253 research outputs found

    Placental Pathology in Relation to Uterine Artery Doppler Findings in Pregnancies with Severe Intrauterine Growth Restriction and Abnormal Umbilical Artery Doppler Changes

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    OBJECTIVES: Current guidelines for diagnosis and management of early-onset intrauterine growth restriction (IUGR) rely on umbilical artery Doppler (UAD), without including uterine artery Doppler (UtAD). We hypothesized that IUGR cases with abnormal UAD but normal UtAD has a different spectrum of placental pathology compared with those with abnormal UtAD. STUDY DESIGN: Retrospective review of pregnancies with sonographic evidence of IUGR and abnormal UAD prior to delivery. Cases with ≥ 1 UtAD record(s) after 18(+0) weeks' gestation and placental pathology were included. Cases were stratified according to initial UtAD pulsatility index (PI) values (n = 196): normal (n = 19; PI < 95th centile for gestational age/no notching), intermediate (n = 69; PI ≥ 95th centile/no/unilateral notching) and abnormal (n = 108; PI ≥ 95th centile/bilateral notching). Pregnancy outcomes and placental pathology were compared between groups. RESULTS: Women in the normal group delivered later than those in the abnormal group (30.1 ± 3.5 vs. 28.0 ± 3.5 weeks; mean ± standard deviation; p = 0.03). Their placentas exhibited higher rates of chronic intervillositis (15.8 vs. 0.9%; p = 0.01), chorangiosis (15.8 vs. 0.9%; p < 0.0001), and massive perivillous fibrin deposition (21.1 vs. 7.4%; p = 0.05), but had lower rates of uteroplacental vascular insufficiency (26.3 vs. 79.6%; p < 0.0001). CONCLUSION: Approximately 10% of pregnancies with early-onset IUGR and abnormal UAD exhibited normal UtAD waveforms. They delivered later, and their placentas exhibited unusual placental pathologies

    Initial fixation placement in face images is driven by top-down guidance

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    The eyes are often inspected first and for longer period during face exploration. To examine whether this saliency of the eye region at the early stage of face inspection is attributed to its local structure properties or to the knowledge of its essence in facial communication, in this study we investigated the pattern of eye movements produced by rhesus monkeys (Macaca mulatta) as they free viewed images of monkey faces. Eye positions were recorded accurately using implanted eye coils, while images of original faces, faces with scrambled eyes, and scrambled faces except for the eyes were presented on a computer screen. The eye region in the scrambled faces attracted the same proportion of viewing time and fixations as it did in the original faces, even the scrambled eyes attracted substantial proportion of viewing time and fixations. Furthermore, the monkeys often made the first saccade towards to the location of the eyes regardless of image content. Our results suggest that the initial fixation placement in faces is driven predominantly by ‘top-down’ or internal factors, such as the prior knowledge of the location of “eyes” within the context of a face

    Evaluation of alternative mosquito sampling methods for malaria vectors in Lowland South - East Zambia.

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    Sampling malaria vectors and measuring their biting density is of paramount importance for entomological surveys of malaria transmission. Human landing catch (HLC) has been traditionally regarded as a gold standard method for surveying human exposure to mosquito bites. However, due to the risk of human participant exposure to mosquito-borne parasites and viruses, a variety of alternative, exposure-free trapping methods were compared in lowland, south-east Zambia. Centres for Disease Control and Prevention miniature light trap (CDC-LT), Ifakara Tent Trap model C (ITT-C), resting boxes (RB) and window exit traps (WET) were all compared with HLC using a 3 × 3 Latin Squares design replicated in 4 blocks of 3 houses with long lasting insecticidal nets, half of which were also sprayed with a residual deltamethrin formulation, which was repeated for 10 rounds of 3 nights of rotation each during both the dry and wet seasons. The mean catches of HLC indoor, HLC outdoor, CDC-LT, ITT-C, WET, RB indoor and RB outdoor, were 1.687, 1.004, 3.267, 0.088, 0.004, 0.000 and 0.008 for Anopheles quadriannulatus Theobald respectively, and 7.287, 6.784, 10.958, 5.875, 0.296, 0.158 and 0.458, for An. funestus Giles, respectively. Indoor CDC-LT was more efficient in sampling An. quadriannulatus and An. funestus than HLC indoor (Relative rate [95% Confidence Interval] = 1.873 [1.653, 2.122] and 1.532 [1.441, 1.628], respectively, P < 0.001 for both). ITT-C was the only other alternative which had comparable sensitivity (RR = 0.821 [0.765, 0.881], P < 0.001), relative to HLC indoor other than CDC-LT for sampling An. funestus. While the two most sensitive exposure-free techniques primarily capture host-seeking mosquitoes, both have substantial disadvantages for routine community-based surveillance applications: the CDC-LT requires regular recharging of batteries while the bulkiness of ITT-C makes it difficult to move between sampling locations. RB placed indoors or outdoors and WET had consistently poor sensitivity so it may be useful to evaluate additional alternative methods, such as pyrethrum spray catches and back packer aspirators, for catching resting mosquitoes

    A critical base pair in k-turns that confers folding characteristics and correlates with biological function

