The murine natural cytotoxic receptor NKp46/NCR1 controls TRAIL protein expression in NK cells and ILC1

TRAIL is an apoptosis-inducing ligand constitutively expressed on liver resident type 1 innate lymphoid cells (ILC1) and a subset of Natural Killer (NK) cells where it contributes to NK cell anti-tumor, anti-viral and immunoregulatory functions. Yet the intrinsic pathways involved in TRAIL expression in ILC remain unidentified. Here we demonstrate that the murine natural cytotoxic receptor mNKp46/NCR1, expressed on ILC1 and NK cells, controls TRAIL protein expression. Using NKp46-deficient mice, we show that liver ILC1 lack constitutive expression of TRAIL protein and that NK cells activated in vitro and in vivo fail to upregulate cell-surface TRAIL in the absence of NKp46. We show that NKp46 regulates TRAIL expression in a dose-dependent manner and that the reintroduction of NKp46 in mature NK cells deficient for NKp46 is sufficient to restore TRAIL surface expression. These studies uncover a link between NKp46 and TRAIL expression in ILC with potential implications in pathologies involving NKp46-expressing cells

Lead Exposure Is Associated with Decreased Serum Paraoxonase 1 (PON1) Activity and Genotypes

Lead exposure causes cardiac and vascular damage in experimental animals. However, there is considerable debate regarding the causal relationship between lead exposure and cardiovascular dysfunction in humans. Paraoxonase 1 (PON1), a high-density lipoprotein-associated antioxidant enzyme, is capable of hydrolyzing oxidized lipids and thus protects against atherosclerosis. Previous studies have shown that lead and several other metal ions are able to inhibit PON1 activity in vitro. To investigate whether lead exposure has influence on serum PON1 activity, we conducted a cross-sectional study of workers from a lead battery manufactory and lead recycling plant. Blood samples were analyzed for whole-blood lead levels, serum PON1 activity, and three common PON1 polymorphisms (Q192R, L55M, −108C/T). The mean blood lead level (± SD) of this cohort was 27.1 ± 15 μg/dL. Multiple linear regression analysis showed that blood lead levels were significantly associated with decreased serum PON1 activity (p < 0.001) in lead workers. This negative correlation was more evident for workers who carry the R192 allele, which has been suggested to be a risk factor for coronary heart disease. Taken together, our results suggest that the decrease in serum PON1 activity due to lead exposure may render individuals more susceptible to atherosclerosis, particularly subjects who are homozygous for the R192 allele

Bone mineral density enhances use of clinical risk factors in predicting ten-year risk of osteoporotic fractures in Chinese men: the Hong Kong Osteoporosis Study

This prospective study aimed to determine the risk factors and the 10-year probability of osteoporotic fracture in Southern Chinese men. The findings show substantial population differences in fracture incidence and risk prediction compared to the FRAX TM model, and the addition of BMD information to clinical risk factor assessment improved fracture risk prediction in Chinese men. Introduction: Clinical risk factors with or without bone mineral density (BMD) measurements are increasingly recognized as reliable predictors of fracture risk. Prospective data on fracture incidence in Asian men remain sparse. This prospective study aimed to determine the risk factors and the 10-year absolute fracture risk in Southern Chinese men. Methods: This is a part of the Hong Kong Osteoporosis Study. One thousand eight hundred ten (1,810) community-dwelling, treatment-naive men aged 50 years or above were evaluated. Baseline demographic characteristics, clinical risk factors and BMD were recorded. Ten-year risk of osteoporotic fracture was calculated using Cox proportional hazards models. Results: The mean age of subjects was 68.0 ± 10.3 years. After a mean follow-up period of 3.5±2.9 years (range 1 to 14 years), 37 incident low-trauma fractures were recorded. The incidence for all osteoporotic fractures and hip fractures was 635/100,000 and 123/100,000 person-years, respectively. The most significant predictors of osteoporotic fracture were history of fall (RR 14.5), femoral neck BMD T-score < -2.5 (RR 13.8) and history of fracture (RR 4.4). Each SD reduction in BMD was associated with a 1.8 to 2.6-fold increase in fracture risk. Subjects with seven clinical risk factors and BMD T-score of -1 had an absolute 10-year risk of osteoporotic fracture of 8.9%, but this increased to 22.7% if they also had a femoral neck BMD T-score of -2.5. Conclusions: These findings show substantial population differences in fracture incidence and risk prediction. The addition of BMD information to clinical risk factor assessment improved fracture risk prediction in Chinese men. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Apparent Shear Sensitivity of Molecular Rotors in Various Solvents

Fluorescent environment-sensitive dyes often change their spectral properties concomitantly with multiple solvent properties, such as polarity, protonation, hydrogen bond formation, or viscosity. Careful consideration of the response is needed when a fluorescent dye is used to report a single property. Recently, we observed an increase of emission intensity of viscosity-sensitive molecular rotors in fluids subject to flow and speculated that either polar-polar interaction or hydrogen bond formation play a role in the apparent flow sensitivity. In this study, we show experimental evidence that photoisomerization to an isomer with a lower quantum yield, first proposed by Rumble et al. (J Phys Chem A 116(44):10786-10792, 2012), plays a key role in the observed phenomenon. We subjected four molecular rotors with different electron acceptor motifs to fluid flow in solvents of different polarity and ability to form hydrogen bonds. We also measured the isomerization dynamics in a custom fluorophotometer with extremely low light exposure. Our results indicate that the photoisomerization rate depends both on the solvent and on the electron acceptor group, as does the recovery of the original isomer in the dark. In most solvents, recovery of the dark isomer is much more rapid than originally reported, and a state of quasi-equilibrium between both isomers is possible. Moreover, the sensitivity (i.e., relative intensity increase at the same flow rate) is also solvent-dependent. The intensity increase can be detected at very low velocities (as low as 0.06 mm/s). Characteristic for fluorescent dyes is the high spatial resolution, and no flow measurement device with comparable sensitivity and spatial resolution exists, although the nature of the solvent needs to be taken into account for quantitative flow measurement

