Impaired pain sensation in mice lacking prokineticin 2

Prokineticins (PKs), consisting of PK1 and PK2, are a pair of newly identified regulatory peptides. Two closely related G-protein coupled receptors, PKR1 and PKR2, mediate the signaling of PKs. PKs/PKRs participate in the regulation of diverse biological processes, ranging from development to adult physiology. A number of studies have indicated the involvement of PKs/PKRs in nociception. Here we show that PK2 is a sensitizer for nociception. Intraplantar injection of recombinant PK2 resulted in a strong and localized hyperalgesia with reduced thresholds to nociceptive stimuli. PK2 mobilizes calcium in dissociated dorsal root ganglion (DRG) neurons. Mice lacking the PK2 gene displayed strong reduction in nociception induced by thermal and chemical stimuli, including capsaicin. However, PK2 mutant mice showed no difference in inflammatory response to capsaicin. As the majority of PK2-responsive DRG neurons also expressed transient receptor potential vanilloid (TRPV1) and exhibited sensitivity to capsaicin, TRPV1 is likely a significant downstream molecule of PK2 signaling. Taken together, these results reveal that PK2 sensitize nociception without affecting inflammation

A single low-energy, iron-poor supernova as the source of metals in the star SMSS J 031300.36-670839.3

The element abundance ratios of four low-mass stars with extremely low metallicities indicate that the gas out of which the stars formed was enriched in each case by at most a few, and potentially only one low-energy, supernova. Such supernovae yield large quantities of light elements such as carbon but very little iron. The dominance of low-energy supernovae is surprising, because it has been expected that the first stars were extremely massive, and that they disintegrated in pair-instability explosions that would rapidly enrich galaxies in iron. What has remained unclear is the yield of iron from the first supernovae, because hitherto no star is unambiguously interpreted as encapsulating the yield of a single supernova. Here we report the optical spectrum of SMSS J031300.36- 670839.3, which shows no evidence of iron (with an upper limit of 10^-7.1 times solar abundance). Based on a comparison of its abundance pattern with those of models, we conclude that the star was seeded with material from a single supernova with an original mass of ~60 Mo (and that the supernova left behind a black hole). Taken together with the previously mentioned low-metallicity stars, we conclude that low-energy supernovae were common in the early Universe, and that such supernovae yield light element enrichment with insignificant iron. Reduced stellar feedback both chemically and mechanically from low-energy supernovae would have enabled first-generation stars to form over an extended period. We speculate that such stars may perhaps have had an important role in the epoch of cosmic reionization and the chemical evolution of early galaxies.Comment: 28 pages, 6 figures, Natur

Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters

Recent progress in studies of globular clusters has shown that they are not simple stellar populations, being rather made of multiple generations. Evidence stems both from photometry and spectroscopy. A new paradigm is then arising for the formation of massive star clusters, which includes several episodes of star formation. While this provides an explanation for several features of globular clusters, including the second parameter problem, it also opens new perspectives about the relation between globular clusters and the halo of our Galaxy, and by extension of all populations with a high specific frequency of globular clusters, such as, e.g., giant elliptical galaxies. We review progress in this area, focusing on the most recent studies. Several points remain to be properly understood, in particular those concerning the nature of the polluters producing the abundance pattern in the clusters and the typical timescale, the range of cluster masses where this phenomenon is active, and the relation between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review

A Case of Crohn's Disease with Improvement after Azathioprine-Induced Pancytopenia

The immunosuppressant azathioprine (AZA) is widely used in the treatment of inflammatory bowel disease (IBD) for both inducing and maintaining remission. However, the adverse effects of AZA can often necessitate a dose reduction or discontinuation. Bone marrow suppression is one of the most serious complications with AZA treatment. On the other hand, some reports have suggested that neutropenia during AZA therapy reduced the relapse rates of IBD patients, and there have been some cases where eradication of the sensitized leukocytes by leukapheresis or bone marrow transplantation improved the IBD, which may explain the relevant role of neutropenia in controlling disease activity. This report describes the case of a 22-year-old male patient who had Crohn's colitis and complicated perianal fistulas that required immunosuppression; he achieved endoscopically determined remission and showed accelerated mucosal healing as well as clinical remission following the AZA-induced pancytopenia

Necessary and sufficient conditions for path-independence of Girsanov transformation for infinite-dimensional stochastic evolution equations

Based on a recent result on linking stochastic differential equations on ℝ d to (finite-dimensional) Burger-KPZ type nonlinear parabolic partial differential equations, we utilize Galerkin type finite-dimensional approximations to characterize the path-independence of the density process of Girsanov transformation for the infinite-dimensional stochastic evolution equations. Our result provides a link of infinite-dimensional semi-linear stochastic differential equations to infinite-dimensional Burgers-KPZ type nonlinear parabolic partial differential equations. As an application, this characterization result is applied to stochastic heat equation in one space dimension over the unit interval

