associated with access to housing subsidies and supportive housing, the relationship between personal characteristics and housing status, and the relationship between housing status and sexual risk behaviors among low-income urban residents.</p> <p>Methods</p> <p>Surveys were conducted with 392 low-income residents from Hartford and East Harford, Connecticut through a targeted sampling plan. We measured personal characteristics (income, education, use of crack, heroin, or cocaine in the last 6 months, receipt of welfare benefits, mental illness diagnosis, arrest, criminal conviction, longest prison term served, and self-reported HIV diagnosis); access to housing subsidies or supportive housing programs; current housing status; and sexual risk behaviors. To answer the aims above, we performed univariate analyses using Chi-square or 2-sided ANOVA's. Those with significance levels above (0.10) were included in multivariate analyses. We performed 2 separate multiple regressions to determine the effects of personal characteristics on access to housing subsidies and access to supportive housing respectively. We used multinomial main effects logistic regression to determine the effects of housing status on sexual risk behavior.</p> <p>Results</p> <p>Being HIV positive or having a mental illness predicted access to housing subsidies and supportive housing, while having a criminal conviction was not related to access to either housing subsidies or supportive housing. Drug use was associated with poorer housing statuses such as living on the street or in a shelter, or temporarily doubling up with friends, acquaintances or sex partners. Living with friends, acquaintances or sex partners was associated with greater sexual risk than those living on the street or in other stable housing situations.</p> <p>Conclusions</p> <p>Results suggest that providing low-income and supportive housing may be an effective structural HIV prevention intervention, but that the availability and accessibility of these programs must be increased.</p

Alcohol consumption and lifetime change in cognitive ability:a gene × environment interaction study

Studies of the effect of alcohol consumption on cognitive ability are often confounded. One approach to avoid confounding is the Mendelian randomization design. Here, we used such a design to test the hypothesis that a genetic score for alcohol processing capacity moderates the association between alcohol consumption and lifetime change in cognitive ability. Members of the Lothian Birth Cohort 1936 completed the same test of intelligence at age 11 and 70 years. They were assessed for recent alcohol consumption in later life and genotyped for a set of four single-nucleotide polymorphisms in three alcohol dehydrogenase genes. These variants were unrelated to late-life cognition or to socioeconomic status. We found a significant gene × alcohol consumption interaction on lifetime cognitive change (p = 0.007). Individuals with higher genetic ability to process alcohol showed relative improvements in cognitive ability with more consumption, whereas those with low processing capacity showed a negative relationship between cognitive change and alcohol consumption with more consumption. The effect of alcohol consumption on cognitive change may thus depend on genetic differences in the ability to metabolize alcohol

The use of caspase inhibitors in pulsed-field gel electrophoresis may improve the estimation of radiation-induced DNA repair and apoptosis

<p>Abstract</p> <p>Background</p> <p>Radiation-induced DNA double-strand break (DSB) repair can be tested by using pulsed-field gel electrophoresis (PFGE) in agarose-encapsulated cells. However, previous studies have reported that this assay is impaired by the spontaneous DNA breakage in this medium. We investigated the mechanisms of this fragmentation with the principal aim of eliminating it in order to improve the estimation of radiation-induced DNA repair.</p> <p>Methods</p> <p>Samples from cancer cell cultures or xenografted tumours were encapsulated in agarose plugs. The cell plugs were then irradiated, incubated to allow them to repair, and evaluated by PFGE, caspase-3, and histone H2AX activation (γH2AX). In addition, apoptosis inhibition was evaluated through chemical caspase inhibitors.</p> <p>Results</p> <p>We confirmed that spontaneous DNA fragmentation was associated with the process of encapsulation, regardless of whether cells were irradiated or not. This DNA fragmentation was also correlated to apoptosis activation in a fraction of the cells encapsulated in agarose, while non-apoptotic cell fraction could rejoin DNA fragments as was measured by γH2AX decrease and PFGE data. We were able to eliminate interference of apoptosis by applying specific caspase inhibitors, and improve the estimation of DNA repair, and apoptosis itself.</p> <p>Conclusions</p> <p>The estimation of radiation-induced DNA repair by PFGE may be improved by the use of apoptosis inhibitors. The ability to simultaneously determine DNA repair and apoptosis, which are involved in cell fate, provides new insights for using the PFGE methodology as functional assay.</p

Geographic Coincidence of Increased Malaria Transmission Hazard and Vulnerability Occurring at the Periphery of two Tanzanian Villages.

The goal of malaria elimination necessitates an improved understanding of any fine-scale geographic variations in transmission risk so that complementary vector control tools can be integrated into current vector control programmes as supplementary measures that are spatially targeted to maximize impact upon residual transmission. This study examines the distribution of host-seeking malaria vectors at households within two villages in rural Tanzania. Host-seeking mosquitoes were sampled from 72 randomly selected households in two villages on a monthly basis throughout 2008 using CDC light-traps placed beside occupied nets. Spatial autocorrelation in the dataset was examined using the Moran's I statistic and the location of any clusters was identified using the Getis-Ord Gi* statistic. Statistical associations between the household characteristics and clusters of mosquitoes were assessed using a generalized linear model for each species. For both Anopheles gambiae sensu lato and Anopheles funestus, the density of host-seeking females was spatially autocorrelated, or clustered. For both species, houses with low densities were clustered in the semi-urban village centre while houses with high densities were clustered in the periphery of the villages. Clusters of houses with low or high densities of An. gambiae s.l. were influenced by the number of residents in nearby houses. The occurrence of high-density clusters of An. gambiae s.l. was associated with lower elevations while An. funestus was also associated with higher elevations. Distance from the village centre was also positively correlated with the number of household occupants and having houses constructed with open eaves. The results of the current study highlight that complementary vector control tools could be most effectively targeted to the periphery of villages where the households potentially have a higher hazard (mosquito densities) and vulnerability (open eaves and larger households) to malaria infection

Evidence for an Epigenetic Mechanism by which Hsp90 Acts as a Capacitor for Morphological Evolution

Morphological alterations have been shown to occur in Drosophila melanogaster when function of Hsp90 (heat shock 0-kDa protein 1α, encoded by Hsp83) is compromised during development1. Genetic selection maintains the altered phenotypes in subsequent generations1. Recent experiments have shown, however, that phenotypic variation still occurs in nearly isogenic recombinant inbred strains of Arabidopsis thaliana2. Using a sensitized isogenic D. melanogaster strain, iso-KrIf-1, we confirm this finding and present evidence supporting an epigenetic mechanism for Hsp90’s capacitor function, whereby reduced activity of Hsp90 induces a heritably altered chromatin state. The altered chromatin state is evidenced by ectopic expression of the morphogen wingless in eye imaginal discs and a corresponding abnormal eye phenotype, both of which are epigenetically heritable in subsequent generations, even when function of Hsp90 is restored. Mutations in nine different genes of the trithorax group that encode chromatin-remodeling proteins also induce the abnormal phenotype. These findings suggest that Hsp90 acts as a capacitor for morphological evolution through epigenetic and genetic mechanisms