CD36 Mediates the Innate Host Response to β-Amyloid

Accumulation of inflammatory microglia in Alzheimer's senile plaques is a hallmark of the innate response to β-amyloid fibrils and can initiate and propagate neurodegeneration characteristic of Alzheimer's disease (AD). The molecular mechanism whereby fibrillar β-amyloid activates the inflammatory response has not been elucidated. CD36, a class B scavenger receptor, is expressed on microglia in normal and AD brains and binds to β-amyloid fibrils in vitro. We report here that microglia and macrophages, isolated from CD36 null mice, had marked reductions in fibrillar β-amyloid–induced secretion of cytokines, chemokines, and reactive oxygen species. Intraperitoneal and stereotaxic intracerebral injection of fibrillar β-amyloid in CD36 null mice induced significantly less macrophage and microglial recruitment into the peritoneum and brain, respectively, than in wild-type mice. Our data reveal that CD36, a major pattern recognition receptor, mediates microglial and macrophage response to β-amyloid, and imply that CD36 plays a key role in the proinflammatory events associated with AD

Experimental assessment of crack prediction methods in international design codes for edge restrained walls

Through cracking resulting from external restraint of early-age thermal and long-term shrinkage strain is a significant issue in the construction industry as it causes leakage in water retaining and resisting structures. Concerningly, a recent field study found restraint induced crack widths to frequently exceed crack widths calculated in accordance with UK design practice (BS EN 1992-3 and CIRIA C766). Due to a lack of pertinent data, the reasons for this are uncertain. This paper compares measured and predicted crack widths in a series of 12 full-scale edge restrained walls constructed in the laboratory. The tests examine the influence on cracking of key parameters including concrete mix design, wall reinforcement ratio, wall aspect ratio and relative wall to base cross-sectional area. The measured and calculated crack widths are compared at first cracking and at the end of monitoring. Two types of behaviour were noted in the tests, dependent on when the first cracks formed. Cracking either occurred at early age, within 24 h of stripping the formwork, or later due to restraint of combined early age thermal contraction and shrinkage. The final crack widths were greatest, by a considerable margin, in walls where cracks formed at early age, despite the initial cracks being very narrow. BS EN 1992-3 gives the best estimates of crack width in the two walls that cracked at early age. Crack widths in these walls were significantly underestimated by C766. In the other 10 walls, which cracked later, C766 tends to give the best estimate of crack width

The Helium-Rich Cataclysmic Variable ES Ceti

We report photometry of the helium-rich cataclysmic variable ES Ceti during 2001-2004. The star is roughly stable at V ~ 17.0 and has a light curve dominated by a single period of 620 s, which remains measurably constant over the 3 year baseline. The weight of evidence suggests that this is the true orbital period of the underlying binary, not a "superhump" as initially assumed. We report GALEX ultraviolet magnitudes, which establish a very blue flux distribution (F_nu ~ nu^1.3), and therefore a large bolometric correction. Other evidence (the very strong He II 4686 emission, and a ROSAT detection in soft X-rays) also indicates a strong EUV source, and comparison to helium-atmosphere models suggests a temperature of 130+-10 kK. For a distance of 350 pc, we estimate a luminosity of (0.8-1.7)x10^34 erg/s, yielding a mass accretion rate of (2-4)x10^-9 M_sol/yr onto an assumed 0.7 M_sol white dwarf. This appears to be about as expected for white dwarfs orbiting each other in a 10 minute binary, assuming that mass transfer is powered by gravitational radiation losses. We estimate mean accretion rates for other helium-rich cataclysmic variables, and find that they also follow the expected M-dot ~ P_o^-5 relation. There is some evidence (the lack of superhumps, and the small apparent size of the luminous region) that the mass transfer stream in ES Cet directly strikes the white dwarf, rather than circularizing to form an accretion disk.Comment: PDF, 26 pages, 3 tables, 9 figures; accepted, in press, to appear February 2005, PASP; more info at http://cba.phys.columbia.edu

