Low-Mach-number turbulence in interstellar gas revealed by radio polarization gradients

The interstellar medium of the Milky Way is multi-phase, magnetized and turbulent. Turbulence in the interstellar medium produces a global cascade of random gas motions, spanning scales ranging from 100 parsecs to 1000 kilometres. Fundamental parameters of interstellar turbulence such as the sonic Mach number (the speed of sound) have been difficult to determine because observations have lacked the sensitivity and resolution to directly image the small-scale structure associated with turbulent motion. Observations of linear polarization and Faraday rotation in radio emission from the Milky Way have identified unusual polarized structures that often have no counterparts in the total radiation intensity or at other wavelengths, and whose physical significance has been unclear. Here we report that the gradient of the Stokes vector (Q,U), where Q and U are parameters describing the polarization state of radiation, provides an image of magnetized turbulence in diffuse ionized gas, manifested as a complex filamentary web of discontinuities in gas density and magnetic field. Through comparison with simulations, we demonstrate that turbulence in the warm ionized medium has a relatively low sonic Mach number, M_s <~ 2. The development of statistical tools for the analysis of polarization gradients will allow accurate determinations of the Mach number, Reynolds number and magnetic field strength in interstellar turbulence over a wide range of conditions.Comment: 5 pages, 3 figures, published in Nature on 13 Oct 201

A modeling case for high atmospheric oxygen concentrations during the Mesozoic and Cenozoic

Changes in atmospheric oxygen concentration over Earth history are commonly related to the evolution of animals and plants. But there is no direct geochemical proxy for O2 levels, meaning that estimations rely heavily on modeling approaches. The results of such studies differ greatly, to the extent that today's atmospheric mixing ratio of 21% might be either the highest or lowest level during the past 200 m.y. Long-term oxygen sources, such as the burial in sediments of reduced carbon and sulfur species, are calculated in models by representation of nutrient cycling and estimation of productivity, or by isotope mass balance (IMB)—a technique in which burial rates are inferred in order to match known isotope records. Studies utilizing these different techniques produce conflicting estimates for paleoatmospheric O2, with nutrient-weathering models estimating concentrations close to, or above, that of the present day, and IMB models estimating low O2, especially during the Mesozoic. Here we re-assess the IMB technique using the COPSE biogeochemical model. IMB modelling is confirmed to be highly sensitive to assumed carbonate δ13C, and when this input is defined following recent compilations, predicted O2 is significantly higher and in reasonable agreement with that of non-IMB techniques. We conclude that there is no model-based support for low atmospheric oxygen concentrations during the past 200 m.y. High Mesozoic O2 is consistent with wildfire records and the development of plant fire adaptions, but links between O2 and mammal evolution appear more tenuous

Heat Shock Protein-90 Inhibitors Enhance Antigen Expression on Melanomas and Increase T Cell Recognition of Tumor Cells

In an effort to enhance antigen-specific T cell recognition of cancer cells, we have examined numerous modulators of antigen-expression. In this report we demonstrate that twelve different Hsp90 inhibitors (iHsp90) share the ability to increase the expression of differentiation antigens and MHC Class I antigens. These iHsp90 are active in several molecular and cellular assays on a series of tumor cell lines, including eleven human melanomas, a murine B16 melanoma, and two human glioma-derived cell lines. Intra-cytoplasmic antibody staining showed that all of the tested iHsp90 increased expression of the melanocyte differentiation antigens Melan-A/MART-1, gp100, and TRP-2, as well as MHC Class I. The gliomas showed enhanced gp100 and MHC staining. Quantitative analysis of mRNA levels showed a parallel increase in message transcription, and a reporter assay shows induction of promoter activity for Melan-A/MART-1 gene. In addition, iHsp90 increased recognition of tumor cells by T cells specific for Melan-A/MART-1. In contrast to direct Hsp90 client proteins, the increased levels of full-length differentiation antigens that result from iHsp90 treatment are most likely the result of transcriptional activation of their encoding genes. In combination, these results suggest that iHsp90 improve recognition of tumor cells by T cells specific for a melanoma-associated antigen as a result of increasing the expressed intracellular antigen pool available for processing and presentation by MHC Class I, along with increased levels of MHC Class I itself. As these Hsp90 inhibitors do not interfere with T cell function, they could have potential for use in immunotherapy of cancer

Comparing the effectiveness of a short-term vertical jump vs. weightlifting program on athletic power development

Efficient training of neuromuscular power and the translation of this power to sport-specific tasks is a key objective in the preparation of athletes involved in team-based sports. The purpose of the current study was to compare changes in center of mass (COM) neuromuscular power and performance of sport-specific tasks following short-term (6-week) training adopting either Olympic Style Weightlifting (WL) exercises or vertical jump (VJ) exercises. Twenty six recreationally active males (18-30 years; height: 178.7±8.3 cm; mass: 78.6±12.2 kg) were randomly allocated to either a WL or VJ training group and performance during the countermovement jump (CMJ), squat jump (SJ), depth jump (DJ), 20m sprint and the 5-0-5 agility test assessed pre- and post-training. Despite the WL group demonstrating larger increases in peak power output during the CMJ (WL group: 10% increase, d=0.701; VJ group: 5.78% increase, d=0.328) and SJ (WL group: 12.73% increase, d=0.854; VJ group: 7.27% increase, d=0.382), no significant between-group differences were observed in any outcome measure studied. There was a significant main effect of time observed for the three vertical jumps (CMJ, SJ, DJ), 0-5m and 0-20m sprint times, and the 5-0-5 agility test time, which were all shown to improve following the training (all main effects of time p<0.01). Irrespective of the training approach adopted by coaches or athletes, addition of either WL or VJ training for development of power can improve performance in tasks associated with team-based sports, even in athletes with limited pre-season training periods

Sterol metabolism regulates neuroserpin polymer degradation in the absence of the unfolded protein response in the dementia FENIB.