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    Kink turns (k-turns) are widespread elements in RNA that mediate tertiary contacts by kinking the helical axis. We have found that the ability of k-turns to undergo ion-induced folding is conferred by a single base pair that follows the conserved A·G pairs, that is, the 3b·3n position. A Watson–Crick pair leads to an inability to fold in metal ions alone, while 3n=G or 3b=C (but not both) permits folding. Crystallographic study reveals two hydrated metal ions coordinated to O6 of G3n and G2n of Kt-7. Removal of either atom impairs Mg(2+)-induced folding in solution. While SAM-I riboswitches have 3b·3n sequences that would predispose them to ion-induced folding, U4 snRNA are strongly biased to an inability to such folding. Thus riboswitch sequences allow folding to occur independently of protein binding, while U4 should remain unfolded until bound by protein. The empirical rules deduced for k-turn folding have strong predictive value

    The Epstein-Barr Virus G-Protein-Coupled Receptor Contributes to Immune Evasion by Targeting MHC Class I Molecules for Degradation

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    Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. Recent evidence indicates that an important component of the persistence strategy involves active interference with the MHC class I antigen processing pathway during the lytic replication cycle. We have now identified a novel role for the lytic cycle gene, BILF1, which encodes a glycoprotein with the properties of a constitutive signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC class I at the cell surface and inhibited CD8+ T cell recognition of endogenous target antigens. The underlying mechanism involves physical association of BILF1 with MHC class I molecules, an increased turnover from the cell surface, and enhanced degradation via lysosomal proteases. The BILF1 protein of the closely related CeHV15 c1-herpesvirus of the Rhesus Old World primate (80% amino acid sequence identity) downregulated surface MHC class I similarly to EBV BILF1. Amongst the human herpesviruses, the GPCR encoded by the ORF74 of the KSHV c2-herpesvirus is most closely related to EBV BILF1 (15% amino acid sequence identity) but did not affect levels of surface MHC class I. An engineered mutant of BILF1 that was unable to activate G protein signaling pathways retained the ability to downregulate MHC class I, indicating that the immune-modulating and GPCR-signaling properties are two distinct functions of BILF1. These findings extend our understanding of the normal biology of an important human pathogen. The discovery of a third EBV lytic cycle gene that cooperates to interfere with MHC class I antigen processing underscores the importance of the need for EBV to be able to evade CD8+ T cell responses during the lytic replication cycle, at a time when such a large number of potential viral targets are expressed

    Post-depositional fracturing and subsidence of pumice flow deposits: Lascar Volcano, Chile

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    Unconsolidated pyroclastic flow deposits of the 1993 eruption of Lascar Volcano, Chile, have, with time, become increasingly dissected by a network of deeply penetrating fractures. The fracture network comprises orthogonal sets of decimeter-wide linear voids that form a pseudo-polygonal grid visible on the deposit surface. In this work, we combine shallow surface geophysical imaging tools with remote sensing observations and direct field measurements of the deposit to investigate these fractures and their underlying causal mechanisms. Based on ground penetrating radar images, the fractures are observed to have propagated to depths of up to 10 m. In addition, orbiting radar interferometry shows that deposit subsidence of up to 1 cm/year occurred between 1993 and 1996 with continued subsidence occurring at a slower rate thereafter. In situ measurements show that 1 m below the surface, the 1993 deposits remain 5°C to 15°C hotter, 18 years after emplacement, than adjacent deposits. Based on the observed subsidence as well as estimated cooling rates, the fractures are inferred to be the combined result of deaeration, thermal contraction, and sedimentary compaction in the months to years following deposition. Significant environmental factors, including regional earthquakes in 1995 and 2007, accelerated settling at punctuated moments in time. The spatially variable fracture pattern relates to surface slope and lithofacies variations as well as substrate lithology. Similar fractures have been reported in other ignimbrites but are generally exposed only in cross section and are often attributed to formation by external forces. Here we suggest that such interpretations should be invoked with caution, and deformation including post-emplacement subsidence and fracturing of loosely packed ash-rich deposits in the months to years postemplacement is a process inherent in the settling of pyroclastic material

    Genome-Wide Association Studies in Atherosclerosis

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    Cardiovascular disease remains the major cause of worldwide morbidity and mortality. Its pathophysiology is complex and multifactorial. Because the phenotype of cardiovascular disease often shows a marked heritable pattern, it is likely that genetic factors play an important role. In recent years, large genome-wide association studies have been conducted to decipher the molecular mechanisms underlying this heritable and prevalent phenotype. The emphasis of this review is on the recently identified 17 susceptibility loci for coronary artery disease. Implications of their discovery for biology and clinical medicine are discussed. A description of the landscape of human genetics in the near future in the context of next-generation sequence technologies is provided at the conclusion of this review

    Physics, Astrophysics and Cosmology with Gravitational Waves

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    Gravitational wave detectors are already operating at interesting sensitivity levels, and they have an upgrade path that should result in secure detections by 2014. We review the physics of gravitational waves, how they interact with detectors (bars and interferometers), and how these detectors operate. We study the most likely sources of gravitational waves and review the data analysis methods that are used to extract their signals from detector noise. Then we consider the consequences of gravitational wave detections and observations for physics, astrophysics, and cosmology.Comment: 137 pages, 16 figures, Published version <http://www.livingreviews.org/lrr-2009-2
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