Arbitrarily Degenerate Helium White Dwarfs as Donors in AM CVn Binaries

We apply the Deloye & Bildsten (2003) isentropic models for donors in ultracompact low-mass X-ray binaries to the AM CVn population of ultracompact, interacting binaries. The mass-radius relations of these systems' donors in the mass range of interest (M_2<0.1 \msun) are not single-valued, but parameterized by the donor's specific entropy. This produces a range in the relationships between system observables, such as orbital period, \Porb, and mass transfer rate, \Mdot. For a reasonable range in donor specific entropy, \Mdot can range over several orders of magnitude at fixed \Porb. We determine the unique relation between \Mdot and $M_2$ in the AM CVn systems with known donor to accretor mass ratios, $q=M_2/M_1$. We use structural arguments, as well as each system's photometric behavior, to place limits on \Mdot and $M_2$ in each. Most systems allow a factor of about 3 variation in \Mdot, although V803 Cen, if the current estimates of its $q$ are accurate, is an exception and must have M_2 \approx 0.02 \msun and \Mdot \approx 10^{-10} \msun yr$^{-1}$. Our donor models also constrain each donor's core temperature, $T_c$, range and correlate $T_c$ with $M_2$. We examine how variations in donor specific entropy across the white dwarf family \citep{nele01a} of AM CVn systems affects this population's current galactic distribution. Allowing for donors that are not fully degenerate produces a shift in systems towards longer \Porb and higher \Mdot increasing the parameter space in which these systems can be found. This shift increases the fraction of systems whose \Porb is long enough that their gravity wave (GW) signal is obscured by the background of detached double white dwarf binaries that dominate the GW spectrum below a frequency $\approx 2$ mHz.Comment: 13 pages, 10 figures, uses emulateapj.cls. Accepted to Astrophysical Journa

Polymorphisms within the COL5A1 gene and regulators of the extracellular matrix modify the risk of Achilles tendon pathology in a British case control study

Several genetic loci have been associated with risk of Achilles tendon pathology (ATP) within South African and Australian populations. The aim of this study was, therefore, to evaluate eight previously implicated genetic variants in an independent British population. A total of 130 asymptomatic controls (CON) and 112 participants clinically diagnosed with ATP comprising 87 individuals with chronic Achilles tendinopathy (TEN) and 25 with Achilles tendon ruptures (RUP) were included. All participants were genotyped for variants within the COL5A1, MIR608, IL-1β, IL-6 and CASP8 genes. Primary findings implicated COL5A1 and CASP8. Three inferred allele combinations constructed from COL5A1 rs12722, rs3196378 and rs71746744 were identified as risk modifiers. The T–C–D combination was associated with increased risk of ATP (P = 0.023) and RUP (P < 0.001), the C–A–I combination was associated with increased risk of ATP (P = 0.011), TEN (P = 0.011) and RUP (P = 0.011) and the C–C–D combination was associated with decreased risk of ATP (P = 0.011) and RUP (P = 0.004). The CASP8 rs3834129 DD genotype was associated with decreased risk of TEN (P = 0.020, odds ratio: 0.45, 95% confidence interval: 0.22–0.90) and the CASP8 I–G (rs3834129–rs1045485) inferred allele combination was associated with increased risk of TEN (P = 0.031). This study further highlights the importance of polymorphisms within COL5A1 and CASP8 in the aetiology of ATP

Lay perceptions of predictive testing for diabetes based on DNA test results versus family history assessment: a focus group study

<p>Abstract</p> <p>Background</p> <p>This study assessed lay perceptions of issues related to predictive genetic testing for multifactorial diseases. These perceived issues may differ from the "classic" issues, e.g. autonomy, discrimination, and psychological harm that are considered important in predictive testing for monogenic disorders. In this study, type 2 diabetes was used as an example, and perceptions with regard to predictive testing based on DNA test results and family history assessment were compared.</p> <p>Methods</p> <p>Eight focus group interviews were held with 45 individuals aged 35-70 years with (n = 3) and without (n = 1) a family history of diabetes, mixed groups of these two (n = 2), and diabetes patients (n = 2). All interviews were transcribed and analysed using Atlas-ti.</p> <p>Results</p> <p>Most participants believed in the ability of a predictive test to identify people at risk for diabetes and to motivate preventive behaviour. Different reasons underlying motivation were considered when comparing DNA test results and a family history risk assessment. A perceived drawback of DNA testing was that diabetes was considered not severe enough for this type of risk assessment. In addition, diabetes family history assessment was not considered useful by some participants, since there are also other risk factors involved, not everyone has a diabetes family history or knows their family history, and it might have a negative influence on family relations. Respect for autonomy of individuals was emphasized more with regard to DNA testing than family history assessment. Other issues such as psychological harm, discrimination, and privacy were only briefly mentioned for both tests.</p> <p>Conclusion</p> <p>The results suggest that most participants believe a predictive genetic test could be used in the prevention of multifactorial disorders, such as diabetes, but indicate points to consider before both these tests are applied. These considerations differ with regard to the method of assessment (DNA test or obtaining family history) and also differ from monogenic disorders.</p