Mutants of neuroserpin are retained as polymers within the endoplasmic reticulum (ER) of neurones to cause the autosomal dominant dementia familial encephalopathy with neuroserpin inclusion bodies or FENIB. The cellular consequences are unusual in that the ordered polymers activate the ER overload response (EOR) in the absence of the canonical unfolded protein response. We use both cell lines and Drosophila models to show that the G392E mutant of neuroserpin that forms polymers is degraded by UBE2j1 E2 ligase and Hrd1 E3 ligase while truncated neuroserpin, a protein that lacks 132 amino acids, is degraded by UBE2g2 (E2) and gp78 (E3) ligases. The degradation of G392E neuroserpin results from SREBP-dependent activation of the cholesterol biosynthetic pathway in cells that express polymers of neuroserpin (G392E). Inhibition of HMGCoA reductase, the limiting enzyme of the cholesterol biosynthetic pathway, reduced the ubiquitination of G392E neuroserpin in our cell lines and increased the retention of neuroserpin polymers in both HeLa cells and primary neurones. Our data reveal a reciprocal relationship between cholesterol biosynthesis and the clearance of mutant neuroserpin. This represents the first description of a link between sterol metabolism and modulation of the proteotoxicity mediated by the EOR

Legionella pneumophila strain 130b possesses a unique combination of type IV secretion systems and novel Dot/Icm secretion system effector proteins

Legionella pneumophila is a ubiquitous inhabitant of environmental water reservoirs. The bacteria infect a wide variety of protozoa and, after accidental inhalation, human alveolar macrophages, which can lead to severe pneumonia. The capability to thrive in phagocytic hosts is dependent on the Dot/Icm type IV secretion system (T4SS), which translocates multiple effector proteins into the host cell. In this study, we determined the draft genome sequence of L. pneumophila strain 130b (Wadsworth). We found that the 130b genome encodes a unique set of T4SSs, namely, the Dot/Icm T4SS, a Trb-1-like T4SS, and two Lvh T4SS gene clusters. Sequence analysis substantiated that a core set of 107 Dot/Icm T4SS effectors was conserved among the sequenced L. pneumophila strains Philadelphia-1, Lens, Paris, Corby, Alcoy, and 130b. We also identified new effector candidates and validated the translocation of 10 novel Dot/Icm T4SS effectors that are not present in L. pneumophila strain Philadelphia-1. We examined the prevalence of the new effector genes among 87 environmental and clinical L. pneumophila isolates. Five of the new effectors were identified in 34 to 62% of the isolates, while less than 15% of the strains tested positive for the other five genes. Collectively, our data show that the core set of conserved Dot/Icm T4SS effector proteins is supplemented by a variable repertoire of accessory effectors that may partly account for differences in the virulences and prevalences of particular L. pneumophila strains. Copyright © 2010, American Society for Microbiology. All Rights Reserved

Quality of antimalarial drugs and antibiotics in Papua New Guinea: A survey of the health facility supply chain

Background: Poor-quality life-saving medicines are a major public health threat, particularly in settings with a weak regulatory environment. Insufficient amounts of active pharmaceutical ingredients (API) endanger patient safety and may contribute to the development of drug resistance. In the case of malaria, concerns relate to implications for the efficacy of artemisinin-based combination therapies (ACT). In Papua New Guinea (PNG), Plasmodium falciparum and P. vivax are both endemic and health facilities are the main source of treatment. ACT has been introduced as first-line treatment but other drugs, such as primaquine for the treatment of P. vivax hypnozoites, are widely available. This study investigated the quality of antimalarial drugs and selected antibiotics at all levels of the health facility supply chain in PNG.Methods and Findings: Medicines were obtained from randomly sampled health facilities and selected warehouses and hospitals across PNG and analysed for API content using validated high performance liquid chromatography (HPLC). Of 360 tablet/capsule samples from 60 providers, 9.7% (95% CI 6.9, 13.3) contained less, and 0.6% more, API than pharmacopoeial reference ranges, including 29/37 (78.4%) primaquine, 3/70 (4.3%) amodiaquine, and one sample each of quinine, artemether, sulphadoxine-pyrimethamine and amoxicillin. According to the package label, 86.5% of poor-quality samples originated from India. Poor-quality medicines were found in 48.3% of providers at all levels of the supply chain. Drug quality was unrelated to storage conditions.Conclusions: This study documents the presence of poor-quality medicines, particularly primaquine, throughout PNG. Primaquine is the only available transmission-blocking antimalarial, likely to become important to prevent the spread of artemisinin-resistant P. falciparum and eliminating P. vivax hypnozoites. The availability of poor-quality medicines reflects the lack of adequate quality control and regulatory mechanisms. Measures to stop the availability of poor-quality medicines should include limiting procurement to WHO prequalified products and implementing routine quality testing