Imaging of Flow Patterns with Fluorescent Molecular Rotors

Molecular rotors are a group of fluorescent molecules that form twisted intramolecular charge transfer states (TICT) upon photoexcitation. Some classes of molecular rotors, among them those that are built on the benzylidene malononitrile motif, return to the ground state either by nonradiative intramolecular rotation or by fluorescence emission. In low-viscosity solvents, intramolecular rotation dominates, and the fluorescence quantum yield is low. Higher solvent viscosities reduce the intramolecular rotation rate, thus increasing the quantum yield. We recently described a different mechanism whereby the fluorescence quantum yield of the molecular rotor also depends on the shear stress of the solvent. In this study, we examined a possible application for shear-sensitive molecular rotors for imaging flow patterns in fluidic chambers. Flow chambers with different geometries were constructed from polycarbonate or acrylic. Solutions of molecular rotors in ethylene glycol were injected into the chamber under controlled flow rates. LED-induced fluorescence (LIF) images of the flow chambers were taken with a digital camera, and the intensity difference between flow and no-flow images was visualized and compared to computed fluid dynamics (CFD) simulations. Intensity differences were detectable with average flow rates as low as 0.1 mm/s, and an exponential association between flow rate and intensity increase was found. Furthermore, a good qualitative match to computed fluid dynamics simulations was seen. On the other hand, prolonged exposure to light reduced the emission intensity. With its high sensitivity and high spatial and temporal resolution, imaging of flow patterns with molecular rotors may become a useful tool in microfluidics, flow measurement, and control

Morphology, ultrastructure and molecular characterisation of Spiroxys japonica Morishita, 1926 (Spirurida: Gnathostomatidae) from Pelophylax nigromaculatus (Hallowell) (Amphibia: Ranidae)

Gnathostomatid nematodes identified morphologically as Spiroxys japonica Morishita, 1926 were collected from the dark-spotted frog Pelophylax nigromaculatus (Hallowell) (Amphibia: Ranidae) in China. Light and scanning electron microscopy were used to study the morphology of this species in detail. Previously unreported morphological features are revealed and others corrected. In addition, adult nematodes of S. japonica collected from P. nigromaculatus and Spiroxys hanzaki Hasegawa, Miyata & Doi, 1998 collected from Andrias japonicus (Temminck) (Caudata: Cryptobranchidae) in China and Japan, respectively, and the third-stage larva of S. japonica collected from Lithobates catesbeianus (Shaw) (Anura: Ranidae) in Japan, were characterised using molecular methods by sequencing and analysing ribosomal [large ribosomal DNA (18S) and internal transcribed space] and mitochondrial [cytochrome c oxidase subunit 1] target regions, respectively. The new morphological and genetic data contributes to a more accurate diagnosis of this hitherto little known nematode genus

Glutathione and Adaptive Immune Responses against Mycobacterium tuberculosis Infection in Healthy and HIV Infected Individuals

Glutathione (GSH), a tripeptide antioxidant, is essential for cellular homeostasis and plays a vital role in diverse cellular functions. Individuals who are infected with Human immuno deficiency virus (HIV) are known to be susceptible to Mycobacterium tuberculosis (M. tb) infection. We report that by enhancing GSH levels, T-cells are able to inhibit the growth of M. tb inside macrophages. In addition, those GSH-replenished T cell cultures produced increased levels of Interleukin-2 (IL-2), Interleukin-12 (IL-12), and Interferon-gamma (IFN-γ), cytokines, which are known to be crucial for the control of intracellular pathogens. Our study reveals that T lymphocytes that are derived from HIV infected individuals are deficient in GSH, and that this deficiency correlates with decreased levels of Th1 cytokines and enhanced growth of M. tb inside human macrophages

Clinical Value of Prognostic Instruments to Identify Patients with an Increased Risk for Osteoporotic Fractures: Systematic Review

There is a plethora of evidence available studying the association of risk profiles and the development of osteoporotic fractures. The small number of out-of-sample validations, the large variety of study characteristics, outcomes and follow-up periods impedes from deriving robust summaries and from conclusions regarding the clinical performance of many tools. First and foremost, future activity in this field should aim at reaching a consensus among clinical experts in respect to the existing instruments. Then we call for careful validations and expedient adaptations for local circumstances of the most promising candidates

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Relative gut lengths of coral reef butterflyfishes (Pisces: Chaetodontidae)

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Coral Reefs 30 (2011): 1005-1010, doi:10.1007/s00338-011-0791-x.Variation in gut length of closely related animals is known to generally be a good predictor of dietary habits. We examined gut length in 28 species of butterflyfishes (Chaetodontidae), which encompass a wide range of dietary types (planktivores, omnivores, corallivores). We found general dietary patterns to be a good predictor of relative gut length, although we found high variation among groups and covariance with body size. The longest gut lengths are found in species that exclusively feed on the living tissue of corals, while the shortest gut length is found in a planktivorous species. Although we tried to control for phylogeny, corallivory has arisen multiple times in this family, confounding our analyses. The butterflyfishes, a speciose family with a wide range of dietary habits, may nonetheless provide an ideal system for future work studying gut physiology associated with specialisation and foraging behaviours.This project was funded in part by a National Science Foundation (USA) Graduate Research Fellowship to MLB.2012-06-1