I-HAZE: a dehazing benchmark with real hazy and haze-free indoor images

Image dehazing has become an important computational imaging topic in the recent years. However, due to the lack of ground truth images, the comparison of dehazing methods is not straightforward, nor objective. To overcome this issue we introduce a new dataset -named I-HAZE- that contains 35 image pairs of hazy and corresponding haze-free (ground-truth) indoor images. Different from most of the existing dehazing databases, hazy images have been generated using real haze produced by a professional haze machine. For easy color calibration and improved assessment of dehazing algorithms, each scene include a MacBeth color checker. Moreover, since the images are captured in a controlled environment, both haze-free and hazy images are captured under the same illumination conditions. This represents an important advantage of the I-HAZE dataset that allows us to objectively compare the existing image dehazing techniques using traditional image quality metrics such as PSNR and SSIM

A mechanism for the extension and unfolding of parallel telomeric G-quadruplexes by human telomerase at single-molecule resolution

30 pags., 10 figs., 1 tab.Telomeric G-quadruplexes (G4) were long believed to form a protective structure at telomeres, preventing their extension by the ribonucleoprotein telomerase. Contrary to this belief, we have previously demonstrated that parallel-stranded conformations of telomeric G4 can be extended by human and ciliate telomerase. However, a mechanistic understanding of the interaction of telomerase with structured DNA remained elusive. Here, we use single-molecule fluorescence resonance energy transfer (smFRET) microscopy and bulk-phase enzymology to propose a mechanism for the resolution and extension of parallel G4 by telomerase. Binding is initiated by the RNA template of telomerase interacting with the G-quadruplex; nucleotide addition then proceeds to the end of the RNA template. It is only through the large conformational change of translocation following synthesis that the G-quadruplex structure is completely unfolded to a linear product. Surprisingly, parallel G4 stabilization with either small molecule ligands or by chemical modification does not always inhibit G4 unfolding and extension by telomerase. These data reveal that telomerase is a parallel G-quadruplex resolvase.Cancer Council NSW RG 11-07 Tracy M Bryan, Cancer Institute NSW Aaron Lavel Moye, Australian Research Council FL140100027 Antoine M van Oijen, Ernest and Piroska Major Foundation Scott B Cohen, Natural Sciences and Engineering Research Council of Canada, Masad J Damha Centre of Excellence for Innovation in Chemistry PERCH-CIC Siritron Samosorn Research Unit of Natural Products and Organic Synthesis for Drug Discovery NPOS 405/2560 Siritron Samosorn Cancer Council NSW RG 16-10 Tracy M Brya

Dietary soy and meat proteins induce distinct physiological and gene expression changes in rats

This study reports on a comprehensive comparison of the effects of soy and meat proteins given at the recommended level on physiological markers of metabolic syndrome and the hepatic transcriptome. Male rats were fed semi-synthetic diets for 1 wk that differed only regarding protein source, with casein serving as reference. Body weight gain and adipose tissue mass were significantly reduced by soy but not meat proteins. The insulin resistance index was improved by soy, and to a lesser extent by meat proteins. Liver triacylglycerol contents were reduced by both protein sources, which coincided with increased plasma triacylglycerol concentrations. Both soy and meat proteins changed plasma amino acid patterns. The expression of 1571 and 1369 genes were altered by soy and meat proteins respectively. Functional classification revealed that lipid, energy and amino acid metabolic pathways, as well as insulin signaling pathways were regulated differently by soy and meat proteins. Several transcriptional regulators, including NFE2L2, ATF4, Srebf1 and Rictor were identified as potential key upstream regulators. These results suggest that soy and meat proteins induce distinct physiological and gene expression responses in rats and provide novel evidence and suggestions for the health effects of different protein sources in human diets