Estimating PM 2.5 concentrations in Xi'an City using a generalized additive model with multi-source monitoring data

© 2015 Song et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Particulate matter with an aerodynamic diameter <2.5 μm (PM2.5) represents a severe environmental problem and is of negative impact on human health. Xi'an City, with a population of 6.5 million, is among the highest concentrations of PM2.5 in China. In 2013, in total, there were 191 days in Xi'an City on which PM2.5 concentrations were greater than 100 μg/m3. Recently, a few studies have explored the potential causes of high PM2.5 concentration using remote sensing data such as the MODIS aerosol optical thickness (AOT) product. Linear regression is a commonly used method to find statistical relationships among PM2.5 concentrations and other pollutants, including CO, NO2, SO2, and O3, which can be indicative of emission sources. The relationships of these variables, however, are usually complicated and non-linear. Therefore, a generalized additive model (GAM) is used to estimate the statistical relationships between potential variables and PM2.5 concentrations. This model contains linear functions of SO2 and CO, univariate smoothing non-linear functions of NO2, O3, AOT and temperature, and bivariate smoothing non-linear functions of location and wind variables. The model can explain 69.50% of PM2.5 concentrations, with R2 = 0.691, which improves the result of a stepwise linear regression (R2 = 0.582) by 18.73%. The two most significant variables, CO concentration and AOT, represent 20.65% and 19.54% of the deviance, respectively, while the three other gas-phase concentrations, SO2, NO2, and O3 account for 10.88% of the total deviance. These results show that in Xi'an City, the traffic and other industrial emissions are the primary source of PM2.5. Temperature, location, and wind variables also non-linearly related with PM2.5

B Cell Activating Factor (BAFF) and T Cells Cooperate to Breach B Cell Tolerance in Lupus-Prone New Zealand Black (NZB) Mice

The presence of autoantibodies in New Zealand Black (NZB) mice suggests a B cell tolerance defect however the nature of this defect is unknown. To determine whether defects in B cell anergy contribute to the autoimmune phenotype in NZB mice, soluble hen egg lysozyme (sHEL) and anti-HEL Ig transgenes were bred onto the NZB background to generate double transgenic (dTg) mice. NZB dTg mice had elevated levels of anti-HEL antibodies, despite apparently normal B cell functional anergy in-vitro. NZB dTg B cells also demonstrated increased survival and abnormal entry into the follicular compartment following transfer into sHEL mice. Since this process is dependent on BAFF, BAFF serum and mRNA levels were assessed and were found to be significantly elevated in NZB dTg mice. Treatment of NZB sHEL recipient mice with TACI-Ig reduced NZB dTg B cell survival following adoptive transfer, confirming the role of BAFF in this process. Although NZB mice had modestly elevated BAFF, the enhanced NZB B cell survival response appeared to result from an altered response to BAFF. In contrast, T cell blockade had a minimal effect on B cell survival, but inhibited anti-HEL antibody production. The findings suggest that the modest BAFF elevations in NZB mice are sufficient to perturb B cell tolerance, particularly when acting in concert with B cell functional abnormalities and T cell help

A 160-kilobit molecular electronic memory patterned at 10^(11) bits per square centimetre

The primary metric for gauging progress in the various semiconductor integrated circuit technologies is the spacing, or pitch, between the most closely spaced wires within a dynamic random access memory (DRAM) circuit. Modern DRAM circuits have 140nm pitch wires and a memory cell size of 0.0408 μm^2. Improving integrated circuit technology will require that these dimensions decrease over time. However, at present a large fraction of the patterning and materials requirements that we expect to need for the construction of new integrated circuit technologies in 2013 have ‘no known solution’. Promising ingredients for advances in integrated circuit technology are nanowires, molecular electronics and defect-tolerant architectures, as demonstrated by reports of single devices and small circuits. Methods of extending these approaches to large-scale, high-density circuitry are largely undeveloped. Here we describe a 160,000-bit molecular electronic memory circuit, fabricated at a density of 10^(11) bits cm^(-2) (pitch 33 nm; memory cell size 0.0011 mm^2), that is, roughly analogous to the dimensions of a DRAM circuit projected to be available by 2020. A monolayer of bistable, [2]rotaxane molecules 10 served as the data storage elements. Although the circuit has large numbers of defects, those defects could be readily identified through electronic testing and isolated using software coding. The working bits were then configured to form a fully functional random access memory circuit for storing and retrieving information